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Impact of Breath Control and Breath-holding on Stress in Medically Assisted Reproduction Patients (MAR) – Breath Hold to Breath Better Program – BHBB

DOI: 10.31038/IGOJ.2024714

Abstract

Objective of the study: Infertility affects millions of couples worldwide. Treatments have positive effects on fertility, but they also increase stress levels and disrupt emotional life. Often longer and more difficult than expected, they are a source of exhaustion and frequently cited as the cause of abandonment. The aim of this article is to evaluate the effects of a breathing control and breath hold program on stress and emotional life of patients undergoing MAP.

Method: In this randomized, single-center study, 12 MAR patients took part in a 4-week breathing control and breath hold program inspired by free diving breathing techniques, to be integrated into a care routine.

Results: Participants improved their psychological well-being in terms of stress, anxiety and depression. Negative thoughts decreased while positive thoughts increased. Sense of internal control increased positively, and quality of life improved.

Adherence to the program was very high and no side effects were reported.

Conclusion: This study tested the possibility of introducing and integrating free diving breathing techniques to help people regulate the negative impact of treatment on their emotional life. The program was very well accepted and tolerated. It met with great interest from participants and could be proposed as routine care in MPA and experimented with in other areas of mental health, such as PTSD (Post Traumatic Stress Disorder).

Keywords

Infertility, Stress, Anxiety, Depression, Breath control, Internal control, Quality of life, Emotional regulation

Introduction

Infertility affects several million couples worldwide. In France, almost a quarter of couples are unable to have children after one year of trying without contraception, and over 10% are still unable to do so after two years. In Europe, experts predict that this trend will double over the next ten years, partly due to the involvement of behavioral and environmental factors, which are increasingly suspected of affecting fertility. People eligible for assisted reproduction benefit from technical and medical advances to realize their desire for a child, but this is often at the cost of a long, difficult and psychologically challenging process. It has been observed that 40.2% of women undergoing MAP have a psychiatric disorder, the most common being generalized anxiety disorder (23.2%), followed by major depression (17%) and dysthymic disorder (9.8%). The levels of anxiety and depression observed in infertile women are equivalent to those found in women with heart disease, cancer or HIV infection [3]. However, before starting treatment, patients do not present more depressive disorders than the general population [1-6].

The percentage of couples who voluntarily abandon MAP can reach 50% after one year, and 60% after three cycles of treatment. In the opinion of couples, psychological reasons are more responsible for discontinuing protocols than medical refusal to continue attempts, physical exhaustion or medical pathologies. These abandonments are linked to emotional or psychological difficulties, anxiety and depression [7-12].

The European Society of Human Reproduction and Embryology (ESHRE) Psychosocial Routine Guide recommends access to psychological support [13].

Current psychological interventions aim to improve adaptation to the treatment process. A meta-analysis by Frederiksen et al (2015) showed that 56% of studies applying methods combining relaxation and cognitive behavioral therapies reduced stress and improved MPA outcome [14-16].

In either fields, studies have shown that the way we breathe influences our bodily, emotional and cognitive functioning [17-20]. Breathing has been shown to affect blood pressure, heart rate variability and certain brain regions such as the hypothalamus, amygdala and hippocampus [21,22]. Properly controlled, it helps us to regulate stress [23-25] and anxiety [26], with a reduction in cortisol concentrations in saliva. Conversely, high levels of stress have a detrimental effect on our breathing, causing hyperventilation [27-30].

Breath-holding is a special case of controlled breathing. It lies at the heart of apnea practice. The Danish national freediving team has created a respiratory rehabilitation program for patients with respiratory insufficiency. The program has met with a high level of acceptance (96.3%), while in conventional treatments, we observe patients’ difficulty in staying motivated and taking care of themselves over time [31].

It also improved exercise capacity and quality of life, with no reported side effects.

We propose to evaluate the impact of a breathing control and breath hold program, on stress for people undergoing MPA. Guillaume NERY, world champion freediver, created this specific program for the study.

Material and Method

Study Population

  1. This randomized study included 12 patients undergoing MPA, either as couples (female couples, female/male couples) or as singles (unmarried women). It was proposed between 05/27/2024 and 07/02/2024.
  2. Inclusions were entered into REDcap by the Randomization was also performed by REDcap.
  3. Inclusion criteria were a diagnosis of no pregnancy after 12 months without contraception and societal infertility. The program had to take place before receiving hormonal stimulation treatment or between two medical protocols.
  4. Non-inclusion criteria were heart failure, epilepsy or pregnancy.

Intervention

The intervention consisted of a program of breathing control and retention techniques used in freediving practice (Figure 1).

Each session lasted 1h and took place every week for 4 weeks. It consisted of:

  1. Introduction with a presentation of the session and a Warm up breath (observation of breath and ventilatory mechanics).
  2. A cycle of breath control and retention (progressive lengthening of exhalation) with body movements targeting the ribcage.
  3. Prolonged breath retention.
  4. A return to calm.

Figure 1: Program

Program Summary

This program has been proposed to patients undergoing MPA because they are confronted with high levels of stress, leading to difficult emotional elevators, a feeling of loss of control, emotional deregulation and reduced quality of life. The psychological implications are consequential in the various spheres of personal and professional life, and are a source of abandonment [7-12]. The aim was to be able to offer a stress management tool accessible to everyone, with no prerequisites and at anytime. The idea was also to propose an activity that could be shared as a couple, to create an opportunity to meet other people who live the same journey, particularly for solo women who often feel isolated in their treatment. Being able to accompany patients outside the medical treatment setting, outside the walls of the CHU (University Hospital Center) was an important point in fostering a climate of relaxation and conviviality in the AMP course. Last but not least, the aim was to accompany and support treatment protocols with a totally innovative approach.The breathing control and breath hold program was created by a renowned freediver, who is keen to pass on his practice and the associated breathing techniques to as many people as possible.

Results

Patient Characteristics

  1. Patient characteristics are presented in Table 1.
  2. The average age of the participants was 34.
  3. In both groups, almost all were women, as MPA is mainly aimed at women (solo women, female couples and female/ male couples).
  4. In the active group, 8 patients were couples and 4 were unmarried women.
  5. In both groups, all participants were working at the time of the As far as infertility is concerned, none of the participants had ever had a child. The infertility of each participant was therefore primary.
  6. In both groups, we observe the same distribution of 2/3 of patients in the gamete donation AMP program and 1/3 in the intra-marital program. It should be noted that half of the participants were affected by societal infertility, and therefore by gamete donation. Generally speaking, the average duration of infertility does not exceed 3 years. Only a minority in both groups had not yet received hormonal treatment.

Table 1: Characteristics of the patients.

 

Breath Group

Control Group

Average Age

33

35

Female

5

5

Male

1

1

FM Couple

2

3

Couple FF

2

1

Solo Women

2

2

Women in Employment

5

5

Men in Employment

1

1

Infertility

6

6

Primary Secondary

0

0

Type of Fertility    
Female

2

2

Male

0

0

Mixed

0

1

Societal

3

3

Societal and Feminine

1

0

Idiopathic

0

0

Conception mode    
With Gamete Donation

4

4

Oocyte Donation

0

1

Sperm Donation

4

3

Without Gamete Donation

2

2

Duration of Treatment    
0-1 Year

2

4

1-2 Year

4

1

2-3 Year

0

1

>3 Year

0

0

No of Treatments

1

2

Not Yet Treated

13

7

Attendence at 4 Meetings

5

/

Study Output

0

/

Graduation and Participation in the program

/

4

Out of Sight

1

1

Study Results

The patients in the control group, motivated by the proposed program, indicated that they wished to leave the study to take part in the program sessions. They joined the active group and completed the entire program. Comparison at M1 was therefore not possible (Table 2).

Comparison of the “Control and Breath-holding” Group and the Control Group at M0

Table 2: Main results of the emotional scales.

 

Breath Group

Control Group Breath Group

Control Group

 

M0

M1 M0

M1

 

n=6

n=6 n=6

n=6

Stress

21.8

19.8 17,5

20,5

Anxiety T

46.8

40.6 42

33

Anxiety E

60.8

43.4 36

36,6

Depression

12

2.8 5.5

2

Positive Thoughts

35.6

37 32

38

Negative Thoughts

23.8

20.6 18,5

19

Internal Control

11.6

12 12

13

Control A

9.6

8 6

5

Control C

8.2

8.8 7

7

QOL Core

64.6

71.6 67

68

QOL Treatment

58.75

62 100

68.5

QOL Total Score

92

82 58,48

67,5

The control group is made up of 2/3 patients who will not receive hormone treatment (men or women who will not carry the pregnancy) although the “control and breath-holding” group is composed by women who’ll take the treatment at 100%.Before starting the program (M0), the control group had less stress, less treatment anxiety, fewer positive and negative thoughts, slightly more internal control, and a similar emotional quality of life. However, there were significant differences with regard to state anxiety, with rates significantly lower than those of the “control and breath-holding” group. Treatment related quality of life was significantly higher in the control group. The relationship is reversed for the overall quality of life score which is better in the “control and breath-hold” group.

For methodological reasons, the self-questionnaire scores returned by people who left the study at (M1) cannot be used. They were nevertheless reported with an improvement in parameters between (M0) and (M1).We note the positive impact of the program between M0 and M1 for the control group, particularly for depression, trait anxiety, positive thoughts and overall quality of life. When patients in the control group look ahead to treatment, however, scores drop and are lower than those in the “control and breath-hold” group.

Stress Levels

After completing the program, stress levels fell to below the pathological threshold.

Anxiety

The results show that people do not have a basic anxious personality, but they feel anxious about the medical protocol. While their habitual anxious background diminished after the program, anxiety about the treatment tended to in- crease.

Depression

A clear reduction in depressive affect was observed, with the threshold becoming almost zero at M1.

Positive and Negative Affects

The results show that patients have more positive thoughts after the program, while at the same time there is a greater reduction in negative thoughts.

Locus of Control

The patients all increased their sense of internal control over external elements, and the feeling that their actions were producing the desired effects.

Quality of Life

The results obtained show a trend towards an improvement in quality of life, at the global, emotional and treatment levels.

Program Compliance

Patients in the breathing group attended all 4 sessions, except for 1 person who was unable to attend a session for professional reasons. People in the control group left the study to take part in the breath- hold program.

Three people were lost to follow-up. They had expressed changes in their schedules shortly after signing the consent form. They did not complete any questionnaires. With the exception of those lost to follow-up, the response rate to the self-questionnaires was 100%. Patients who left the study to participate in the breathing sessions wished to complete the self-questionnaires.

Adverse Events

No adverse events were reported during the program.

Discussion

At M0, those who did not receive the hormonal treatment were less anxious about the treatment, and less depressed, than those who were to take it and carry the pregnancy. This trend is also reflected in the assessment of treatment item in quality of life, which is lower in those who will take the treatment. Treatment seems to be a factor that differentiates the two groups emotionally. Those taking the treatment will be more sensitive to emotional imbalance. On the other hand, those who do not take the treatment will be exposed to passivity. It can be hypothesized that being a “spectator” of the process represents a stress factor and a deterioration in overall quality of life, with a feeling of not being able to act concretely on the difficulties encountered by women in protocol.

Patients were sensitive to the fact that care teams were concerned about the emotional impact of treatment, and that they were offered help with an innovative activity created by a top-level athlete. Interest in and compliance with this type of program corroborates the results of a Danish study carried out by the Danish national free diving team. It proposed a respiratory rehabilitation program for patients suffering from respiratory failure. The study showed a high level of adherence (96.3%) and compliance for patients who usually have difficulty sustaining rehabilitation activities over time [31].

For infertility patients, couples wished to participate as a couple, and were very receptive and motivated by the idea of being able to share together an activity linked to their MPA journey, outside the medical context in which the man or woman who will not carry the pregnancy often finds it difficult to find their place in the journey. Only one woman in a couple did not participate with her partner, for scheduling reasons.

Those lost to follow-up expressed a lack of stability in their professional schedules (business travel, monthly schedule changes) before withdrawing.

Despite this enthusiasm, we encountered several obstacles to recruitment. Recruitment time was short (6 weeks), as sessions had to be carried out before starting the first protocol or between two protocols, and in the absence of pregnancy. Geographical remoteness was also an important factor, with the expression of excessively long travel times and the anticipation of parking difficulties. Dense or unstable schedules, compounded by numerous medical appointments, were also mentioned. In addition, patients’ availability slots were not always compatible with those of the room in which the sessions were held (mid and late afternoon times too early for most patients, who were unable to make themselves available). Finally, it was not possible to present this study to the clinical-biological team before starting the inclusions.

Raising awareness, informing and training care teams in the value of a complementary approach to limit the risks of exhaustion and abandonment in MPA could have provided a better understanding of the issues at stake in the study. Psychological burden is more difficult to bear than physiological burden. It is responsible for the majority of withdrawals from MPA, with a rate of 60% after 3 cycles of treatment.

The use of apnea breathing techniques is totally new in MPA and in the healthcare field.

Raising doctors’ awareness is particularly important, as it has been shown that the gynecologist remains the central figure in the lives of patients undergoing MPA. His word is therefore of decisive value in introducing this kind of program [32]. At an emotional level, the results of self-questionnaires show that the breath control and retention program reduces stress levels, improves psychological well- being, quality of life and feelings of internal control, and increases positive thoughts.

This trend is similar to that observed in Huberman’s study [21], which showed that, when properly controlled, breathing has significant effects on the regulation of stress, emotions and mood. The results show reduced levels of cortisol concentration in saliva and a positive impact of these breathing techniques on the hippocampus and various other brain areas, involving, among other things, an action on the vagus nerve and cardiac variability.

Similarly, he observed that voluntary breathing re-establishes a sense of control over internal states and increases positive affect. These results corroborate the trends observed in our study, whether in terms of internal locus control, positive and negative affect scale. This is particularly interesting for patients who suffer from a sense of loss of control and often dominated by negative thoughts, particularly in women after embryo transfer [33-35]. Reestablishing a sense of control could help patients regain confidence, reassuring themselves that it is possible to act on their thoughts and emotions, and that they can choose which actions to take to adapt. Better internal control will help to filter thoughts and to encourage positive ones. Patients will move from a mindset of “fighting against loss of control” to “working to control the things I can do something about”. Feeling able to act on their internal physiological and psychological state enables them to become active rather than being passive face to the treatment, to feel involved and no longer have the feeling of being subjected to treatment. In terms of anxiety, we note that trait anxiety, which relates to the treatment experience, tends to increase, while state anxiety decreases. It may be hypothesized that breath control and retention reduce general anxiety, but more practice or other tools should be considered to deal with treatment related anxiety.

The quality of life results show an improvement in overall quality of life, including emotional life and treatment experience, between M0 and M1. The medical protocols are better experienced, but they nevertheless give rise to massive anxiety, which is difficult to reduce.

Depression remains moderate at M0 and becomes almost non- existent at M1. After IVF treatment, 1 in 4 women and 1 in 10 men experience depression when the pregnancy test is negative [36- 38]. Having a regulatory tool at your disposal would help to limit depressive affects, reduce emotional elevators and better apprehend the fear of results for the next protocol.

The Breath control and breath hold program in this study is characterized by alternating sequences of breath control and retention, during which the patient moves out of his or her comfort zone, experiment phases of long exhalations, which promote a return to calm.

By focusing on the sequence of different moments, the patients live instead of experience, through the body, moments of discomfort and “challenge” during the retention phase. During the return to calm, the long exhalation repositions them in their own safety zone, fostering a sense of reassurance and confidence. It’s also interested to note that the design of a session is quite similar than MPA mental sequences. The sequence of a session includes 3Steps: a preparation of the body(before the protocol), a moment of challenge (during the protocol, action phase) with breath control and retention, and a recovery time (after the protocol). Treatment sequences follow the same triptych, with pre- treatment preparation (physical, mental, lifestyle, medical examinations), an uncomfortable period of action, during treatment, at the moment of results and afterwards, a control phase, followed by a return to everyday life and the usual balance.

Progressive preparation for the next breathing cycle allows each individual to progress at his or her own space, working on internal control and reinforcing a sense of security. At the start of the session, zone-by-zone stretching exercises prepare the body to expand the breathing space. During the session, the freediving instructor provides precise guidance, meticulously respecting the sequence and duration of each exercise. This sets a clear framework and rhythm. The freediver takes the mental load off the patient, providing warm, enveloping and deliberately minimalist guidance. The fact that there is no visualization, no mental images to suggest or elaborate, no hint of stress to evacuate, no interpretation with psychological connotations means that the patient demobilizes his mind. Patients don’t have to concentrate on memorizing breathing rhythms or program sequences. They let themselves be carried along by the voice of the freediver, who follows the program without seeking to comment or observe. The spirit of the program calms and eases the mind in favor of an intimate relationship with oneself, an active, unique and direct focus on one’s breathing body.

This mental “off-loading” is further reinforced by the fact that the instructor himself takes care of setting up and taking down the yoga mats .The duration of each breathing sequence is shared by the group. The result is a kind of “group breath” that creates a sense of unity. In this space of shared breath, everyone experiments with their own breathing rhythm and challenges, while feeling carried, accompanied, secured and supported. At the end of the program, other related benefits were observed. For example, the solo women were able to meet outside after the sessions, in a convivial atmosphere. They were able to get to know each other and share their experiences with others going through the same process. They were able to say how much these encounters had changed their experience of treatment and the precious, reassuring bonds they had forged.

Limitations

It would have been preferable to begin with a feasibility study, and to plan a training and information period with the healthcare professionals concerned before starting the study. Furthermore, randomization was carried out on an individual basis, which was a real hindrance. There was a lot of disappointments at the time of group allocation, with a feeling of failure and bad luck for those in the control group, particularly the women. It also led to people leaving the study to join their partner. As a result, the study could not be randomized.

Conclusions

This study shows that a breath control and breath hold program is an interesting stress management tool in MAR, while it can promote social bonding and improve emotional regulation. We suggest that it can be proposed as a preventive measure, by the gynecologist, to limit the risks of burn out, avoid the deterioration of the emotional state, the risks of abandonment and also multiply the chances of success. Progress must be made to take into account the psychological issues of MAR and that accompanying proposals in an integrative approach are part of the care paths. A respiratory program could be tried in other clinical fields such as PTSD (Post-traumatic Stress Disorder). This program could be considered in zoom or via an application, to broaden access, without geographical constraints or audio to do at home.

Abbreviations

MAR: Medical Assisted Reproduction; MAP: Medical Assistance for Procreation; CHU: Universitaire Hospital Center; HS: Shrinkage According Height; DS: Shrinkage According Diameter; Anxiety T: Anxiety Trait; Anxiety E: State Anxiety; Control I: Internal Control; Control A: Others Control; Control C: Chance Control; QOL Core: Quality of Life Core; QOLT: Quality of Life Treatment; QOL Total Score: Quality of Life Score Total

Acknowledgments

We thank the « Bluenery Academy and Guillaume Nery » for its contribution of this program.

Author Contributions

Valérie Benoit: Conceptualization, investigation, organization, data curation, formal analysis, funding acquisition, investigation, methodology, writing – original draft, writing – review and editing. Véronique Isnard: conceptualization, recruitment, organization. Methodology – Clémence Cirade: conceptualization, recruitment Sarah Dupuis: conceptualization, recruitment Marion Causeret: project administration, supervision

You can see full list of contributor roles below:

  1. Conceptualization
  2. Data curation
  3. Formal Analysis
  4. Funding acquisition
  5. Investigation
  6. Methodology
  7. Project administration
  8. Resources
  9. Software
  10. Supervision
  11. Validation
  12. Visualization
  13. Writing – original draft
  14. Writing – review & editing

We kindly recommend referring to CRediT Taxonomy (https://credit.niso.org/) for the detailed term explanation.

Funding

This work is supported by University Hospital Center if Nice (Grant No. XXXXX).

Data Availability Statement

Not applicable.

Conflicts of Interest

“The authors declare no conflicts of interest.”

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Integrative Treatment of Mammary Neoplasm in a Cat Induced by Injectable Hormonal Contraceptive

DOI: 10.31038/IJVB.2025912

Abstract

Mammary neoplasms are among the most common malignancies in cats, representing the third most frequent tumor type. In some cases, these neoplasms may be associated with the prolonged use of injectable hormonal contraceptives. The standard treatment protocol typically involves ovariohysterectomy, bilateral mastectomy, and, when clinically indicated, chemotherapy. This case study reports on a cat diagnosed with mammary carcinoma, potentially induced by the administration of hormonal contraceptives. Due to financial constraints, the recommended ovariohysterectomy, mastectomy, and chemotherapy were not performed. Instead, the patient was treated using an integrative veterinary approach, with the injectable homeopathic Viscum album as the primary therapeutic agent. The treatment protocol resulted in a marked reduction in tumor volume, improved overall patient condition, and no observed adverse effects. This case highlights the potential of Viscum album as a complementary therapeutic option to manage feline mammary neoplasms, emphasizing the importance of integrative strategies that prioritize patient well-being. Further research is warranted to validate the efficacy and elucidate the mechanisms of this treatment in broader clinical applications.

Keywords

Mammary neoplasm; Female cats; Hormonal contraceptive; Viscum album; Integrative veterinary medicine; Homeopathy

Introduction

Mammary neoplasms represent one of the most prevalent tumors in intact female cats, ranking as the third most common tumor type within the species. These neoplasms are frequently malignant and characterized by a high metastatic rate and poor prognosis [1]. The incidence of mammary tumors is significantly higher in females that are either not spayed or spayed after their first estrus cycle, compared to those undergoing ovariohysterectomy before their first estrus [2]. Prolonged use of hormonal contraceptives, particularly injectable formulations, has been identified as a major risk factor for the development of mammary neoplasms. This is attributed to the hormonal influence on receptors present within mammary tissue [3].

Standard treatment modalities include surgical interventions such as bilateral mastectomy, chemotherapy [4], radiotherapy [5], and electrochemotherapy [6]. However, these conventional approaches are often accompanied by significant adverse effects and present considerable challenges related to cost and accessibility, particularly in resource-limited settings. Integrative veterinary medicine has gained recognition as a promising alternative, combining conventional and complementary therapeutic modalities to enhance treatment efficacy and improve patient quality of life [7].

Amongcomplementarytherapies, Viscumalbum, amedicinalagent widely employed in anthroposophical and homeopathic medicine, has garnered attention for its antitumor and immunomodulatory properties. Research indicates that Viscum album extracts inhibit cell proliferation, induce apoptosis in tumor cells, and enhance the quality of life of cancer patients [8]. Despite these promising attributes, the application of Viscum album in veterinary medicine remains underexplored, with only limited preliminary studies available [9].

This report details a clinical case of a feline patient with mammary neoplasms, potentially induced by injectable hormonal contraceptives. The patient was treated primarily with the injectable administration of Viscum album as part of an integrative therapeutic approach. Furthermore, the report discusses the possible mechanisms of action and the broader implications of utilizing this therapeutic agent to manage feline neoplasms.

Case Report

A 2-year-old female cat weighing 3.1 kg, intact, was evaluated during a veterinary home visit. The cat had a six-month history of mammary gland enlargement, which subsequently developed ulceration in part of the affected area. The cat was fed a commercial diet ad libitum. The owners reported the use of injectable progestins as a contraceptive method since the cat’s first estrus, which occurred at five months of age. On physical examination, the animal exhibited pale mucous membranes, a capillary refill time (CRT) of 3 seconds, and an alert demeanor with a good appetite. No abdominal discomfort was noted, and the animal demonstrated a calm temperament. Examination of the mammary glands revealed a sizable ulcerated mass without apparent bleeding (Figure 1), clinically indicative of a mammary tumor. Due to financial constraints, no blood tests or imaging studies could be performed, as the family lacked resources. The service was provided voluntarily, and all medications were donated. The treatment protocol included oral administration of vitamin D3 (1000 IU/SID), vitamin C (500 mg/SID), omega-3 fatty acids (1000 mg/SID), and Ganoderma lucidum (90 mg/SID). Injectable treatments administered subcutaneously consisted of Viscum album D3 (1 ampoule, 1.1 mL, Injectcenter) every other day for 60 days and a combination of Viscum album D4, Viscum album D30, and Lachesis D15 (1 ampoule, 1.1 mL) administered SID, three times weekly for 60 days.

Figure 1: Image of the mammary tumor of varying dimensions in August 2024, at the initiation of treatment.

Results

Follow-up I – At the beginning of treatment (September 2024), the owner reported an improvement in the patient’s overall condition. The cat was more active, well-disposed, and had an improved appetite (Figure 2). The treatment protocol was recommended to be continued.

Figure 2: Image of the ulcerated tumor in September 2024, after treatment initiation.

Follow-up II – By October 2024, the owner observed a notable reduction in the lesion’s size, with approximately 50% improvement (Figure 3). The cat’s behavior remained stable and unchanged throughout the period. The treatment protocol was advised to be continued.

Figure 3: Image of the ulcerated tumor in October 2024, showing significant reduction following treatment initiation.

Follow-up III – In December 2024, theowner reported approximately 90% improvement in the lesion (Figure 4). The cat’s behavior remained stable and unchanged. The treatment protocol was continued.

Figure 4: Image of tumor regression in December 2024, demonstrating significant reduction following treatment.

Follow-up IV – By January 2025, the lesion showed continuous improvement, with complete remission observed (Figure 5). The patient’s behavior remained stable, and the treatment protocol was maintained.

Figure 5: Image of tumor regression in January 2025, showing complete remission following treatment.

The patient remained stable throughout the treatment period, and no adverse effects were reported over the six months of therapy. The tumor regressed progressively and completely without bleeding (Figure 6).

Figure 6: Image of tumor regression in January 2025, showing complete remission following treatment.

Discussion

The association between the use of hormonal contraceptives and the development of mammary neoplasms in cats is well-documented in the literature. These contraceptives provide continuous hormonal stimulation, predisposing mammary tissue to tumor development [1]. The inability to perform ovariohysterectomy, compounded by the administration of progestins in the present case, underscores the significant impact of hormonal factors on tumor development and progression.

This case highlights the potential therapeutic role of the injectable homeopathic medicine Viscum album as an adjunctive tool in managing feline mammary neoplasms, particularly when surgical intervention is not feasible due to financial constraints or comorbidities. Over six months, the treatment achieved complete tumor remission, demonstrating promise as a complementary approach for feline oncology.

The therapeutic use of Viscum album in integrative veterinary medicine, though not extensively explored, is supported by studies demonstrating its ability to stimulate the immune system, selectively induce apoptosis in tumor cells, and improve the quality of life of cancer patients [10,11]. The results of this case are consistent with these findings, suggesting that Viscum album can effectively reduce tumor mass and control disease progression in feline patients. Similar outcomes have been reported by Valle & Carvalho (2021), who documented complete remission of squamous cell carcinoma in a dog treated with injectable homeopathic Viscum album.

The rapid and progressive remission of the mammary tumor within six months highlights the potential of this approach, particularly in resource-limited settings where surgical or chemotherapeutic interventions are inaccessible. Furthermore, the absence of adverse effects in the treated patient supports the safety of Viscum album administration, aligning with previous findings from both veterinary and human medicine [12]. Despite the encouraging outcomes, the lack of complementary diagnostic tests in this case presents a limitation in confirming precise tumor characteristics or prognosis. Nonetheless, the clinical progression and photographic evidence demonstrate favorable therapeutic outcomes.

This case underscores the importance of integrative therapies in veterinary medicine and highlights the need for further scientific investigation into using Viscum album in veterinary oncology. For patients with limited access to conventional treatments or contraindications to surgery and chemotherapy, complementary approaches such as Viscum album therapy may represent a viable and effective alternative for managing various neoplasms, improving quality of life, and, in some cases, achieving complete disease remission. These results contribute to the growing body of evidence supporting the antitumor and immunomodulatory potential of Viscum album, suggesting expanded applications in integrative veterinary oncology.

Conclusion

The successful use of Viscum album, in this case, demonstrates its potential as a valuable adjunctive therapy for feline mammary neoplasms, particularly in resource-limited settings where conventional treatments may not be accessible. Despite the absence of standard diagnostic tools and surgical interventions, the observed tumor regression and the lack of adverse effects suggest that Viscum album could offer a promising alternative. This case contributes to the growing body of evidence supporting the role of integrative medicine in veterinary oncology, highlighting the need for further exploration into its clinical applications and therapeutic mechanisms.

References

  1. SILVA, Natalia Asevedo, OLIVEIRA, Ludimila Rodrigues, RIOS, Paula Baeta (2021) Mammary neoplasms in cats – Literature In: Proceedings of the II Web Minas Gerais Veterinary Medicine Congress: COMVET and IV Academic Veterinary Medicine Conference (JAVET)
  2. NELSON R W & COUTO CG (2010) Postpartum and mammary gland In: NELSON RW, COUTO CG. Small Animal Internal Medicine. 4th ed. Rio de Janeiro: Guanabara Koogan.
  3. LANA S E, WITHROW SJ, VAIL D M (2007) Tumors of the mammary In: WITHROW S J, VAIL D M. Withrow and MacEwen’s Small Animal Clinical Oncology. 4. St. Louis: Elsevier.
  4. LOPES MCT (2017) Clinical, pathological, epidemiological, and survival study of mammary tumors in cats treated at the Veterinary Hospital of the State University of State University of Londrina. Master´s thesis submitted to the Professional Master’s Program in Veterinary Clinics at the State University of Londrina. Londrina.
  5. WITHROW S J, VAIL D M (2007) Withrow and MacEwen’s Small Animal Clinical 4. ed. St. Louis: Elsevier.
  6. SPUGNINI E P, ESPOSITO T, TOGNONI A, BALDI A (2016) Electroporation-based treatments for cancer: An effective therapeutic option. Oncology Reports.
  7. VALLE ACV, VALLE MLPV, CARVALHO AC (2025) Homeopathic treatment for feline hyperesthesia.
  8. VALLE A C V (2020) In vitro and in vivo evaluation of the ultra-diluted Viscum album efficacy and safety. Doctoral thesis. Catholic University of Brasilia – UCB. Brasilia, Brazil.
  9. VALLE A C V & CARVALHO A C (2021) Homeopathic Viscum Album on the Treatment of Scamous Cell Carcinoma Lesion in a Dog (Canis familiaris)-Case Report. Integrative Journal of Veterinary Biosciences, 5, 1–3.
  10. VALLE ACV and CARVALHO AC (2023) Long-Term Survival of a Dog With Hepatocellular Carcinoma Under Treatment with Viscum album – Case Report, Medical Research Archives.
  11. VALLE A C V, CARVALHO A C (2021) Squamous Cell Carcinoma in a Dog (Canis familiaris) Treated by the Viscum album Therapy – Case Integr J Vet Biosci.
  12. Magalhães M, Oliveira FS, Hataka A, Costa FVA (2009) Mammary neoplasms in cats – Literature Rev Clin Vet.

Predictors of Occupational Therapy Services among Adolescents with Substance Use Disorder in Uganda

DOI: 10.31038/AWHC.2025812

Abstract

Background: Substance use remains high among adolescents in Uganda. The use of occupational therapy services has been found to restore cognitive function among individuals with substance use disorder, with limited data in Uganda.

Objective: This study assessed the uptake of occupational therapy services and factors associated with the utilization of occupational therapy use among adolescents with substance use disorder.

Methods: A cross-sectional study was conducted using consecutive sampling to select 106 adolescents. Data were analyzed using SPSS, reporting descriptive statistics and influencing factors utilizing linear regression.

Results: Overall awareness and utilization of occupational therapy services were 54.7% and 67%, respectively. However, the variables of age (aPR=0.48, 95% CI=0.32-1.70), religion (aPR=0.54, 95% CI=0.63-2.52), education (aPR=0.31, 95% CI=0.74-2.63), occupation (aPR=0.86, 95% CI=0.43-2.78), did not show a statistically significant association with the utilization of these services at the multivariate level.

Conclusion: The overall awareness and uptake of occupational services among adolescents remain suboptimal. For occupational therapy to effectively address substance use disorder in adolescents, it’s crucial to proactively define and deliver innovative services tailored to their needs. Further research should focus on conducting qualitative studies to explore the barriers and facilitators that adolescents encounter in accessing occupational therapy services.

Keywords

Associated factors, Adolescents, Occupational therapy, Substance use, Uganda

Introduction

Substance use still remains high among adolescents . Globally the prevalence of mental health disorders in children and adolescents due to substance use ranges from 6.7% to 13.4% and 41.6% in sub-Saharan Africa by 2016, with the highest rate in central Africa at 55.5%. In Uganda, the prevalence of substance use among youth stands at 26% of which Mbarara City accounts for 5. More studies have looked at adults with substance use disorder, leaving behind the most at-risk group, which is adolescents [1-3].

Continuous use of drug substances causes cognitive impairments among adolescents, such as limiting individual performance of daily activities. Furthermore, It has been demonstrated that individuals with substance use disorders have a restricted sense of themselves as active agents (Davidson & Strauss) and are less autonomous in leisure activities and socialization compared to a non-disabled sample which reduces productivity [4,5].

Occupational therapy services are an important part of substance use rehabilitation programs as they enable clients to restore cognitive function and foster engagement in meaningful occupations a activities. A historical review of the profession identified its strong foundations in the treatment of mental illness, originating in substance use disorder. Factors such as sociodemographic characteristics, knowledge and awareness have been reported to predict the use of occupational therapy services. A study done in a US psychiatric department identified physical factors like refusal of patients to participate in these activities and social-cultural factors to be associated with poor utilization of occupational therapy among people with mental disorder [6-9].

Mbarara regional referral provides a range of occupational therapy interventions that enable individuals and groups of people to participate in their occupations of self-care, such as brushing teeth or eating, productivity, such as going to work or school, craft making, tailoring and leisure/play such as swimming or soccer. Despite the availability of the services, low attendance is still recorded, and no study has been carried out in the mental health units of Mbarara Regional Referral Hospital to identify the factors influencing the utilization of these occupational therapy services among adolescents with substance use disorders.

Therefore, we determined the factors associated with the utilisation of occupational therapy services among adolescents with substance use disorder. The findings of this study will inform tailor-made interventions aimed at increasing access to and utilization of occupational therapy among adolescents with substance use in Uganda and other similar sub-Saharan African settings.

Methods

Study Design and Setting

This was a quantitative cross-sectional study. The study was conducted at the Mental Health Unit of Mbarara Regional Referral Hospital, situated in Mbarara city in the southwestern region. This hospital, government-owned and serving as both a referral and teaching facility, is affiliated with the Medical School of Mbarara University of Science and Technology. It offers occupational therapy services to around 150 adolescents who are diagnosed with substance use disorder within a period of two months.

Study Population, Size and Sampling

The study was conducted among adolescents (both male and female) aged 10 to 19, as well as caregivers of adolescents who were unable to provide the necessary information themselves.. The Yamane formula (1975) was used to calculate the sample size. The hospital receives an average of 400 people who are diagnosed with mental health illness, and approximately 150 clients are adolescents with substance use disorder who are recorded in a period of two months. Out of the 109 participants sampled and approached, 106 provided informed consent and participated in the study, resulting in a response rate of 97.2%. Only three participants declined to provide informed consent and participate in the study due to their unstable mental status. Because of the limited number of adolescents in the rehabilitation program, we employed consecutive sampling.

Data Collection Procedure

A semi-structured questionnaire was used to collect data. The questionnaire was developed from the literature. The tool contained items on occupational therapy services, demographic characteristics, awareness of occupational therapy services, and utilization of occupational therapy services. Patients were identified from mental health unit records, the selected ones were taken in a secluded, quiet room to guarantee privacy and confidentiality. A researcher then consented the patient and carried interview. After interview, researcher thanked participants for participating in the study.

Data Management and Analysis

The data collected was carefully checked for completeness before safety storage. The data collected from the respondents was securely stored in a confidential manner, accessible only to the researcher and their assistants.

Data was entered into MS Excel and then transferred to Statistical Program Statistical Package for Social Sciences Version 20 (SPSS) for analysis. Descriptive statistics were computed and presented as tables and frequencies. The sum score of each outcome was assessed based on Bloom’s cut-off point and from the literature. Having a score above the cut-off point was equated with having high levels of awareness and better utilization of occupational therapy services. Participants ‘overall awareness was categorized using Bloom’s cut-off point, as high if the score is between 75% and 100% (4 points), moderate if the score was between 60% and 74% (2-3points), and poor if the score was less than 50% (<1 points). (No awareness,0 points; little awareness, 1 point; moderate awareness, 2 points; high awareness, 3-4 points.

Subsequently, the level of utilization was classified into good utilization (>50%) and poor utilization less than 50%). At bivariate analysis, used descriptive statistics and binary regression at multivariate, significant variables of p-value <0.05 and CI 95% were considered.

Ethical Considerations

Ethical approval was secured from the research ethics committee at Bishop Stuart University, with administrative clearance obtained from Mbarara Regional Referral Hospital.

Adolescents were presented with assent forms, empowering them to choose freely whether to participate in the study. They were also assured the right to ask questions, refuse to disclose information, seek clarification, or withdraw from the study at any juncture. Consent was obtained from caretakers of adolescents under 18 years who were not emancipated minors.

Interviews were conducted individually with selected participants in a secluded, quiet room to guarantee privacy and confidentiality. Participant anonymity was maintained by excluding their names from all study documentation.

Results

The majority of participants were male 87(82.1)% and adolescents aged below 18 years, with a median age of 14years (60%) and interquartile range of 2.

Most participants (63.2%) had resided in the city for more than 5 years, with a median of 6 years. The majority (77.4%) identified as Christians, with 82 (77.4%) being single, and holding primary (80.0%) or ordinary level certificates (24.5%). In terms of occupation, the majority (81.1%) were engaged in subsistence farming, followed by commercial farming (9.4%) and other occupations (9.4%). Regarding income, most (78.3%) earned a monthly income ranging from 100,000 to 200,000/=, and finally, a majority (58.5%) of participants resided or stayed within 1-5 kilometers of the nearest health facility, with a median distance of 3 kilometers. (Table 1).

Table 1: Demographic characteristics of participants.

Variable

Category

N (%)

Age 9-12

29 (27.4)

13-15

60 (56.6)

16-18

17 (16.0)

Gender Male

87 (82.1)

Female

19 (17.9)

Marital status Not married

82 (77.4)

Married

24 (22.6)

Religion Catholic

32 (30.2)

Anglican

41 (38.7)

Pentecost

31 (29.2)

Moslem

2 (1.9)

Occupation Subsistence farming

86 (81.1)

Commercial farming

10 (9.4)

Any other

10 (9.4)

Salary (UGX) 0-100000

83 (78.3)

100000-200000

7 (6.6)

above 200000

16 (15.1)

Education None

51 (48.1)

Primary

29 (27.4)

Ordinary

14 (13.2)

Advanced level

7 (6.6)

Tertially

5 (4.7)

UGX- Uganda Shillings

Awareness of Occupational Therapy Services (Univariate)

Recognizing that prior the awareness of occupational therapy is crucial for its utilization, we asked participants to define it and identify the services they were aware of, along with the sources of this knowledge. The majority, 58 (54.7%) of the participants, were familiar with the definition of occupational therapy services, and a significant portion (88%) knew more than one service. Notably, the dressing was recognized by 55 (51.9%) participants, followed by self-care/hygiene with 42 (39.6%), tailoring with 41 (38.7%), the development of morning/evening routines with 36 (34.0%), craft-making with 28 (26.4%), and other services with 21 (19.8%). Furthermore, majority 102(96.2%) had gained awareness of occupational therapy services from healthcare workers (Table 2).

Table 2: Awareness of occupational therapy services.

Variable

N%

0ccupatinal therapy services definition  
YES

58 (54.7)

NO

48 (45.3)

Services
Self-care/Hygiene

42 (39.6)

Dressing

55 (51.9)

Development of morning/evening routines

36 (34.0)

Tailoring

41 (38.7)

Craft making

28 (26.4)

Any other

21 (19.8)

Source of information
Health worker

102 (96.2)

Media/TV

3 (2.8)

Any other

1 (1.0)

Utilization of Occupational Therapy Services

The findings indicate that most participants in this study, 71 (67.0%), had utilized one or more occupational therapy services within a one-year period. The most commonly used service was dressing, with 55 participants (51.9%) reporting its use, followed by self-care/hygiene with 42 participants (39.6%), tailoring with 41 participants (38.7%), development of morning/evening routines with 36 participants (34.0%), craft making with 28 participants (26.4%), and any other service with 21 participants (19.8%), Majority, 105 (99.1%), did not incur any expenses for occupational therapy services when they utilized them (Table 3).

Table 3: Occupational therapy service.

Utilization of each occupational therapy service
Variable

N%

Have you ever used occupational therapy services
YES

 71 (67)

NO

25 (33)

Self-care/hygiene

33 (30.0)

Tailoring

 23 (24.0)

Dressing

 41 (37.0)

Craft making

19 (17.9)

Development of morning/evening routines

21 (19.8)

Any other

18 (17.0)

Source of information
Mbarara Regional Referral Hospital

106 (100)

Pay for services
YES

1 (0.9)

NO

105 (99.1)

Factors Associated with the Awareness of Occupational Therapy Services

In the bivariate analysis, the results reveal that Occupation (p=<0.001), marital status (p=<0.001), age of the participants (p=<0.001), level of income (p=<0.001), education (p=<0.001), and gender (p=0.000) are statistically significantly associated with awareness of occupational therapy services, unlike religion (p=0.924) (Table 4).

Table 4: Association of Demographics with Awareness of Occupational therapy services.

Variable

Poor awareness (<49) (n=count, % of total) Good awareness (>50) n (%) Asymp. sig. (2 sided)

 Unadjusted prevalence ratios (uPRs))

Occupation

48 (45.3)

58 (54.7) 0.060

1.00

0.998 (0.056-0.000)

Subsistence farming

48 (45.3)

38 (35.8)

   
Commercial farming

0 (0.0)

10 (9.4)

   
Any other

0 (0.0)

10 (9.4)

   
Age

48 (45.3)

58 (54.7) 0.000

1.00

0.582 (0.514-3.275)

12-17

38 (35.8)

22 (20.8)

   
18-24

10 (9.4)

11 (10.4)

   
>24

0 (0.0)

25 (23.6)

   
Religion

48 (45.3)

58 (54.7) 0.924

1.00

0.910 (0.078-0.000)

Christians

47 (44.4)

57 (53.8)

   
Others

1 (0.9)

1 (0.9)

   
Education

48 (45.3)

58 (54.7) 0.000

1.00

0.003 (0.113-0.641)

Primary and <

48 (45.3)

32 (30.2)

   
Secondary and >

0 (0.0)

26 (24.5)

   

Factors Associated with the Utilization of Occupational Therapy Services

Factors age (p-value 0.00), education, (p-value 0.02, religion (0.03) were not statistically significant at multivariate level (Table 5).

All the factors that were statistically significant at bivariate analysis were not significant at multivariate analysis.

Table 5: Relationship of demographics and use of occupational therapy services.

Relationship of demographics and use of occupational therapy services

Unadjusted prevalence ratios (uPRs)

Variable

1 and + (Yes) (n=count, % of total) No service (No) (%) Asymp. sig. (2 sided)

uPRs (95% CI)

Gender

71 (67.0)

35 (33.0) .493

1.00

0.769 (0.563-2.664)

Male

57 (53.8)

30 (28.3)

   
Female

14 (13.2)

5 (4.7)

   
Occupation

71 (67.0)

35 (33.0)

.624

 
Subsistence

56 (52.8.)

30 (28.3)  

1.00

0.862 (0.425-2.779)

Commercial

8 (7.5)

2 (1.9)

   
Any other

7 (6.6)

3 (2.8)

   
Age

71 (67.0)

35 (33.0)

0.000*

 
12-17

39 (36.8)

21 (19.8)  

1.00

0.485 (0.325-1.704)

18-24

15 (14.2)

6 (5.7)

   
>24

17 (16.0)

8 (7.5)

   
Religion

35 (33.0)

71 (66.6) .003*

1.00

0.547 (0.637-2.528

Christians

34 (32.1)

70 (65.7)

   
Others

1 (0.9)

1 (0.9)

   
Education

71 (66.9)

35 (33.1)

.002*

 
Primary and <

53 (50.0)

27 (22.5)  

1.00

0.311 (0.735-2.628)

Secondary and >

18 (16.9)

8 (7.6)

   

Discussion

This study investigated factors that influence the utilization of occupational therapy services among adolescents with substance use disorder attending Mbarara regional referral hospital in south western Uganda. While previous studies have looked at use of occupational therapy use in adults, this study addressed factors influencing use of occupational therapy services among adolescents with substance use disorder.

Findings of this survey suggest awareness about occupational therapy services among the majority of the adolescents was above average (54.7%).

The overall use of occupational therapy service was 67% and most utilized services by adolescents in rehabilitation, dressing (37%), hand hygiene/self-care (30%) and tailoring (24%).

Findings of this study suggest that awareness and utilisation of occupational therapy services among the majority of the adolescents was above average (54.7%,67%), its high compared to studies conducted in Jordan, Australia and Hong Kong which ranged from 35-45.4% [10]. The reasons for higher a warenesss of occupational therapy services in this study was attributed to the fact that most adolescents attained services from Mbarara regional referral hospital and thus most had got enough information about occupational therapy services, secondly the availability of various of occupational therapies contributed to their awareness since they could get access to be introduced to them while in rehabilitation. This can relate to the reasons for poor awareness and utilisation in other countries where by poor awareness among adolescents in other countries was due to poor accessibility of occupational therapy services, inadequate physicians trained for occupational therapy services and community perceptions.

Other studies have indicated that unsustainable public and private health care spending growth, an increased prevalence of chronic health conditions, and rising demand for health care services because of the aging of the population and the expected growth in the number of people with health insurance interferes with occupational therapy services among adolescents with substance use disorder due to competition for the scarce services (Roberts, Farmer, Lamb, Muir, & Siebert, 2014). Although the overall awareness utilisation on use of occupational therapy services among adolescents with substance use disorder in this study is above average, gaps still exist that require increasing accessibility of occupational therapy services among adolescents with substance use disorder and address community perceptions about people who use occupational therapy services (Roberts et al., 2014). So more training of occupational therapists is highly needed and more education programs about occupational therapy services should be implemented to increase awareness [11].

In addition, this study found out most 102(96.2%) participants had got information about occupational therapy use from health workers, a small pertange 3(2.8%) had got information from the TV/media. This is because TV recquires subscription and most practiced subsistence farming where they earned less 27.7 USD. Thus they could not manage to pay subscription and so were unable to get information from the media. Government should try to increase sensitization among the public to increase awareness of occupational therapy use among the general population to increase utilization of these services since most can’t afford to watch TV and listen to media.

On utilization of occupational therapy services, this study found out uptake of occupational therapy was 67% and the most used utilized services by adolescents in rehabilitation were dressing (37%), hand hygiene/self-care (30%) tailoring (24%) and 1(1.0%). This was high compared to a study done in Germany. Utilization of single services corresponds to what is in literature where by the most utilized occupational therapies include Self-care/hygiene with percentage of 41%, dressing 34%, development of morning /evening routines27% and, shopping, tailoring, use of assistive devices at 13% [8].

On the same ground , our results do not differ from findings of the study done in USA among children with bell’s palsy were dressing and self-care were the most occupational therapy services utilized by retired soldiers (Shah, Hawks, Walker, & Egede, 2024) [12]. These services are key in effective restoring of individual cognitive processes who have got cognitive impairment as a result of substance use disorder. In reducing substance use in adolescents, Welty et al. (2019) recommends school-based interventions such as (yoga, animal-assisted therapy, and skills-building), 12-step programs, self-driven virtual interventions, motivational interviewing and multidimensional family therapy have also been found effective in restoring cognitive impairment [12]. A less percentage 1(1.0%) had used other occupational services like swimming which the hospitals did not provide, others reported bricklaying, of which were not in the rehabilitation center. So such activities which can be carried at home should be emphasized to keep these adolescents with substance use disorder active in order to restore cognitive function faster, more so patients will not incur transport to travel to hospital for the services since they can access them from their homes. This will improve service delivery and utilization of occupational therapy services.

Association of Demographics with Awareness of Occupational Therapy

Findings of this study indicate that awareness of occupational therapy services was highly linked with Age, education, and religion. Participants who had acquired a secondary or above level of education were more likely to have good awareness of occupational therapy services compared to those who had accomplished primary or no education at all. On a contrary, participant’s occupation, gender marital status had no influence on occupation therapy service awareness. This is in line with the study done in Eastern Cape that assessed factors affecting utilisation of occupational therapy services among people with mental illness, that found out awareness and uptake of the occupational therapy services was high in patients who were educated compared to those who were not educated. Education raises awareness of the occupational therapy and the benefits of the services. This could be the reason why uptake was high in educated patients. So more sensitization among the community should be done to increase awareness among adolescents with substance use disorder to increase uptake of the occupational therapy services.

In addition, Age group of 12-17 was highly associated with awareness of occupational therapy services, this is because in this stage, most children miss use drugs and end up getting mental problems and thus are enrolled in rehabilitation for occupational therapy services where they got to know the services from. Also they were able to listen to their care takers when it came to time for review and attending sessions for occupational therapy services which increased their awareness. This is supported by NIDA report 2014 that points out high substance use and increasing occupational therapy use in adolescents and Alzheimer patients.

Association of Demographics with Utilization of OTS

In this study, Age, Occupation, Education, Level of income, length of stay negatively influenced use of occupational therapy services. Our study differs with the previous studies. For example study done in North America which was done to assess factors influencing occupational therapy use among adolescents with substance use disorder found out age and education were associated with use of occupational therapy services [13].

Age

In our study, age did not predict the use of occupational therapy services. This differs to a study in Jordan among adolescents to identify factors associated with uptake of occupational therapy services that found out adolescence stage [12-17] was highly linked to substance use and thus more clients were under rehabilitation getting occupational therapy services [11,12]. We attributed reasons for age not being associated with occupational therapy use, because most adolescents who were interviewed where living with grandparents who could not force them to cover for the services at the hospitals. In related study done in England rehabilitation centers offering occupational therapy services found out adults above 60 years were more likely to stick to the treatment and services compared to men who were middle aged and young. This can be associated with many factors like low income, community perceptions and others that interfere with use of occupational therapy services among this age group [11]. We also thought that because these adolescents were young and thus did not have money for transport to attend the services.

Education

Unlike our study, education was found associated with use of occupational therapy in a study conducted in Jordan to assess factors associated with utilisation of occupational therapy services among adolescents with substance use disorder and people with Alzheimer’s disease found out that patients who were not educated were less likely to continue with treatment after first appointment of treatment [14]. This is because education provides knowledge and importance of using occupational therapy services in restoring congntive function of which un educated people don’t have time and thus mind less in participating in these occupational therapy rehabilitation programs. So continuous sensitisation is needed to address the adolescents and the public on importance of occupational therapy services in line to increase uptake of occupational therapy services. In our study most participants where not educated but most had used the occupational services since they often visited hospital.

Occupation

Unlike other studies, our study found out occupation was not associated with use of occupational therapy services. This was explained in a way that since most were mentally unstable and thus were receiving free services. This differs with other studies like a study done in USA among patients with Alzheimer’s disease that assessed factors influencing utilisation of occupational therapy services among Alzheimer patients which found out occupation, level of education affected adherence of occupational therapy services among these patients. Patients who had occupations that earned less could not return to rehabilitation centres for occupational therapy services [15]. Occupational therapy services should be improved and increased in government facilities to make it easily accessible by patients who are under rehabilitation.

Length of Stay in an Area

Staying in a city for more years was not associated with use of occupational therapy services among adolescents. This is because in city most adolescents live in peer groups in town and thus we think their age mates could not convince them to come for the services since they don’t have knowledge on those services. However this factor was not mentioned in the previous studies that assessed factors influencing utilisation of occupational therapy. Awareness of people on occupational therapy and more occupational services should be provided in mental health units caring adolescents with substance use disorder and should train peers who can identify adolescents who have substance use disorder to recruit them for treatment

Strength and Limitations

This study sheds light on the use of occupational therapy services at regional referral hospital among adolescents with substance use disorder unlike the previous studies. Therefore, the findings of the study can be integrated to lower district health facilities with mental health units to improve occupational therapy use among adolescents with substance use disorder.

The sample size obtained was reduced compared to what was formally calculated, this was because most patients were discharged from the unit and others were to come for review after 3 months. Secondly, some care takers didn’t give accurate information we needed from their children. Further research should consider to do the study in more than two facilities to get accurate sample size

Implications for Future Research

This was a mixed study which was predominantly quantitative, further research should aim on doing qualitative studies to explore adolescent’s barriers and facilitators on use of occupational therapy services.

Conclusion

The overall awareness and uptake of occupational services among adolescents remains suboptimal. If occupational therapy is to successfully work in adolescents with substance use disorder, we will need to proactively define and deliver innovative services that match the needs of the adolescents. Further research should aim on doing qualitative studies to explore adolescent’s barriers and facilitators on use of occupational therapy services.

Community need to become involved in the reform of health care and to advocate assertively for Occupational therapy services in their community as there’s much perception among people who use occupational therapy services. Finally, and perhaps most importantly, health workers will need to build coalitions with other professionals and with consumers and their families to foster better mental health practices and policies that last longer because of their broad base of support.

Acknowledgement

Special thanks go to the adolescent and their care takers, hospital administration, and the Director of Health Services Mbarara district where the study was conducted.

References

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  7. Agbese E, Stein BD, Druss BG, Dick AW, Pacula RL, et al. (2022) Mental Health Conditions and Substance Use Disorders Among Youth Subsequently Diagnosed With Opioid Use Disorder or Opioid Poisoning. J Addict Med 16(3): 357-359. [crossref]
  8. Rommel A, Hintzpeter B, Urbanski D (2018) Utilization of physical therapy, speech therapy and occupational therapy by children and adolescents in Germany.Results of the cross-sectional KiGGS Wave 2 study and trends. J Health Monit 3(4): 20-34. [crossref]
  9. Islam MI, Khanam R, Kabir E (2020) The use of mental health services by Australian adolescents with mental disorders and suicidality: Findings from a nationwide cross-sectional survey. PLoS One 15(4): e0231180. [crossref]
  10. Carlsson A (2018) occupational performance in adults with substance use disorder.
  11. Roberts P, Farmer ME, Lamb AJ, Muir S, Siebert C (2014) The role of occupational therapy in primary care. AJOT: American Journal of Occupational Therapy 68(S3): S25-S25.
  12. Shah H, Hawks L, Walker RJ, Egede LE (2024) Substance Use Disorders, Mental Illness, and Health Care Utilization Among Adults With Recent Criminal Legal Involvement. Psychiatr Serv 75(3). [crossref]
  13. Lewicki EL, Smith SL, Cash SH, Madigan MJ, Simons DF (2019) Factors influencing practice area preference in occupational therapy. Occupational Therapy in Mental Health 14(4): 1-19.
  14. Ahmed AO, Marino BA, Rosenthal E, Buckner A, Hunter KM, et al. (2016) Recovery in schizophrenia: what consumers know and do not know. Psychiatric Clinics 39(2): 313-330.
  15. Reitz SM, Scaffa ME, Dorsey J (2020) Occupational Therapy in the Promotion of Health and Well-Being. American Journal of Occupational Therapy 74(3). [crossref]

Association of Podoplanin Expression with Histological Grade and Prognosis in Oral Squamous Cell Carcinoma in a Tertiary Care Hospital in Bangladesh

DOI: 10.31038/CST.20251014

Abstract

Background: Oral carcinogenesis involves genetic changes affecting proto-oncogenes and tumor suppressor genes like P16, P53, H-ras, cyclinD1, and EGFR. Podoplanin, a transmembrane glycoprotein, is a biomarker linked to tumor progression and prognosis in oral squamous cell carcinoma (OSCC). This study aimed to assess podoplanin expression across OSCC grades and its relationship with clinicopathological factors such as age, gender, habits, tumor site, lymphovascular invasion, perineural invasion, and tumor-infiltrating lymphocytes.

Methods: A cross-sectional study at BIRDEM Hospital, Dhaka, analyzed 56 OSCC cases over two years using hematoxylin and eosin-stained slides and tissue blocks. Podoplanin expression was evaluated immunohistochemically and classified as high or low based on staining intensity and extent.

Results: High podoplanin expression was observed in 33.90% of cases, predominantly in moderately and poorly differentiated OSCC, compared to well-differentiated tumors. A significant association was found between podoplanin expression and histological grade (p<0.05). However, no significant relationships were observed with age, gender, habits, anatomical site, lymphovascular or perineural invasion, or tumor-infiltrating lymphocytes.

Conclusion: Podoplanin expression correlates significantly with OSCC histological grade, suggesting its potential as a prognostic marker. High expression may indicate aggressive tumors and poorer outcomes, highlighting its relevance in evaluating and managing OSCC.

Keywords

Podoplanin, Oral Squamous Cell Carcinoma, Immunohistochemistry, Histological Grade, Prognosis, Biomarker

Introduction

Oral cancer is the sixth most common malignancy worldwide and is one of the major public health problems [1]. Oral squamous cell carcinoma (OSCC) is the most common type of malignancy, representing up to 90 percent of all oral neoplasms [2]. Oral cancer ranks 3rd, 2nd, and 3rd in five-year prevalence, incidence, and mortality rate respectively in Bangladesh [3]. Common risk factors for developing OSCC are tobacco smoking, betel nut chewing, and alcohol consumption. Other predisposing factors are viral infection, chronic irritation, oral candidiasis, poor oral hygiene, ionizing radiation, etc [4].

Podoplanin (PDPN) is known to be expressed in numerous human tumors, including squamous cell carcinoma of the oral cavity, mesothelioma, testicular seminoma, soft tissue tumors, thymoma, and brain tumors [5]. PDPN seems to be expressed in aggressive tumors, with higher invasive and metastatic potential [6].

PDPN consists of an extracellular or transmembrane domain and a cytoplasmic domain. The extracellular domain is longer and carries four platelet aggregation-stimulating (PLAG) domains with plenty of potential O-glycosylation sites, crucial for interaction with platelets. The interaction between PDPN and c-type lectin (CLEC2) may regulate tumor invasion and metastasis [7]. The shorter cytoplasmic domain is associated with ezrin/radixin/moesin (ERM) protein that bridges plasma membrane proteins and the actin cytoskeleton [8]. PDPN overexpression causes marked phosphorylation of ERM proteins. It causes adhesion and cancer cell migration through modulating the actin cytoskeleton, Rho A, and epithelial-mesenchymal transition. PDPN causes down-regulation of E-cadherin and overexpression of matrix metalloproteinase [6].

It is upregulated in the invasive front of OSCC. It causes upregulation of TGF-β1 secretion and increases Epidermal Growth Factor Receptor phosphorylation as well as downstream effectors of AKT and ERK. PDPN also causes OSCC progression by interacting with matrix metalloproteinase and induces cytoskeletal remodelling, extracellular matrix degradation, and invasion [9].

PDPN in oral SCC causes tumor cell motility and metastasis by activation of endogenous lectin that binds to extracellular carbohydrate moieties. These cancer cells are remarkably resistant to currently available chemotherapy. Thus, PDPN becomes a chemotherapeutic target for oral SCC [10]. Anti-human Podoplanin antibody (NZ-1) would be an important target for the prevention of metastasis in the future for OSCC [6].

Materials and Methods

Study Design and Subjects

This cross-sectional observational study was conducted at the Department of Pathology, Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorder (BIRDEM), during the period of March 2022 to February 2024. This study was approved by the Institutional Review Board (IRB) of BIRDEM Hospital, Dhaka, Bangladesh. Written informed consent was obtained from all participants, and confidentiality of patient data was maintained in compliance with ethical standards. A total of 56 histologically diagnosed cases of oral squamous cell carcinoma (OSCC) were included in this study, meeting the following inclusion criteria: small and resected biopsy cases of OSCC. Exclusion criteria included carcinoma in situ, dysplastic lesions of the oral cavity, and patients who received neoadjuvant therapy or radiotherapy before surgery.

Demographic and clinical information, such as age, sex, clinical presentation, and histopathological diagnosis (including grade), were collected from the departmental records of the pathology department.

Sample Collection

The 56 cases of oral SCC were retrieved from the Department of Pathology, BIRDEM, including H&E stained slides and paraffin- embedded blocks. All slides were reviewed to assess tumor grade and other prognostic factors, including tumor-infiltrating lymphocytes (TILs), and the presence of lymphovascular and perineural invasion.

Immunohistochemical Staining for Podoplanin

After confirming the diagnosis of OSCC, immunohistochemical (IHC) staining for podoplanin was performed at Bangabandhu Sheikh Mujib Medical University (BSMMU), using an appropriate positive control. Paraffin-embedded tissue blocks were sectioned at 3 µm thickness. The slides were gently lowered onto a water bath set to 45°C, spread without wrinkles onto slides coated with 0.1% poly-L- lysine, and air-dried. Slides were then baked at 60°C for 30 minutes on a hot plate. Dewaxing was performed by treating the slides in xylene, followed by rehydration through a graded series of alcohols.

For antigen retrieval, the slides were immersed in preheated citrate buffer in a pressure cooker, boiled, and allowed to cool naturally. To block endogenous enzyme activity, hydrogen peroxide was added in a moist chamber at room temperature.

Primary and Secondary Antibodies

  • Primary antibody: Monoclonal Rabbit d2-40 (pre-diluted, ready-to-use).
  • Secondary antibody: DAKO REAL™ Envision™ (HRP Rabbit/ Mouse) (ENV).
  • Positive control: Appedicular tissue was used as a positive
  • Chromogen: 3,3’-diaminobenzidine (DAB) was used for visualizing the antigen-antibody Finally, slides were counterstained with hematoxylin.

Scoring of Podoplanin Expression

Podoplanin expression was assessed by reviewing 10 representative areas from each slide. For each area, 100 tumor cells were counted, and both the percentage of positive cells and the intensity of podoplanin expression were evaluated. The following scoring system, as introduced by Yuan et al. (2006), was applied:

Quantitative Score

  • 0: 0% positive cells
  • 1: 1-10% positive cells
  • 2: 11-30% positive cells
  • 3: 31-50% positive cells
  • 4: 51-80% positive cells
  • 5: 81-100% positive cells

Intensity Score

  • 0: Negative (no staining)
  • 1: Weak (faint staining)
  • 2: Moderate (staining between weak and dark brown)
  • 3: Strong (dark brown staining)

The immunoreactive score (IRS) for podoplanin expression was calculated by multiplying the quantitative score by the intensity score, yielding a final score ranging from 0 to 15. According to this score, the expression was classified as follows:

  • 0-7: Low expression
  • ≥8: High expression

Statistical Analysis

All collected data were compiled and analyzed using SPSS (Statistical Package for Social Sciences), version 25. The Chi-square test was used to assess statistical significance between different clinicopathologic variables. A p-value of <0.05 was considered statistically significant.

Results

A total of 56 oral squamous cell carcinoma (OSCC) patients were included in the study, and their clinicopathologic characteristics along with Podoplanin expression were analyzed. The association between Podoplanin expression and various clinicopathologic parameters, as well as histological grading, was evaluated (Tables 1 and 2).

Table 1: Clinicopathologic parameters of OSCC patients and their association with Podoplanin expression (n =56).

Clinicopathologic Parameter

Podoplanin Expression P value
High

Low

Age distribution
Up to 40 years

2(33.3)

4(66.7)

 

 

 

0.58

41-50 years

3 (42.9)

4(57.1)

51-60 years

4(25.0)

12(75.0)

61-70 years

7(50.0)

7(50.0)

Above 70 years

3(23.1)

10(76.9)

Gender
Female

8(29.6)

19(70.4)

 

0.58

Male

11(37.9)

18(62.1)

Clinical Presentation
Ulcer

15(35.7)

27(64.3)

 

 

0.58

Red patches

2(33.3)

4(66.7)

White patches

1 (33.3)

2(66.7)

Exophytic growth

1 (20.0)

4(66.1)

Characteristics
Tobacco Yes

9(39.1)

14(60.9)

0.57

No

6(46.2)

7(53.8)

Betel quid Yes

12 (34.3)

23(65.7)

1

No

7(33.3)

14(63.8)

Tobacco & betel quid both Yes

3 (30.0)

7(70.0)

1

No

16(34.8)

30(66.1)

Anatomic Location
Tongue

7(46.7)

8(53.3)

 

0.24

Buccal mucosa

11(34.4)

21(65.6)

Others

1 (11.1)

8(88.9)

The table summarizes the distribution of Podoplanin expression (high vs. low) based on various clinicopathologic parameters, including age, gender, clinical presentation, tobacco use, betel quid use, and anatomic location of the tumor. The P values indicate the statistical significance of the associations between Podoplanin expression and each parameter. No significant associations were observed between Podoplanin expression and age, gender, clinical presentation, or personal habits. The only significant association found was between Podoplanin expression and histological grading (not shown in this table).

Podoplanin Expression and Clinicopathologic Parameters

Podoplanin expression was classified as high or low based on immunohistochemical staining. High Podoplanin expression was observed in 19 cases (33.90%) of OSCC. The distribution of high and low Podoplanin expression did not show any statistically significant association with age, gender, clinical presentation, or personal habits (tobacco use, betel quid use). Specifically, no significant differences in Podoplanin expression were noted across different age groups (P = 0.58), between genders (P = 0.58), or based on the clinical presentation (P = 0.58). Furthermore, Podoplanin expression did not correlate with tobacco use (P = 0.57), betel quid use (P = 1.0), or both tobacco and betel quid use (P = 1.0). Similarly, no significant association was found between Podoplanin expression and the anatomic location of the tumors (P = 0.24) (Table 1 & 2).

Podoplanin Expression and Histological Grading

The association between Podoplanin expression and the histological grading of OSCC was found to be statistically significant (P = 0.00) (Table 2). Podoplanin expression varied considerably across different grades of differentiation. In well-differentiated OSCC (n = 25), no cases exhibited high Podoplanin expression, with all tumors showing low expression. In moderately differentiated OSCC (n = 27), 17 cases (63.0%) exhibited high Podoplanin expression, while 10 cases (37.0%) showed low expression. In poorly differentiated OSCC (n = 4), high Podoplanin expression was observed in 2 cases (50.0%) and low expression in the remaining 2 cases (50.0%) (Table 2).

This significant association between Podoplanin expression and histological grading suggests that Podoplanin expression is higher in less differentiated OSCC, with well-differentiated tumors showing predominantly low expression. The findings suggest that Podoplanin may serve as a useful marker of tumor differentiation, with higher expression being indicative of greater aggressiveness and poorer differentiation (Figures 4-7).

Table 2: Histological grading of OSCC and immune-histochemical expression of podoplanin (n=56).

 

Histological grading

Expression of Podoplanin

 

P Value*

High

Low

Well differentiated

0 (0.0)

25 (100)

 

 

0.00

Moderately differentiated

17 (63.0)

10 (37)

Poorly differentiated

2 (50.0)

2 (50.0)

Figure 1: Gender distribution of the patients with Oral SCC (n =56). The pie chart illustrates the gender distribution among the study participants. The results indicate a higher prevalence of oral SCC in males, with a male-to-female ratio of 1.07: 1.

Figure 2: Locations of SCC in the oral cavity (n=56). The figure shows the distribution of oral squamous cell carcinoma (SCC) cases based on their anatomical location within the oral cavity. Among the 56 patients, the majority of biopsies (57.1%) were taken from the buccal mucosa, followed by the tongue. The remaining cases were found in the retromolar trigone (16.1%), alveolus (10.7%), and gingiva (3.6%). A small percentage of cases (1.8%) were located in other areas of the oral cavity.

Figure 3: Histological grade of oral SCC (n=56). The histological grade of oral SCC was assessed as per criteria set by WHO 2017. Among 56 patients, 48.2% were moderately differentiated (grade 2) followed by 44.6% of well differentiated (grade 1). Only 7.1% showed poorly differentiated (grade 3).

Figure 4: High expression of podoplanin IRS – in Moderately Differentiated Squamous Cell Carcinoma.

Figure 5: High expression of podoplanin IRS – in Moderately Differentiated Squamous Cell Carcinoma.

Figure 6: Low expression of Podoplanin IRS – in well Differentiated Squamous Cell Carcinoma.

Figure 7: Low expression of Podoplanin IRS – in well Differentiated Squamous Cell Carcinoma.

Discussion

The present study demonstrates that Podoplanin expression is present in nearly all cases of oral squamous cell carcinoma (OSCC), with a statistically significant association observed with histological grading. Specifically, the expression of Podoplanin was found to be higher in moderately and poorly differentiated OSCC cases, while all well-differentiated tumors exhibited low expression. This finding supports the hypothesis that Podoplanin could serve as an important biomarker for the aggressive nature of OSCC, with its expression correlating with poorer histological differentiation.

In this study, 33.9% of the cases showed high Podoplanin expression, while the remaining 66.1% exhibited low expression. These findings are consistent with those of other studies, although variability in the levels of Podoplanin expression has been reported in different populations globally. Previous studies have documented a range of Podoplanin expression, with high expression varying from 20% to 60% and low expression ranging from 21.6% to 80%. For instance, Yuan et al. (2006) reported that 60% of oral SCC cases exhibited high Podoplanin expression, while other investigators, such as Parhar et al. (2015), Patil et al. (2015), Kim et al. (2015), and Sgaramella et al. (2016), reported high expression rates of 56.6%, 20%, 51.3%, and 51%, respectively [12,14-17]. The considerable variability in these findings can be attributed to several factors, including genetic and ethnic diversity, personal habits such as tobacco and betel quid use, and environmental influences that contribute to the development of oral cancer [1,4].

It is important to note that while the current study found no significant association between Podoplanin expression and factors such as age, gender, anatomic site, clinical presentation, or the use of tobacco and betel quid, other studies have suggested that Podoplanin expression correlates with tumor size, nodal involvement, advanced stage, poor treatment response, and reduced survival rates [5,7,19]. These associations indicate the potential of Podoplanin as a prognostic marker in OSCC, which could aid in predicting clinical outcomes and guiding therapeutic decisions.

Furthermore, the observed relationship between Podoplanin expression and histological grading is in line with studies by Kim et al. (2015), Pradhan et al. (2019), and Patil et al. (2015), who also reported significant associations between high Podoplanin expression and poorly differentiated or moderately differentiated tumors [16,18,19]. However, our results differ from studies by Yuan et al. (2006), Aiswariya et al. (2019), and Prasad et al. (2015), who did not observe the same level of correlation between Podoplanin expression and histological grade [12,13,19].

The reasons for these discrepancies can likely be attributed to differences in study design, sample sizes, and the specific characteristics of the populations studied. For instance, genetic and environmental factors, as well as variations in diagnostic and histopathological assessment methods, may contribute to differing findings. Therefore, while the relationship between Podoplanin expression and OSCC is becoming increasingly recognized, further research involving larger and more diverse cohorts is necessary to better understand the complex interplay of factors that influence its expression and its potential as a prognostic biomarker.

In conclusion, the current study reinforces the notion that Podoplanin expression is closely linked to the histological grading of OSCC, particularly with higher expression observed in more aggressive, poorly differentiated tumors. Despite some inconsistencies in the literature, the potential of Podoplanin as a prognostic marker for OSCC, especially in predicting tumor progression and patient outcomes, remains promising and warrants further exploration.

Conclusion

In recent years, numerous studies have sought to elucidate the role of Podoplanin in oral squamous cell carcinoma (OSCC), yet significant controversies remain in the scientific literature. In this study, we observed that Podoplanin expression was present in nearly all OSCC cases in Bangladesh, with high expression predominantly associated with higher-grade tumors. Furthermore, tumors originating from the tongue and those exhibiting lymphovascular and perineural invasion showed elevated levels of Podoplanin expression. While these findings are promising, the study’s interpretation is limited by the small sample size, reliance on small biopsy specimens, and the absence of follow-up data. To solidify these results, further research with a larger cohort, utilizing resected specimens, is essential. Additionally, future studies should explore the role of Podoplanin in tumor staging, nodal metastasis, overall survival, and its potential as a target for novel therapies. By advancing our understanding of Podoplanin’s prognostic value, we can pave the way for more precise diagnostic and therapeutic strategies in OSCC management.

Acknowledgement

The study was guided and supported by Dr. Nazma Afroze, Professor of Pathology, whose expert advice and encouragement were invaluable throughout the research.

Gratitude is extended to the medical technologists and staff at BIRDEM General Hospital, Dhaka, and Bangabandhu Sheikh Mujib Medical University (BSMMU) for their diligent assistance. Special recognition is given to Md. Joynal Abedin, Md. Fazle Elahi, Mrs. Shimu Akhter, Mr. Sojib Sorder, Md. Aorango Jeb Sheikh, and Mr. Ruhul Amin Bhuiyan for their contributions.

Appreciation is also expressed to all the patients and their attendants who participated in this study, and to the colleagues and contemporary MD student Dr. Bilkis for their cooperation and support.

Finally, sincere thanks are given to the families, including first author’s parents, in-laws, husband Md. A. Rahim, and daughter Manha, for their unwavering support and encouragement.

Data Availability Statement

The data supporting the findings of this study are available from the corresponding author upon reasonable request.

Funding Statement

No specific funding was received for this study.

Conflict of Interest Disclosure

The authors declare that there are no financial, personal, or professional conflicts of interest that could have influenced the work presented in this manuscript. All authors have disclosed any potential conflicts, and no competing interests exist.

Ethics Approval Statement

This study was approved by the institutional ethics committee of Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM) General Hospital, Dhaka, Bangladesh

Patient Consent Statement

Informed consent was obtained from all patients or their legal guardians prior to participation in the study.

Contribution Statement

The project was designed by the Principal Investigator, Mst. Rubeyatul Jannat. The data collection and article writing were primarily conducted by Mst. Rubeyatul Jannat, Nafisa Abedin, Sayeed Kishwara Kashfi, Shamim Ahamed, and Shahana Sultana. Sayed Kishwara Kashfi also contributed to the literature review. Sadia Shirin provided essential photographic documentation for the study. Shamim Ahamed played a significant role in preparing the manuscript for publication. Shahana Sultana contributed extensively to the discussion section. Prof. Mousumi Ahmed provided crucial intellectual input, offered critical feedback on the manuscript drafts, and guided the team through key methodological and analytical aspects of the study. Prof. Rita Rani Barua offered critical advice regarding the publication process. Nafisa Abedin performed the final proofreading and served as the corresponding author.

Data Availability Statement

The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request. All relevant data, including patient demographic details, clinicopathological features, and podoplanin immunohistochemical expression levels, have been anonymized to ensure patient confidentiality in compliance with ethical guidelines.

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Emmprin Expression in Urothelial Carcinoma of the Bladder: Correlation with Histological Grade and Muscle Invasion in a Tertiary Care Hospital in Bangladesh

DOI: 10.31038/CST.20251013

Abstract

Urinary bladder cancer is the 10th most prevalent cancer globally, with rising incidence rates, particularly in developing countries. Accurate identification is essential for early diagnosis, prognosis, and treatment monitoring. Emmprin (CD147) has emerged as a potential biomarker linked to cell invasion and metastasis in bladder cancer. This study aimed to evaluate Emmprin expression in urothelial carcinoma and its correlation with histological grade and muscle invasion.

A cross-sectional observational study was conducted on 40 patients diagnosed with urothelial carcinoma. Immunohistochemical staining for Emmprin was performed on tissue sections, and its expression was correlated with tumor grade and muscle invasion. Among the participants, 85% were male, with an average age of 62.2 ± 9.6 years. High-grade urothelial carcinoma was observed in 70% of cases, and 50% had muscle-invasive disease. Emmprin expression was high in 52.5% of cases and low in 47.5%. High Emmprin expression showed a significant association with high-grade tumors (p<0.001) and muscle invasion (p=0.001). A moderate positive correlation was noted between Emmprin expression and tumor grade (rs=0.582, p<0.001) as well as muscle invasion (rs=0.538, p<0.001).

In conclusion, Emmprin overexpression is significantly linked to high-grade and muscle-invasive urothelial carcinoma. Its expression could serve as a valuable biomarker for assessing bladder cancer prognosis and progression, offering insights into tumor behavior and potential therapeutic targets.

Keywords

Emmprin, Urothelial carcinoma, Bladder cancer, Histological grade, Muscle invasion, Biomarker

Introduction

Urinary bladder cancer is the 10th most prevalent cancer globally, with an increasing incidence, particularly in developing countries. It is the 6th most common cancer in males and the 17th most common in females. The incidence rates in males are almost four times higher than in females. Although the incidence and mortality rates are higher in industrialized countries, they are also rising in regions such as Bangladesh, where factors like urbanization, industrialization, and tobacco consumption contribute to this trend [1,2,20].

The majority of bladder tumors are of epithelial origin, with urothelial carcinoma being the most frequent type, accounting for approximately 90% of all bladder cancers [3]. Urothelial carcinoma can be classified into two forms: non-muscle invasive and muscle-invasive. The non-muscle invasive form is characterized by a high recurrence rate (50-70%) and progression to muscle-invasive disease in about 10-20% of cases. In contrast, muscle-invasive bladder cancer (MIBC) presents with more aggressive behavior and a worse prognosis [4,5,17].

Currently, the diagnosis and prognosis of bladder cancer primarily rely on histological grading and staging. However, conventional prognostic factors such as tumor grade and stage are often insufficient to predict the disease’s behavior and clinical course accurately. This variability in patient outcomes highlights the need for reliable biomarkers to improve early diagnosis, prognostication, and therapeutic decision-making. Moreover, identifying molecular markers that can predict treatment responses and monitor recurrence remains an ongoing challenge [6-8,18,19].

Emmprin (CD147), an extracellular matrix metalloproteinase inducer, has gained attention as a potential biomarker for bladder cancer. It is overexpressed in several malignancies, including bladder cancer, where it plays a role in tumor proliferation, invasion, and metastasis. Emmprin expression has been shown to correlate with tumor grade and muscle invasion, suggesting that it could serve as a useful indicator of disease progression and prognosis [9-12,14,15].

The aim of this study was to evaluate the immunohistochemical expression of Emmprin in urothelial carcinoma of the bladder and to explore its correlation with histological grade and muscle invasion. We hypothesize that Emmprin expression is significantly correlated with the aggressiveness of the tumor, offering insights into its potential as a prognostic biomarker for bladder cancer.

Materials and Methods

Study Design and Ethical Considerations

This cross-sectional study was conducted at the Department of Pathology, Sir Salimullah Medical College (SSMC), and immunohistochemistry was performed at Bangabandhu Sheikh Mujib Medical University (BSMMU) from March 2022 to February 2024. Ethical approval (SSMC/2023/490, dated 25 February 2023) was obtained, and informed written consent was acquired from all participants.

Study Population

The cohort included 40 patients with histopathologically confirmed urothelial carcinoma of the bladder. Of the initial 45 cases, five were excluded due to inadequate tissue. Participants ranged from 45 to 85 years, with a mean age of 62.2 ± 9.6 years. Of the 40 participants, 85% were male, and 70% were smokers.

Specimen Collection and Processing

Specimens were fixed in 10% neutral buffered formalin, processed using standard histopathological methods, and stained with H&E. Tumor grading and staging followed the 2016 WHO guidelines.

Immunohistochemical Evaluation

Emmprin expression was evaluated by immunohistochemistry. Sections were cut (4 µm), deparaffinized, and antigen retrieval was performed. Primary antibody (Emmprin, 1: 100) was applied, followed by secondary antibody and DAB chromogen. Slides were analyzed by two pathologists at 400x magnification. An infiltrating duct carcinoma section served as a positive control.

Scoring of Emmprin Expression

Emmprin expression was scored based on the percentage of stained tumor cells and staining intensity:

  • Percentage: 0 (<10%), 1 (10-24%), 2 (25-49%), 3 (50-74%), 4 (≥75%)
  • Intensity: 0 (negative), 1 (weak), 2 (moderate), 3 (strong)

Final scores ranged from 0 to 7, with scores of 6-7 indicating strong Emmprin overexpression [16].

Ethical Issues

The study followed the Declaration of Helsinki (1975, revised 1983). Written informed consent was obtained from participants, and confidentiality was maintained by anonymizing data. Ethical standards for human research were strictly adhered to, with no animal experimentation involved.

Statistical Analysis

Data were analyzed using SPSS version 26. Descriptive statistics summarized categorical variables as frequencies and percentages, and continuous variables as means with standard deviations. The Chi-square test assessed categorical variables, while Spearman’s Rank Correlation Coefficient was used for continuous variables. A p-value of <0.05 was considered statistically significant.

Results

A total of 40 patients with histopathologically confirmed urothelial carcinoma were enrolled in the study. The age distribution of the patients was as follows: 8 patients (20.0%) were aged ≤50 years, 9 patients (22.5%) were aged 51-60 years, 18 patients (45.0%) were aged 61-70 years, and 5 patients (12.5%) were aged >70 years. The mean age of the cohort was 62.2 ± 9.6 years, with an age range spanning from 45 to 85 years. Regarding smoking status, 12 patients (30.0%) were non- smokers, while 28 patients (70.0%) were smokers (Table 1).

Table 1: Demographic and Smoking History of Study Participants.

Characteristic

Category Frequency

Percentage (%)

Age Group (in years)

≤50

8 20.0
  51-60 9

22.5

 

61-70

18 45.0
  >70 5

12.5

  Total

40

100

  Mean ± SD

62.2 ± 9.6

 
Smoking History Non-smoker

12

30.0

  Smoker

28

70.0

  Total

40

100

Tumor localization revealed that 19 patients (47.5%) had urothelial carcinoma on the lateral wall, 11 patients (27.5%) on the posterior wall, 5 patients (12.5%) on the anterior wall, 2 patients (5%) on the trigone, 2 patients (5%) on the neck, and 1 patient (2.5%) on the dome. Histopathological grading showed that 28 patients (70.0%) had high-grade urothelial carcinoma, while 12 patients (30.0%) had low-grade urothelial carcinoma (Table 2).

Table 2: Distribution of Cases by Site, Grade, and Muscularis Propria Invasion (N=40).

Site

Lateral wall Posterior wall Anterior wall Trigone Neck Dome

Total

Frequency

19

11 5 2 2 1 40

Percentage(%)

47.5 27.5 12.5 5 5 2.5

100

Muscularis propria invasion

High grade Low grade

Total

Present (MIBC)

19(95%)

1 (5%)

20

Absent (NMIBC)

9(45%)

11(55%)

20

Total

28

12

40

Muscularis propria invasion was observed in 20 cases (50.0%), while the remaining 20 cases (50.0%) did not exhibit muscularis propria invasion. Among the 20 patients with muscle-invasive bladder cancer (MIBC), 19 (95%) had high-grade tumors, and 1 (5%) had a low-grade tumor. In contrast, among the 20 patients with non-muscle- invasive bladder cancer (NMIBC), 9 (45%) were high-grade and 11 (55%) were low-grade (Table 2).

Emmprin expression was categorized as low in 19 patients (47.5%) and high in 21 patients (52.5%) (Table 3). Among the 12 cases with low- grade urothelial carcinoma (LGUC), only 1 case (8.3%) demonstrated high Emmprin expression. In contrast, 20 of the 28 cases (71.4%) with high-grade urothelial carcinoma (HGUC) exhibited high Emmprin expression. Statistical analysis using the Chi-square test revealed that high-grade urothelial carcinoma had significantly higher Emmprin expression compared to low-grade urothelial carcinoma (p<0.001) (Table 3).

Table 3: Association of Histological Grading and Muscle Invasion with Emmprin Expression in Urothelial Carcinoma of the Urinary Bladder (n=40).

Criteria

Total Cases (n) Low Emmprin (n, %) High Emmprin (n, %) p-value Correlation (rs)

Grading

      <0.001

0.582

Low Grade

12

11 (91.7%) 1 (8.3%)    

High Grade

28 8 (28.6%)

20 (71.4%)

   
Muscle Invasion      

0.001

0.538

Absent

20

15 (75.0%)

5 (25.0%)

   
Present

20

4 (20.0%)

16 (80.0%)

   
Total

40

19 (47.5%)

21 (52.5%)

   

When considering muscle invasion, 5 patients (25.0%) without muscle invasion exhibited high Emmprin expression, whereas 16 patients (80.0%) with muscle invasion showed high Emmprin expression. The Chi-square test revealed a significant association between muscle invasion and increased Emmprin expression in muscle-invasive bladder cancer (MIBC) compared to non-muscle- invasive bladder cancer (NMIBC) (p=0.001) (Table 3).

Additionally, a moderate positive correlation was found between tumor grading and Emmprin expression (rs=0.582, p<0.001) (Figure 1). There was also a significant positive correlation between muscle invasion and Emmprin expression (rs=0.538, p<0.001) (Figure 2).

Figure 1: Scatter plot diagram showing relationship between grading of urothelial carcinoma and emmprin score.

Figure 2: Scatter plot diagram showing relationship between muscle invasion and emmprin score.

This table presents the age distribution and smoking history of 40 participants. The age groups are divided as ≤50, 51-60, 61-70, and >70 years. The largest group (45%) was in the 61-70 age range. The mean age of participants was 62.2 ± 9.6 years. In terms of smoking history, 70% of participants were smokers, while 30% were non-smokers.

This combined table provides two sets of data for 40 cases: the distribution by anatomical site and by grade and muscularis propria invasion. The first section shows the distribution of cases across six sites, with the lateral wall being the most commonly affected site (47.5%). The second section presents the distribution of cases based on grade and muscularis propria invasion, with 19 high-grade cases having muscularis propria invasion (MIBC) and 9 high-grade cases without invasion (NMIBC). The total number of cases is 40 for both sections).

Statistical tests: Chi-square test (Grading & Muscle Invasion), Spearman’s correlation (Grading & Muscle Invasion with Emmprin expression). Significance: p<0.05. A significant association was found between Grading and Muscle Invasion with Emmprin expression (p<0.001 for grading, p=0.001 for muscle invasion). Positive correlations were observed between Emmprin expression and Grading (rs=0.582), as well as Muscle Invasion (rs=0.538), indicating higher Emmprin expression correlates with more aggressive tumor characteristics.

X-axis: Tumor grading (Low grade vs. High grade), Y-axis (Vertical): Emmprin score (Scale indicating levels of Emmprin expression). Each point represents an individual case, plotted based on tumor grading and corresponding Emmprin score. Trend Line Shows the positive correlation between tumor grading and Emmprin expression, where higher tumor grades tend to have higher Emmprin scores. A moderate positive correlation was found between tumor grading and Emmprin expression (rs=0.582, p<0.001), suggesting that higher tumor grade is associated with higher Emmprin expression.

X-axis: Muscle invasion status. Y-axis: Emmprin score (Scale indicating levels of Emmprin expression). Each point represents an individual case, plotted based on muscle invasion status and corresponding Emmprin score. Trend Line Shows the positive correlation between muscle invasion and Emmprin expression. The presence of muscle invasion tends to be associated with higher Emmprin scores. A moderate positive correlation was observed between muscle invasion and Emmprin expression (rs=0.538, p<0.001), indicating that higher Emmprin expression is linked with the presence of muscle invasion (Figures 3 and 4).

Figure 3: The photomicrograph shows a tissue section from a low-grade urothelial carcinoma (case no-39). The first panel features H&E staining, highlighting neoplastic cell structures with mild atypia. The second panel shows low Emmprin expression, indicating less aggressive tumor behavior, with a magnification of 200X.

Figure 4: The photomicrograph shows a tissue section from a high-grade muscularis propria invasive urothelial carcinoma (case no-29). The first panel displays H&E staining, highlighting abnormal cellular structures, while the second panel shows high Emmprin expression, indicating tumor aggressiveness. The magnification is 200X.

Discussion

The present study provides significant insights into the role of Emmprin expression in the pathogenesis of bladder cancer (BC). We found a marked correlation between elevated Emmprin levels and both high-grade urothelial carcinoma (HGUC) and muscle-invasive bladder cancer (MIBC), supporting its potential as a prognostic biomarker in BC. These findings offer an important contribution to the understanding of BC aggressiveness and may have clinical implications for guiding therapeutic decisions.

Our study revealed that Emmprin expression was significantly higher in HGUC compared to low-grade urothelial carcinoma (LGUC), which is consistent with previous research suggesting that Emmprin overexpression is associated with tumor progression and invasiveness [6,13,21]. The correlation between Emmprin expression and tumor grade (rs=0.582, p<0.001) reinforces the notion that Emmprin could serve as an indicator of tumor aggressiveness, as high- grade tumors are often associated with poorer outcomes. This finding aligns with other studies that have established emmprin as a key player in promoting the malignant phenotype of various cancers, including bladder cancer [21].

Additionally, our data demonstrated that Emmprin expression was significantly higher in MIBC compared to NMIBC, with a positive correlation between muscle invasion and Emmprin levels (rs=0.538, p<0.001). These results are in line with findings from Xue et al. [21] and Wittschieber et al. [13], who also reported a strong association between emmprin expression and the invasive potential of tumors. The ability to distinguish MIBC from NMIBC based on Emmprin expression could offer a valuable tool for predicting disease progression, allowing clinicians to identify patients who may benefit from more aggressive treatment strategies.

While our study contributes valuable insights into the prognostic value of Emmprin in BC, it is not without limitations. The sample size of 40 patients may not fully represent the heterogeneity of the BC population, limiting the generalizability of the results. Furthermore, the retrospective nature of the study, relying on archival tissue samples, introduces potential biases in patient selection. Larger, multicenter, and prospective studies are needed to validate these findings and explore the broader applicability of Emmprin as a biomarker in BC. It would also be valuable to assess the molecular mechanisms underlying emmprin’s role in BC, including its interaction with other key players in the tumor microenvironment, such as extracellular matrix components and immune cells [11,15].

Another limitation is the lack of longitudinal data, which prevents us from drawing definitive conclusions regarding the prognostic utility of Emmprin in predicting clinical outcomes, such as recurrence, metastasis, and overall survival. Future studies should aim to follow patients prospectively to assess whether Emmprin expression correlates with patient prognosis and treatment response over time.

Despite these limitations, our findings suggest that Emmprin expression could serve as a useful biomarker for predicting tumor grade and muscle invasion in BC. This could aid in identifying patients at high risk for aggressive disease, thus informing treatment decisions and enabling personalized therapeutic approaches. Further research is warranted to investigate the potential of emmprin as a therapeutic target in BC, as targeting Emmprin may hold promise for improving patient outcomes [13,15,21].

To conclude, this study provides compelling evidence that elevated emmprin expression is correlated with high-grade and muscle- invasive bladder cancer. These results suggest that Emmprin could be a valuable prognostic marker, offering potential clinical utility in predicting disease aggressiveness and guiding treatment decisions. However, additional studies with larger cohorts and longitudinal follow-up are necessary to validate these findings and to elucidate the underlying mechanisms by which Emmprin contributes to bladder cancer progression [6,13,21].

Conclusion

The findings of this study establish a significant positive correlation between Emmprin expression and both histological grade and muscle invasion in urothelial carcinoma, highlighting its potential as a key biomarker for bladder cancer aggressiveness. Elevated emmprin levels may not only serve as a prognostic indicator but also represent a promising therapeutic target for chemotherapy, paving the way for novel, targeted treatment strategies aimed at improving clinical outcomes in bladder cancer management. These results underscore the potential of Emmprin as a critical player in bladder cancer progression, warranting further investigation into its molecular mechanisms and therapeutic targeting.

Acknowledgement

The authors would like to express their heartfelt gratitude to Dr. Md Zahirul Islam, Lecturer, Department of Pathology, Sher-e-Bangla Medical College, Barisal, for his invaluable support throughout the research process. We are also deeply thankful to all the doctors from the Department of Urology, Sir Salimullah Medical College, whose unwavering assistance was instrumental in making this study possible. Special acknowledgment goes to the patients, from whom specimens were collected, and their attendants, for their active participation and cooperation in this study.

Contribution of the Authors

Shamim Ahamed conceptualized the study, designed the methodology, and revised the manuscript. Nafisa Abedin, as the corresponding author, led the data analysis, and manuscript drafting. Jannat Ara and Ummey Qoraiman Tahira contributed to data collection, analysis, and drafting. Sayeed Kishwara Kashfi and Shahana Sultana supervised the methodology and reviewed the manuscript. Mst Rubeyatul Jannat and Mashrufa Rahman assisted with literature review, statistical analysis, and manuscript revisions. Shahnaj Begum provided senior supervision and final approval of the manuscript.

Data Availability Statement

The data that support the findings of this study are fully available and can be obtained from the corresponding author, Nafisa Abedin, upon request.

Data supporting the findings of this study are available from the corresponding author upon reasonable request.

Funding Statement

No specific funding was received for this study.

Conflict of Interest Disclosure

The authors declare no conflict of interest.

Ethics Approval Statement

Ethical approval was obtained from the appropriate institutional ethics committee.

Patient Consent Statement

Informed consent was obtained from all patients included in this study.

Permission to Reproduce Material from Other Sources

Permission was obtained where necessary.

Clinical Trial Registration

Not applicable.

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Sustainability of Biofloc Technology in Enhancing the Productivity of Aquatic Organisms in Aquaponic Systems: A Review

DOI: 10.31038/AFS.2024614

Abstract

Aquaponics is based on the principle of integrating the cultivation of aquatic organisms with plant farming to minimize waste and maximize productivity. However, certain aspects of conventional aquaponics can pose health risks to aquatic species. A novel technique that combines Biofloc technology with hydroponics offers an alternative approach to aquaponics for addressing these challenges. Biofloc-based aquaponics employs a dense microbial co-culture that enhances nutrient cycling, typically reducing feed requirements and minimizing the need for mechanical and biological filters. The technical advantages of BFT can lower costs compared to conventional intensive methods. However, this technique is still in its early stages of research, primarily due to inconsistencies in experimental design and system configuration. This article focuses on the cultivation of aquatic animal and plant species using BFT. The review analyzes effective development of BFT in aquaponics, guiding future research to make this method economically viable and improve sustainable aquaculture production.

Keywords

Aquaponics, Biofloc technology, Aquaculture sustainability

Introduction

Climate change poses a major threat to global food security, poverty reduction efforts, and sustainable development. Therefore, reforming the aquaculture sector is crucial [1]. The substantial potential of aquaculture has become increasingly evident through the advancement of hyper-intensive and intensive production systems [2]. There is an increasing need for the sustainable intensification of aquaculture production systems to meet rising food demands and address environmental challenges [3]. As a result, several studies have documented innovative production systems. Aquaponics is a method that integrates soil-less plant growth (hydroponics) with the cultivation of fish and crustaceans in a recirculating water system [4].

Aquaponics is a technique for producing food that involves the simultaneous cultivation of aquatic animals and terrestrial plants, enabling the sharing of water and nutrients among the various species involved [4,5]. In intensive animal aquaculture systems, waste nutrients are generated, as aquatic animals typically assimilate only a fraction of the feed provided [6,7]. For instance, marine shrimps typically improve about 22–32% of nitrogen and 11–14% of phosphorus [8]. However, this waste can be beneficial for plants, as they can utilize these nutrients, thereby reducing or eliminating the need for nutrient solutions, as seen in traditional hydroponic systems [9,10]. Furthermore, this enables the system to diversify and enhance its total production while simultaneously mitigating net environmental effects. By utilizing a water supply that is typically dedicated to plant production, it may also be used for the cultivation of aquatic animals [5].

BFT has been proven to be a viable aquaculture technique for aquaponics. This process comprises the transformation of harmful nitrogenous waste produced by animals into less harmful forms, such as nitrate, and the growth of bacterial biomass inside the same unit. Unlike conventional systems that rely on water renewal or recirculating aquaculture systems that use external biofilters, this method utilizes microbial processes like immobilization and nitrification to achieve this conversion. The bioflocs, which are formed by the combination of organic matter and microbes, are kept suspended in the water and can serve as an additional food source for the cultured animal. This facilitates the conversion of aquatic animal nutritional wastes into biomass via the microbial loop route. Furthermore, this system enhanced biosecurity eliminates the necessity of continuously sourcing water from the natural environment [11-15].

Aquaponics systems that utilize BFT can achieve high productivity for both fish and plants, while also offering significant ecological benefits through nutrient recycling, the elimination of pesticides, and efficient use of water and space [16]. Recent research suggests that combining hydroponics with BFT can enhance the production of marine shrimp [17] and tilapia [18]. FLOCponics is an evolution of traditional aquaponics in which the aquaculture subsystem utilizes BFT instead of RAS [19,20]. The BFT fundamentally relies on the growth of specific microbial communities that act as biological filters, facilitating the cycling of nutrients. FLOCponics research is becoming increasingly popular because it requires less fish feed, enables continuous nutrient cycling, and eliminates the need for complex filters compared to RAS production methods [16,17]. Despite the theoretical benefits of FLOCponics systems, [19] found that 63% of the plants grown using water from a mature biofloc-based fish system exhibited unappealing visual characteristics for the market. These findings raise concerns about the economic viability of FLOCponics [15]. When investing in new technologies, it is crucial to assess the financial feasibility of the enterprise [19,20].

Diversifying and sustaining aquaculture production through new technologies like FLOCponics necessitates profitability for producers [21]. Therefore, it is essential to assess the profitability of integrating biofloc technology (BFT) with hydroponics, as well as the impact of plant visual quality on FLOCponics production [22,23]. This study provides a thorough analysis on cultivation of aquatic animal and plant species using biofloc technology in Aquaponics system. The review analyzes effective development of BFT in aquaponics, guiding future research to make this method economically viable and improve sustainable aquaculture production.

History and Basics of Aquaponics System

The term “aquaponics” was coined in the late 1970s and early 1980s by Mark McMurtry and researchers at the New Alchemy Institute and North Carolina State University in the United States. This system, known as the “Integrated Aqua-Vegeculture System” (IAVS), combines aquaculture and hydroponics. The origins of aquaponics may be traced back to ancient civilizations such as the Aztec Chinampas, Egypt, Babylon, and Far Eastern countries like China and Thailand. These societies used a combination of fish and vegetable growing [24]. According to [25] William McLarney, Nancy Todd, and John Todd recreated the Aztec aquaponics system prototype in 1969, leading to the creation of the first commercially effective aquaponics system. In 1981, Dr. James Rakocy and his colleagues at the University of the Virgin Islands pioneered modern commercial-scale aquaponics. Most of the research on aquaponics began in the early 1970 [26].

Aquaponics is a kind of farming that combines the production of aquatic creatures in tanks with hydroponics. This technology utilizes microbial processes to convert nutrient-rich wastewater from aquaculture into valuable resources for plant nourishment and irrigation [27]. Aquaponics systems utilize resource reutilization and recycling to produce healthy food while minimizing or eliminating the need for chemicals such as fertilizers, pesticides, and antimicrobials. Consequently, compared to traditional aquaculture and hydroponics systems, aquaponics offers several advantages and has been designed to serve as a more sustainable and cyclical method of food production [5,23].

Nitrifying bacteria in aquaponics systems convert aquaculture effluents into plant-available nutrients, allowing plants to grow and use their feed to its maximum potential [13,22]. To maintain a stable operation of the aquaponics system, it is necessary to establish a nitrogen cycle. Ammonia is discharged and transformed into nitrite by ammonia-oxidizing bacteria during the process of fish breeding. Nitrite is subsequently converted into nitrate by oxidation by nitrite-oxidizing bacteria, mainly Nitrospira sp. and Nitrobacter sp. [28,29].

The nitrates produced in aquariums serve as nutrients for plants, promoting their growth. Efficient circulation can only be achieved when there is a balanced equilibrium between the production of nitrates by aquatic animals and the amount of plant biomass in the system [30]. Furthermore, unlike conventional aquaponics systems, integrated systems offer the benefit of fulfilling plant’s nutritional requirements without the use of fertilizers. This is achieved by supplying plants with a diverse range of nutrients (such as phosphorus, nitrogen, potassium, calcium, Sulphur, iron, magnesium, copper, manganese, zinc, molybdenum, boron, and aluminum) through the utilization of food and excrement from cultured organisms [31]. Aquaponics reduces the need for fertilizer in hydroponics and minimizes water treatment in RAS systems, leading to nutrient recovery and increased profitability by allowing the simultaneous production of two cash crops within the same system. [16]

DAPS (Decoupled Aquaponic System)

The primary obstacle to the profitability of conventional aquaponics is its capacity to provide an ideal environment for the development of both fish and plants [27]. To address this issue, a decoupled aquaponic system was created. This system separates the hydroponic components and aquaculture and allows for the adjustment or adaptation of the environmental conditions of each component to meet the individual needs of the fish and plants [32]. To maximize the growth efficacy of the system, the compromise between pH, temperature, and nutrient needs must be minimized [33]. The decoupled aquaponic system consisted of two independent loops, one for the RAS and another for the hydroponic components [34]. This arrangement enabled the recirculation of process water within each component, allowing for better control of the system tailored to the specific needs of the species involved [32,33].

The mineralization loop utilizes microorganisms to break down sludge, enhancing the availability of dissolved nutrients for plants [35]. Additionally, the acidification process lowers the pH, producing an ideal environment for plant development [36]. The demineralization loop is used in hydroponics to separate the nutrients and dissolved salts from the process water. The process water is then returned to the hydroponic unit, while the demineralized water is circulated back to the RAS [37]. This helps to improve control over the nutrient concentration in the respective subsystem of Dynamic Aquaponics System [38]. Decoupled aquaponics involves a reduction in the strength of interconnections between subsystems, resulting in the autonomous construction of the system in accordance with the nutritional needs of plants [27,33]. This results in a one-way flow where fish do not receive any benefits from the plants. Nevertheless, a connection is being established between the two subsystems, and the remineralization unit and other loops work together to maintain water quality [39]. This creates a virtuous cycle wherein fish, bacteria, plants, retained water, and fish all benefit from each other [27]. The phrase “decoupled” refers to the process of restructuring software systems by breaking down a huge monolithic system into smaller, independent pieces [37]. The DAPS design enables independent control of water recirculation in aquaculture and hydroponic systems, ensuring optimal water quality for promoting healthy growth of both plants and fish [40].

In contrast to a traditional aquaponic system, [40] asserted that the enhanced production of the hydroponic component was a result of the decoupled system’s superior control over water quality. African catfish and basil exhibited satisfactory growth in the decoupled aquaponic system when the feeding rate was reduced by 30% of the fish’s actual feeding rate [41]. In a decoupled aquaponic system, increased plant production was the result of higher fertilizer concentrations in hydroponics, whereas enhanced water quality for fish was the consequence of lower nutrient levels in RAS. When comparing DAPS to traditional aquaponics, found that improved pH and fertilizer control led to a 36% increase in tomato fruit output. Compared to hydroponics, the DAPS achieved the same yield while using 100% less freshwater and 62.8% fewer mineral nutrients for production [36].

The decoupled system’s net present value (NPV) was shown to be higher than that of traditional aquaponics in the cost-benefit analysis [40]. Contrarily, [36] proposed using the decoupled system for large-scale production and using conventional aquaponics to cultivate plants with lower nutrient requirements and fruiting vegetables with higher nutrient requirements. While DAPS offers improved sub-system control and increased productivity, it is much more sophisticated than connected aquaponics and hydroponic systems, requiring a far larger initial investment [41]. Additionally, the extra loops lessen the system’s economic viability for small-scale entrepreneurs; instead, they are appropriate for commercial production systems operating on a large scale or in regions with access to energy sources. Therefore, to expand DAPS, or on-demand coupled aquaponic systems, on a commercial scale, substantial research should be adopted [40,27].

Ecological Prospectives of Aquaponics

Due to the growing global population, limited resources, and advancements in production technology, aquaponics is seen as a promising ecological solution to the global food crisis and its environmental impacts [42,43]. Aquaponics possesses the capacity to significantly augment ecological and sustainable intensification in agriculture through the following mechanisms: reduction of resource consumption (e.g., water and land), optimization of wastewater and nutrient reuse efficiency, generation of zero waste, attainment of high productivity, and obviation of chemical fertilizer requirements. Because of this, it contributes significantly to climate-smart agriculture and the circular economy [44,45].

Aquaponics uses 90% less water than soil-based systems, with water consumption amounting to only 1% of that used in pond aquaculture. The extensive claims about the sustainability of aquaponics and its potential to reduce environmental costs have raised questions, leading to increased interest in evaluating the validity of these assertions (Chen et al., 2020) [45]. Life cycle assessment has become a comprehensive method for evaluating the sustainability of aquaponics and measuring the direct and indirect environmental effects of processes or products over their entire life cycle, from inception to disposal [43,45].

One possible way to describe aquaponics’ environmental performance is to use life cycle assessment to explicitly evaluate midway and endpoint impacts [46]. Endpoint impact analysis focuses on assessing the impact of a particular activity on quality, ecosystem resources, and human welfare [22]. In contrast, midpoint evaluation does not consider the environmental costs that occur earlier in the cause-effect chain, such as eutrophication, acidification, depletion of abiotic resources, and global warming potential. Compared to hydroponics, the midpoint impact of aquaponics is 1.7 times lower, and the endpoint impact is 50% lower [45]. Conversely, RAS incurs the highest environmental costs in terms of operation and infrastructure, primarily due to their high energy consumption and the technical infrastructure needed for water recycling. This significantly contributes to the exacerbation of global warming [34]. The environmental impact of aquaponics is considerably reduced in comparison to that of conventional hydroponics and aquaculture systems. The overall negative impacts on fish culture are mitigated by the coexistence of plant and fish production, which is achieved through climatic control, efficient use of water and resources, and plant biofiltration [46].

These variables help mitigate harm to the ecosystem and conserve resources [47]. A recent advancement in aquaponics research involves the development of customized aquafeeds tailored to different species. To achieve this, it is essential to modify the diet to meet the nutritional requirements of both the plants and fish within the system [48]. The primary goal was to reduce reliance on fishmeal and fish oil as protein sources and to identify viable alternatives. This approach aims to alleviate pressure on overexploited marine capture fisheries, decrease carbon emissions, protect biodiversity, and mitigate the environmental impacts of this sustainable production system, all within the framework of a circular economy [43].

From both socioeconomic and environmental perspectives, aquaponics encompasses a range of factors. This method recycles nutrients and wastewater, reduces pollution from aquaculture discharge, and supports economic development and food security. Additionally, it contributes to the reduction of greenhouse gas emission [46]. Moreover, as a tool for combating climate change, this climate-resilient system shows great promise. It can adapt to various environments by employing a method that meticulously controls abiotic factors [16]. When managed effectively, it becomes less susceptible to environmental fluctuations and climate change, leading to improved disease management, increased production, and reduced resource use [49].

Use of Biofloc Technology in Aquaponics for Culturing Aquatic Animals

The application of biofloc technology to aquaponic systems is a relatively recent phenomenon (Barbosa et al., 2022) [21]. Microorganisms constitute vital constituents within BFT systems [50,51]]. To maintain water quality, the bacterial population is managed to restrict the growth of autotrophic microorganisms. This is achieved by maintaining a high carbon-to-nitrogen ratio, as heterotrophic bacteria can efficiently consume nitrogenous by-products [14]. At the beginning of the culture cycles, a high carbon-to-nitrogen ratio is essential to promote optimal development of heterotrophic bacteria (Pinho et al., 2022) [16]. This energy is utilized by the bacteria for their maintenance and growth. Additionally, various species of microorganisms are crucial components of biofloc technology (BFT) systems. The population of chemoautotrophic bacteria, specifically nitrifying bacteria, stabilizes after approximately 20 to 40 days [7,50].

Approximately two-thirds of the ammonia absorption in the system may be attributed to these bacteria [52]. Therefore, it is important to reduce the amount of external carbon added, while replenishing the alkalinity consumed by the microbes with alternative carbonate and bicarbonate sources [11]. The dynamic interaction of diverse populations of naturally occurring species, including fungi, bacteria, nematodes, microalgae, rotifers, and protozoans determines the stability of zero or minimal water exchange [51]. Bioflocs, which are aggregates consisting of proteins and lipids, serve as a natural food supply. These bioflocs are available throughout the day because of the intricate interplay between physical substrate, organic matter, and a diverse array of microbes [14].

The production of microorganisms in tanks, raceways, or lined ponds serves three primary purposes: first, it helps maintain water quality by reducing nitrogen compounds and generating in-situ microbial protein. Second, it provides nutrition, which lowers feed costs and enhances the feasibility of the culture. Third, it helps combat harmful microbes [51]. In BFT, key concerns regarding water quality for cultured organisms include excess particulate organic matter, harmful nitrogen compounds, and oxygen levels, among other factors [53]. There are three ways that ammonia nitrogen is removed in this environment: first, photoautotrophic removal by algae; second, heterotrophic bacteria turn ammonia nitrogen into microbial biomass; and third, autotrophic bacteria turn ammonia into nitrate [51]. Plants grown in aquaponic systems can utilize nitrates and other nutrients, both macronutrients and micronutrients, that accumulate throughout the growth cycle as substrates [54]. In summary, the findings indicate that BFT is beneficial for shrimp and fish growth. BFT enhances fish yields and improves water quality compared to traditional aquaculture systems [55]. This improvement may be attributed to increased microbial activity, which enhances nutrient availability [13].

Biofloc serves as a high-quality food source for cultured organisms, resulting in significant cost reductions in aquaculture, where feed accounts for 40–60% of operational expenses [50]. Utilizing biofloc as a food source can improve feed efficiency by reducing protein requirements and increasing nitrogen utilization. Biofloc consists of various components, including proteins, lipids, carbohydrates, essential amino acids, essential fatty acids, antioxidants, and vitamins [7]. These elements contribute to positive outcomes such as enhanced growth, improved immunity, increased survival rates, and better reproductive performance in cultured organisms [56]. Additionally, the beneficial microorganisms present in the BFT play a crucial role in supporting aquaculture species. They compete with pathogenic bacteria in the environment, leading to a significant reduction in both the abundance and virulence of these harmful bacteria [57]. BFT eliminates the need for water exchange by utilizing microorganisms to naturally filter the water. This zero-water-exchange system enhances biological security by preventing the spread of pathogenic microorganisms that can occur during water exchange [57]. Additionally, this technology is vital for preventing pollution and ensuring biosecurity by stopping the transmission of diseases from aquaculture wastewater into the natural environment [11]. This system effectively prevents the escape of aquaculture organisms while maintaining optimal temperatures for aquaculture, all while minimizing energy consumption. This suggests that stable production of aquatic products is achievable through BFT [14].

FLOCponics: Combination of Biofloc Technology and Aquaponics

Aquaponics and aquaculture based on BFT are considered environmentally friendly methods of food production. Both are intensive aquaculture systems that prioritize water conservation and nutrient recycling [59]. FLOCponics shares similar characteristics. By integrating the principles of aquaponics and bioflocs, FLOCponics has the potential to serve as an additional tool in addressing the challenges of the global sustainable food supply [16]. Hydroponics and BFT are combined in FLOCponics, an integrated biofloc-based food production system [60]. Based on the same ideas of maximizing and recycling nutrients, water, energy, and land, it is a subset of aquaponics [58]. Plants grown in water can utilize the nutrients present to their advantage, which is why hydroponic loops are being integrated into biofloc-based farms [27]. This integration helps diversify production and provides aquaculture growers with additional products to sell [61]. Microbial interactions in BFT can enhance nutrient recycling and promote greater fish development, making it a viable alternative to RAS for aquaculture producers [11,62]. In addition to the advantages already mentioned, the use of bioflocs in shrimp and fish production may result in more efficient and sustainable use of water and nutrients [27].

Research on FLOCponics has primarily focused on comparing its yields to those of other production systems, as well as evaluating its nutritional profile and water quality [51,46]. Although the studies covered a wide range of topics, their overarching goal was to enhance FLOCponics and facilitate its market entry. FLOCponics has demonstrated promise not only in producing fish and shrimp and recovering nutrients but also in meeting sustainability standards [62]. However, some studies have reported operational challenges when implementing FLOCponics in a permanently connected setup [16,62]. Large-scale farmers are more inclined to adopt FLOCponics for educational and social purposes compared to RAS-based aquaponics, which are primarily used for commercial objectives [63]. One drawback of FLOCponics is the high cost of the infrastructure needed to maintain the biofloc bacteria and keep the system operational, making it challenging to implement the technology for social initiatives [64]. In terms of real-world applications, FLOCponics is still in its early stages. The private sector typically does not share data, resulting in limited information on the commercial uses of FLOCponics [62]. However, there have been documented instances of BFT farmers integrating hydroponic subsystems into their production units to conduct small-scale experiments with FLOCponics [46]. Optimal system design, target species to be cultivated, and overall economic viability are determined by environmental factors, production goals and scale, and management tactics [54,16]. FLOCponics typically operates in a closed setup, requiring very little land and water to produce nutritious food, which gives it an advantage over aquaponics and BFT systems [62].

Aquatic Animal Species Cultured in FLOCponics

In a study done by [65] it was shown that among 256 aquaponic participants, 70% utilized Tilapia (Oreochromis niloticus) [18], and 27% utilized Catfish (Siluriformes) [66] in their commercial operations. Additional fish species frequently utilized in commercial aquaponics are Rainbow trout (Oncorhynchus mykiss) [67], Common carp (Cyprinus carpio) [68], Largemouth bass (Micropterus salmoides) [69], Barramundi (Lates calcarifer) [70], Pacu (Piaractus mesopotamicus) [65-71], and Murray cod (Maccullochella peelii) [5]. An essential attribute for the successful cultivation of aquatic organisms in aquaponics is their capacity to endure elevated population densities as well as substantial concentrations of total suspended solids, phosphorus, nitrogen, and potassium [69]. It is typically not recommended to exceed a fish stocking density of 0.07 kg/L. However, species that can flourish at this density level are well-suited for aquaponics [67,72]. Furthermore, these species should be feasible for culturing in highly intensive culture system (Figure 1) [69].

Figure 1: The general qualities that fish species need in both coupled and decoupled aquaponics systems to be productive.

In aquaponics, Nile tilapia is the most frequently used and conceivably most successful fish species, followed by carp and African catfish [18]. The literature review revealed that 44% of published works included tilapia species as the primary aquatic organism [54,73]. Tilapia thrives in aquaponic environments due to its remarkable resilience to suboptimal water conditions [73]. This fish is characterized by rapid growth, resistance to stress and disease, tolerance to diverse environmental conditions, and the ability to consume food from lower trophic levels [19,54].

The tilapia fish is a microphagous low-trophic omnivore that feeds on phytoplankton and other tiny organic particles [73]. Since tilapia have a low dissolved oxygen requirement as they don’t need a lot of room to grow. This makes them perfect for aquaponic systems that aim to meet plant nutrient demands [18,73]. The impact of excretion from different species on nutrient concentrations in the aquaponic solution and subsequent plant production remains an open question in the current aquaponic literature [54]. For example, the water effluent from Nile tilapia, African catfish, and common carp contained nitrate levels ranging from 18 to 41.6 mg/L and phosphorus levels between 9.5 and 19 mg/L [66].

In their study, [74] found that using Common carp wastewater resulted in higher cucumber yields compared to tilapia effluent. However, tilapia effluent led to greater tomato yields. Tilapia fish have a higher level of metabolic feeding activity than carp, but the exact explanation for the superior development of tomatoes with tilapia effluent compared to carp effluent is still unknown [74,75]. This suggests that tilapia excreted a greater amount of feces into the water compared to carp. The authors also proposed that using various species might provide benefits in terms of achieving a more comprehensive nutrient water profile [18]. Certain shrimp species, such as Litopenaeus vannamei [46,76] and Penaeus monodon [77], have been utilized in aquaponics. However, the exploration of polyculture, which involves using different aquatic species in aquaponics to enhance plant development has not yet been thoroughly examined [16].

Plant Species Cultured in FLOCponics

Traditionally, leafy vegetables have been cultivated in aquaponic systems due to their short growing seasons, low nutrient requirements, tolerance for nitrogen-rich environments, and high global demand [21]. However, despite their higher economic value compared to leafy greens, cultivating flowering crops in aquaponic systems poses greater challenges. These challenges stem from their increased demand for phosphate and potassium fertilizers, greater susceptibility to pests and diseases, and slower growth cycles (Chu and Brown, 2020) [15]. Furthermore, the same study found that profit does not always correlate with crop value. According to their research, Bibb (Boston) lettuce generated higher revenue per week per m2 ($8.50–9.50 USD) than basil ($4.90–5.90 USD), despite basil having the greatest value per kg ($8.50–10.03 USD) [78]. This was due to improved planting density and yield. The majority of aquaponic economic studies concluded that the system was lucrative by including green vegetables. found that an aquaponics farm producing barramundi and lettuce generated an annual economic return that was $22,850 higher than that of the two independent systems. Over the course of a year, the aquaponic farm saved $1,315 on phosphate and nitrogen fertilizers, $1,270 on wastewater disposal, and $3,390 on all variable expenditures [79].

Integrating a lettuce and basil NFT system with trout farm producing 20,680 kg annually would plants yield a return of 13.8% and increased profit due to lower water remediation costs and higher plant production revenue [78]. This might be the reason why leafy greens and herbs are the main crops grown in commercial aquaponic systems. Basil (81%), salad greens (77%) [78], Solanum lycopersicum (Tomatoes) (66%) (Nadia et al., 2023) [75], Lactuca sativa (69%) [80], Brassica oleracea (56%) [81], Beta vulgaris (53%) [82], Capsicum annuum (pepper) (48%) [83], and Cucumis sativus (Cucumbers) (47%) [40] were the most grown crops by commercial aquaponic growers. In addition, aquaponic systems have been developed to cultivate plants that are capable of flourishing in saline environments [1]. Salicornia persica is a significant plant species suitable for cultivation in aquaponics systems that use salt or brackish water [46]. Salicornia is a halophyte that demonstrates tolerance to high salinity levels and efficiently absorbs significant amounts of phosphate and nitrate [84]. The advancement of aquaponics has also broadened the range of plant species that can be successfully cultivated [75]. However, there is a lack of scholarly studies specifically addressing the use of aquaponics for cultivating flowering plants [78]. Further research should investigate the effectiveness of aquaponics in the floriculture sector [85].

Water Quality and Nutrient Recycling

The ability of BFT microbes to effectively recycle nutrients and maintain optimal water quality for farmed species is a crucial aspect of BFT [52]. Phytoplankton, nitrifying bacteria, and heterotrophic bacteria all participate in the ammonia-nitrogen cycle [50]. They convert harmful ammonia-nitrogen into nitrate or incorporate it into bacterial biomass. Various forms of nitrogen conversion typically occur simultaneously, with the prevalence of each form depending on the nutrient management practices of the system [8]. Furthermore, the physicochemical properties of the water must meet the specific requirements of the microbes. Specifically, it is essential to provide high levels of dissolved oxygen and alkalinity, along with a favorable carbon-to-nitrogen ratio [6,40]. Detailed information is needed regarding the precise water quality required for the development of BFT microorganisms, as well as the recommended values of water parameters that must be maintained in fish or shrimp tanks within BFT systems [7,50].

Most of the physical-chemical quality of water indicators are still within acceptable limits to produce fish or shrimp, according to the findings of studies conducted in FLOCponics systems with an emphasis on animal production [16]. The total volume of suspended solids (bioflocs) was an anomaly, falling below the acceptable level. For instance, the average volume of bioflocs in tilapia culture typically ranges from 2.5 to 4.8 ml/L, 0.4 ml/L, and 0.4 to 0.9 ml/L. These levels are significantly lower than the recommended minimum of 6 ml/L [71]. However, these low numbers do not appear to have affected the ability of microorganisms to recycle nitrogen or maintain water quality [16]. This suggests that the relationship between microbial activity and biofloc volume in both BFT monocultures and FLOCponics remains ambiguous and varies significantly [46]. Some chemical and physical properties of water, particularly those related to pH and the concentration of suspended particles in connected FLOCponics systems, do not always appear to be beneficial for plants [16,65]. Hydroponic production typically recommends a pH range of 5.5 to 7 to ensure optimal nutrient availability for plant uptake [86]. However, most documented FLOCponics systems have been operated at relatively neutral pH values [40].

There is no need to regulate the pH of the FLOCponics system due to the lack of significant impacts on plant development [40]. In hydroponic subsystems, it is essential to maintain a very low concentration of suspended solids to prevent the accumulation of bioflocs in the plant roots, which can impair the ability of plants to respire and absorb nutrients [4]. In contrast, FLOCponics systems are known to have higher solid content in their hydroponic tanks [42]. Maintaining low solids concentrations in the hydroponics subsystems while concurrently preserving the biofloc concentration in the fish tanks at ideal levels for animal production seems to be one of the trade-offs associated with connected FLOCponics [87]. All subsystems require optimal water quality conditions, which depend on the inflow of nutrients and their transformation by microbes [50]. In traditional aquaponics, most of the nutrients used to nourish plants are believed to come from RAS effluent, and this is also expected to hold true for FLOCponics [37].

Feed typically serves as the primary source of nutrients in the aquaculture subsystem of RAS. In contrast, FLOCponics may provide a higher concentration of nutrients, as it integrates both organic and inorganic carbon sources [58]. According [52] both processes are frequently necessary to encourage the proliferation of BFT bacteria. Due to the limited knowledge of the specific features of the nutrient supply used in the FLOCponics systems, it is difficult to accurately estimate the quantity of nutrients that will be accessible for plant growth [46]. Furthermore, the precise rates of nutrient recycling and nutrient intake by the BFT bacteria remain unknown, leading to significant uncertainty in projections. Examining the nutritional composition of the plant biomass enables us to identify the nutrients delivered in the smallest amounts [88].

FLOCponics water often has lower fertilizer concentrations compared to hydroponic solutions [89]. However, in contrast to traditional aquaponics utilizing RAS, the practice of external carbon additive in aquaponics resulted in elevated levels of K, P, S, Ca, and Fe [71]. The process of converting RAS-sludge into minerals utilizing bioreactors and efficiently using the resulting liquid as fertilizer in multi-loop aquaponics [39]. There is limited documentation on the utilization of mineralized solids as a nutrition source for plants in FLOCponics [89]. Investigations in FLOCponics research have explored the use of plants as filters to eliminate nutrients from water as part of nutrient recycling methods. The investigations have mostly focused on the recovery of nitrogen and phosphorus and their conversion into plant biomass [58]. [46] conducted a study on the extraction of nitrogen and phosphorus from BFT effluent using halophyte plants. Combining shrimp and plant production may eliminate between 24.2% and 39.4% of nitrogen (N) and between 14.6% and 19.5% of phosphorus from the to feed input, as indicated by their findings. It is noteworthy that both nutrients often build up in BFT water [68]. When present in large quantities, these compounds can be harmful to the animals being raised. Additionally, if they are released into aquatic ecosystems, they can contribute to water eutrophication [7].

Productive Results of Aquatic Animals Cultivated in FLOCponics

Most of the research utilized Pacific white shrimp (Litopenaeus vannamei) or Nile tilapia (Oreochromis niloticus), except for [90] who cultivated South American catfish (Rhamdia quelen). According to [52] Pacific white shrimp and Tilapia are the predominant species in biofloc-based cultures. Both species exhibit a notable resilience to adverse environmental circumstances, including elevated levels of suspended particles and nitrogenous chemicals in water. This is the primary factor contributing to their ability to thrive in such environments. In addition, their morphological modifications allow them to efficiently exploit bioflocs as an extra food source [91].

The most used species for the nursery period was tilapia, with an initial weight ranging from 0.4 to 4.2 g [18]. Nevertheless, in the context of shrimp farming, the growth-out phase involved the production of shrimp, starting from an initial weight of 1.6 g until they reached an approximate weight of 13 g [76]. Research on the efficacy of FLOCponics for aquatic creature development has examined a wide range of factors. Some examples of treatments include: (i) adjusting the trophic levels of the BFT or the carbon source to evaluate alternative nutrient inputs [90], (ii) varying levels of salt in the water [46], (iii) the impact of using BFT in conjunction with hydroponics [92], (iv) how shrimp performance is affected by plant production-specific management [93] and (v) how classical aquaponics utilizing RAS [71], compares to FLOCponics systems in terms of plant and fish development.

[93] described that tilapia fed with a feed containing 40% protein and no fertilizer addition performed better than those fed with a food containing greater protein content and fertilizer supplement in the FLOCponics system [18]. Using bioflocs from an ex-situ BFT led to better tilapia output and feed conversion ratio [51]. A comparative study between traditional aquaponics and FLOCponics systems was conducted to assess the production of tilapia juveniles. The results showed that the FLOCponics system yielded a higher growth rate, greater final weight, and a lower FCR compared to the traditional aquaponics system. [71]. The authors noted that the average volume of bioflocs in the tank was below the required level for BFT cultivation. A larger supply of natural food in the tank could have improved the performance of the fish. [94] also discovered a similar pattern of low biofloc volume and its effect on fish development in their study, which involved the use of linked systems. The authors of this study did not see any significant statistical differences in Rhamdia quelen production between aquaponics and FLOCponics. Both experiments indicated that enhancing system design might optimize the interaction of BFT with hydroponics.

The reported density of tilapia by Fimbres-Acedo et al., (2020) [93] which is 23 kgm−3, is considerably lower than the maximum density of 50 kgm−3 seen in BFT or the density of 70 kgm−3 achievable in the growth-out phase of commercial aquaponics with RAS [58]. The nursery phase values, ranging from 6.9 to 8.8 kgm−3, are within the expected range of 7 to 9 kgm−3 in BFT systems. Commencing the growth-out phase with a stocking density of 260 to 520 juveniles per cubic meter in shrimp production can lead to the development of marketable shrimp weighing more than 20 grams and achieving yields of 6 to 8 kg/m3 [17]. The FLOCponics shrimp studies employed comparable stocking densities, resulting in lower yields ranging from 2.2 to 2.9 kg/m3 [46]. Connecting a hydroponics system to biofloc tanks affects solids and bioflocs, as discussed earlier. With reduced biofloc, there is less natural food available, which may alter microbial activity. This is likely the reason for FLOCponics’ lower yields compared to monocultures reliant on biofloc [16]. The findings indicate that improving the system’s design and carrying capacity may be able to address issues with yield performance and solids management. This would make FLOCponics work better and get it closer to commercial aquaponics with RAS [46,16].

Productive Results of Plant Cultivated in FLOCponics

One of the main components of FLOCponics systems is the use of nutrient rich BFT effluents to feed hydroponic plants. Nevertheless, there is disagreement among researchers over whether FLOCponics increases or decreases plant yields [46]. Plant growth in this system should be compared with crops in hydroponics, conventional aquaponics utilizing RAS obtain definitive conclusions on the influence of BFT waste on plant productivity [4]. Standardizing the nutritional input composition across all systems may also be accomplished concurrently with this comparison. There were several reviews that contrasted FLOCponics with hydroponics or conventional aquaponics, but none that did so with soil-based techniques [40].

The quantity and type of nutrients supplied to the hydroponics subsystem varied among the treatments and systems in experiments comparing FLOCponics with other approaches. Most studies on FLOCponics have focused on the output of lettuce or salicornia. Leafy plants like lettuce are often used in conventional aquaponics systems due to their rapid growth cycle and low nutritional requirements [4]. Among the studies comparing lettuce grown in FLOCponics to lettuce cultivated in other systems, 19% found that FLOCponics performed better, 13% indicated that traditional aquaponics was more effective, 25% reported better results with hydroponics, and 44% found no significant differences between the systems [60]. The researchers evaluated the production of lettuce using BFT effluents, either treated with filtering devices or left untreated, but neither scenario showed any modifications in plant development. Solids and bioflocs were observed on plant roots, particularly in the absence of filtration systems; therefore, the scientists proposed the development of effective mechanical filters to prevent the accumulation of solids. They evaluated the effects of supplementing the hydroponics subsystems of the FLOCponics treatments with fertilizer on lettuce growth within the same experiment. The authors found that, due to the added fertilizer, the lettuce grew similarly in both the hydroponics and FLOCponics systems [40]. The halophyte salicornia is a very valuable commodity. Researchers in these experiments failed to evaluate FLOCponics in comparison to other methods of crop production. Most of them emphasized how salicornia production and BFT may work together for the better (Table 1) [46].

Table 1: An overview of productive results of aquatic organisms and plant species cultivation in FLOCponics.

Plant

Animal Results

Reference

Lettuce (Lactuca sativa L.) Tilapia (Oreochromis niloticus) Lettuce cultivated in FLOCponics showed noticeably poorer growth performance and visual quality compared to lettuce grown in traditional aquaponics. In contrast, juvenile tilapia demonstrated significantly enhanced zootechnical performance in the FLOCponics system. Pinho et al. (2021)
Cucumber (Cucumis sativus L.) Tilapia (Oreochromis niloticus Variations in pH influenced the availability of macro and micronutrients. However, they did not significantly affect the growth rate of cucumbers. Both cucumbers and tilapia showed significant growth rate in BFT supported aquaponics. Blanchard et al. (2020)
Cherry tomato (Solanum lycopersicum var. cerasiforme) African cichlid (Melanochromis sp.) Tomatoes and fish grown in FLOCponics water exhibited a remarkable 20% increase in growth rate compared to those cultivated in a traditional hydroponics system. This demonstrates the enhanced efficacy of the FLOCponics approach in promoting growth for both crops and aquatic species. Castro-Castellón et al. (2020)
Jalapeño pepper (Capsicum annum) Tilapia (Oreochromis niloticus) Tilapia demonstrated enhanced productivity in tanks employing BFT. However, there were no significant differences in plant productivity among the assessed systems for the pepper plants. Martinez-Cordova et al. (2020)
Tomato (Lycopersicon esculentum) Tilapia (Oreochromis niloticus) The growth performance of tomatoes was not enhanced in BFT supported aquaponics. In contrast, the growth and survival rates of tilapia showed significant improvement. Martinez-Cordova et al. (2020)
Cherry tomato (Solanum lycopersicum var. cerasiforme) Tilapia (Oreochromis niloticus) The cherry tomato ‘Favorita’ yielded similarly in FLOCponics and hydroponics before fish harvest, whereas the tomato ‘Goldita’ yielded more in hydroponics. Both cultivars grew better in hydroponics after the fish harvest. Pickens et al. (2020)
Perennial glasswort

(Sarcocornia ambigua)

Pacific white shrimp (Litopenaeus vannamei) The combined production of L. vannamei and S. ambigua in FLOCponics was recommended at 16–24 psu since the shrimp performed well and the plants grew and removed nitrogen and phosphate compounds. Pinheiro et al. (2020)
Perennial glasswort

(Sarcocornia ambigua)

Tilapia (Oreochromis niloticus) and pacific white shrimp (Litopenaeus vannamei) Compared to BFT, the FLOCponics system’s IMTA produced a better yield. The presence of S. ambigua did not affect the consumption of phosphorus or nitrogen, despite the reduction in nitrate levels. Poli et al. (2019)
Asparagus (Sarcocornia ambigua) Pacific white shrimp (Litopenaeus vannamei) The growth performance of Litopenaeus vannamei and Sarcocornia ambigua cultivated together in FLOCponics was significantly enhanced. Soares et al. (2022)
lettuce (Lactuca sativa L.) Tilapia (Oreochromis niloticus) Growing lettuce in freshwater FLOCponics resulted in a greater harvest than in brackish water. Zappernick et al. (2022)
Lettuce (Lactuca sativa L.) Silver catfish (Rhamdia quelen) Compared to traditional aquaponics, FLOCponics methods utilizing silver catfish wastewater as fertilizer significantly enhanced lettuce growth. Rocha et al. (2017)

 

lettuce (Lactuca sativa L.) Tilapia (Oreochromis niloticus) Lettuce grown using BFT effluent demonstrated greater productivity compared to that cultivated in conventional aquaponics. Among the various types of lettuce examined, butter lettuce exhibited the most favorable growth characteristics, highlighting its suitability for BFT systems. Pinho et al. (2017)
Perennial glasswort

(Sarcocornia ambigua)

Pacific white shrimp (Litopenaeus vannamei) S. ambigua absorebed maximum nutrients from shrimp waste and improved the growth rate. While shrimp growth was not improved by the combination of S. ambigua with shrimp production, while using BFT in aquaponics. Pinheiro et al. (2017)

The BFT trophic level can have an impact on the performance of different plant species, including spinach, lettuce, pak-choi, rocket, basil, and others. Their findings emphasized the significance of determining the species’ suitability for a particular production scenario. [89] conducted a study comparing tomato growth in FLOCponics and hydroponics systems, both before and after fish harvest. Following the fish harvest, the researchers found that the FLOCponics system produced fewer tomatoes than the hydroponics system. This difference was attributed to a lack of nutrients in the water, which hindered the growth of the remaining tomatoes. Although nitrogen levels in the BFT effluent were considered low, the elemental composition of cucumber leaves remained within acceptable ranges [93].

Researchers conducted further examination in FLOCponics research and obtained encouraging outcomes, assessing visual attributes, nutritional content, and stress indicators [57]. Their findings indicated that the growing conditions in FLOCponics did not lead to excessive plant stress. Some studies revealed that BFT had a positive impact on the visual quality of the plants, while others found no visible signs of nutritional deficiencies [54,89]. Research on FLOCponics often associates the presence of particulates or bioflocs on plant roots, as well as high water pH levels (above 7), with poor visual characteristics and inadequate plant growth. These factors can hinder the availability of nutrients in a form that plants can absorb [57]. Furthermore, nutritional imbalances and the consumption of nutrients in water by BFT microbes are additional factors that contribute to these issues [89]. However, the exact role of these bacteria in the processes of nutrient recycling and elimination remains unclear [95]. Additionally, the lack of effective waste management and the failure to optimize nutrients by reusing or demineralizing sediments and bioflocs exacerbate the issue [54].

Sustainability Aspects of FLOCponics

Researchers have developed emerging technologies to promote the transition of aquaculture toward more environmentally sustainable practices. Sustainability in aquaculture encompasses the need for systems to be both technically feasible and economically viable. The objective is to provide safe and nutritious food to meet the needs of current and future generations [59]. Conducting economic evaluations of different aquaculture operations can yield valuable information for implementing managing techniques that enhance the business’s resilience and longevity [89,57]. Sustainability assessments are essential for developing a comprehensive understanding of the social and ecological impacts of a new production system, considering its interconnectedness. This understanding is crucial for establishing effective public strategies that promote the sustainable growth of the industry. It encompasses biological, technical, and economic considerations [96]. Research utilizing Life Cycle Assessment has shown that the primary environmental impacts of aquaponics production are associated with infrastructure, energy consumption, and feed [97,98].

The positive aspects of aquaponics systems are frequently linked to their low water consumption and their potential to support cultural, recreational, educational, and tourism-related benefits, as well as to enhance the landscape [89,99]. While the carbon footprint associated with commercial shrimp production, as determined by life cycle assessment, does not significantly impact biofloc-based production, energy consumption does [59]. The literature reveals a lack of sustainability assessments for FLOCponics systems. This gap is likely due to the absence of a large and comprehensive database necessary for such analyses [16]. [58] described FLOCponics as a novel technique with the potential to mitigate certain unsustainable aspects of traditional aquaculture, despite the lack of available sustainability assessment data. Replacing the RAS with BFT can enhance the advantages and disadvantages of both biofloc-based systems and conventional aquaponics.

An environmentally friendly food production system, already recognized for its effectiveness, can integrate this substitution [16]. Additionally, the key sustainable benefits of FLOCponics systems include the ability to produce a variety of food items close to consumers, in compact urban areas, while minimizing environmental impact and providing social benefits [89]. Furthermore, FLOCponics is a highly significant system in food production, as it yields pesticide-free, nutritious products available to consumers in various forms, including fish and vegetables. A speculative commercial-scale FLOCponics system was modeled to incorporate Litopenaeus vannamei and S. ambigua, a halophyte, with a focus on its profitability. Even in the most pessimistic business projections, the authors assert that the system is financially viable due to the high market value of the species involved. Additionally, they found that FLOCponics requires expensive operational equipment, highly trained personnel, and significant deployment costs. It would be unwise to assume that FLOCponics will be profitable based solely on hypothetical outcomes in specific regions and with products [16,58].

It is crucial to recognize that if the productive capacity of FLOCponics is validated, the expenses could be mitigated by increased biomass production, addressing this economic concern [89,57]. For instance, the cost of electricity per kilogram of food produced in FLOCponics systems is expected to be lower than that in biofloc-based monocultures [85]. Incorporating renewable energy sources such as solar, wind, and biogas from biodigesters, along with durable infrastructure and equipment, could further enhance the environmental sustainability of FLOCponics systems [54,71]. Food production systems inherently affect the environment. Therefore, we recommend supporting systems that achieve high productivity with minimal negative impacts [100]. It is essential to evaluate the trade-offs between the benefits and drawbacks of FLOCponics, as well as to assess the long-term viability of actual systems. To accomplish these goals, we must develop a more comprehensive technical and economic database on FLOCponics, which can then be subjected to sustainability studies [85].

Challenges of Using BFT in Aquaponics

If the technological challenges are addressed, FLOCponics could serve as a viable alternative for investors looking to establish integrated agri-aquaculture farms. To effectively operate a FLOCponics system and achieve optimal results, a thorough understanding of several key subjects remains essential [16.95]. Additionally, the selection of the food production system must consider several elements, including market demand, climatic conditions, producer expertise, technical knowledge, input costs, and availability, among other considerations [100]. While recognizing the potential benefits of FLOCponics, it is essential to conduct a comprehensive review of the entire production process to select the most suitable method for a given situation [80]. The design and construction of FLOCponics systems are crucial elements that require alteration. The configuration of this system must be carefully designed to maximize the favorable environmental situations required for the growth of aquatic plants and organisms, as well as the nourishment of BFT bacteria [71]. The primary goal is to maintain optimal levels of suspended particles in the water to support the growth of both fish and plants. As previously mentioned, the high concentration of solids in FLOCponics systems appears to impede plant growth. Efforts to remove solid particles from the hydroponics subsystem have, however, diminished the availability of food and bioflocs for the animals in their natural environment [19,80]. A potential strategy to address this issue involves developing mechanical separators that efficiently separate the solid and liquid components of the BFT effluent. This would allow for the transfer of nutrients and water from the bioflocs to the hydroponics subsystem, while reintegrating these elements into the aquaculture subsystem [100]. Bag filters with backwash technology, drum filters, and sedimentation containers with meticulously engineered biofloc return flow should be considered for FLOCponics [71].

Additionally, it is essential to establish the regularity of their operation and control the water discharge rate into these filtration systems. It is important to emphasize that each of these filters can be utilized in interconnected FLOCponics systems [100]. However, in all interconnected systems, there will inevitably be a trade-off between the needs of plants and animals [36,80]. The enhancement of the technical components of FLOCponics systems should effectively mitigate or perhaps resolve these issues, mostly associated with solids management [19]. Furthermore, implementing a decoupled design would enable effective adjustments of pH levels to optimal values for each subsystem and allow for the direct addition of specific minerals to the hydroponics subsystem. Unlike commercial hydroponics that rely on completely prepared fertilizers, FLOCponics might potentially lower production costs by using only particular nutrients [46]. This is feasible because BFT effluent already contains a diverse array of nutrients. To achieve this goal, it is crucial to obtain detailed information about the quantities of nutrients present in the feed and the carbon source. Additionally, it is important to analyze the micronutrient content in the process water of the BFT system, as these micronutrients significantly impact plant physiological processes, such as photosynthesis [36,80]. An examination of the differences in the quality and diversity of micronutrients between FLOCponics systems and a properly balanced hydroponic fertilizer will shed light on the possibility of a specific nutrient deficiency. This could facilitate the creation of tailored supplementation regimens for each plant species, thereby maximizing both yield and quality of the vegetables [75,78].

Furthermore, it is essential to conduct this research at high densities to achieve greater yields. Only a limited number of animal species that can be efficiently cultivated in BFT systems, and consequently in FLOCponics systems, possess the necessary traits . However, several studies have identified additional species that may also be viable [91]. Pacific white shrimp and Nile tilapia are the most widely cultivated species using BFT. Both species are extensively farmed and make significant contributions to the global food supply. Although the limited availability of other high-value species poses a challenge for FLOCponics, focusing on established products while developing innovative technologies is advantageous [55].

Conclusions

Aquaponics involves the integrated cultivation of aquatic organisms and plants, where most nutrients required for plant growth come from aquaculture effluent. In a conventional aquaponics system, a recirculating aquaculture system is linked to a hydroponic system, allowing for the continuous exchange of water and nutrients. In conventional aquaponics, a key challenge is managing the conversion of ammonia produced during the cultivation of aquatic animals into nitrate, while simultaneously maintaining a balance between the concentrations in the aquatic animal tank and the plant growth layer. Integrating BFT into aquaponics is expected to effectively address this issue and provide innovative solutions to the challenges facing the aquaculture sector. The combined system, known as FLOCponics, merges BFT and aquaponics, and is designed to be environmentally sustainable. This integrated system can enhance economic diversity by producing value-added plant products while reducing the accumulation of nitrate and phosphorus in the BFT management system. Further research is needed to assess the environmental, social, educational, and economic impacts of implementing FLOCponics in urban settings. Such an evaluation will support the promotion of sustainable practices in aquaculture.

Author Contribution

Bilal Raza conceived designed and wrote the manuscript. M. Naeem Ramzan, and Fatima Khan assisted in drafting the manuscript. Faisal Tasleem and Arslan Emmanuel helped in review the manuscript. All authors reviewed and approved the final manuscript.

Conflicts of Interest

The authors declare no conflicts of interest.

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A Bridge Too Far? – An Academic Reflection on Blood Transfusion

DOI: 10.31038/JCRM.2025812

Abstract

Blood transfusion, as the clinical element of Transfusion Medicine (TM), is an integral part of the Health Care System, a supportive treatment modality of a manifold of diseases, inborn as well as acquired. The source material is healthy human blood or its components to be donated regularly by adult and healthy donors in a voluntary, anonymous and non-remunerated way; altruistically. That source material should be safe, effective and quality-assured to protect the recipient as well as the provider, the blood donor. In principle blood donation is an act of social solidarity and should be organized patient centered, observing moral-ethical principles and attitudes or behaviors.

There is a need for a governmental oversight and comprehension of what a blood system and Transfusion Medicine mean as an integrated element of the national health care system in the health care. But also the development of stewardship, education and a quality culture among the potential and present TM professionals, whether medical, nursing or laboratory.

Introduction

Despite the numerous stimulating recommendations of national and international organizations [1-7], the TM world has still not managed to achieve 100% voluntary and non-remunerated donation as a gift of life and starting crude biomaterial in blood transfusion. Sad enough, currently [8] in total 79 countries collect over 90% of their blood supply from voluntary unpaid blood donors; however, 54 countries (40.6%) – all Low-and Medium-Income Countries (LMICs)- collect over 50% of their blood supply from family/replacement or paid donors putting patients at avoidable risk. Many of these situations are caused by inefficient governance and inadequate and incomplete legislation, and shortcomings in regulations [9].

National Blood Legislation, Policy and Governance

Blood transfusion supports saving lives and improving health, but many patients in need of transfusion do not have timely access to safe, effective and quality-assured blood. Providing safe, effective and quality-assured blood should be an integral part of every country’s national health care policy and infrastructure.

WHO recommends [7] that all activities related to blood collection, testing, processing, storage and distribution – the manufacture – be coordinated at the national level through effective organization and integrated blood supply networks of independent blood establishments: a national blood system. This national blood system should be governed by a national blood policy [10] and legislative framework [11,12] to promote uniform implementation of current standards, consistency in the quality, safety and clinical efficacy of blood and blood products.

In 2018, 73 % or 125 out of 171 reporting countries mentioned they have a national blood policy [8]. However, only 66% or 113 out of 171, have a specific framework legislation covering the safety and quality of blood transfusion, largely in high-income countries, including:

  • 79% of high-income countries (HICs)
  • 63% of middle-income countries (MICs)
  • 39% of low-income countries. (LICs)

Blood Supply

About 120 million blood donations are collected worldwide, 40% of these are collected in high-income countries, home to 16 % of the world’s population [8].

About 13,300 blood centers in 169 countries report collecting a total of 106 million donations. Collections at blood centers vary according to income group. In the low-income countries the median annual donations per blood center is 1,300, in lower-middle-income countries 4,400 and in upper-middle-income countries 9,300, as compared to 25,700 in high-income countries. Most of these blood centers are hospital-based and have insufficient economy-of-scale.

There is a marked difference in the level of access to blood between low- and high-income countries. The whole blood donation rate is an indicator for the general availability of blood in a country. The median blood donation rate in high-income countries is 31.5 donations per 1000 people. This compares with 16.4 donations per 1000 people in upper-middle-income countries, 6.6 donations per 1000 people in lower-middle-income countries, and 5.0 donations per 1000 people in low-income countries; 60 countries report collecting fewer than 10 donations per 1000 people. Of these, 34 countries are in the WHO African Region, four in the WHO Region of the Americas, four in the WHO Eastern Mediterranean region, four in the WHO European Region, five in the WHO South-Eastern Asia Region, and nine in the WHO Western Pacific Region [9]. All are low- or middle-income countries.

Many factors influence the requirements for blood to meet the health care needs of a population, as with all other treatment modalities. These include health care policies, income levels, current status and rate of development of the health care system, and accessibility of health care facilities to the public, all intimately related to the Universal Health Coverage (UHC) program and the seventeen Sustainable Development Goals (SDG) [13,14]. The need for, demand for, and use of blood in a country could be affected by geography, population migration, and epidemiology of diseases for which blood is needed but also competency of governance and stewardship, levels of knowledge acquirement, and transfusion medicine education and its environment. Therefore it is important to agree on definitions of need for, demand for, and use of blood [9] –

Need:

An estimation of the amount of blood needed to meet the transfusion requirements of the patient population according to current policies, clinical guidelines and best practices.

Demand:

The amount of blood that would be transfused if all prescriptions for blood were met. Demand may reflect appropriate or inappropriate indications and practices.

Use:

The actual amount of blood currently transfused; use may be appropriate or inappropriate.

Ideally there should be a balance between the demand and the need, translated into a demand–supply equilibrium based on appropriate and evidence-based use and demand-based manufacturing of collected units of blood; hence the two important interfaces to which the blood establishments are connected – clinical and societal. A model of need for, demand for, and use of blood in the LMIC is given in Figure 1.

Figure 1: Paradigm or model of need for, demand for, and use of blood (9). Red = current use; green = unmet demand (in the box) and total (above the box); black = total population need. Below the black box = inappropriate demand and transfusion.

Need

Based on data reported by 157 countries to the Global Database on Blood Safety (GDBS) (9), 89% of whole blood donations collected globally were processed into components: 96% in high-income countries, 96% in upper-middle-income countries, but 75% in lower- middle-income countries, and only 38% in low-income countries. Across the six WHO regions, the percentages for processing blood into transfusable components were 42% in the African Region (AFR, 18/43 countries), 50% in the South-East Asia Region (SEAR, 5/10 countries), 57% in the Eastern Mediterranean Region (EMR, 8/14 countries), 60% in the Western Pacific Region (WPR, 12/20 countries), 71% in the Region of the Americas (AMR, 22/31 countries), and 95% in the European Region (EUR, 37/39 countries). These data provide a global picture of clinical blood component need and demand in the six WHO regions in the world.

Demand

Shortages of blood, whether real, f ictitious or potential, have impacted all countries at different times and periods, including more recently during the COVID-19 pandemic and ongoing humanitarian emergencies. In the early stages of the pandemic there were major concerns about lack of availability of blood for transfusion. Strategies and recommendations for responding to potential blood shortages must be incorporated into resilience planning for the blood supply by countries, and blood system and service operators and institutions [7,15,16].

Use

Data reported indicate significant differences in the age distribution of patients transfused. In high-income countries, the most frequently transfused patient group is aged over 60 years, which accounts for up to 76 % of all transfusions. In low-income countries, up to 54% of all transfusions are for children aged under 5 years (mostly malaria anemia), usually followed by females aged between 15 and 45 years (obstetrics). The WHO 2018 data [9] on distribution of units of blood transfused in different clinical departments in hospitals or other transfusion prescribing and performing health facilities from 19 countries in the African Region (AFR) revealed that among 2,248,721 units of blood were transfused; 466,625 (21%) were transfused to patients in pediatric departments, and 427,289 (19%) to patients in obstetrics and gynecology departments. In five of the 19 countries, more than 30% of blood was transfused to pediatric patients: Democratic Republic of the Congo 60%, Benin 58%, Burkina Faso 39%, Congo 33%, and Comoros 31%. Five countries reported that more than 30% of blood was transfused to gynecological and obstetric patients: Burkina Faso 61%, Cameroon 55%, Comoros 40%, Eswatini 32%, and Burundi 32%. Blood use for trauma and major bleeding varied considerably, although generally at lower rates than for patients in pediatrics, obstetrics and gynecology departments. The same data from the WHO AFR suggest that rates of usage in emergency and resuscitation departments in some countries approaches 23% to 34% (Madagascar 23%, Gabon 26%, Sao Tome and Principe 28%, and Cabo Verde 34%). Although these data indicate that children and women are the recipients who are most frequently transfused in low-income countries, it should be noted that these results are dependent on the accuracy of disease coding and documentation – e.g., it is possible that blood use in emergency departments is covered by surgery departments in some countries [9].

Another, often disrespected, observation is the almost daily occurring under transfusion and late transfusion due to poor logistics, organization and governance of the blood system, and poor to failing communication between prescribing and treating clinicians and blood manufacturers and suppliers. A number of studies have highlighted the burden of severe anemia in under 5 years of age children, often due to malaria. Mortality rates are significant, and deaths may occur within a few hours of arrival in hospital, indicating the importance of ambulance transport, access to timely blood transfusion support, which is often not available [15-19] and road conditions. Failure to recognize the presence of severe anemia resulted in lack of transfusion in some cases [20]. Currently, there are very limited data or studies available on unmet needs for blood transfusion in LMICs.

Consequences

So far, available and practicable knowledge seems a precious asset, because of the hampering and poorly organized Academic (tertiary) education and the lack of knowledge economy in most developing countries [21,22]. Consequence is not only the existence of a weak health care system but also the weakness of the supporting blood system. That leads to gaps in availability, safety, processing and clinical efficacy of blood transfusion in most LIMCs.

Unnecessary transfusions and unsafe transfusion practices expose patients to the risk of serious adverse transfusion events and transfusion-transmissible infections. Evidently, unnecessary transfusions also reduce the availability of blood and blood products for patients who are in need.

WHO recommends over the last decades the development of systems, such as hospital transfusion committees and hemovigilance [23], to monitor and improve the safety of transfusion processes. In this regard [9]:

  • 128 countries have national guidelines on the appropriate clinical use of blood: 32 countries in the African region (74% of reporting countries in the region), 23 in the Americas Region (70%), 12 in the Eastern Mediterranean Region (67%), 33 in the Europe Region (80%), 9 in the South East Asia Region (90%), and 19 in the Western Pacific Region (76%). However, many of these guidelines have never been updated.
  • Hospital transfusion committees (HTCs) are present in 48% of the hospitals performing transfusions: 62% in hospitals in high-income countries, 35% in upper-middle-income countries, 31% in lower-middle-income countries and 25% in low-income countries. However, many of these HTCs are dormant.
  • Systems for reporting adverse transfusion events are present in only 55% of the hospitals performing transfusions: 74% in hospitals in high-income countries, 35% in upper-middle- income countries, 22% in lower-middle-income countries and 18% in low-income countries. However, these reporting systems are often stand alone and not embedded in a quality system and its management.
  • Of reporting countries 49% have a hemovigilance The European Region, due to the European Union, has the highest percentage of countries with active hemovigilance systems (81%), followed by the Western Pacific Region (50%), the Eastern Mediterranean Region (50%), Africa Region (40%), South-East Asia Region (40%), and the Americas (21%), almost exclusively in North America and some in Latin America.

Other aspects such as manufacturing, cold chain and transportation have not been discussed as they represent the laboratory technical field of the vein-to-vein operations and are in fact the most easy and artisan parts of the chain.

Finally

There are remarkable epidemiological variations between countries and regions. The risk of transmission of serious infections, including HIV and hepatitis, through inadequately tested or even not tested unsafe blood, and existing chronic blood shortages brought global attention to the importance of blood safety and availability. With the goal of ensuring universal access to safe blood and blood products, WHO but also several professional associations and individual experts have been at the forefront to improve blood safety and availability, and recommend an integrated strategy for blood safety and availability [1- 3,7,10,24,25].

Lessons to Learn

WHO supports countries in developing national blood systems to ensure timely access to safe and sufficient supplies of blood and blood products and good transfusion practices to meet patient needs whether normal or emergency situations [7,20,21].

WHO provides policy guidance [10] and technical assistance [7,24-26] through development projects to countries for ensuring universal access to safe blood and blood products and works towards self-sufficiency in safe blood and blood products based on voluntary unpaid blood donations to achieve Universal Health Coverage (UHC). Unfortunately, that resulted in insufficient positive effects and often seems to be a bridge too far because of the shortage in knowledge and inadequate legislation and regulations.

To develop a sustainable and well-functioning national and integrated blood system that consistently meets the changing supportive needs of blood and blood components including the plasma-derived medicinal products (PDMPs), the principles should translate in knowledge and comprehension through a well- designed education system (education environment and teaching climate) anchored in a specific law and related regulatory mechanism [7,21].

There needs to be a governmental oversight and comprehension of what a blood system and Transfusion Medicine mean as integrated elements of the national health care system in the public health [7]. But also the development of stewardship, professionalism and a quality culture among the TM professionals, whether medical, nursing, laboratory or apprentice [27-29].

After all, blood transfusion is the most frequently practiced human transplant where Transfusion Medicine, after a long history, is now a fully accepted clinical discipline and science.

References

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Spatio-Temporal Variation and Factors Associated with Skilled Birth Attendant Delivery Among Women of Reproductive Age in Ethiopia: From EDHS 2016-EMDHS 2019

DOI: 10.31038/AWHC.2025811

Abstract

Background: Skilled birth attendant delivery is vital for the health of mothers and newborns, as most maternal and newborn deaths occur at the time of childbirth. Skilled delivery care service utilization in Ethiopia is still far-below any acceptable standards. However, Ethiopia still falls considerably below acceptable standards in providing skilled birth care services. Moreover, there is limited evidence regarding geographical distribution, and factors influencing access to skilled birth care services.

Objectives: The aim of this study is to assess magnitude, spatio-temporal variations and determinants of skilled birth attendant delivery among reproductive age women in Ethiopia between Demographic and Health Survey 2016 and 2019.

Design: Survey-based cross-sectional study design was employed for EDHS.

Setting: Data for both EDHS were collected in all nine regions and two city administrations of Ethiopia in 2016 and 2019.

Participants: The source population for this study was all fertile women of reproductive age in Ethiopia and the study population was all reproductive age women who gave birth in the last 5 years preceding each survey year in selected enumeration areas.

Outcome measure: Skilled birth attendant delivery was the outcome variable for this study.

Results: Skilled birth attendant delivery utilization was increased from 27.7% in 2016 to 49.6% in 2019. The spatial pattern of skilled birth attendant delivery was non-random across the country and its distribution varied across regions. The spatial scan stastics analysis detected a total of 56 clusters (relative risk (RR)=3.12, p-value<0.01) in 2016 and 28 clusters (relative risk (RR)=2.02, p-value<0.01) in 2019 significant most likely (primary) clusters. Maternal education, parity, household wealth index, ever use of family planning, media exposure, health insurance coverage, maternal age at first birth, distance from health facility, type of place of residence, region, community child care burden and community poverty level were significant determinants.

Conclusion: Skilled birth attendant delivery remains far-below national acceptable standards and had significant spatial variation across the country. Individual-level and community-level factors were associated with skilled birth attendant delivery. Therefore, a geographic specific intervention should be launched by the government and respective local administrators supported by small area researches done by academia in regions with low skilled birth attendant delivery, to intensify individual and aggregated community level variables.

Keywords

Skilled birth attendant delivery, Spatio-temporal variation, Multilevel analysis, Ethiopia

Introduction

In 2015, an estimated 303, 000 women died during pregnancy and childbirth. One woman in 41 in low-income countries died from maternal causes. In 2016, maternal mortality as the second leading cause of death for 15-49 age women. Most maternal deaths (95%) happened in low and lower middle income countries, and About 65% death recorded in African countries. Worldwide, about 295,000 maternal deaths occurred in 2017 which is 38% of decreament from the year 2000 with an average decreament of 3% each year. Even though a significant decline was recorded in the last 25 years, still the death of reproducive age women is high. Approximately 810 women perished per day from avoidable pregnancy and childbirth-related causes, which is the vast majority of these deaths (94%) that occurred in low-resource setting countries. Maternal mortality ratios dropped globally from 385 per 100,000 new births in 1990 to 216 in 2015. Despite this global decrement, there is still high rates of maternal death in Africa’s sub-Saharan region and South Asia; which accounts for 88% of worldwide maternal death. In spite of tremendous progress made on maternal health at the global level with the implementation of Millennium Development Goals (MDGs), there is slower progress in sub-Saharan Africa (SSA). Ethiopia’s maternal mortality rate decreased by 71.8% between 1990 and 2015, from 1250 deaths per 100,000 livebirths to 353, which is less than the goal of the maternal mortality-related Millennium Development Goals (MDGs). In Ethiopia, maternal mortality ratio declines from 676 every 100,000 live births in 2011 to 412 every 100,000 live births in 2016. Despite this decrement, the plan of reducing the maternal mortality ratio to 199 maternal deaths per 100,000 live births by 2020 was unachieve [1-8].

In the year 2000, The United Nations (UN) Millennium Declaration set eight Millennium Development Goals (MDGs) for its member states to reach by 2015. One of these goals was to cut the maternal mortality ratio (MMR) by 75% (MDG-5). In the event that the MMR is not reduced by 2015, the worldwide community reviewed the goals and redeveloped them as 17 Sustainable Development Goals (SDGs). One of these SDGs is to cut MMR globally to less than 70 by 2030 [2]. Maternal mortality reduction remains a priority agenda under goal three in the UN Goals for Sustainable Development (SDGs) through 2030. one of the best ways to achieve this objective is through providing skilled care during delivery [1,9]. Skilled birth attendance Through the prevention or treatment of the majority of obstetric complications, the labour, delivery, and early postpartum period can dramatically lower mother and newborn morbidity and mortality complications. Ending preventable maternal death remain at the top of the global agenda [10,11].

In recent decades, the world has made significant progress reducing new born and maternal deaths. Between 1990 and 2020, the new born mortality rate was almost halved. However, the number of women and new-borns dying is still unacceptably high, primarily due to treatable or preventable conditions such infectious illnesses and pregnancy-related problems or childbirth. In Sub-saharan Africa one in every two deliveries occurs outside of a health facility and without skilled assistant care. In Sub-Saharan Africa, childbearing women face a 1 in 39 risks of dying in childbirth [12-14]. In addition to indirect reasons including anaemia, malaria, and heart disease, the most frequent direct causes of maternal injury and death are excessive blood loss, infection, high blood pressure, botched abortion, and obstructed labour [11].

The majority of maternal deaths can be avoided with prompt intervention by a qualified healthcare provider operating in a nurturing environment [11]. Reducing maternal mortality is the target of Sustainable Development Goal (SDG) 3.1, and achieving this goal is thought to depend on skilled attendance at birth. If a woman receives care from qualified medical professionals, many maternal deaths can be avoided. In childbearing, women need a continuum of care to ensure the best possible health outcome for them and their new born. The skilled attendant is at the centre of the continuum of care [15].

Skilled care referred to as when a woman and her child receive care during pregnancy, childbirth, and the immediate postpartum period from a licenced and qualified healthcare professional who has access to the required tools and the backing of an operational healthcare system-including transportation and facilities for emergency obstetric care. An skilled birth attendant is defined as “an accredited health professional such as a midwife, doctor or nurse who has been educated and trained to proficiency in the skills needed to manage normal (uncomplicated) pregnancies, childbirth and the immediate postnatal period, and in the identification, management and referral of complications in women and new born” [16].

Skilled birth attendant delivery refers to births delivered with the assistance of either doctors, nurses, midwives, health officers or health extension workers [17].

According to studies, the percentage of women using trained health professionals to give birth has increased slightly over the past 20 years across all regions and as a result, the global rate of births attended by skilled health professionals has increased significantly from 64% in 2000 to 83% in 2020. Just 80% of live births worldwide between 2012 and 2017 took place in medical facilities with the assistance of skilled birth attndants. Globally, 70% of births in rural areas and 90% of births in cities worldwide are attended by skilled birth attndants. Sub-Saharan Africa shows the biggest differences, with 49% of rural births and 81% of urban births in Western and Central Africa being attended by trained medical professionals. But in Sub-Saharan Africa, where maternal mortality is highest, only 59% of live births were attended by trained health personnel. Despite the fact that competent prenatal, intrapartum, and postpartum care can save women’s lives, in Ethiopia, 28% of births in 2016 and 50% of births in 2019 were attended by qualified professionals, which is unacceptable high [18,19].

Approximately 73% of all maternal deaths resulted from direct obstetric cases, while 27% were caused by indirect factors. Approximately 25% of maternal fatalities happened during the prepartum phase, followed by 25% during the intrapartum and immediate postpartum phases, 33% during the sub-acute and delayed postpartum phases, and 12% during the late postpartum phase [20,21].

Evidences from different studies indicated that women’s age at first birth, household wealth index, participation in household decisions, mother’s/father’s education, health insurance coverage, religion, frequency of ANC visit, knowledge of critical pregnancy and delivery danger signs, parity, ANC visit, media exposure, History of still birth, Maternal occupation, place residence, geopolitical region, perception of distance from the health facility and community childcare burden were factors of skilled birth attendant delivery [22-29].

Numerous small-scale research on skilled birth attendance delivery utilizations have been conducted at the regional and lower administrative levels of the country, But at the national level little was done on the spatio – temporal patterns of skilled birth attendant delivery and associated factors after EDHS year 2016. Moreover, the trend of skilled birth attendant utlization from EDHS year 2016 upto 2019 not well known. Therefore, this study attempts to fill these evedence gap by investigating the spatial and temporal varation of SBA delivery and its associated factors using multilevel model analysis using EDHS survey 2016 and 2019 data.

Methods and Materials

Study Design, Setting and Period

For this investigation, cross-sectional survey data from two EDHS (2016 and 2019) were utilised. At the national level, complete surveys were carried out every five years, with micro surveys in between. The study was conduct in Ethiopia, which is a developing country, whose economy is mainly dependent on agriculture. Ethiopia is found throughout the Horn of Africa and shares a border with Eritrea, Djibouti, Somalia, Sudan, South Sudan and Kenya. (3°–14° N and 33°–48° E) is where it is. Administratively, it is divided into two city administrations (Addis Ababa and Dire Dawa) and nine regions (Afar, Amhara, Benishangul-Gumuz, Gambelia, Harari, Oromia, Somali, Southern Nations Nationalities and People’s Region (SNNPR), and Tigray) and further divided into Zones, districts, towns, and kebeles.

Source and Study Population

Every fertile woman in reproductive age in Ethiopia were the study’s source population and all reproductive age women who gave birth in the last 5 years preceding each survey year in selected enumeration areas were study population.

Sample Size & Sampling Procedures

A total of 16,394 reproductive age women, who had a live birth five years prior to the study were included in this study. The study included the two city administrations as well as all nine regions in Ethiopia. A stratified two-stage cluster sampling procedure was used to select the nationally representative sample in both surveys, with a high overall response rate that ranged from 98% to 99%. In the first stage, total EAs (in urban and rural) were chosen independently in each sampling stratum and with a probability corresponding to the size of the enumeration area. In the second stage, a set number of households per cluster were chosen using an equal probability systematic selection process. For spatial analysis, a total of 624 clusters in 2016 and 305 clusters in 2019 were used after removing clusters with zero coordinates. The entire sampling technique were available in both survey year report [17,30].

Data Collection Tools and Procedures

Face-to-face interviews with structured questionnaires were used to gather EDHS data. For this analysis, the data were taken from the measure DHS programme (Demographic and Health Survey) website (www.measuredhsprogram.com), after gaining permission for download and additional analysis on Nov 30, 2022. Similarly location information (longitudinal and latitude) was extracted from the downloaded GPS (Global Positioning System) file. Data extraction was performed using STATA version 12. After extraction, observations with in cluster of having zero latitude and longitude were left out for spatial analysis.

Variables

Dependent Variable

Skilled birth attendant delivery was the outcome variable for this study and it was coded as 1 if the woman received assistance during delivery from competent delivery attendants and 0 otherwise.

Independent Variables

Socio-demographic and socio-economic variables (maternal age, religion, household wealth index, mother’s education, mother’s occupation and health insurance coverage), Obstetrics related variables (parity, ever use of family planning and age of Mather at birth) and community-level variables (region, place of residence, community poverty level, distance from health facility and community level childcare burden). For this study community poverty level and community child care burden variables were computed by adding up all of individual level variables within their clusters by utilising the median values of the percentage of women in each category of a given variable, since not all aggregates were normally distributed.

Data Management and Analysis

Following, extracting the EDHS data; STATA version 12 and Microsoft Excel was used for editing, cleaning and recoding. Prior to analysis, the data was weighted using sampling weight to ensure that the survey was representative again and to instruct STATA to use the sampling design when calculating standard errors to produce accurate statistical estimates. The joining variable was used to combine the datasets to the Global Positioning System (GPS) coordinates of the EDHS clusters.

Spatial Analysis

The spatial analysis was carried out using Arc-GIS 10. 7 and Sat Scan 9.6. A cross tabulation was performed using the result variable’s weighted frequency and cluster number in STATA software and exported to excel to get the case to total proportion. Then excel file was imported to Arc-GIS 10.7 for spatial analysis and joined to the geographic coordinates based on each cluster unique identification code. The units of spatial analysis were DHS clusters (geographic coordinates of EDHS were collected at cluster level). The Ethiopian Poly-conic Projected Coordinate System was utilised to create the map of Ethiopia.

Spatial Autocorrelation Analysis

Global spatial autocorrelation was measured with Arc-GIS using the Global Moran’s-I statistics to determine whether the pattern expressed is clustered, scattered, or random throughout the study areas. Moran’s I is a spatial statistics that measures spatial autocorrelation by yielding a single output value between -1 and +1. Moran’s I Values close to −1 indicate disease/intervention is dispersed, whereas moron’s I close to +1 indicate disease clustered and disease distributed randomly if I value is zero. The presence of spatial autocorrelation is indicated by a statistically significant Moran’s I (p < 0.05), which leads to the rejection of the null hypothesis (skilled birth attendance is randomly distributed). Local Anselin Moran’s In terms of positively connected (high-high and low-low) or negatively correlated (high-low and low-high) clusters, used to look into the local level cluster locations of skilled birth attendance. A positive value for ‘I’ indicated that a case with adjacent cases that had similar values. A negative value for “I” indicated that a case was surrounded by cases that had values that were different from its own.

Host Spot Analysis (Getis-Ord Gi* Statistic)

The Getis-Ord Gi* statistic was calculated to quantify how spatial autocorrelation varied over the research location. The statistical significance of the clustering was assessed using the Z-score and the p-value. Spatial clusters with high values (hot spots) and low values (cold spots) were distinguished by the Getis-Ord Gi* statistic. Gi* is a measure of local autocorrelation, i.e. it measures how spatial autocorrelation varies locally over an area and provide statistic for each data points. If z-score is higher, the intensity of the clustering is stronger. A z-score that is close to zero denotes no clustering, a positive z-score suggests high value clustering, and a negative z-score suggests low value clustering.

Spatial Interpolation

Spatial interpolation is the process of estimating values (spatially continuous variables) for spatial locations which have not value from spatial location using known values. It is the method of determining the unknown value for any given set of points with known values. Spatial interpolation technique was used to predict SBA delivery on the un-sampled areas in the country based on sampled EAs. Numerous deterministic and geo-statistical interpolation techniques exist. Ordinary Kriging and empirical Bayesian Kriging are regarded as the best techniques out of all of them since they statistically optimise the weight and take into account spatial autocorrelation. For this study, the Ordinary Kriging spatial interpolation approach was employed to forecast SBA delivery in Ethiopian regions that were not sampled.

Spatial Scan Statistical Analysis

Statistical analysis using Sat Scan version 9.6, a Bernoulli-based model was used to determine whether statistically significant spatial clusters of SBA delivery were present or not. The spatial scan statistic uses a circular scanning window that moves across the study area. To suit the Bernoulli model, women who gave delivery with a skilled birth attendant were classified as cases, and those who did not were classified as controls. Each location’s case count followed a Bernoulli distribution, and the model needed information on cases, controls, and geographic coordinates. The number of observed SBA inside each probable cluster was compared to the expected number using the likelihood ratio test statistic and p-value to see if there was a significant difference. By comparing the rank of the maximum likelihood from the real data with the maximum likelihood from the random datasets, Monte Carlo hypothesis testing was used to assign a p-value to each cluster. The scanning window with the largest likelihood was the most likely performing cluster. Based on Monte Carlo replications, the primary and secondary clusters were found, given p-values, and ranked according to their likelihood ratio tests [31].

Multi-Level Analysis

The multi-level mixed effect logistic regression model was employed for the proper determinant estimate due to the hierarchical nature of the DHS data. Two-level multilevel Multivariable logistic regression (mixed effect model) was used to analyse factors associated with SBA delivery at two levels, at individual and community (cluster) levels. Four models were built. The first model was an empty model without any explanatory variables, to calculate the degree of variance within the cluster on SBA delivery. The second model was adjusted with individual level variables; the third model was adjusted for community level variables while the fourth was fitted with both individual and community level variables simultaneously. ICC (Intra-class correlation), MOR (median odds ratio) and the difference across clusters were measured using PCV (proportional change in variance). The ICC is a measure of within cluster variation (i.e., the variation between individuals within the same cluster) [32]. MOR refers the median value of the odds ratio between the cluster at high risk and the cluster at reduced risk when two clusters are randomly selected [33]. In comparison to the null model, PCV calculates the overall variation in the multilevel model that is attributable to individual and community level influences. The formulas for these measurements are as follows;

𝐼𝐶𝐶=𝑐𝑙𝑢𝑠𝑡𝑒𝑟 𝑙𝑒𝑣𝑒𝑙 𝑣𝑎𝑟𝑖𝑎𝑛𝑐𝑒 / 𝑡𝑜𝑡𝑎𝑙 𝑣𝑎𝑟𝑖𝑎𝑛𝑐𝑒: i.e. 𝐼𝐶𝐶=𝑣𝑖/ (𝑣𝑖+𝜋2/3) were VI=estimated variance in each model, which has been described elsewhere.

𝑀𝑂𝑅=(0.95√𝑣𝑧) (put reference) where vz=the variance at the cluster level

PCV=(Vn1−Vn2)/ Vn1; (put reference) where Vn1 is the neighbourhood variance in the empty model and Vn2 is the neighbourhood variance in the subsequent model. Models were compared, based on the log-likelihood ratio (LLR) and deviation. The model with the highest LLR and with lowest deviance was considered as a best fitted model. Variables in the multivariable multilevel logistic regression analysis were deemed statistically significant if their p-value was less than 0.05. Finding the Adjusted Odds Ratio (AOR) and its corresponding 95% confidence interval was used for identifying factors associated to SBA delivery. The variance inflation factor (VIF) was also used to test for multi-colinearity. There is multi-co linearity if variable have VIF>10 and tolerance< 0.1

Dissemination of the Finding

As part of a Master of Public Health (MPH) thesis, the findings of the study will be present and disseminated to the Bahir Dar University, College of Medicine and Health Sciences, School public health, department of health system management and health economics. The findings will also be shared with the Regional health bureaus, and other relevant governmental and nongovernmental organizations. It will be submitted to scientific Journals for publication and possibly presented to other research conferences and seminars for concerned governmental and non-governmental organizations and stakeholders.

Results

Descriptive Characteristics of the Study Population

A weighted sample of 11,023 from EDHS 2016 and 5,527 from EMDHS 2019 reproductive age women were incorporated into this research. However, the data of 21 clusters from EDHS 2016 were not included in the spatial analysis as geographical information was missed. 66.1% of study participants in EDHS 2016 and 53.6% in EMDHSB2019 had no formal education. About 96.5% of the study participant’s health expenditure was not protected by health insurance in EDHS 2016. Regarding media exposure, about 81.9% of participants had no media exposure in EDHS 2016. The median age of participants upon first birth, was 18 years in both survey years. Large of study participants 88.9% and 75.3% were lived in rural area in EDHS 2016 and EMDHS 2019 respectively. From the total participants more than half, 56.6% in EDHS 2016 and 57.1% in EMDHS 2019 were lived in communities with low poverty level. The percentage of women delivery with the assistance skilled professional was 27.7% and 49.6% in 2016 and 2019 respectively.

Spatial and Temporal Distribution of Skilled Birth Attendant Delivery

The proportion of skilled birth attendant delivery across regions of Ethiopia was increased over survey periods in all regions, except in Addis Ababa.

The overall Skilled birth attendant delivery showed increasing pattern in the country between survey years (2016 to 2019).

Spatial autocorrelation analysis indicated that the distribution of skilled birth attendant delivery was non-random across the two survey periods. Using a global Moran’s I statistic value of (I=0.36, P-value <0.001, for EDHS 2016 and I=0.17, P-value<0.001, for EMDHS 2019). This test result shows the existence of significant global positive spatial autocorrelation. The geographical dispersion of skilled birth attendant delivery varies throughout geographical areas in both surveys. It, suggests that there is local clustering in the distribution of skilled delivery that needs to be further explained using local statistics.

Hot Spot Analysis

The geographical distribution of SBA delivery was different in both survey periods. The Getis Ord Gi* statistical analysis identified the significant geographical distribution of hotspots and significant clustering of cold spots of SBA delivery. In EDHS 2016, hotspot of skilled birth attendant delivery was discovered in Dire Dawa, Harari, Addis Ababa, Northern part of SNNPR (Gurage) and Southern part of Amhara (north Shewa) regions. On the contrary, Afar, most part of Amhara, Benshangul-Gumuz, Western Gambela (Nuer), Central Oromia, SNNPR and Somali were regions with cold spots.

In EMDHS 2019, hotspot of SBA delivery was clustered in Dire Dawa, Addis Ababa, Harari and South west part of Benshangul-Gumuze (Asosa) regions; whereas Afar, Somali, Amhara and Eastern part of SNNPR were cold spot areas of SBA delivery. The overall spatial pattern of skilled birth attendant delivery was different across regions of Ethiopia over survey periods except Addis Ababa, Dire Dawa and Harari showed similar spatial pattern over the two survey years.

Spatial Interpolation

The spatial interpolation methods allow estimating values for locations where no samples have been taken and also used to assess the uncertainty of these estimates. We have used geo-statistical spatial interpolation with Ordinary Kriging technique in ArcGIS 10.7 software for estimating values for locations where no samples have been taken. From EDHS 2016, geo-statistical ordinary kriging analysis predicted that the highest frequency of skilled birth attendant delivery (77.7% to 98.5%) was discovered in Dire Dawa, Harari, Addis Ababa and south east part of Tigray. In contrast, area with relatively low prevalence (5.1%-15.5%) was predicted in Eastern part of Somali (Doolo), Southern Oromia (Borena and Guji), Western Gambela (Nuer), Benshagul (Metekel), Central Amhara (South Gondar) and Afar regions. Based on EDHS-2019 data, ordinary kriging analysis predicted that the prevalence of skilled birth attendant delivery was the highest percent about (79.09% to 98%) predicted in Addis Ababa, Dire Dawa, Harari and Western Benshangul-Gumuz (Asosa). In contrast, area with relatively low prevalence (13%-22.4%) was predicted in most part of Somali, southern Afar and south part of Oromia (Borena, Guji and Liben).

Spatial Scan Statistics

For detection of purely spatial clusters of SBA delivery, spatial analysis was carried out with the Culldorff spatial sat scan analysis. The circular window with highest likelihood ratio and containing more cases than expected was identified as the most likely (primary) cluster. A significance level of P < 0.05 was used to test whether the cluster was significant or not. A total of 13 significant clusters were found in the EDHS 2016. Of which, 1 was most likely (primary) cluster and 12 of them were secondary clusters. The primary cluster spatial window was found in Addis Ababa which was located at (8.977567 N, 38.738050 E) of geographic location with 14.56 km radius, as well as the Log-Likelihood ratio (LLR) of 441.312466 which was detected as the most likely cluster with maximum Likelihood. It demonstrated that women within this spatial window had 3.12 times more probable to deliver with SBAs than the women outside that area of the spatial window. The scanning window for the secondary clusters was found in Dire Dawa and Tigray, Northern SNNPR, Southern Gambela, Western Amhara and Western border of Oromia, with a LLR range from 9.7-441.3. In EMDHS 2019, A total of 9 significant cluster with p-value <0.05 were detected. 28 locations with overall sampled population of 337 were found as primary clusters. The spatial window of primary cluster was situated in Addis Ababa. The spatial window of primary cluster was located at (8.651588 N,39.118340 E) / 68.57 km in radius, with a log-likelihood ratio (LLR) of 181.62 and a relative risk (RR) of 2.02. It demonstrated that women within this spatial window had 2.02 times more probable to get SBA than the women outside areas of the spatial window. The location of the secondary cluster spatial window was in Dire Dawa, Benshangul, Tigray, South East and central Amhara, Eastern Afar, SNNPR and Eastern Gambela regions, with a log-likelihood ratio (LLR) of 9.6-181.6.

Determinant Factors of Skilled Birth Attendant Delivery

Intra-cluster correlation coefficient (ICC) in the empty model indicated that 16.8% and 36.7% of the overall fluctuation for skilled birth attendant delivery was caused by variations amongst clusters in EDHS 2016 and EMDHS 2019 respectively. The remaining unexplained (83.2% in EDHS 2016 and 63.3% in EMDHS 2019) was due to individual variations. The null model’s median odds ratio (MOR) was 2.8 and 3.8 in EDHS 2016 and EMDHS 2019 respectively. Which indicates in the event that two women are chosen at random from two distinct clusters, those in the cluster with the highest skilled birth attendant delivery had 2.8 and 3.8 times more likely to experience skilled birth attendant delivery as compared with women from the cluster that has a lower skilled birth attendant delivery utilization. Bi-variable logistic regression analysis was performed to find the variables for the multivariable multilevel logistic analysis. Variables with p-value <0.05 were taken into account for the multivariate study. Multi-collinearity was also checked using VIF, which was found with maximum value of 2.2 in EDHS 2016 and 2.1 in EMDHS 2019. It indicates that there was no multi-collinearity among independent variables. With the highest log-likelihood and the lowest deviation, the final model (model-4) was the best suited model.

Individual-Level Predictors

In multivariable multilevel mixed-effect logistic regression analysis; wealth index, maternal education level and parity were significantly linked to the delivery by skilled birth attendants in both survey periods, However, health insurance coverage, media exposure, ever use of family planning and maternal age at first birth was strongly correlated with the delivery by a skilled birth attendant in EDHS 2016 (Table 1).

Table 1: Multilevel logistic result of individual level and community level factors associated with SBA delivery in Ethiopia, EDHS 2016 regression analysis.

Key: 1: Reference group; *Significant with p-value 0.01-0.05; **Significant with p-value<0.01; — Not applied

Table 2: Multilevel logistic regression analysis result of individual level and community level factors associated with SBA delivery in Ethiopia, EMDHS 2019.

Key: 1: Reference; *Significant with p-value 0.01-0.05; **Significant with p-value <0.01; — Not applicable

For variables showing significant association in both surveys, by taking the recent survey (EMDHS 2019), The likelihood of using SBA delivery for those women residing with household wealth index of poorer, middle, richer and richest increased with 1.46 times (AOR=1.46, 95%CI=1.16-1.85), 1.51 times (AOR=1.51, 95%CI=1.17-1.96), 2.44 times (AOR=2.44, 95%CI=1.83-3.26) and 3.67 times (AOR=3.67, 95%CI=2.48-5.43) respectively in contrast with women in poorest wealth index.

The likelihood of having SBA delivery for those women with primary education and those with secondary and higher were 2.18 times (AOR=2.18, 95% CI=1.82-2.61) and 4.43 times (AOR=4.43, 95%CI=3.18-6.17) higher as compared with no formal education respectively.

Women having 2-4 children and those who had 5 or above were 46.2% (AOR=0.538, 95% CI=0.42-0.69) and 54.1% (AOR=0.459, 95%CI=0.33-0.64) less likely to experience SBA delivery in contrast to those who had only one child respectively.

The likelihood of experiencing SBA delivery for those women reside in rural areas were lower by 75% (AOR=0.25, 95%CI=0.15-0.43) in contrast to those who live in urban areas.

The odds of experiencing SBA delivery for those women whose medical expenditure was covered by health insurance were 1.61 times (AOR=1.61, 95% CI=1.13-2.29) higher in contrast to those who don’t have health insurance.

The likelihood of having SBA delivery for those women who had media exposure were 1.34 times (AOR=1.34, 95% CI=1.13-2.29) higher compared to those who had no media exposure.

The likelihood of experiencing SBA delivery for those women who had ever used family planning were 1.72 times (AOR=1.72, 95% CI=1.49-1.99) higher compared to those who never used family planning.

The likelihood of having SBA delivery for those women with age at first birth was ≥25 years were 1.66 times (AOR=1.66, 95% CI=1.29-2.14) higher compared to those whose age at first birth was ≤19 years. But the proportion of women deliver with the assistance of SBAs with age at first birth between 20 and 24 had no significant difference with reference age of ≤19 years.

Community-Level Predictors

Multivariable multilevel mixed-effect logistic regression analysis showed that; region, type of location of the residence and community poverty level in both survey periods (2016 and 2019) and distance from health facility and community childcare burden only in EDHS 2016 were strongly linked to the delivery by a skilled birth attendant in EDHS 2016(Table 1 and 2).

For variables showing significant association in both surveys, by taking the recent survey (2019), The probability of women residing in Afar 84.9% (AOR=0.151, 95% CI=0.06-0.37), Oromia 73.3% (AOR=0.267, 95% CI=0.12-.58), Somalia 88.7% (AOR=0.113, 95% CI=0.045-0.29), SNNPR 59.9% (AOR=0.401, 95% CI=0.18-0.87), Gambela 57.4% (AOR=0.426, 95% CI=0.19-0.98) and Harari 69.2% (AOR=0.308, 95% CI=0.12-0.78) less likely to experience SBA delivery in contrast to those who live in Tigray region. Whereas, Addis Ababa, Dire Dawa, Amhara and Benshangul-Gumuz region had not changed all that much in proportion of SBA delivery from the region of reference Tigray.

The likelihood of having SBA delivery for those women reside in rural areas were lower by 75% (AOR=0.25, 95%CI=0.15-0.43) in contrast to those who live in urban areas.

Women who reside in areas with high rates of poverty in the community were 57.6% (AOR=0.424, 95%CI=0.28-0.64) less likely experiencing of SBA delivery in contrast t with those women live in a region with low rates of poverty.

The odds of experiencing SBA delivery for those women who perceive distance from health facility as not a big problem were 1.34 times (AOR=1.34, 95% CI=1.2-1.56) greater than those who perceive distance from health facility as a significant problem.

The probability of receiving SBA delivery for those women live with a community of high childcare burden were lower by 31.1% (AOR=0.689, 95%CI=0.54-0.88) as compared with low community childcare burden.

Discussion

This study was amid to explore spatio-temporal variation and determinants of SBA delivery among reproductive age women in Ethiopia over 3 years.

The finding of this study revealed that, the recent prevalence of SBA delivery was 49.6% (in EMDHS 2019). This finding is in consistent with previous study done in Kembata tambaro , Zone in Ethiopia 50.9% [28], whereas higher than study done in North west Ethiopia 18.8%, another study in Ethiopia 15.6% and Galkacyo district in Somalia 27%. This inequality may be because of the deference in study setting, sample size and period. In addition, it might be because of socio-demographic and cultural differences across regions. But this finding is lower than the result from Ghana 60.5%, Pooled prevalence in 12 East African Countries 67.18%, Rwanda 90.68%, Malawi 89.8%, Burundi 85.13%, Comoros 83.78, Zimbabwe 78.14%, Uganda 75.19%, Zambia 64.21%, Kenya 61.81% and Mozambique 53.65%. This may be as a result of the difference in accessing the service as well as due to the fact that women in those countries had better economic and educational status. This study showed that the delivery attended by skilled birth attendant increased from 27.7% to 49.6% between survey year 2016 and 2019. This improvement might be due to the focus of government since the inclusion of SBA as a key outcome indicator in the MDGs. In addition, some socio-demographic improvement in the country might contribute for the improvement of SBA delivery [35-39].

This finding revealed that the proportion of SBA delivery varies across the regions of the country. Studies conducted in developing countries also pointed out the significant regional variations in the use of SBA delivery [29,40]. This might be due to the socio-cultural and socioeconomic differences among regions of the country. The highest prevalence was observed in Addis Ababa (95.5%) and Tigray (73%), whereas the lowest prevalence was obtained in Afar (30.2%) and Somali (25.7%). This might be because of inequalities in the distribution of resources like skilled birth attendants. Moreover, women from pastoral regions might have limited access to information regarding maternal health services than those in agrarian and urban regions. Maternal health service utilization by pastoralists is extremely low because of lack of awareness, cultural beliefs, seasonal mobility and limited availability of health facilities and health staff [41].

Global Moran’s I value showed that spatial distribution of SBA delivery was non- random across the country and there was statistically significant clustering of SBA delivery. In this study significant cold spot areas of SBA delivery were observed in Afar, Amhara, Benshangul Gumuz, Gambelia, Oromia and Somali regions. One explanation could be the discrepancy in the provision of maternal health services, as well as the poor accessibility of infrastructure such as roads for transportation in those regions. Furthermore, the communities in these regions were more pastoral; as a consequence, relative to the rest, health facilities are not nearly available [41]. This finding shows that public health planners and programmers should develop successful public health actions to improve SBA delivery in these substantial cold spot regions.

Women from households of better economic status were more likely to use SBA during delivery in contrast to women raised from poorest household. This finding has also been demonstrated in similar studies in Ethiopia [29,35,40], Kenya [42], Nigeria [26], Ghana [23], India [43] and Bangladesh [44,45]. This might be due to the reason that women in a higher wealth index had greater autonomy in decision-making on reproductive health and more likely delivered under skilled birth attendance [46]. Women with better economic status often have the financial empowerment to access skilled attendance during delivery [47]. In contrast women in the poorest households are less likely to get health access because of economical constraint, which is backbone to get education and health services. Even though maternal health services in Ethiopia are free, this could not give a guaranty for the use of SBA delivery, because of the presence of other costs such as time and transportation. Sometimes mothers may be asked to buy supplies that are not available at the health facility at the time of delivery.

This study also indicated that women with increased education were more experiencing SBA delivery as compared with those not has formal education. This finding was consistent with studies conducted in Ethiopia [28,29,34,40,48], Kenya [42,49], Zambia [24], Nigeria [26], Bangladesh [22], Ghana [37] and east Africa [38]. This could be explained by the fact that women who are educated had knowledge about the delivery complication and their consequences on them and their child, which could push them to deliver with the help of SBAs. Educated women had more open and better communication with the husband, more decision-making power and better negotiating skills thus better ability to demand adequate services [50]. As a result, more emphasis is required in educating women specifically those with no formal education on the importance of skilled delivery services and its association with reduced maternal mortalities.

Those women whose health expenditure was covered by health insurance had higher odds of experiencing SBA delivery in contrast to those not have health insurance. This finding is in line with previous study done in Ethiopia [29] and Ghana [23]. This might be because of women’s health expenditure is covered by health insurance, they sense free and seek any medical care frequently and it might be narrows the difference between rich households and poor households in using SBA delivery service. This is supported by this study in which wealth index is a significant factor associated with SBA delivery.

The finding of this study indicated that women who exposed to media had more likely to use SBA delivery service as compared to those women who were not exposed to media. This finding was line with a previous study done in Ethiopia [35], Niger, Sierra Leone and Mali [27]. The possible reason is that health information may improve health-seeking habits, as information about what services are available, where and when to get them, as well as the benefits and risks of accessing specific services, can be communicated via different Medias.

Women with parity of more children were less likely to experience SBA delivery as compared with who had only one child. This finding was in line with previous studies in Ethiopia [29,38], Nigeria [26] and southern Ghana [51].This might be because women with higher parity might not have any complications before and take childbirth as a natural process or might have bad contact with a health professional previously, so they may prefer delivering without SBA [52]. Another possible explanation for this is that women who are pregnant with their first child are usually more likely to have difficulties during delivery than women of more parity. This may result in low parity women being more motivated to deliver with assistance of SBAs than women with more parity.

Women who had used any family planning services were more likely to deliver with the help of SBA in contrast to those women who had never used family planning. The finding is in agreement with studies conducted in Bangladesh [22]. Family planning service could empower women by exposing them to the health education about the benefit of skilled birth attendance. Moreover, women could understand the complication before, during and after delivery and early detection of complications arising during birth preparedness and complication planning which push them to visit skilled birth attendants.

The odds of experiencing SBA delivery for those women with age at first birth ≥25 year was higher as compared with those whose age at first birth was <=19 years. This finding is consistent with a study conducted in Bangladesh [22] and sub-Saharan Africa [53]. The possible reason for this finding could be the fear of stigmatization, devaluation and shaming young pregnant women to receive at maternal health services [54].

The odds of experiencing SBA delivery were lower among women who lived in Afar, Oromia, Somali, SNNPR, Gambelia, and Harari as compared to Tigray region. This finding indicated that SBA delivery vary across regions and in line with a study in Ethiopia [29] and Nigeria [26]. Regional variation in the health infrastructure can cause significant health service disparity. Another potential reason might be women in pastoral regions have poor access to education and are not permanent residents and because of these, there is limited availability and accessibility of maternal health services.

The likelihood of having SBA delivery for those women reside in rural was decreased by 75% compared to those women live in urban areas. The result was comparable with studies conducted in Kambata Tembaro Zone [28], North West Ethiopia [34,55], Ethiopia [29,40], Nigeria [26], East Africa [38] and Bangladesh [22]. Women living in urban areas have much easy access to skilled birth attendance compared to rural areas due to the proximity of the health facilities and better availability of transportation [56,57]. Another possible reason might be urban women in Ethiopia tend to benefit from increased knowledge and access to maternal health services compared with their rural counterparts, because, various health promotion programs uses urban-focused mass media work to the advantage of urban residents and explain the close connection between urban residence and use of maternal health services. Moreover, rural women are more readily influenced by traditional practices that are contrary to modern health care.

Women residing in communities with high poverty levels had lower odds to give birth by SBA as compared to women residing in communities with low poverty level. This finding is supported by a study done in Ethiopia [29, 35, 40], Bangladesh [22], India [43] and East Africa [38]. This is due to communities with high poverty level even might not be able to pay for health insurance and health insurance coverage is associated with SBA delivery in this study [58].

Women who perceive distance from health facilities as big problem were less likely to receive SBA delivery compared to those perceive distance from nearest health facility was not a big problem. The finding is also in agreement with studies conducted in Ethiopia [29,40]. This is due to the fact that long distance from health facilities is important factors to prevent mothers from seeking and utilizing skilled maternity care services. Moreover, some women at times deliver on the way to the health facility due to long distances [59,60].

Women who live in communities with high childcare burden had less likely to deliver with SBA as compared to those with low child care burden and this finding is in line with study in Ethiopia (29).This might be due to a high childcare burden may need cost and time for carrying children, which may prevent mothers from seeking and utilizing maternal health services like SBA delivery [61].

Conclusion

In spite of the above limitations, this study tries to explore spatio-temporal variation and determinants of SBA delivery among reproductive age women in Ethiopia. The magnitude of SBA delivery was lower in EDHS 2016 and it showed improvement in 2019. But if it continue with the current pace, it will be difficult to achieve the national Health Sector Transformation Plan II target. Despite the efforts that have been made in recent years to improve maternal health outcomes in Ethiopia, the proportion of women who receive assistance from SBAs is still unacceptably low.

The spatial pattern of SBA delivery in Ethiopia was clustered non-randomly across regions of Ethiopia. The most prominent low SBA delivery were detected in Afar, Amhara, SNNPR and Somali regions more or less consistently over survey periods. Benshangul-Gumuz, Gambela and Oromia showed improvements after survey year 2016. High proportion of SBA delivery was detected in Addis Ababa, Dire Dawa and Harari regions in both survey years.

Household wealth index, maternal birth, region, type of place of residence, community poverty level, distance from health facility and community child care burden were significant predictors of SBA delivery among reproductive age women.

Strengths and Limitations of This Study

Strengths of the Study

This study applied spatial pattern analysis tools and a multi-level mixed effect logistic regression model because of nested nature of the data. The study was used large dataset representing the whole regions of the country and applied sample weighting of data considering sample designs during analysis of cross-tabulation and estimation to be representative of the Ethiopian population.

Limitations of the Study

Since the study was a cross-sectional it doesn’t confirm a causal relationship between the independent and dependent variables. Respondents’ data with geographic coordinates didn’t specify were excluded for spatial analysis which could affect the generalizability of the findings. The DHS data depend on the respondent’s report, so there might be a recall bias.Moreover, medical and health facility related factors that might influence the outcome variable were not assessed.

Abbreviations

ANC: Antenatal care, ARC-GIS: Aeronautical Reconnaissance Coverage Geographic Information System, CMHS: College of Medicine and Health Sciences, CSA: Central Statistical Agency, DHS: Demographic Health Survey, Dr: Doctor, EA: Enumeration Area, EDHS: Ethiopian Demographic and Health Survey, EMEDHS: Ethiopian Mini Demographic and Health Survey, EmOC: Emergency Obstetric Centre, EPHI: Ethiopia Public Health Institute, GIS: Geographic Information System, ICC: Intra-Class Correlation, ICF: Inner-City Fund, MDGs: Millennium Development Goals, MoH: Ministry of Health, MOR: Median Odds Ratio, MPH: Master of Public Health, Mr: Mister, NGOs: Non-Governmental Organizations, PCV: Proportional Change in Variance, PHC: Population and Housing Census, SBA: Skilled Birth Attendant, SDGs: Sustainable Development Goals, SNNP: Southern Nations and Nationality of People , SPSS: Statistical Package for Social Science , UN: United Nation, USAID: United States of America International Development, WHO: World Health Organization.

Acknowledgment

We would like to thanks Bahir Dar University, College of Medicine and Health Sciences for providing this opportunity and support to conduct this research. Thanks a lot Ethiopian Central Statistical Agency (CSA) for providing Ethiopian Demographic and Health Survey data for this study.

Authors’ Contributions

YAM was responsible for a significant contribution to the conceptualization, study selection, data extraction, investigation, methodology, formal analysis and original and final draft preparation. Project administration, resources, software, supervision, validation, visualization, and reviewing are all handled by MAA, HAG and EMA and the final draft of the work was read, edited and approved by all authors.

Funding

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Competing Interests

None declared

Patient and Public Involvement

Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

Patient Consent for Publication

Not required

Ethical Approval

Ethical clearance was obtained from the ethical review committee of Bahir Dar University, CMHS. In addition a permission for data access was obtained from a measure Demographic and Health Survey through an online request at (http://www.dhsprogram.com). The data used for this study were publicly available with no personal identifier. Our study was based on secondary data from Ethiopian Demographic and Health Survey and we have secured the permission letter from the Measure Demographic Health and Survey.

Data Availability

The data used in this study are the third-party data which is Demographic and Health Survey available at (http://www.dhsprogram.com). So, to access the data, someone needs to follow the steps and protocol outlined under the methods section or the data is available upon reasonable request from the corresponding author.

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Clear Aligners in Maxillary First Premolar Extraction Case with Space Closure: Biomechanics Studied Using Three-Dimensional Finite Element Analysis

DOI: 10.31038/JDMR.2024724

Abstract

Background: The biomechanics of clear aligner (CA) orthodontics in maxillary first premolar extraction cases with space closure are not yet fully understood. This study aimed to investigate the biomechanics of en-mass retraction(EMR)(0.2mm) of maxillary anterior teeth after first premolar extraction using a CA system, employing the finite element model (FEM). The goal was to provide a more comprehensive theoretical foundation for both clear aligner treatment (CAT) and its design for cases with EMR of maxillary anterior teeth.

Methods: Using Cone-Beam Computed Tomography (CBCT), an adult volunteer with normal occlusion who met the modelling standards in the Stomatological Hospital of Nankai University was scanned. Models including a maxillary dentition without first premolars, the periodontal ligament (PDL), alveolar bone, and a CA were established using Mimics 17.0, Geomagic Studio 12.0, and UG NX software packages. ANSYS Workbench 19.0 was used for preprocessing, parametric design, mesh generation, and data analysis.

Results: The maxillary anterior teeth exhibited distal and palatal tipping, accompanied by extrusion and torque loss. Mesial tipping, intrusion and anchorage loss of the posterior teeth were observed. This is a typical roller coaster effect (RCE) in orthodontics. Stress distribution within the PDL and alveolar fossa was concentrated in the cervical and apical regions, aligning with the trend of tipping tooth movement. The entire CA showed tendencies to dislocate and bow bend with more pushing stress distribution on the labial aspect of the CA’s anterior region and mesial wall of the canine area suggesting a pushing device. In addition, the premolar extraction junction area and posterior regions were identified as primary stress-bearing components.

Conclusion: In treatments involving premolar extraction using the CA technique, it is crucial to implement strategies to counteract RCE caused by CA bow bending during retraction. Moreover, it is imperative to enhance torque control in the anterior teeth and protect anchorage in the posterior teeth.

Keywords

EMR, Biomechanics, CA, RCE, FEM

Introduction

Both fixed and removable orthodontic appliances correct malocclusion, characterized by uneven teeth or misalignment of dental arches, through tooth movement using the premolar extraction protocol in most cases [1-3]. This approach poses challenges to controlling precise tooth movement in three-dimensional directions [4]. In 1999, Align Technology, Inc. (San Jose, CA, USA) introduced clear aligner treatment (CAT), leveraging computer-aided design (CAD) and manufacturing. Based on virtual tooth movement designs created by CAD software [5], aligners incrementally induce tooth movements through a series of aligners to achieve intended outcomes [6]. CAT offers several advantages over traditional wire-bracket systems, such as aesthetic appeal, reduced discomfort, lower forces, and improved time efficiency with fewer visits and emergencies [6]. However, the efficacy of CAT, particularly in complex malocclusions requiring extractions, especially for premolar extraction protocol, is subject to debate due to unclear force interplay and biomechanics mechanisms [7-12]. Unlike fixed orthodontics where tooth movement results from wire-bracket interactions, CAT relies on force from aligner-teeth shape mismatches [11], and the complete coverage of tooth crowns by aligners complicates the assessment of force and moment application on the tooth [12]. Although introducing auxiliary devices such as attachments improves the control of the clear aligner (CA) on tooth movements, its effectiveness remains unsatisfactory. In CAT, normally, treatment strategies adopt a step-by-step movement to reduce side effects, such as roller coaster effect (RCE) [13,14] in premolar extraction cases. Although this method is effective, it inevitably leads to an extension of the treatment cycle. To enhance efficiency and shorten the treatment span, the technique of en-mass retraction (EMR) has become a future trend in the development of CAT. EMR is particularly suitable for cases requiring minimal to moderate anchorage but is also frequently used in most cases to close small gaps in the progress and refinement stages of treatment. From these perspectives, EMR will play an important role in future CAT and be used in many cases. However, the biomechanics of EMR in practice are not fully understood, and the related side effects, as well as how to effectively prevent and manage them, have not been fully resolved. Therefore, investigating the biomechanics of EMR, along with gaining a deeper understanding of the biomechanics of CAT to prevent unwanted tooth movements, is crucial. Such endeavors establish a significant foundation for enhancing clinical CAT and supporting further scientific studies.

Finite element model (FEM) analysis, known for its non-invasive precision, is crucial in examining mechanical impacts of orthodontic devices (including clear aligners) and quantifying stresses and movements in orthodontic studies [15-17]. This study aims to elucidate the biomechanical principles and side effects of EMR without auxiliary equipment, providing a scientific basis for optimizing CAT. The objectives are to prevent unwanted tooth movements,  refine treatment planning, reduce duration, minimize patient discomfort, establish a foundation for future research, and contribute to the advancement of CA orthodontics.

Methods

Model Construction

Jaw and Dentition Scanning: The jaw and dentition of the volunteer were scanned using cone-beam computed tomography (CBCT) (EW00-VATECH, South Korea). The exposure settings were as follows: 15×15 cm field of view, 10.0 mA, 90 kVp, total scanning time of 15.0 seconds, effective radiation time of 4.0 seconds, and voxel size of 0.3 mm. During image acquisition, the subject was seated upright, and an ear rod was used to stabilize their heads so that the Frankfort horizontal plane was parallel to the floor. The acquired Digital Imaging and Communications in Medicine (DICOM) format data were imported into Mimics 17.0 (Materialise, Belgium). The alveolar bone and teeth data were extracted using threshold segmentation in the 900–3095 HU range. Following grey value selection, region growing, noise reduction, and binarization, a three-dimensional (3D) model of the maxillary dentition and jaw was developed. This model was refined, smoothed, and glossed in Geomagic Studio 12.0 (Raindrop, USA) to create a high-precision solid 3D model. It was then imported into UG NX 12.0 (UGS, USA) to solidify the geometric structure. The bilateral maxillary first premolars were removed in this software to create premolar spaces, and the dentition without first premolars was remarked as initial dentition M. High-precision geometric models were obtained (Figure 1), serving as the foundation for subsequent experimental models, ensuring no software error superposition. According to the scientific literature, the roots of the teeth are spread uniformly along the outer surface to obtain the PDL (continuous 0.25 mm) [7]. Research indicates that tooth movement per step in CAT ranges from 0.20 to 0.33 mm, typically designed as 0.2 mm per step in both clinical and scientific studies [18]. Therefore, based on the initial dentition (M), the maxillary anterior teeth were retracted bodily by 0.2 mm in the sagittal direction (Consistent with the Z-axis), and the obtained new dentition was marked as N [19]. Next, N was imported into Geomagic Studio 12.0 software to process the space between every two teeth separately. The outer surface of the crown was extracted as the inner surface of the CA and sliced through the boundary curve of the crown. The template thickness was 0.5 mm, and the Boolean operation was carried out with N to obtain a solid geometric model of CA (Figure 1). These solid models were assembled (Figure 1) and imported  into ANSYS Workbench 19.0 (ANSYS, USA) for parameter setting, mesh generation, loading, and other simulations. The EMR of the maxillary anterior teeth was simulated with a bodily displacement of 0.2 mm (per aligner) in the sagittal direction. The postprocessing function was used to evaluate the data. For the baseline, no auxiliary devices (like attachments) were introduced in this study. All experimental procedures conformed to the guidelines of the Stomatological Hospital Medical Ethics Committee of Nankai University, and informed consent was obtained from the volunteer.

Figure 1: The three-dimensional finite element models of maxillary teeth, alveolar bone, PDL and CA. Maxillary teeth (A), Periodontal ligament (B), Assembly (C), Maxillary alveolar bone (D), Maxillary clear aligner (E), Assembly section (F).

Material Properties, Interaction, and Boundary-Settings

The model substances were defined as continuously homogeneous and isotropic, and the orbital floor of the maxillary alveolar bone served as a fixed constraint. A frictional interaction between the crown and the CA was set, with a coefficient of 0.2. Binding restrictions were applied between the teeth, PDL and alveolar bone. The elastic moduli for the alveolar bone, teeth, PDL, and CA were set to 2,000, 20,000, 0.05, and 450 Mpa, respectively, with Poisson’s ratios of 0.30, 0.30, 0.35 and 0.40, respectively [20].

Mesh Division and Results

The CA used triangular six-node shell elements, and the other models adopted tetrahedral ten-node elements, both of which have properties such as plasticity, wiggling ability, large deformation, and high tensility. Node counts for the entire model, alveolar bone, teeth, PDL, and CA were 1138046, 257810, 569455, 117193, and 193598, respectively, with component counts of 726808, 162931, 390852, 58026, and 114999, respectively.

Coordinate System Setting

The global coordinate system was used to define the direction of x, y, and z axes. The X-axis is positively directed to the patient’s left side, parallel to the occlusal plane. The Z-axis positively directed perpendicularly to the X-axis towards the tooth root apex. The Y-axis, positive in the direction perpendicular to both X- and Z-axes, pointed towards the incisor. Opposite directions corresponded to their respective negatives.

Calculation and Analysis

The bilaterally symmetrical model was analyzed using the right maxillary model. The analysis focused on tooth displacement, periodontal tissue stress distribution, CA deformation, and CAbearing stress distribution.

Results

Maxillary Dentition, PDL, CA, 3D-FEM

High-quality 3D FEMs of the maxillary teeth, PDL, alveolar bone, CA, along with their assembly were obtained in this study (Figure 1).

Initial Displacement Trend and Value of Teeth

Figure 2 shows the teeth displacement trend and Table 1 presents measurements of the incisor edge midpoint, canine cusp, buccal cusp of the second premolar, and both buccal and palatal cusps of the first molar, as well as the tooth root apex. The initial displacement value of the maxillary teeth corresponded with the movement trend, exhibiting tipping movements in the opposite direction of the crown and root. The incisor crown has tipped distally, and the palatally root is inclining labially and mesially. A similar pattern was observed in the canine. The central incisor, lateral incisor, and cuspid showed increasing distal tipping, decreasing palatal tipping, and occlusal extrusion. Posterior crowns tipped mesially and palatally, with roots on the distal and buccal sides. Vertically, the second premolar was intruded, the mesial cusp of the first molar was intruded, while the distal cusp extruded. These tooth movement patterns align with a typical side effect of RCE. RCE occurs during canine retraction with a light, flexible NiTi (nickel-titanium) wire. Due to its insufficient stiffness, the wire bends under retracting forces, causing the molar and premolar crowns to tip mesially and extrude distally. This bending leads to the canine crown tipping distally, which, influenced by the orientation of the canine bracket, results in the extrusion of the incisors and a deepened bite [21]. Significant 3D movement was also observed in the lateral incisor, along with notable buccal movement of the cuspid and palatal movement of the second premolar.

Table 1: Initial displacement of maxillary anterior teeth on X,Y and Z axes(mm)

Tooth

Position X-axis Y-axis

Z-axis

Central incisor crown

-0.02597

0.13336

-0.23133

root tip

0.00724

0.04616

-0.08820

Lateral incisor crown

-0.21951

-0.22496

-0.15497

root tip

0.08623

0.07647

-0.05400

Canine crown

-0.27002

-0.03771

-0.01360

root tip

0.03566

0.03715

-0.02142

Second premolar crown

0.08141

0.30111

0.01008

root tip

-0.03286

-0.13297

-0.00267

First molar Mesial buccal cusp

0.05133

0.03523

0.02731

Mesial lingual cusp

0.04913

0.02863

0.01610

Distal buccal cusp

0.04857

0.02082

-0.02108

Distal lingual cusp

0.07070

0.02105

-0.02410

Mesial apex

-0.04498

-0.02054

0.00088

Distal apex

-0.04719

-0.01927

-0.00143

Palatal apex

-0.02016

-0.00962

-0.00055

Note: The left side of the X-axis is positive; the direction of the central incisor on the Y-axis is positive; the direction of the apex of the tooth on the Z-axis is positive.

Figure 2: Initial displacement trend of maxillary teeth. Central incisor (A), Lateral incisor, Canine (B), Second premolar (C), First molar (D). The front, middle, and back rows represent the palatal, mesial, and distal views, respectively. The direction and length of the arrows indicate the displacement direction and magnitude, as well as the deformation extent.

Stress Distribution of Periodontal Tissue

Figure 3 depicts PDL stress concentrated in the cervical and apical regions of the maxillary teeth. Anterior teeth stress is primarily located on the palatal and distal surfaces in cervical areas and the buccal and mesial zones in apical regions. Posterior teeth stress predominated in the mesial cervical areas and the distal apical regions. Figure 4 illustrates PDL’s tensile and compressive stresses, defined as the negative and positive maximum principal stress, respectively. Incisors exhibited compressive stress on the palatal-distal cervical and labial-mesial apical regions, and tensile stress on the labial-mesial cervical areas and palatal-distal apical areas. The canines showed similar stress patterns as the incisors. For the posterior teeth, compressive stress appeared in the mesial cervical and distal apical regions, while tensile stress was found in the distal cervical and mesial apical areas. Notably, in the lateral incisor, stress concentrations were also observed in the labial and mesial cervical surfaces and palatal and distal apical regions. According to Figure 3 and Table 2, the highest stress appeared in the anterior teeth’ distal and palatal cervical regions, the mesial cervical regions of the second premolar and the first molar, and the apical areas. Figure 5 shows stress in the alveolar socket localized in the cervical regions and not evident in other areas. Table 2 indicates that the absolute value of peak tensile stress was more significant than that of compressive stress, with high stress on both sides of the extraction region. Moreover, the stress in posterior teeth was evidently greater than that in anterior teeth.

Table 2: Comparison of peak PDL stress in maxillary teeth (MPa)

Tooth

Equivalent stress Tensile stress

Compressive stress

Central incisor

0.025

0.013

-0.007

Lateral incisor

0.023

0.020

-0.006

Canine

0.037

0.018

-0.013

Second premolar

0.042

0.037

-0.011

First molar

0.046

0.021

-0.008

Figure 3: The equivalent stress distribution of PDL in maxillary. Central incisor (A), Lateral incisor (B), Canine (C), Second premolar (D), First molar (E).

Figure 4: The tensile and compressive stress of periodontal ligament in maxillary teeth. Central incisor (A), Lateral incisor (B), Canine (C), Second premolar (D), First molar (E).

Figure 5: The equivalent stress distribution of alveolar socket. Central incisor (A), Lateral incisor (B), Canine (C), Second premolar (D), First molar (E).

Figure 6: Overlay of CA: The grey is the original CA, and the colour is the stretched CA. Right (A), Front (B), Left (C).

Figure 7: CA deformation trend. Anterior region (A), Posterior region (B). The direction and length of the arrows indicate the displacement direction and magnitude, as well as the deformation trend.

Figure 8: The equivalent stress distribution of CA. Labiolingual side of anterior area (A and B), Buccal and palatal sides of posterior area (C and D).

CA Displacement Deformation and Stress Distribution

Figure 6 indicates that the entire CA exhibited typical bow bending, characterized by distal-palatal tipping of the anterior region with occlusal disengagement, and the posterior part shifting palatalmesial and detaching occlusally. Figure 7 illustrates the propensity for deformation and detachment of the CA. The mesial region of the second premolar was intruded, the second molar area was poorly dislocated, and the extraction segment was the most severely deformed. The deformation prosperities of CA directly contribute to RCE. Table 3 reveals the average movement values of the mesial, distal, and middle edges of CA in each tooth location on the X-, Y-, and Z-axes, reflecting the displacement of CA and the 3D shift of CA margins. As per Figure 8, CA stress was primarily concentrated at the junctions, widespread in the posterior region, with the highest peak value at the mesial junction of the second premolar. Stress was almost absent on the palatal side of the CA incisor region and the distal side of the CA canine area, but prevalent in the labial area of the CA incisor region and mesial region of the CA canine area, suggesting that the CA functions as a pushing orthodontic appliance.

Table 3: Initial displacement of CA on X, Y and Z axes (mm).

Position

X-axis Y-axis Z-axis
labial/buccal lingual/palatal labial/buccal lingual/palatal labial/buccal

lingual/palatal

Central incisor

-0.014

-0.016 0.128 0.174 -0.047

0.061

Lateral incisor

-0.083

-0.097 0.095 0.173 -0.024

0.051

Canine

-0.053

-0.125 -0.167 -0.177 -0.025

0.037

1st premolar

-0.009

-0.003 0.074 0.118 -0.019

-0.052

2nd premolar

-0.016

-0.075 0.209 0.181 -0.029

-0.040

1st molar

-0.015

-0.037 0.198 0.137 -0.120

-0.072

Note: The left side of the X-axis is positive; the direction of the central incisor on the Y-axis is positive; the direction of the apex of the tooth on the Z-axis is positive.

Discussion

FEM analysis is the only method for studying the biomechanics of CAT that includes the periodontium, allowing the calculation of stresses and movement in any part of the loaded model. The validity of the FEM analysis is confirmed when its calculated outcomes align with actual clinical situations. In FEM analysis, the traditional loading method was shorting the aligner directly, which was not compatible with the actual design and manufacture of aligners [22]. Our loading approach referred to related research in the field. Firstly, we developed the CA based on the dental model (N) with a 0.2 mm em-mass retraction of maxillary anterior teeth in the sagittal direction (Specific descriptions included in the model construction part). Subsequently, the constructed CA from the first step was loaded into the initial dentition (M) to complete the loading [20]. The CA and teeth were designed to be in frictional contact, with a coefficient of 0.2 [23]. The outcomes of this study align with those of clinical practice [11,19], supporting its validity of FEM analysis. Numerous clinical studies have identified the RCE phenomenon in premolar extraction cases treated with CAT [24], consistent with the findings of this study. The RCE is observed under large forces when a light, flexible, round NiTi archwire of low strength is used for retracting anterior teeth. NiTi does not have the stiffness to remain rigid when a retracting force, such as an elastic chain, is stretched from the molar to the canine. The molar and premolar crowns tend to tip mesially and extrude distally. The flexible NiTi then bends gingivally and, as a result, tends to tip the canine crown distally. The orientation of the canine bracket when the crown tips distally tends to extrude the incisors and deepen the bite. The CA functions similarly to the described NiTi wire.

Limitations in achieving 3D orientation of teeth with CAT can diminish orthodontic treatment efficiency and hinder the development of a healthy, balanced, stable, and aesthetically pleasing stomatognathic system [25-27]. In this study, the central incisor, lateral incisor, and cuspid exhibited an increase in distal tipping and a decrease in palatal tipping during EMR. This pattern indicates a predominant palatal tipping of the incisors and a primarily distal tipping of the cuspids. It has been proposed that CA cannot perform root-controlled tooth movement because retraction forces are applied to crowns, bypassing the occlusal side of the resistance center [28,29]. For another, from a biomechanical perspective, it is also challenging for CAs to produce an effective counterclockwise moment (The counterclockwise moment is from the CA deformation facilitating resisting the tipping) on incisors during retraction. These effects lead to more clockwise than counterclockwise moments on anterior teeth and finally cause inadequate torque control and resultant palatal tipping of the incisors. Such limited torque control may also result in increased gingival exposure of incisors, reduced overjet, and occlusal interference, which in turn could lead to diminished smile aesthetics, hindered retraction, and potentially cause buccal open bite or even anchorage loss [30,31]. In addition, tipping movement has been linked to an increased risk of root resorption, particularly in cases with maximal retraction and a root apex near the labial cortical bone [32,33]. It is natural to conclude that the effective expression of torque in upper incisors is crucial for controlling root movement in the sagittal plane. However, the CA covers the incisor crowns, and the elasticity of the gingival margin makes it difficult to apply force in this region [34]. These challenges, along with the limited properties of the materials used and irregular morphology of anatomical crowns, contribute to a torque control efficiency that is reduced to around 35.21%. To overcome this weakness, Invisalign has introduced power ridges. These ridges improve torque control by utilizing the elastic force generated from the aligner’s reversible deformation near the gingival margin and the counterforce produced by tooth movement against the inner opposite surface of the aligner at the incisor edge. Additionally, research indicates that using attachments can provide similar effectiveness in controlling torque. However, aligners are prone to detachment during torquing, significantly affecting the fit between the incisor edge and the aligner. Consequently, the force couple generated by the CA may be insufficient. Torque loss can be avoided within a 10° range, but a 50% loss still exists beyond the range of 10°. Furthermore, research indicates that maxillary incisor torque control error can be as high as 8.5° [30], even with conventional fixed orthodontic appliances, torque control is not complete even when using thick steel wires. I would mention this for completeness, with adults more susceptible to torque loss than adolescents [35], and the actual amount of incisor tipping often exceeds predictions [36]. Therefore, besides using power ridges and attachments, enhancing torque control through overcorrection, adding steps, maintaining scattered spaces in incisor regions, and increasing CA wrapping is recommended. In canine retraction, the canine can be first pushed distally against by incisors, followed by incisor retraction [25]. This approach maintains a space between the canine and lateral incisor, enhancing the aligner’s wrapping for better canine translation, and ensures a good fit between the aligner and incisors, thereby increasing torque expression. Additionally, the G6 root-control attachment can be applied to cuspids to create a counterclockwise moment, preventing distal tipping. However, studies have reported an accuracy error of 0.6 to 5° with this attachment. Consequently, some researchers recommend designing an additional 5–10° of cuspids root distal tipping or crowns mesial tipping for overcorrection and using a power arm (combine CA and fixed appliance) to support bodily cuspid movement. There is a belief among some experts that a smaller tipping force is beneficial for anchorage protection and periodontal health. CAT might take cues from the Begg orthodontic technique [37], which allows initial anterior teeth tipping followed by axis uprightness. Yet, there are concerns that uprighting can cause periodontal stress in the alveolar crest and root apex, potentially leading to bone height loss and root resorption in these areas. Moreover, the effectiveness of this technique in reducing molar anchorage burden remains a topic of debate and warrants further research. Combined fixed orthodontics is thought to extend treatment duration and be less aesthetically pleasing [38].

This study also noted mesial tipping in posterior teeth, especially the second premolar, indicating that the CA might not produce a sufficient clockwise moment. This tendency increases the risk of anchorage loss (posterior mesial tipping results in inadequate anchorage mean anchorage loss), particularly in adolescents, who are more prone to physiological anchorage loss when using invisible orthodontics. To counteract this, Invisalign introduced the G6 anchorage attachment for the first premolar extraction solution [39]. The play between the small functional plane of the attachment and the aligner generates a maximum force arm by activating force perpendicular to the tangent of the tooth’s rotational circle, thereby creating a substantial clockwise moment to resist mesial tipping. However, when the generated clockwise moment is inadequate to counter mesial tipping, it can lead to aligner detachment in the attachment zone, particularly in the vertical direction. This detachment disrupts the critical force-generating alignment between the aligner and the vertical functional plane of the anchorage attachment, ultimately resulting in a diminished effective clockwise moment. Horizontal rectangular attachments, due to their large vertical stress surface and good retention, provide more effective clockwise movement than vertical rectangular attachments, which achieve less movement due to their smaller vertical force surface and poor aligner wrapping and retention. Both 3 mm and 5 mm horizontal rectangular attachments offer better anchorage control than a 3 mm vertical rectangular attachment. Despite these strategies, achieving optimal anchorage control remains a challenge, as mesial tipping can be more significant than predicted [36], and anchorage control is influenced by multiple factors [40]. To enhance anchorage control, it is recommended to perform posterior crown distal tipping and draw on Tweed-Merrifield method [41] (A distalizing force is applied to the maxillary second molar, the distalization force is supported with Class II elastics, anterior vertical elastics, and a high-pull headgear) for anchorage preparation, including a 6.6° distal tipping preparation of the first molar for bodily movement. Additionally, employing Class II intermaxillary elastics, mini-implants, and designing stepwise anterior tooth movement strategies like two-step internal or frog-pattern retraction can be beneficial [42,43]. For optimal anchorage using CA alone, employing stepwise movement for anterior retraction is preferable to reduce the anchorage burden. Additionally, initial anchorage preparation is a good choice. Combining both approaches can effectively protect the anchorage and minimize the burden.

Regarding vertical movements, this study found that anterior teeth were extruded and posterior teeth were intruded, which is in line with other research. The CA’s insufficient vertical control, due to material stiffness limitations and lack of tooth support at extraction sites, leads to anterior tooth extrusion and deepening of the overbite [44]. It’s noteworthy that anterior tooth torque loss can exacerbate a deep overbite. The study showed a decreasing trend in extrusion for central incisors, lateral incisors, and cuspids. And researchers have found that maxillary incisor extrusion often exceeds expectations and the intrusion realization rate of maxillary central incisors and lateral incisors in non-extraction casers were only 51.83% and 58.12%, respectively [45]. Therefore, intruding and overcorrecting anterior teeth, particularly central incisors, is essential for enhanced vertical control in the digital solution. CAs apply a downward force along the incisor tooth axis assisted by pressure areas located at the palatal cingulum. Importantly, when retraction is combined with intrusion, it will further result in a shorter aligner length. This, in turn, increases the palatal force exerted on the incisors and the mesial force on the posterior teeth [24]. Therefore, evaluating the incisor torque and root-bone relationships to prevent palatal tipping of the incisors and cortical anchorage formation is crucial. Equally important is maintaining the cuspid axis upright and enhancing both posterior anchorage and aligner retention. Additionally, for anterior tooth intrusion, a mini-screw can be placed between the central incisors, and an elastic device connecting the precision cuts of the aligner palatal side, bypassing beneath the aligner incisal edge to the mini-screw, can facilitate intrusion while enhancing palatal root torque. It presents a posterior open bite and an intrusion of the first molar by 1 mm more than expected during the closure of premolar spaces using CAs. Posterior intrusion is attributed to aligner sagging and the occlusal splint effect; thus, designing heavy posterior occlusal contacts or vertical elastics to resist sagging [46] and cutting the distal portion of the aligner to allow vertical tooth eruption are recommended strategies.

Teeth are linked to alveolar bone via the PDL, forming a structural unit with standardized form and function. Orthodontic forces on teeth transmit appropriate mechanical forces to periodontal tissues, generating tissue modification and tooth movement [47]. In our study, the stress distribution on tooth PDL aligned with tooth movement patterns. Additionally, the compressive-tensile distribution was also consistent with the tooth movement trend. The evidence again demonstrates the rationality of our study and the reliability of our findings. Consistent with our results, other studies using 3D-FEMs to analyze the sagittal movement of anterior teeth have observed that PDL compressive stresses are distributed in the distal cervical and mesial apex areas, with tensile stresses in the mesial cervical and distal apex. However, for the lateral incisor, the forces on PDL do not entirely correspond with the direction of tooth movement. This suggests a change in the direction of force transmission, resulting in inefficient utilization of force and ultimately leading to inefficient tooth movement towards its target position. In this study, significant stress concentration was observed in the apical periodontium. This indicates a higher stress level at the root apex of the counterpart tooth, raising concerns for potential hyaline degeneration-like periodontal injuries, which necessitate preventive measures in clinical settings. Notably, the stress levels in the posterior region were substantially higher than in the anterior region. This finding underscores the need for enhanced anchorage protection and prevention of CA dislocation. It suggests the utilization of attachments to modify tooth morphology and contact areas for improved anchorage control and CA retention.

A material’s stiffness (E) is inversely related to its susceptibility to deformation forces. The E value of a similar size CA is 40–50 times lower than that of a typical NiTi archwire [48] indicating that CA material is not sufficiently stiff. In this study, the CA exhibited bow bending due to the shortening of the aligner with a force similar to that of a wooden bow with relative pull at both ends. This effect, compounded by insufficient material stiffness and lack of tooth support in the extraction area, led to the observed bow bending of the aligner (Figure 9). This deformation produces a clockwise moment on the anterior segment, leading to palatal tipping and extrusion, intrusion pressure on the middle part, and a counterclockwise moment on the posterior segment, causing mesial tipping. The interference located in anterior teeth resulted in a buccal open bite. These features are the typical RCE effects observed in closing premolar extraction gaps with thin NiTi wires. Fixed orthodontics resolves this issue with larger, stiffer arch-wires. In CAs, due to the uniformity of material in all stages, it is recommended to modify aligner structure to prevent bow bending. Strategies such as designing CAs of maxillary compensating curve shape and incorporating anti-bending elements in extraction areas can help reduce sagging. Changing beam geometry significantly impacts beam properties; for instance, doubling a beam’s length halves its strength and reduces its stiffness eightfold [2]. Designing tooth movement steps can indirectly enhance the stiffness of the aligner, the CA and teeth are similar to a beam, the smaller the distance between the teeth, the greater the CA stiffness, especially in the extraction area. In maximum anchorage cases, the anterior teeth should be retracted in stages. For medium anchorage cases, the cuspids and second premolars can be designed to move alongside each other before moving the other teeth. This approach increases the steps followed by reducing the aligner span without tooth support, and minimizes the step distance, preventing aligner bending and facilitating the continuous application of orthodontic force. CAs, being viscoelastic, can permanently deform under small forces. The larger the force applied (the larger the step distance), the faster the decay, and ultimately, the shorter the effective orthodontic force maintained. With the development of 3D printing technology, biomechanically oriented CAs can be designed using different materials at varied orthodontic stages and in various parts of the CA [49]. This study also found substantial aligner dislocation, with significant 3D movement in lateral incisor and a tendency to lose grip, attributed to inadequate inversion of the lateral incisor crown, suggesting designing attachment for better retention, and lowering tooth movement speed for preventing tooth derailment. Remarkable buccal movement of the cuspid and palatal movement of the second premolar may stem from poor aligner stability on either side of extraction areas, altering stress distribution. Clinically, attachments and intra-maxillary elastics can bolster appliance strength and reduce changes in the direction of force transfer. Enhancing CA retention involves strengthening attachment design and modifying diaphragm material structure, such as forming a natural chemical bond between the diaphragm and teeth through saliva. The displacement values indicated a labial-buccal shift in the CA edge, consistent with the CA’s deformation, as the body and edge of the CA rotated in opposite directions, which further proves the CA undergoes bow bending during the retraction of anterior teeth and also provides strong evidence for the RCE we observed in our study. The CA stress distribution suggested the extraction area is susceptible to damage and the material is easily fractured. Therefore, aligner structural design in extraction areas should be reinforced to prevent mechanical system disruption through CA fracture, affecting force transmission and aligner effectiveness. During retraction, stresses in the CA’s incisal region are primarily labially distributed, with almost no palatal stress, and more stress areas are in the mesial region of the cuspid than in the distal region. This differential stress distribution suggests that during anterior teeth retraction, the CA primarily exerts a pushing force, indicating that it functions as a pushing orthodontic appliance rather than a pulling one, and employing the aligner pushing technique is advantageous for facilitating canine translation.

Figure 9: The bowing bending of CA causes the roller coaster effect. Clear aligner sagging (A), Counterclockwise moment (B), Clockwise moment (C).

Conclusions

This study determined that RCE occurs during premolar space closure with CAs, primarily due to the biomechanical properties of the aligners themselves. During space closure, a noticeable occlusal detachment of the CA was observed, accompanied by characteristic bow-bending deformation. Additionally, this study identified that CAs function as a pushing device, exerting a direct pushing force on the teeth. Thus, understanding the biomechanics of CAT is crucial for optimizing clinical outcomes. This includes enhancing torque control and anterior tooth intrusion, improving anchorage, increasing resistance to tipping and intrusion of posterior teeth, preventing bowbending deformation, and improving appliance retention.

Abbreviations

CBCT: Cone-Beam Computed Tomography; CA: Clear Aligner; CAT: Clear Aligner Treatment; FEM: Finite Element Model; 3D: Three-Dimensional; PDL: Periodontal Ligament; RCE: Roller Coaster Effect; EMR: En-Mass Retraction.

Availability of Data and Materials

The datasets used and or analysed during the current study are available from the corresponding author upon reasonable request.

Authors’ Contributions

Song Cang, Xiaosong Xiang, and Chunlin Wang conceptualized and designed the study, contributed to the manuscript framework, collected and analyzed the data, and drafted and revised the manuscript. Xiaosong Xiang and Chunlin Wang contributed equally as co-first authors. C. Maarten Suttorp and Frank A. D. T. G. Wagener revised the manuscript. Zhihao Wang assisted with data collection and analysis. All authors reviewed and approved the final manuscript..

Competing Interests

The authors declare that they have no competing interests.

Consent for Publication

Not applicable.

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Personal Traits that Influence Resilience in Women Who Completed Chemotherapy for Breast Cancer

DOI: 10.31038/CST.20251012

Abstract

Background: In Ghana, chemotherapy is the primary treatment for breast cancer, often leading to significant physical and emotional challenges due to drug side effects. While global literature highlights improved breast cancer survival rates, there is limited research on the personal traits influencing resilience in Ghanaian women who undergo chemotherapy for breast cancer, despite their remarkable ability to navigate treatment challenges and its aftermath.

Methods: This exploratory descriptive qualitative study investigated the perspectives of 14 breast cancer survivors in Accra who endured chemotherapy- related distress. Participants were recruited purposively, meeting specific criteria, and interviewed in English using a semi-structured guide. Data collection and analysis were conducted concurrently. Data were analyzed inductively to uncover themes without predefined frameworks. Trustworthiness was ensured through strategies like member checking, triangulation, and reflexivity. Ethical approval was obtained from Noguchi Memorial Institute for Medical Research (NMIMR), and participants provided informed consent before being audio-recorded. Interviews lasted 45–60 minutes, achieving saturation by the 12th interview, with two additional sessions confirming findings. Identified codes were grouped into sub-themes and themes with findings highlighting survivors’ lived experiences and the care they received.

Results: Four (4) themes; hope, optimism, self-esteem, and confidence and 13 sub-themes emerged from the data.

Conclusions: In the absence of structured support systems, resilience in surviving breast cancer treatment is primarily shaped by individual personality traits such as hope, optimism, self-esteem, and confidence and emotional responses to the illness. A more structured support system aimed at fostering resilience and boosting personal traits among women receiving chemotherapy for breast cancer is highly recommended.

Keywords

Personal traits, Resilience, Women, Breast cancer, Chemotherapy

Background to the Study

Breast cancer remains one of the most prevalent cancers affecting women globally. According to the [1], breast cancer accounts for 12.5% of all new cancer cases worldwide, making it a significant public health challenge. Advances in treatment, including surgery, radiation therapy, and systemic therapies such as chemotherapy, have significantly improved survival rates over the past decades. Despite these advancements, chemotherapy—a cornerstone in breast cancer treatment—is often associated with severe physical and psychological burdens, including fatigue, nausea, emotional distress, and disruption of daily life [2]. For women undergoing chemotherapy, these challenges can impact their overall quality of life and mental health.

In low- and middle-income countries (LMICs), including sub- Saharan Africa, the burden of breast cancer is compounded by late- stage diagnoses, limited access to healthcare resources, and cultural stigmas surrounding cancer [3]. In Ghana, breast cancer is the leading malignancy among women, with an estimated incidence rate of 20.4 per 100,000 women [4]. The increasing survival rates call for a shift in focus from merely treating the disease to addressing the psychosocial and emotional needs of survivors [5].

Women who complete chemotherapy for breast cancer often exhibit remarkable resilience, enabling them to navigate the challenges posed by the treatment and its aftermath. Resilience, defined as the ability to recover from or adapt to adversity, is a multidimensional construct influenced by personal, social, and environmental factors [6]. However, while there is an expanding body of literature on resilience in cancer survivors, the specific personal traits that influence resilience in women who have completed chemotherapy for breast cancer remain underexplored. Existing research highlights the importance of psychological factors such as optimism, emotional regulation, and self-efficacy, as well as the role of social support and lifestyle choices in fostering resilience [7,8].

In the Ghanaian context, breast cancer survivors often face unique cultural and socioeconomic challenges, including limited access to psychosocial support services and societal expectations of stoicism [9]. The lack of context-specific studies addressing the personal traits that contribute to resilience in this population limits the ability of healthcare providers to develop effective, tailored interventions. Understanding these traits is crucial for designing psychosocial programs that enhance the well-being and survivorship experiences of women who have undergone chemotherapy for breast cancer.

Aim of the Study

This study aims to explore the personal traits that influence resilience in women who have completed chemotherapy for breast cancer.

Methods

Research Design

The study utilized an exploratory descriptive qualitative research design, deemed suitable for providing detailed insights into the perspectives of women who survived breast cancer and endured chemotherapy-related distress, supported by the care they received [10,11].

Participants and Setting

The research was conducted in Accra, targeting women aged 18 and older diagnosed with breast cancer and residing within the Accra Metropolis. Participants met specific inclusion criteria: a breast cancer diagnosis, completion of chemotherapy, and fluency in English. Exclusion criteria included newly diagnosed breast cancer patients, those with altered mental status, and individuals who were acutely ill or in pain. A total of 14 participants were recruited using purposive sampling.

Data Collection Method

Individual qualitative interviews were conducted with the 14 participants. Permission was obtained from the Teaching Hospital where the study took place. Eligible participants were recruited and provided with information sheets explained in simple terms. Interview sessions were arranged through phone calls. A semi- structured interview guide ensured the focus of the study. Face-to-face interviews, conducted in English at participants’ convenience, were audio-recorded with their consent and lasted between 45 minutes and an hour. Saturation was achieved after interviewing 12 participants, with two additional interviews conducted to confirm saturation.

Data Analysis

Data were analyzed using inductive content analysis [12]. This method involves deriving categories, subthemes, and themes directly from the data without relying on pre-existing frameworks, allowing for the emergence of new insights. Data analysis was conducted concurrently with data collection [12,13]. Transcriptions were performed verbatim and reviewed multiple times by the first author to extract meaning. Codes representing similar concepts were grouped into subthemes, and related subthemes were organized into overarching themes. To ensure objectivity, the second and third authors reviewed the process to eliminate potential biases.

Trustworthiness and Reflexivity

To ensure rigor, trustworthiness, and reflexivity, various strategies were employed [14-16]. Member checking involved seeking participant clarification on unclear responses and confirming their statements during interviews. Data triangulation compared field notes with transcripts to accurately represent participants’ experiences. Dependability was reinforced by involving impartial reviewers—the second and third authors, who supervised the first author’s process. Reflexivity was maintained through bracketing, separating the researchers’ personal experiences from the study to minimize biases. Confirmability was achieved by meticulously reviewing transcripts before interpretation, while an audit trail documented raw data, analysis notes, field diaries, and recordings.

Ethical Considerations

The study received ethical approval from the Noguchi Memorial Institute for Medical Research in Ghana (NMIMR), under reference number NMIMR-IRB CPN 111/15-16. Participants were provided with detailed information about the study’s objectives, procedures, risks, and benefits. Informed consent was obtained through signed or thumb-printed forms, ensuring inclusivity for participants of varying literacy levels.

Results

Demographic Characteristics of Participants

The study involved 14 women aged 38 to 78 years. Specifically, 3 participants were in their late 30s, 5 in their early 40s, 3 in their early 50s, 1 in their early 60s, and 2 in their late 70s. The mean age was approximately 49.5 years, with a standard deviation of 13.6 years. Educational backgrounds varied, with 4 participants having secondary education, 2 with vocational training, and 8 with tertiary education. Regarding religious affiliations, 10 participants were Christians, 3 Muslims, and 1 Traditionalist.

The majority of participants (79%) were married, with marriage durations ranging from 1 to 38 years; 1 participant was single, and 2 were widows. The number of children ranged from 1 to 5. Participants’ occupations included teachers, nurses, fashion designers, bankers, and businesswomen. Breast cancer diagnoses were made between 2013 and 2016, with treatments completed between 2014 and 2017. The participants represented various tribes, including Ga, Akan, Adangbe, Ewe, Hausa, and Dagaare. For more details, refer to Table 1.

Table 1: Demographic characteristics of participants.

Synonyms

Age Level of education Religion Marital status No. of children Occupation Date of diagnosis Date of completing treatment

Tribe

P1

44

Tertiary Christian Married

3

Teacher

2015

2016

Ga

P2

77

Secondary Traditional Widow

5

Trader

2014

2015

Ga

P3

50

Tertiary Christian Married

4

Nursing

2013

2014

Ga

P4

38

Vocational Christian Married

1

Fashion designer

2016

2017

Adangbe

P5

61

Secondary Christian Married

2

Pensioner

2013

2014

Ewe

P6

38

Tertiary Christian Married

2

Fashion designer

2016

2017

Ga

P7

44

Secondary Muslim Married

2

Textile telephones

2014

2015

Dagaare

P8

50

Tertiary Christian Married

3

Teacher

2016

2015

Aka

P9

44

Tertiary Muslim Married

4

Teacher

2013

2014

Hausa

P10

43

Tertiary Christian Married

2

Banker

2015

2016

Akan

p11

43

Vocational Muslim Married

5

Fashion designer

2013

2014

Hausa

P12

39

Tertiary Christian Married

2

Teacher

2016

2017

Akan

P13

78

Tertiary Christian Widow

3

Pensioner

2015

2016

Ewe

P14

51

Secondary Christian Single

2

Business women

2014

2015

Akan

To answer the research question, what are the personal traits that influence resilience among breast cancer women who received chemotherapy for breast cancer, four (4) themes and fourteen sub- themes emerged from the data. The themes are: hope, optimism, self- esteem, and confidence. See Table 2 for details.

Table 2: Themes and Sub-themes.

Themes

Sub-themes

 

 

1.         Hope

•    Hope in nurses

•    Hope in doctors

•    Hope in patients themselves

•    Breast cancer survivors

•    Hope in God

 

2.         Optimism

•    Focus on positive mindset

•    Avoidance coping

•    Acceptance coping

3.         Self-esteem •    Strong inner voice/Self-motivation,

•    Setting of new goals

 

4.         Confidence

•    Self-reliance

•    Preparedness

•    Confidence in health care practitioners

Theme One: Hope

After the analysis of data, the personal trait that influenced resilience in women who completed chemotherapy for breast cancer were; hope in nurses, hope in doctors, hope in patients, themselves, hope in breast cancer survivors and hope in God.

Hope in Doctors

The participants expressed hope and expectations in the doctors that took care of them during chemotherapy. They expressed that they were hopeful that doctors were going to help them to recover because they were under their cared.

“I put my trust in the doctors because I wanted recovery and they were those to care for me and so they became my only hope”. P1

“…so, when I came to the hospital and then the treatment started, I trusted and also had expectation that the doctors were going to help me through my chemotherapy”. P14

Hope in Nurses

Participants narrated that prior to their chemotherapy they were scared based on the unknown outcome of their treatment. However, they reported that their experiences with nurses on the first day at the hospital changed their believe as they received warm reception from nurses. To the participants, that gave them hope that their treatment journey will be smooth and probably end well

“my experience with the first nurse on my first day gave me hope and this expectation kept repeating itself till I finished my treatment”. P10

“…. formerly I perceived nurses as unintelligent workers who don’t care about patients but my chemo provided me with an opportunity to really know them. They offered me hope throughout my days during hospitalization. I can say from day one at the OPD what the nurse there counselled me on gave me hope athat my cancer journey was going to smooth”. P2

“For me, I was hopeful and this was placed within the context of finding meaning in my suffering, the pain and sadness I experienced every day during my chemo was too much but I didn’t give-up. I knew I was going to get hope due to the good relationship the nurses were offering to us, that was quiet assuring”. P4

Hope in Participants Themselves

Majority of the participants also placed their hope in themselves for recovery, as they believed that they are winners and can persevere throughout the treatment.

…so, all days I kept hoping for the best. I didn’t look down upon myself no, no way. I kept telling myself you are a conqueror; you are more than a conqueror”. P2

“I am one person who hardly quit. I persevere. Within me is full of hope”. P8

“I took it easy and I have to, because all I have at that time was hope. Personally, I take everything in my life easy although I was anxious initially, I later told myself that if I am worried, I can’t change anything and so, I have to just hope for the better.”. P6

Hopes in Breast Cancer Survivors

Other participants placed their hopes in breast cancer survivors who reassured them and wished them a speedy recovery. The personal testimonies of the survivors were sources of hope, which took away participants fears.

“There was this organisation called Breast Cancer Survivors Association, whose members came to give me and my family hope by offering us more information about breast cancer and how I can contribute to my survival, after all, they were living testimonies for us”. P9

“…so, I was not afraid, after all some patient had recovered from same condition and others from similar diagnosis and they were all there to offer us any information we wanted. That gave many of us hope because here are people who suffered what I am suffering and if they recovered from it that is assuring”. P12.

Hope in God

Other participants were hopeful that God will see them through their chemotherapy. They believed and trusted in the blood of Jesus.

There were instances when I used to sing this song, “my hope is built on nothing less than Jesus blood and righteousness” (long laugh) oh yeah and you feel God’s presence around you. So, I was hopeful God will do something”. P13

“ Hope is belief and beliefs are found in God. So, all I needed at that time was hope in God so that even if i die as they say it can lead to, i will go to heaven and that if I live I live for Him. So, my hope was only on Christ and Christ alone (laughter)”. P8

Theme Two: Optimism

The second theme that emerged from the data was optimism with the sub-themes; focus on positive mindset, avoidance coping and acceptance coping.

Focus on Positive Mindset

Participants indicated that they looked at the positive side of their conditions. They reported that by focusing on what they could do to keep healthy rather than on the negative circumstances of life kept them moving on with life.

I was inclined to look on the more positive side of my condition and to expect the greatest result from treatment since many women who came to the hospital had recovered, so I tuned my mind that surely I can recover”. P8

“…. believing in myself with much focus enables me to look more on what I could do to help myself. So, I kept saying I can overcome”. P7

Avoidance Coping

Participants narrated that they adopted avoided coping mechanism during their chemotherapy journey because of some misconceptions about breast cancer and it causes.

“…In fact, I was stable in mind that am going to get well. I tried as much not to let my church people know about it except my pastor and even at my work place only my brother-in-law knew about it because I trusted him. People gossip a lot and some of them don’t even think cancer can be cured and I never wanted any bad advice so I kept it to myself because I believed I was going to be healed”. P10.

“…. you know the misconceptions of Ghanaians about cancer. Most of them believed it is gotten through fornication and adultery, and others it is a curse and all that, but with my background as a health worker I was quite certain about the future that I will be well after all, we have discharged many with complete recovery from breast cancer”. P5.

Acceptance Coping

Some participants also narrated that they were able to cope with cancer and treatment duress by acceptance their present condition as a natural phenomenon, a circumstance they have no control of.

“…you know!! a condition like cancer, if you are not a person that is willing to accept that it is a condition you have no control of, it will be difficult to adjust to its treatments…I initially had a similar challenge till my second cycle of thermotherapy when I came to terms with the fact that I need to accept my present situation (cancer diagnosis) and move on. That really did the trick for me”. P14

Without first accepting to the fact that hey, this is the impact of cancer and chemotherapy…my brother, you will run away from the chemo, the drugs are many and come with a lot of side effects and for me to think I can take all these medications and get well, then I needed to be optimistic and accept all the effects knowing that its but for a while”. P12

Self-Esteem

Participants narrated that they were able to cope with cancer and its treatment through a feeling of strong inner voice/self-motivation and setting of new goals.

Strong Inner Voice/Self-Motivation

Participants indicated that their ability to even stretch their hands and switch on their phones was enough motivation for them to trust that their treatment journey will be successful. Other participants revealed that there was a strong inner voice encouraging them to keep going

“To the extent that I find it’s helpful to spend time to switch on my phone and take a selfie and forward it to my loved ones like before was enough for me, actually I had a strong feeling that I am fine and anything from someone to me is the person’s opinion”. P3

“I’m a person with deep feelings; I could hear an inner voice saying to me, this is nothing, God will help you out. It is that voice that kept encouraging me, so I had a positive feeling that I will get well, yeah”. P13

Setting of New Goals

Participants narrated that they never bordered to compare themselves to those who could not successfully recover from breast cancer. According to these participants, they set new goals and tune their minds on happy moments in order to overcome the effects of the chemotherapy and the disease burden.

“Hmmm, I did so many things to help me, like …. I never compare myself to any one…. I mean those who couldn’t make it through treatment, no. I know people died from breast cancer so I set new goals and thought for myself with the feeling, I am born to win. I tell you with that opinion I could move mountains”. P2.

“You see many people focus on the problem and cry and complain meanwhile those you complain to can’t help you out. As for me, the secret has been that this breast cancer is just one of many problems in life so just this specific situation can’t stop me from going on with life, so I set new goals for myself”. P1

Confidence

Confidence is another positive factor that influenced resilience among women with breast cancer who received chemotherapy. Participants revealed that they were self-reliant, prepared and had Confidence in health care practitioners

Self-reliant

participants expressed confidence in themselves and that contributed to their recovery. They said that self-confidence is needed to manage the effect of chemotherapy treatment.

“I needed confidence my-self, because to take chemo for a whole year (long laugh) my son, you need confidence, yes, else you can’t finish the chemo, you will stop because of its effects”. P3

“…to take chemo for almost one year it’s very important to be confident else I couldn’t have been able to finish my treatment. When you are not confident you will say is ok, I won’t take the treatment again because the side effects are a lot”. P5

Confidence is what got me here. I needed confidence to enable me stay and complete my treatment. When you are on chemo, and you are not confident in yourself you can’t stay to complete the chemo the side effects are just too many”. P7.

Preparedness

Participants narrated that they used past experiences from their mensural pains to cope with chemotherapy effects.

“…my mensural cycle pains have not been different from my cancer experiences…so for me I have learn how to cope with pain and life struggles since I started menstruating”. P4

“My past experience on menstrual pains has been a blessing in disguise. It has taught me how to cope with pain, so, I see this cancer experiences as similar to my monthly cycle pains and that helping me adjust to treatment”. P6

Confidence in Health Care Practitioners

Others expressed the opinion that they survived due to the confidence they had in doctors and nurses during the chemotherapy. They were of the conviction that the competence of the health team will help them, most importantly after their first chemotherapy dose.

“I was of the conviction that I needed confidence from the health care team to be able to stay through after receiving my first dose of chemo. My whole system changed and I could feel am no more the same and at this point all I need was to be sure the nurses and doctors knew what they were about’’. P9.

“…So, all I needed was to see them (nurses and doctors) confident in their procedures to assure me I will be fine because of the drug’s effects I was experiencing; and when I saw the confidence level the nurses showed (xxxx name mentioned) to me during my chemo I became ok throughout in my mind and that helped”. P1

Discussion

The findings of this study revealed four themes that encapsulate the personal traits influencing resilience among women who received chemotherapy for breast cancer: hope, optimism, self-esteem, and confidence. These themes are further enriched by fourteen sub- themes that provide deeper insights into the various ways these traits manifest. This discussion examines these findings in the context of existing literature, emphasizing their alignment with prior studies while acknowledging areas of divergence.

Hope

Hope emerged as a pivotal trait, with participants expressing reliance on sources such as nurses, doctors, themselves, breast cancer survivors, and God. This aligns with studies that highlight hope as a critical component of psychological resilience in cancer patients [17]. Hope in healthcare providers, particularly doctors and nurses, was tied to trust in their expertise and care quality. Similar findings are reported by [18], who found that positive patient-provider interactions bolster hope and treatment adherence. Hope derived from breast cancer survivors further supports prior research, such as [19,20], which underscores the impact of peer support on emotional well-being and resilience.

However, the centrality of hope in God reflects cultural and spiritual dimensions unique to the participants. Studies like those of Nyarko and colleagues affirm the significant role of spirituality in the resilience of African cancer patients [21,22], underscoring the interplay between cultural beliefs and coping mechanisms. Conversely, research in predominantly secular contexts [23] places less emphasis on spiritual hope, highlighting a cultural variance.

Optimism

Optimism, expressed through positive mindsets, avoidance coping, and acceptance coping, was another prominent trait. Participants’ ability to focus on the positives aligns with [24] conceptualization of optimism as a vital trait fostering resilience. Avoidance coping, despite its occasional association with negative outcomes, was viewed positively here by participants as a means of reducing exposure to stigma and misconceptions-a finding supported by [25,26] in the context of Ghanaian cancer patients. While participants viewed avoidance as protective, broader literature often critiques avoidance as counterproductive in resilience [27]. This suggests that the efficacy of avoidance coping may be context-dependent, influenced by cultural factors and individual perceptions of stigma and support.

Acceptance coping, where participants embraced their condition as a natural phenomenon, echoes findings of [28,29], who emphasize the role of acceptance in mitigating emotional distress during cancer treatment. However, some literature, such as that of [30], highlights that excessive avoidance can hinder emotional processing and long- term resilience, suggesting a potential area for further exploration.

Self-esteem

Self-esteem emerged as a cornerstone for resilience, with participants citing strong inner voices and goal-setting as pivotal. These findings resonate with studies by Campbell-Sills and colleagues [31]], which emphasize the role of self-motivation and personal agency in building resilience. The emphasis on setting new goals as a way to maintain focus and motivation is supported by the goal-setting theory of resilience [32].

While the study highlights self-esteem as a positive force, it contrasts with findings by Lim colleagues [33], who observed that individuals with lower self-esteem were more likely to experience prolonged emotional distress post-treatment. This divergence underscores the importance of understanding individual differences in resilience pathways.

Confidence

Confidence, encompassing self-reliance, preparedness, and trust in healthcare practitioners, was also crucial. Participants’ self-reliance aligns with [34] self-efficacy theory, which identifies belief in one’s abilities as essential for overcoming adversity. Preparedness, as shaped by prior experiences such as menstrual pain, highlights the role of experiential learning in resilience building, corroborating findings of [35] on post-traumatic growth.

Confidence in healthcare practitioners was tied to perceived competence and empathy, echoing findings of [36,37], which emphasize the significance of trust in healthcare teams. However, this study’s emphasis on cultural variance, such as reliance on healthcare practitioners’ confidence, offers a fresh perspective that is less emphasized in Western-centric studies.

Conclusion

In the absence of structured support systems, resilience in surviving breast cancer treatment is primarily shaped by individual personality traits such as hope, optimism, self-esteem, and confidence and emotional responses to the illness. While most findings resonate with prior studies, the positive framing of avoidance coping introduces a valuable area for further exploration, particularly in culturally diverse populations.

Declarations

Ethics Approval and Consent to Participate

The Noguchi Memorial Institute for Medical Research Institutional Review Board at the University of Ghana (NMIMR-IRB CPN017/17- 18) granted ethical approval for this study. All participants provided informed consent, and the research adhered to the relevant guidelines and regulations by Helsinki Declaration.

Consent for Publication

Not applicable.

Availability of Data and Materials

The datasets utilized and analyzed during this study can be obtained from the corresponding author upon reasonable request.

Conflict of Interest

The authors declare no conflicts of interest.

Funding

This study was not supported by any specific funding or grants from commercial or public entities.

Authors’ Contributions

All authors contributed to the conceptualization of the study. SG was responsible for data collection, and all authors participated in data analysis. SG drafted the manuscript, while LAO, and provided critical revisions. All authors reviewed and approved the final version of the manuscript.

Acknowledgments

The authors extend their heartfelt gratitude to the women who participated in this study.

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