Monthly Archives: September 2019

Use of the Occlusal Device for Prosthetic Rehabilitation in a Patient with the Absence of the Right Mandible Branch

DOI: 10.31038/JDMR.2019234

Introduction

The use of intra-radicular restraint systems for complete dentures, has been indicated as a viable option for decades ago, and have been called “overdentures” [1–6]. The overdentures concept is not new in dentistry and has been used since the 70’s years. Actually, considering its potential benefits, there has been a reduction in the indication over natural supports [2,4,5].

Flaws in the control of dental caries and periodontal disease, possibility of root fractures and the difficulty in understand and reproduce the bilaterally balanced occlusion, takes many professionals to be reluctant to indicates this technique, preferring to remove remaining teeth and install implants [3,4,6]. However, the use of natural tooth roots to support overdentures brings benefits to the patient, assisting the proprioception, eliminating the osseointegration period and reducing the final cost of the prosthesis, because it eliminates the need for the acquisition of prosthetic components, and clinical and laboratory procedures related to installation of implants. Maintaining compliance with oral hygiene and specific care with the natural supports and prosthesis, the time life justifies the indication of this technique. In addition, an appropriate treatment plan for the making of overdentures on natural roots is a mandatory choice for patients who have underwent radiotherapy as a complementary treatment of cancerous lesions. Several authors are unanimous in stating that the radiation is a factor associated with the loss of implants and the decrease in its survival rate [7–16]. The effects of the radiotherapy appear to be more severe in the jaw due the less blood supply in the newly formed bone. So the benefit of the indication of the overdenture on natural roots in these cases, when compared to the overdenture on implant must overcome risk [7].

Patients with changes in the occlusal plane due to absence or inadequate dental position tend naturally to have changes in mandibular positioning, in both vertical (vertical dimension of occlusion) and horizontal plane (distal displacement, midline deviations). Clinical researches have been indicated the use of occlusal devices, occlusal appliance, as a valid resource for the normalization of mandibular position. These devices can be adapted in the superior dental arch on the remaining teeth or alveolar ridge and must be flat and smooth occlusal surface [17–19]. These occlusal devices act as facilitators of the mandibular repositioning, by blocking all or part of the proprioceptive stimuli responsible for the control of masticatory activity, in establishing an ideal position for prosthetic rehabilitation [19,20].

Clinical Case

A male patient, 58 years old, in need of prosthetic rehabilitation, attended the Centre for the Study and Treatment of the Functional Changes of the Stomatognathic System – CETASE, of the School of the Dentistry of Piracicaba – UNICAMP/Brazil, in August 2015, three years after had been submitted to surgical treatment for the removal of a moderately differentiated ulcerating spin cell carcinoma (grade II) in the larynx. The medical history revealed that, in 2004, after the differential diagnosis had been performed, was submitted to supraglottic laryngectomy and cervical bilateral radical deflation followed by postoperative radiotherapy. The treatment was finished in November of the same year. The following year the patient underwent gastrectomy due to a primary tumor of stomach. Three years after they were found metastases in the regions of the base of the tongue and mandible jaw, being subjected to glossopelvemandibulectomy, removing part of the base of the tongue, right inferior part of the mandibular ramus (Figure 1) and the superficial and deep masseter muscles, tendon of the temporal, lateral and medial pterygoid muscles and ligament stylomandibular of the same side. He was not subjected to facial reconstruction and to supplementary feed, used an intestinal bowel probe.

JDMR-19-121-Frederico Anade e Silva_Brazil_F1

Figure 1. Panoramic radiograph showing the complete absence of the mandible branch of the right side due to the removal of the cancerous lesion.

Dental history began to be recorded in 2016, through the use of the Clinical Chart of CETASE, with the goal of identify signs and symptoms of TMJ disorders, according of the severe mandibular misalignment in horizontal and vertical plane. Facial asymmetry with severe jaw offset to the right side (Figure 2), limitation of mouth opening, occlusion vertical dimension decrease, difficulty in pronunciation of words and to swallow, were detected during the clinical examination. It was also observed that the premolars, inferiors central and lateral incisors on both sides had great destruction. The treatment planning initially aimed to give jaw alignment in relation to the median sagittal plan and the restoration of vertical dimension of occlusion in the light of the absence of the muscles masticatory on the right side. Initially, the patient was underwented to the use of a flat and plan occlusal appliance, manufactured with colorless acrylic resin adapted to the mandibular dental arch, for reconstitute the vertical dimension [17–21].

JDMR-19-121-Frederico Anade e Silva_Brazil_F2

Figure 2. Mandibular deviation to the right side, due to the removal of lateral and medial pterygoid superficial and deep masseter muscles on the same side.

The patient used the appliance for a period of thirty days, every day, removing it only for the meals. At the end of the period it was observed that the jaw was not completely aligned to the median sagittal plan, because of the removal of muscles on the right side. So a ramp was added on the appliance occlusal surface in the right side (Figure 3) direct the jaw to median sagittal plan. The alignment was got at the 60’s days of use (Figure 4).

JDMR-19-121-Frederico Anade e Silva_Brazil_F3

Figure 3. Ramp built on the right side of the unit, to the alignment of the mandible in the sagittal plane.

JDMR-19-121-Frederico Anade e Silva_Brazil_F4

Figure 4. Recovery of facial aesthetics after the alignment of the mandible in relation to the sagittal plane and normalization on the vertical dimension of occlusion.

The use of the appliance allowed not only the jaw alignment to the median sagittal plan, but the occlusal vertical dimension was normalized. Then the patient underwent to a preventive duodenum and stomach endoscopy and the medical report showed that the oral cavity, the oropharynx and the hypopharynx were aligned with the upper structures of the digestive system. Due to the surgical therapy for the oncological treatment, the patient had a supplementary feeding through intestinal probe.

All the mandibular teeth were underwented to an endodontic treatment to receive o’rings systems and copings (Figure 5). The roots of the mandibular canines and premolars of both sides received the o’rings systems. After the cementing of the restraint systems and copings (Figure 6) the over denture was made as usual and the technique determines the capsules with the rubber rings held routinely [1–3]. The patient was instructed to make use of pasty foods in the first 15 days and your new prostheses were submitted to weekly setting. After this period, he began to use solid foods more resilient and more fibrous gradually. The patient expressed sense of satisfaction and comfort with the use of the prosthesis (Figure 7 and 8) and reported an increase in body weight of ten kilograms and plans to the removal of the intestinal probe.

JDMR-19-121-Frederico Anade e Silva_Brazil_F5

Figure 5. Mandibular teeth received short copings or ball attachment systems for overdenture o’ring type. The illustration shows the restraint systems and the copings being proven in the roots of the teeth.

JDMR-19-121-Frederico Anade e Silva_Brazil_F6

Figure 6. After casting and machining procedures ball attachment systems and the copings were installed in the mouth.

JDMR-19-121-Frederico Anade e Silva_Brazil_F7

Figure 7. Prosthesis adapted on restraint systems and in teeth occlusion antagonists.

JDMR-19-121-Frederico Anade e Silva_Brazil_F8

Figure 8. Facial aesthetics re-established masticatory function, within the limitations of clinical case.

Summary

Male patient undergo laryngectomy and supraglottic glossopelvemandibulectomy cervical bilateral radical emptying due to an ulcerated moderately differentiated spin cell carcinoma and invasive (degree II). Underwent successful before treatment of prosthetic rehabilitation treatment with occlusal appliance smooth and flat and later device with lateral ramp to align the mandible in relation to the median sagittal plan. The prosthetic rehabilitation occurred through mandibular overdenture with o’ring retention system. After a period of adaptation, the patient reported satisfaction and comfort and an increase in body weight of 10 kilograms.

Discussion

Surgical treatment of carcinogenic head and neck injuries often results in often severe intraoral and extraoral defects that lead to changes in chewing, swallowing, phonation and aesthetics, influencing the patient’s quality of life. As a means of restoring function and partially or totally aesthetics, prosthetic rehabilitation becomes the main recommendation for this purpose. Overdenture has been described as a technique indicated for prosthetic rehabilitation, where removal of part of the maxilla or mandible is necessary as a preventive approach to recurrence of invasive carcinomas. The o’ring system is indicated as a form of retention of overdentures whether installed on natural or artificial abutments.

The indication of implant overdenture in irradiated patients who underwent chemotherapy presents a risk of osseointegration loss and, as a consequence, impairment of the prosthesis. In these cases the use of natural teeth as o’ring system receptors are more indicated, having the advantage of maintaining dental proprioception. The concept of a physiological mandibular position, from which the vertical occlusion dimension and the maximum intercuspal position for the construction of prosthetic rehabilitation can be established, is unanimous in the dental environment. Although there are discussions regarding the procedures for obtaining such positions, the tendency of the researchers is to adopt technical procedures to first seek neuromuscular balance and then the vertical dimension of occlusion and maximum intercuspal position. It is noticed that the initial or pre-rehabilitative objective is proprioceptive block, so that the masticatory muscles and associated muscles can equalize their functions, bilaterally.

The use of a rigid, smooth and flat intraoral device that blocks proprioception and as a consequence allows the electromyographic equalization of the masticatory muscles, as a consequence brings the mandible in harmony with the position of the condyles in the mandibular fossae and the muscular electrical activity. Thus, the jaw responding to bilateral functional activity of the muscles in balance, reaches a therapeutic position, ready to receive prosthetic rehabilitation. The case described in this article was planned and executed using initially a rigid, smooth and flat intraoral device, seated on the lower teeth to initially promote muscle equalization. As it was necessary the total removal of the right mandibular ramus and all the muscles inserted in it, later, the intraoral device was transformed, receiving an inclined plane, in its right side to dislocate the mandible, towards the midline of the median sagittal plane and thus centralizing it. After stabilization of the mandible in this position, an o’ring overdenture was performed on the remaining lower teeth, in addition to functional and aesthetic rehabilitation, seeking to improve the patient’s quality of life.

References

  1. Burns DR (2004) The mandibular complete overdenture. Dent Clin North Am 48: 603–623. [crossref]
  2. Mericske-Stern R (1994) Overdentures with roots or implants for elderly patients: a comparison. J Prosthet Dent 72: 543–550. [crossref]
  3. Ledger E (1856) On preparing the mouth for the reception of a full set of artificial teeth. Br J Dent Sci 1: 90.
  4. PRINCE IB (1965) CONSERVATION OF THE SUPPORTIVE MECHANISM. J Prosthet Dent 15: 327–338. [crossref]
  5. Fenton AH1 (1998) The decade of overdentures: 1970–1980. J Prosthet Dent 79: 31–36. [crossref]
  6. Morrow RM, Powell JM, Jameson WS, Jewson CG, Rudd KD (1969) Tooth supported complete dentures: an approach to preventive prosthodontics. J Prosthet Dent 21: 513–522.
  7. Chrcanovic BR, Albrektsson T, Wennerberg A (2016) Dental implants in irradiated versus nonirradiated patients: A meta-analysis. Head Neck 38: 448–481. [crossref]
  8. Garg A, Guez G (2011) Head and neck cancer, dental implants, and dental oncology. Dent Implantol Update 22: 1–8. [crossref]
  9. De la Plata M, Gías LN, Díez PM, Muñoz-Guerra M, González-García R, et al. (2012) Osseointegrated implant rehabilitation of irradiated oral cancer patients. J Oral Maxillofac Surg 70: 1052–1063.
  10. Yerit KC, Posch M, Seemann M, Hainich S, Dörtbudak O, et al. (2006) Implant survival in mandibles of irradiated oral cancer patients. Clin Oral Implants Res 17: 337–344. [crossref]
  11. Marx RE, Johnson RP (1987) Studies in the radiobiology of osteoradionecrosis and their clinical significance. Oral Surg Oral Med Oral Pathol 64: 379–390. [crossref]
  12. Jacobsson M, Tjellström A, Thomsen P, Albrektsson T, Turesson I (1988) Integration of titanium implants in irradiated bone. Histologic and clinical study. Ann Otol Rhinol Laryngol 97: 337–340. [crossref]
  13. Sammartino G, Marenzi G, Cioffi I, Teté S, Mortellaro C (2011) Implant therapy in irradiated patients. J Craniofac Surg 22: 443–445. [crossref]
  14. Schiegnitz E, Al-Nawas B, Kämmerer PW, Grötz KA (2014) Oral rehabilitation with dental implants in irradiated patients: a meta-analysis on implant survival. Clin Oral Investig 18: 687–698.
  15. Zheng M, Li L, Tang Y, Liang XH (2014) How to improve the survival rate of implants after radiotherapy for head and neck cancer? J Periodontal Implant Sci 44: 2–7.
  16. Ihde S, Kopp S, Gundlach K, Konstantinović VS (2009) Effects of radiation therapy on craniofacial and dental implants: a review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 107: 56–65. [crossref]
  17. Casselli H, Landulpho AB, Silva WA, Silva FA (2007) Electrognatographic evaluation of rehabilitated edentulous patients. Braz Oral Res 21: 355–361.
  18. Landulpho AB, Silva WA, Silva FA, Vitti M (2002) The effect of the oclusal splints on the treatment of temporomandibular disorders – a computerized electromyographic study of masseter and anterior temporalis muscles. Electromyogr Clin Neurophysiol 42: 187–191.
  19. Landulpho AB, Silva WA, Silva FA, Vitti M (2004) Electromyographic evaliation of masseter and anterior temporalis muscles in patients with temporomandibular disorders following interocclusal appliance treatment. J Oral Rehabil 31: 95–98.
  20. Landulpho AP, Silva WAB, Silva FA, Casselli H, Silva LLB (2004) Electrosonographic evaluation in patients with temporomandibular disorders, treated by interoclusal appliance. Braz J Oral Sci 11: 624–627.
  21. Silva WAB, Silva FA (2000) Epidemiologic study of the temporomandibular disorders. J Dent Res 79: 584–588.

Current Status of Local Drug Delivery Systems in the Treatment of Periodontal Diseases

DOI: 10.31038/JDMR.2019233

Abstract

Periodontal disease includes many pathological conditions affecting the periodontium, but gingivitis and periodontitis are the more common types. Gingivitis is a progressive condition, although it is reversible, when left untreated it can lead to periodontitis. Microbial species have a major role in the aetiology of periodontitis.

Method:Information was derived from research papers using PubMed, Science Direct, and Google Scholar using the keywords local drug delivery system, treatment, and periodontal disease. The search included articles up to 2018 with majorly in vivo studies in patients with periodontitis. The usage of local drug delivery systems with controlled or sustained release mechanisms may provide slightly better therapeutic effect in comparison with patients who undergo scaling and root planning only.

Conclusion: The present review of the literature of the currently available local drug delivery systems in the treatment of periodontal diseases.

Keywords

Gingivitis, Periodontal Diseases, Periodontium, Scaling

Introduction

Periodontal disease is a term which comprises several pathological conditions involving the periodontium, which includes the gum, alveolar bone, dental cementum, and periodontal ligament [1]. The more common conditions of periodontal diseases are gingivitis and periodontitis. Periodontal disease is the most prevalent oral condition of the worldwide population, with gingivitis affecting 50% to 90% of adults [2,3]. Gingivitis is the mildest type of periodontal disease. It is a localised inflammation of the gum tissue (gingiva) caused by bacteria in the dental plaque, which is a microbial biofilm that forms on the teeth and the gingiva. Cultural studies have shown that there are more than 700 distinct microbial species that can be found in the dental plaque, although only a small group has been confirmed to contribute to the cause and progression of periodontal disease [3,4]

Gingivitis, when left untreated, can progress to periodontitis [3,5]. Unlike gingivitis, which is confined to the gingiva, periodontitis leads to the loss of connective tissues supporting or surrounding the teeth. This loss of gingiva, alveolar bone, and periodontal ligament creates deep “pockets”. When these deep periodontal pockets have formed and is filled with microbes, the condition becomes highly irreversible, and eventually may lead to loss of teeth [5].

Literature Research

Search strategy

A literature search with several restrictions was done electronically through the following databases: PubMed, Google Scholar, and Science Direct, using search terms that have been summarised in (Table 1).

Table 1. Number of results yielded by searching using keywords through three different databases.

Database

Search term(s)

Number of results

PubMed

(local drug delivery system) AND periodontal disease

149

(local drug delivery system) AND “periodontal disease”

38

(local drug delivery system [Title/Abstract]) AND periodontal disease [Title/Abstract]

6

Science Direct

local drug delivery system in treatment of periodontal disease

2,458

“local drug delivery system” AND “periodontal disease”

46

“local drug delivery system” AND “treatment of periodontal disease”

20

Google Scholar

local drug delivery system in treatment of periodontal disease

58,600

“local drug delivery system” AND “periodontal disease”

807

“local drug delivery system” AND “treatment of periodontal disease”

321

Inclusion and exclusion criteria

The search was restricted to research articles written in English, and the search included studies from 1979 up to 2018, since 1979 was the year that local drug delivery systems were first considered. Apart from articles that do not meet the criteria mentioned, animal studies were also not included.

History of Treatment

As mentioned previously, it has been proven that the bacteria-filled film is one of the main causes of periodontal diseases. The traditional methods of non-surgical treatment of periodontal disease, including mechanical scaling and root planing, did not guarantee improvements of the disease. Treatment of periodontitis focuses mainly on reducing the total microbial count, hence scaling and root planing needs to have an adjunct therapy, in other words, the antimicrobial agents. It was Dr. Max Goodson who pioneered and developed the concept of local drug delivery systems in 1979 [6]. This discovery has led to the increase of studies regarding local drug delivery systems pertaining to periodontal disease in the last decade.

Advantages of local antimicrobial drug delivery directly into periodontal pocket

The advantages of delivering antimicrobial agents directly to the target instead of taking systemic agents [7,8]. These are included and not limited to direct access to the targeted diseases, first-pass metabolism is bypassed, avoids problems regarding the gastrointestinal system, which is a common occurrence with drugs that are orally administered, able to provide more rapid absorption because of the rich blood supply’ reduction in cost of treatment, less chances of antimicrobial resistance and suitable for patients who cannot swallow. However, there are still some limitations, which include inability to administer local irritants, limited dose because of the small area and cost to manufacture delivery devices may get expensive.

Local drug delivery systems

Drugs that need to be delivered locally are done so by inserting them into a vehicle in the form of fibres, gels, strips, among others, which will be discussed in Table 2 below. The ideal characteristics for that are desired for a local anti-microbial agent are able to deliver the drug to the target, in other words, the base of the pocket, has a therapeutic concentration in the pocket, able to maintain the concentration of drug for a period of time where the drug gives therapeutic effect and exhibits little side effects.

Table 2. Summary of some local drug delivery systems [9].

Local drug delivery system

Polymer matrix

Incorporated drug

Reference

Fibres

Cellulose acetate

1. Tetracycline HCl

2. Chlorhexidine

[6]

[10]

Ethylene vinyl acetate

Tetracycline HCl

[11]

Poly-(Ɛ-caprolactone) (PCL)

Tetracycline HCl

[11]

Films

Ethyl cellulose

1. Metronidazole

2. Tetracycline HCl

3. Minocycline

[12]

[13]

[14]

Cross-linked atelocollagen

Tetracycline

[15]

Gelatin (Byco® protein)

Chlorhexidine diacetate

[16]

Collagen

Chlorhexidine gluconate

[17]

Chitosan

Taurine

[18]

Chitosan + Polylactide-co-glycolic acid (PLGA)

Iproflavone

[19]

Chitosan + PCL

Metronidazole

[20]

Polyvinyl alcohol + carboxymethyl chitosan

Ornidazole

[21]

PLGA

1. Tetracycline

2. Amoxycillin + metronidazole

[22]

[23]

Eudragit L® and Eudragit S®

Clindamycin

[24]

PCL

Minocycline

[25]

Gels

Chitosan

Metronidazole

[26]

Hydroxyethyl cellulose + polyvinylpyrrolidone

Tetracycline

[27]

Poloxamer 407 + Carbopol 934P

Propolis

[28]

Poly(α-lactide) + N-methyl 2-pyrrolidone

1. Sanguinarium

2. Doxycycline hyclate

[29]

[30]

Glycerol monooleate + sesame oil

Metronidazole

[31]

PLGA

Tetracycline

[32]

Strips

Polyethylmetha acrylate (acrylic)

1. Tetracycline HCl

2. Metronidazole

[33]

[34]

Hydroxypropyl cellulose

1. Chlorhexidine, tetracycline

2. Doxycycline

[35]

[36]

Hydroxypropyl cellulose + methacrylic acid

Ofloxacin

[37, 38]

Polyhydroxybutyric acid

Tetracycline HCl

[39]

PLGA

Tetracycline HCl

[40]

Xanthan

Chlorhexidine

[41]

Ethyl cellulose

Chlorhexidine

[42]

Vesicular liposomal systems

Phosphatidylinositol

Triclosan

[43]

Immunoliposomes

Anti-oralis

[44]

Microparticle systems

PLGA

Tetracycline

[45]

Nanoparticle systems

PLGA

Triclosan

[46]

Cellulose acetate phthalate

Triclosan

[46]

Chitosan

Antisense oligonucleotide

[47]

Fibres

Fibres are thread-like devices with a reservoir-based sustained release system. They are circumferentially placed inside the periodontal pockets using an applicator, and to ensure the controlled release of drug, the fibres are secured by applying cyanoacrylate as an adhesive [9].

Actisite®

Actisite was introduced in 1994 and was the first controlled-release antimicrobial product to be commercialised. It is 23 cm long and 0.55 mm wide, delivering 12.7 mg of tetracycline hydrochloride. The fibre is non-biodegradable and has to be removed after 10 days, which is the end of the therapy. In comparison with 250 mg of tetracycline delivered orally which results in 1 μg/ml in the gingival crevicular fluid, the locally delivered Actisite achieves an initial concentration of 1590 μg/ml in the periodontal pocket. The concentration level remained at a mean of 1300 μg/ml for 7 days [7]

Films

Film is a form of matrix delivery system where the drug is distributed throughout the polymer, and it is released by either drug diffusion, or erosion or dissolution of matrix. This system is more commonly used as it has several advantageous characteristics. The size and shape of the films is flexible it can be easily changed to fit the dimensions of pocket needed to be treated. Larger-sized films can be applied onto the cheek mucosa, or they can also be divided into smaller sizes to be placed into the pocket [9].

Injectable systems

Injectable systems have an added advantage of easy and rapid application. Antimicrobial agents can be delivered using a syringe directly into the periodontal pocket, without the patient experiencing pain. The cost and time taken for the therapy is also considerably lower when compared to delivery systems that need to be applied securely. Furthermore, the injectable system should be able to fill the pocket, hence reaching more pathogens [48].

Gels

Gels are semisolid mucoadhesive systems that have also received attention for the targeted delivery of antimicrobial agents, offering some advantages [8]creation of periodontal pocket and resorption of alveolar bone, resulting in the disruption of the support structure of teeth. According to WHO, 10–15% of the global population suffers from severe periodontitis. The disease results from the growth of a diverse microflora (especially anaerobes. For instance, in terms of preparation and administration, they are easier to prepare. A downside is that gels have faster drug releasing rates. Gels are applied sublingually using a blunt cannula and a syringe [48].

Strips and compacts

Strips are thin and elongated matrix bands where the drug will be distributed throughout the system. Acrylic strips filled with different antimicrobial agents have been developed, and those containing tetracycline or metronidazole were found to have best improved the parameters of periodontitis [49].

Vesicular liposomal systems

Vesicular liposomal systems are investigated intently in order to be used in periodontal diseases. This is because they are designed to mimic the bio-membranes in terms of structure and their behaviour [9].

Microparticle systems

Microspheres are solid structures that are spherical in shape, with sizes ranging from 1 to 1000 μm. The drug is dispersed throughout the matrix. To prepare microspheres, non-biodegradable and biodegradable materials are both being investigated. These materials include natural polymers, modified natural substances, and synthetics. They can be formulated into chips, dental paste, or even directly injected into the targeted area [8,49]creation of periodontal pocket and resorption of alveolar bone, resulting in the disruption of the support structure of teeth. According to WHO, 10–15% of the global population suffers from severe periodontitis. The disease results from the growth of a diverse microflora (especially anaerobes.

Nanoparticle systems

Nanoparticles have sizes ranging from 10 to 1000 nm, which enables them to penetrate through regions that may not be reached by other delivery systems. This is a major advantage above the other systems like microparticles, since the ability to reach these otherwise neglected areas result in a decreased frequency of administration and it also provides a more uniform distribution of the drug [9]. For most of the local drug delivery systems, there is only a limited number of studies that have been published. Even though there are studies available, it is difficult to compare between different trials as the therapy given to the participating patients vary greatly.

Conclusion

Local delivery drug systems are seemingly a good alternative to deliver antimicrobial agents compared to systemic delivery. They produce fewer side effects, which could improve patient compliance. Since there are no studies proving the effective use of locally delivered drugs as a monotherapy, local drug delivery system remains to be a good adjunct therapy.

Acknowledgement

This literature review promoted by the Universiti Brunei Darussalam through the Pharmacy and dentistry team for their bachelor student’s studentship.

References

  1. Kaplish V, Walia MK, Kumar SLH (2013) Local drug delivery systems in the treatment of periodontitis: A review. Pharmacophore 4: 39–49.
  2. Nazir MA (2017) Prevalence of periodontal disease, its association with systemic diseases and prevention. International journal of health sciences 11: 72–80.
  3. Pihlstrom BL, Michalowicz BS, Johnson NW (2005) Periodontal diseases. Lancet 366: 1809–1820.
  4. Herrera D, Matesanz P, Bascones-Martínez A, Sanz M (2012) Local and systemic antimicrobial therapy in periodontics. Journal of Evidence-Based Dental Practice 12: 50–60.
  5. Kinane DF, Stathopoulou PG, Papapanou PN (2017) Periodontal diseases. Nature Reviews Disease Primers 3: 1–14.
  6. Goodson JM, Haffajee A, Socransky SS (1979) Periodontal therapy by local delivery of tetracycline. Journal of Clinical Periodontology 6: 83–92.
  7. Nair SC, Anoop KR (2012) Intraperiodontal pocket: An ideal route for local antimicrobial drug delivery. Journal of advanced pharmaceutical technology & research 3: 9–15.
  8. Joshi D, Garg T, Goyal AK, Rath G (2016) Advanced drug delivery approaches against periodontitis. Drug Delivery 23: 363–377.
  9. Jain N, Jain GK, Javed S, Iqbal Z, Talegaonkar S, Ahmad FJ, Khar RK (2008) Recent approaches for the treatment of periodontitis. Drug discovery today 13: 932–943.
  10. Coventry J, Newman HN (1982) Experimental use of a slow release device employing chlorhexidine gluconate in areas of acute periodontal inflammation. Journal of Clinical Periodontology 9: 129–133.
  11. Tonetti M, Cugini MA, Goodson JM (1990) Zero-order delivery with periodontal placement of tetracycline-loaded ethylene vinyl acetate fibers. Journal of Periodontal Research 25: 243–249.
  12. Golomb G, Friedman M, Soskolne A, Stabholz A, Sela MN (1984) Sustained Release Device Containing Metronidazole for Periodontal Use. Journal of Dental Research 63: 1149–1153.
  13. Azoury R, Elkayam R, Friedman M (1988) Nuclear Magnetic Resonance Study of an Ethyl Cellulose Sustained-Release Delivery System II: Release Rate Behavior of Tetracycline. Journal of Pharmaceutical Sciences 77: 428–431.
  14. Elkayam R, Friedman M, Stabholz A, Soskolne AW, Sela MN, Golub L (1988) Sustained release device containing minocycline for local treatment of periodontal disease. Journal of Controlled Release 7: 231–236.
  15. Minabe M, Uematsu A, Nishijima K, Tomomatsu E, Tamura T, Hori T, Hino T (1989) Application of a Local Drug Delivery System to Periodontal Therapy: Journal of Periodontology 60: 113–117.
  16. Steinberg D, Friedman M, Soskolne A, Sela MN (1990) A New Degradable Controlled Release Device for Treatment of Periodontal Disease: In Vitro Release Study. Journal of Periodontology 61: 393–398.
  17. Kondreddy K, Ambalavanan N, Ramakrishna T, Kumar RS (2012) Effectiveness of a controlled release chlorhexidine chip (PerioColTM-CG) as an adjunctive to scaling and root planing when compared to scaling and root planing alone in the treatment of chronic periodontitis: A comparative study. Journal of Indian Society of Periodontology 16: 553–557.
  18. Ozmeriç N, Ozcan G, Haytaç CM, Alaaddinoğlu EE, Sargon MF, Senel S (2000) Chitosan film enriched with an antioxidant agent, taurine, in fenestration defects. Journal of biomedical materials research 51: 500–503.
  19. Perugini P, Genta I, Conti B, Modena T, Pavanetto F (2003) Periodontal delivery of ipriflavone: new chitosan/PLGA film delivery system for a lipophilic drug. International journal of pharmaceutics 252: 1–9.
  20. El-Kamel AH, Ashri LY, Alsarra IA (2007) Micromatricial metronidazole benzoate film as a local mucoadhesive delivery system for treatment of periodontal diseases. AAPS PharmSciTech 8: 184–194.
  21. Wang LC, Chen XG, Zhong DY, Xu QC (2007) Study on poly(vinyl alcohol)/carboxymethyl-chitosan blend film as local drug delivery system. Journal of Materials Science: Materials in Medicine 18: 1125–1133.
  22. Agarwal RK, Robinson DH, Maze GI, Reinhardt RA (1993). Development and characterization of tetracycline-poly(lactide/glycolide) films for the treatment of periodontitis. Journal of Controlled Release, 23: 137–146.
  23. Ahuja A, Ali J, Rahman S (2006) Biodegradable periodontal intrapocket device containing metronidazole and amoxycillin: formulation and characterisation. Die Pharmazie 61: 25–29.
  24. Higashi K, Matsushita M, Morisaki K, Hayashi S, Mayumi T (1991) Local drug delivery systems for the treatment of periodontal disease. Journal of pharmacobio-dynamics 14: 72–81.
  25. Kyun KD, Yun KS, Young JS, Pyoung CC, Heui SS (1990) Development of minocycline containing polycaprolactone film as a local drug delivery. Taehan Ch’ikkwa Uisa Hyophoe chi 28: 279–290.
  26. Akıncıbay H, Şenel S, Yetkin Ay Z (2007) Application of chitosan gel in the treatment of chronic periodontitis. Journal of Biomedical Materials Research Part B: Applied Biomaterials 80: 290–296.
  27. Jones DS, Woolfson AD, Djokic J, Coulter WA (1996) Development and mechanical characterization of bioadhesive semi-solid, polymeric systems containing tetracycline for the treatment of periodontal diseases. Pharmaceutical research 13: 1734–1738.
  28. Bruschi ML, Jones DS, Panzeri H, Gremião MPD, de Freitas O, Lara EHG (2007) Semisolid Systems Containing Propolis for the Treatment of Periodontal Disease: In Vitro Release Kinetics, Syringeability, Rheological, Textural, and Mucoadhesive Properties. Journal of Pharmaceutical Sciences 96: 2074–2089.
  29. Poison AM, Stoller NH, Hanes PJ, Bandt CL, Garrett S, Southard G (1996). 2 multi-center trials assessing the clinical efficacy of 5% sanguinarine in a biodegradable drug delivery system. Journal of Clinical Periodontology 23: 782–788.
  30. Polson AM, Garrett S, Stoller NH, Bandt CL, Hanes PJ, Killoy WJ, Friesen LR (1997) Multi-Center Comparative Evaluation of Subgingivally Delivered Sanguinarine and Doxycycline in the Treatment of Periodontitis. II. Clinical Results. Journal of Periodontology 68: 119–126.
  31. Noyan U, Yilmaz S, Kuru B, Kadir T, Acar O, Büget E (1997) A clinical and microbiological evaluation of systemic and local metronidazole delivery in adult periodontitis patients. Journal of clinical periodontology 24: 158–165.
  32. Maze GI, Reinhardt RA, Payne JB, Maze C, Baker RA, Bouwsma OJ, Gerlach RW (1996) Gingival fluid tetracycline release from bioerodible gels. Journal of Clinical Periodontology, 23: 1133–1136.
  33. Addy M, Langeroudi M (1984) Comparison of the immediate effects on the sub-gingival microflora of acrylic strips containing 40% chlorhexidine, metronidazole or tetracycline. Journal of Clinical Periodontology 11: 379–386.
  34. Addy M, Hassan H, Moran J, Wade W, Newcombe R (1988) Use of Antimicrobial Containing Acrylic Strips in the Treatment of Chronic Periodontal Disease. Journal of Periodontology 59: 557–564.
  35. Noguchi T, Izumizawa K, Fukuda M, Kitamura S, Suzuki Y, Ikura H (1984) New method for local drug delivery using resorbable base material in periodontal therapy. The Bulletin of Tokyo Medical and Dental University 31: 145–153.
  36. Taner IL, Özcan G, Doganay T, Iscanolu M, Taplamacioglu B, Gültekin SE, Balos K (1994) Comparison of the Antibacterial Effects on Subgingival Microflora of Two Different Resorbable Base Materials Containing Doxycycline. The Journal of Nihon University School of Dentistry 36: 183–190.
  37. Higashi K, Morisaki K, Hayashi S, Kitamura M, Fujimoto N, Kimura S, Okada H (1990) Local ofloxacin delivery using a controlled-release insert (PT-01) in the human periodontal pocket. Journal of periodontal research 25: 1–5.
  38. Kimura S, Toda H, Shimabukuro Y, Kitamura M, Fujimoto N, Miki Y, Okada H (1991) Topical chemotherapy in human periodontitis using a new controlled-release insert containing ofloxacin. I. Microbiological observation. Journal of Periodontal Research 26: 33–41.
  39. Deasy PB, Collins AE, MacCarthy DJ, Russell RJ (1989) Use of strips containing tetracycline hydrochloride or metronidazole for the treatment of advanced periodontal disease. The Journal of pharmacy and pharmacology 41: 694–699.
  40. Maze GI, Reinhardt RA, Agarwal RK, Dyer JK, Robinson DH, DuBois LM, Maze CR (1995). Response to intracrevicular controlled delivery of 25% tetracycline from poly(lactide/glycolide) film strips in SPT patients. Journal of clinical periodontology 22: 860–867.
  41. Paolantonio M, D’Ercole S, Pilloni A, D’Archivio D, Lisanti L, Graziani F, Perinetti G (2009) Clinical, Microbiologic, and Biochemical Effects of Subgingival Administration of a Xanthan-Based Chlorhexidine Gel in the Treatment of Periodontitis: A Randomized Multicenter Trial. Journal of Periodontology 80: 1479–1492.
  42. Friedman M, Golomb G (1982) New sustained release dosage form of chlorhexidine for dental use. I. Development and kinetics of release. Journal of periodontal research 17: 323–328.
  43. Jones MN, Kaszuba M (1994) Polyhydroxy-mediated interactions between liposomes and bacterial biofilms. Biochimica et Biophysica Acta (BBA) – Biomembranes 1193: 48–54.
  44. Jones MN, Song YH, Kaszuba M, Reboiras MD (1997) The Interaction of Phospholipid Liposomes with Bacteria and Their Use in the Delivery of Bactericides. Journal of Drug Targeting 5: 25–34.
  45. Esposito E, Cortesi R, Cervellati F, Menegatti E, Nastruzzi C (1997) Biodegradable microparticles for sustained delivery of tetracycline to the periodontal pocket: formulatory and drug release studies. Journal of Microencapsulation 14: 175–187.
  46. Piñón-Segundo E, Ganem-Quintanar A, Alonso-Pérez V, Quintanar-Guerrero D (2005) Preparation and characterization of triclosan nanoparticles for periodontal treatment. International Journal of Pharmaceutics 294: 217–232.
  47. Dung TH, Lee SR, Han SD, Kim SJ, Ju YM, Kim MS, Yoo H (2007) Chitosan-TPP nanoparticle as a release system of antisense oligonucleotide in the oral environment. Journal of nanoscience and nanotechnology 7: 3695–3699.
  48. Kaplish V, Walia MK, Kumar SLH (2013) Local Drug Delivery Systems in the Treatment of Peridontitis: A Review. Pharmacophore 4: 39–49.
  49. Ahmad F, Iqbal Z, Jain N, Jain G, Talegaonkar S, Ahuja A, Khar R (2008) Dental Therapeutic Systems. Recent Patents on Drug Delivery & Formulation 2: 58–67.

Orbital Blowout Fractures Due to Globe-to-Wall Contact Mechanism

DOI: 10.31038/IJOT.2019243

 

There is still much controversy surrounding the mechanisms that produce orbital blowout fractures. Since the first report of blowout fracture, theories have evolved and experiments been conducted to elucidate and demonstrate three mechanisms which are the globe-to-wall contact, hydraulic, and buckling.

Erling et al [1] resurrected older mechanism on the etiology of inferomedial orbital fractures first espoused by Pfeiffer [2] in 1943. They proposed that the responsible mechanism of inferomedial orbital fracture is a direct globe-to-wall contact; that is, posterior movement of the globe, in response to an external force, results in a fracture upon direct contact with an orbital wall. They investigated CT scans of blowout fractures of the pure medial and inferomedial wall, demonstrated that the size of the orbital displacement exactly fitted the shape of the globe in many cases. We also examined the charts of estimated 45 cases of this mechanism for the clinical information. According to Erling’s description [1], CT scans were reviewed by overlaying a tracing of the globe displaced directly down the longitudinal orbital axis to evaluate the likelihood of posterior globe displacement as a mechanism of fracture. The size of the orbital wall displacement exactly fit the globe in 46.7 % (20/45) patients [3] (Figure 1). All fractures were occurred in the inferomedial area of the orbital wall. In our study, serious complications like corneal laceration, globe rapture, 3rd cranial nerve paralysis, and ophthalmic nerve neuropathy plus 3rd, 4th, 6th cranial nerve paralysis (Orbital Apex Syndrome) were seen more frequently than other reports. These serious complications seem great impact had acted the globes. It is necessary to take enough care for delayed neuropathy, when CT scan of patient shows orbital fracture due to “globe-to-wall contact mechanism”, even if he dose not complain any symptom immediate after injury.

IJOT 19 - 123_Sugamata A_f1

Figure 1. A-53-year man fell down and hit the right eye region to the floor. The CT finding showed the displacement of the right inferomedial wall. The size of the orbital wall displacement exactly fit the globe (A, B).

There is no doubt that almost blowout fractures of the orbit could be due to a single mechanism alone or a combination of 2 or more mechanisms clinically [4]. We conclude that “globe-to-wall contact mechanism” advocated by Pfeiffer acts in some respect to making fracture formation in some orbital blowout fractures in the inferomedial area of the orbital wall.

Key words

Blowout Fracture; Orbital Fracture; Globe-to-Wall Contact Mechanism.

References

  1. Erling BF, Iliff N, Robertson B, et al. (1999) Footprints of the globe: a practical look at the mechanism of orbital blowout fractures, with a revisit to the work of Raymond Pfeiffer. Plast Reconstr Surg 103: 1313–1316.
  2. Pfeiffer RL (1943) Traumatic enophthalmos. Arch Ophthalmol 30: 718–726.
  3. Sugamata A, Yoshizawa N (2010) Clinical analysis of orbital blowout fractures caused by a globe-to-wall contact mechanism. J Plast Surg Hand Surg 44: 278–281.
  4. Sugamata A (2014) Etiology of orbital blowout fractures. J Tokyo Med Univ 72: 19–24.

Increase in Parental Knowledge and Confidence Following Communication of Dental Imaging Risks versus Benefits

DOI: 10.31038/JDMR.2019232

Abstract

Objective: To explore the role of parental education and communication of risks versus benefits of pediatric dental image on parents’ knowledge, comfort and confidence in allowing their children to receive the necessary imaging procedures.

Methods: Parents of children <18 years of age were recruited during routine dental visits at the Boston University Pediatric Oral Health Care Center and Department of Dentistry at the Boston Medical Center, Boston, Massachusetts. Participants completed two brief questionnaires immediately before and after the educational intervention. A brief two-sided printed informational handout and a mobile application called Medical Imaging Risk (MIR) were used in the educational intervention for parental health education and communication of information on radiation risks. Statistical analysis was conducted using STATA version 14.0 to compare pre-intervention and post-intervention responses of participants.

Results: Among 213 parents, the majorities were mothers (83%), African American (55%), with MassHealth insurance (82%) and reported that their child/children have had previous dental radiographs (75%). A significant improvement in confidence of their knowledge on benefits and risks of dental imaging was observed following the educational intervention (p<0.001). Parents’ level of comfort in allowing the use of dental radiographs for their children significantly improved after the educational intervention (p<0.001). Parents preferred the printed handout (53%) only slightly more than the mobile application (47%).

Conclusion: The results from our study suggest that a simple brief educational intervention that includes easy to understand materials can significantly improve parental level of knowledge and confidence towards pediatric dental imaging. Thus dental practitioners should aim to include risk-benefit dialogues as part of the routine dental care visit to improve communication and acceptance of pediatric imaging.

Keywords

Health Communication, Pediatric Dentistry, Children, Radiation Imaging, Radiation Risks, Dental Imaging, Dental Radiography, Parental Knowledge, Educational Intervention.

Introduction

Patient communication of health information is a key component of patient care and management. In particular, communicating risks and benefits of medical and dental procedures enables better understanding and decreases the level of anxiety among patients. Radiation imaging has been known to cause fear and anxiety among patients due to the general perception of radiation as a ‘hazard’ [1]. This fear, caused mainly by incomplete understanding of the benefits versus risks of radiation imaging, has been further fueled by historical radiation related disasters, media reports, social media, previous experience, experiences or shared by family and friends. Recent evidence in the literature also suggests that significant gaps exist between patient expectations and provider communication of benefits versus risks of medical imaging [2]. These gaps also extend to dental imaging procedures which can be overcome through improved risk-benefit dialogues between practitioners and children, and their parents or guardians. To improve the current practices in risk communication strategies the World Health Organization (WHO) organized an International Workshop on Radiation Risk Communication in Pediatric Imaging in September of 2010 and in collaboration with a working group released a publication titled “Communicating Radiation Risks in Paediatric Imaging” [3]. This publication was developed to aid health professionals on communication of radiation risks in pediatric imaging more efficiently and to provide guidance on risk-benefit dialogues with children and their parents.

Dental radiology has evolved over the years and is currently being used widely in children for diagnosis and management. In pediatric dentistry in particular, dental imaging has played an important role in a child’s first visit to the dentist as it is not only a vital part in a thorough examination of the oral cavity but is a simple procedure that is used to also gain the child’s confidence [4]. While radiation emission from dental imaging is lower than from medical imaging procedures, dental practitioners should weigh the benefit and need for the imaging procedure among children over the risks involved to make a clinical judgement keeping in mind the interest of each patient. In recent years there has been a significant increase in the use of dental radiography in the United States (US) with over 500 million intra-oral bitewing and panoramic radiographic procedures [5]. Also, the number of Cone Beam Computed Tomography (CBCT) procedures have also significantly increased over the years. As a result, the overall contribution of radiation exposure from dental imaging procedures is increasing and is about 50% of the annual per capital radiation dose in the US [6]. In light of these increases the American Dental Association (ADA) in collaboration with 80 other health care organizations developed a program called ‘Image Gently’ in 2007 which is an initiative to raise awareness and educate practitioners to provide safe pediatric imaging [7]. This alliance was also developed to educate providers on selecting imaging procedures based on individual needs and to limit the exposure time among children. The ‘Image Gently in Dentistry’ campaign was specifically launched to promote responsible use of dental radiography and to improve radiation safety in pediatric dental imaging [6]. The main goals of this campaign is based on the concept of reducing radiation exposure in children As Low As Diagnostically Acceptable (ALADA) while achieving effective images that aid in diagnosis.

Radiation exposure is the amount of radiation charge produced by ionizing radiation during imaging procedures whereas absorbed dose describes the amount of emitted radiation absorbed at a point [8]. This absorbed dose is converted to equivalent dose by multiplying the radiation delivered for each type of radiation. Effective dose is the total amount of radiation exposure estimated from the total equivalent dosages and [3] can be expressed in Sieverts (Sv) based on the System International nomenclature [3]. The radiation dose emitted in diagnostic imaging is expressed as milliSieverts (mSv) [9]. When comparing the radiation exposure between medical imaging procedures versus dental imaging, the exposure from dental radiographs are much lower. For example, the radiation dose from a set of four intra-oral bite-wing radiographs is 0.005 mSv and from a single panoramic radiograph is 0.01 mSv which is equivalent to <1 day and 1.5 days of exposure to natural radiation respectively [3,8]. In comparison, the radiation exposure from a chest x-ray for a 5 year old child is 0.02 mSv which is equivalent to 3 days of natural radiation exposure. A Computed Tomography (CT) scan to the head of a 5 year old emits 2 mSv radiation and is equivalent to 10 months of natural radiation exposure whereas one CBCT procedure leads to radiation exposure of 0.107 mSv which is less than five months of natural radiation exposure, demonstrating that dental imaging procedures lead to much lower radiation exposure. The risks from exposure resulting from all types of diagnostic imaging and its effects are not completely understood [3]. Effects such as cell death, hair loss, skin redness etc. occur at much higher doses of exposure than the exposure from dental diagnostic imaging. Long-term risk of developing cancer has been suggested based on some epidemiologic evidence for radiation doses of 50–100 mSv which would be the accumulated dose after multiple CT scans. However, since children have a long period of life ahead, the low dose exposures from diagnostic imaging in the early years of life may accrue and eventually may lead to a small increase in lifetime risk of cancer in the future. Hence given the lack of strong evidence and the uncertainty it is important for dental practitioners to take a precautionary approach when using pediatric imaging. Also, by improving patient and parent-provider communication about risks versus benefits, informed decisions can be made that will ultimately benefit the child patients.

There are only a few studies that explored the perspectives of parents and communication of radiation risks most of which are related to medical imaging procedures. Limited evidence exists on communication of dental radiation risks and parents’ knowledge and perception towards dental radiography. A study in Australia explored parental level of knowledge and attitude towards dental radiography for children [10]. That study analyzed 309 surveys completed by parents and the results showed a low level of knowledge but positive attitude towards dental radiographs. Also in that study, parents’ level of education and parents with children who have had radiographs previously were more likely to have a higher level of knowledge. In the same study when participants were asked about whether they received information on radiation risks, <40% reported that they had been informed of the risks by their providers. Similar findings have been reported in studies on medical imaging where participants have low level of knowledge and report that they did not receive the information on the risks of medical imaging [11,12]. A more recent study evaluated patients’ perception on dental radiographs in Malaysia and reported a significant lack of knowledge about the role of dental radiographs. In that study among the participants 57% believed that dental radiographs should be avoided in pregnant women and 32% believed that dental radiographs should be avoided in children [13]. Studies on communicating risks clearly highlight the gaps in provider-patient or parent communication. Evidence also suggests that parents who did receive information prior to imaging procedures report lower levels of anxiety during the procedures [11]. Insufficient data is available on the preferred method of communication in dental imaging risks versus benefits. One study in Spain among 602 participants reported that participants preferred both oral and written forms of communication with no significant preference of one over the other [14]. With the current technological advances there is an increase in usage of other modes of communication such as online resources, phone applications and text messaging however there is a lack of epidemiological data that supports the use of these methods and there is insufficient evidence on the most effective form of communication of health information.

Our study was developed to explore the role of parental education and communication of risks versus benefits of dental imaging on parents’ knowledge, comfort and confidence in allowing their children to receive the necessary dental imaging. Results from our pilot study has been published previously [15,16]. In this report we describe the study that was conducted and the results obtained from a larger sample with additional investigation on the preferred method of communication of risks versus benefits in comparison to our pilot study. Specifically our hypothesis was that a brief educational intervention by the dental provider will increase the level of confidence and comfort among parents and those parents prefer a specific mode of communication of health information.

Methods

Note: A description of the study methods and results from our pilot study was published previously [15,16].

The sample population in this study included parents or guardians of children under 18 years of age. The participants were recruited during routine dental care visits for their children at either the Pediatric Oral Health Care Center in Boston University Goldman School of Dental Medicine or Department of Pediatric Dentistry at the Boston Medical Center, Boston, Massachusetts. A convenience sampling method was used to recruit any one parent or legal guardian per family and only those who were proficient in the English language were included. Following verbal consent, the parents completed two brief questionnaires and an intervention using a handout and a mobile phone application was conducted as well by the study investigator. The parents completed the questionnaires and the intervention while waiting during their children’s dental treatment. The time taken for participants to complete the questionnaires and the educational intervention was between 15–20 minutes. This study was approved by the Boston University Medical Center Institutional Review Board.

Educational Intervention

The materials utilized for the educational component in this study included a short two-sided informational handout titled ‘Are dental radiographs safe for your children?’ (S1a and S1b Figures), and a mobile application called ‘Medical Imaging Risk (MIR)’ (S2 and S3 Figures). The informational handout used in this study was in English language, easy to read and the content was prepared at the 8th grade level as is the standard when preparing patient related text (S1a and S1b Figures). Colorful images, text and tables were used to educate parents on dental radiography and provide information on sources of radiation and their different dose estimations highlighting the radiation dose with routine dental radiographs. The handout while emphasizing the benefits and importance of dental radiography in early diagnosis and treatment also outlined the possible risks from unnecessary imaging procedures.

JDMR-19-124-Jayapriyaa R. Shanmugham_USA_F1

S1a Figure. Information on side 1 of the printed handout:

JDMR-19-124-Jayapriyaa R. Shanmugham_USA_F2

S1b Figure. Information on side 2 of the printed handout:

S1 Figure. Printed two-sided informational handout used in the educational intervention.

JDMR-19-124-Jayapriyaa R. Shanmugham_USA_F3

S2 Figure. Medical Imaging Risk (MIR) mobile application: Types of radiographic tests listed in the application.

JDMR-19-124-Jayapriyaa R. Shanmugham_USA_F4

S3 Figure. Medical Imaging Risk (MIR) mobile application: Types of dose equivalents for selected radiographic test by age.

Following the discussion using the informational handout, the mobile application (app), MIR was used to continue an interactive discussion on radiation imaging (S2 Figure). The use of the app was demonstrated, and participants were shown that this app can be easily downloaded for free on both the Android and Apple platforms. This user-friendly app provides information on the various dosages and risks by type of radiation imaging (S3 Figure). The app also provides additional resources for further detailed information that the participants can download for free.

Study Questionnaires

Two questionnaires, one immediately before (pre-intervention) and one immediately after (post-intervention) the educational intervention were used to obtain information on parents’ knowledge and perception towards pediatric imaging.

Pre-intervention questionnaire

In the pre-intervention questionnaire, which included 5 questions, parents responded if their child or children ever received dental imaging. Irrespective of their response to this question parents completed the remainder of the questionnaire. Parents responded to questions on the level of confidence in their knowledge on risks and benefits of radiation and were asked to choose from three options: Not confident, somewhat confident and very confident. To evaluate specific knowledge, parents were asked to respond to whether smartphones and electronic devices emitted harmful radiation to which they responded ‘yes’ or ‘no’. Participants also responded to their level of comfort in their child undergoing any type of radiation imaging by choosing from three options: Not comfortable, somewhat comfortable and very comfortable. Demographic information such as participants’ gender, race, ethnicity and insurance type were also obtained in the pre-intervention questionnaire to evaluate differences in parent responses.

Post-intervention questionnaire

The post-intervention questionnaire, which included 8 questions, included the same five questions that was in the pre-intervention questionnaire, to evaluate a change in perception or comfort if any as a result of the intervention. In addition, questions on whether the educational material discussed during the intervention improved their understanding about dental radiographs and if the participants continued to have concerns about them were also included and both of these questions generated a response of ‘yes’ versus ‘no’. One of the goals of the post-intervention questionnaire was also to explore the preferred method of communication when receiving health information during dental care visits and the participants chose between printed materials versus mobile application. This question was not included initially however it was added later during the study as our goal was also to collect data on the parent perspective related to the educational material. As a result not all of the participants responded to this question. The study application was amended with this additional question and IRB approval was obtained to make this change.

Statistical Analysis

Participants’ responses to the questionnaires, pre versus post intervention, were compared and analyzed using STATA version 14.0 statistical analysis software. Differences in knowledge and perception were also evaluated by demographic characteristics. Descriptive and univariate categorical data analysis was conducted to evaluate differences and p-values <0.05 were considered statistically significant.

Results

A total of 213 parents participated in this study, reflecting the population base of the Boston University Goldman School of Dental Medicine. The majority were mothers (82.6%), having Medicaid as their primary dental insurance (81.7%). Also, most of the participants were African Americans, 54.9% followed by 17.8%n White; 7.04% Asian; and 16.4% self-identified as Hispanic/Latino (S1 Table).

Most of the participants in this study (75%) reported that their child/children have had previous dental radiographs (S1 Table). When comparing participants’ level of confidence on their knowledge towards benefits of dental radiographs for their children, 74% of participants reported either not confident or somewhat confident in the pre-intervention questionnaire. This trend changed in the post-intervention period as an improvement in the level of confidence was evident with 65% of the participants reporting that they are very confident. This improvement in the level of confidence was statistically significant with p<0.001 (S1 Table). Similarly, when evaluating the confidence level on the knowledge of risks of dental radiographs for their children, 69% of participants were either not confident or somewhat confident in the pre-intervention questionnaire. However, this trend also changed in the post-intervention period where 58% reported being very confident with statistically significant results (p<0.001).

S1 Table. Characteristics of the study participants (N = 213).

Characteristic

n (%)

Gender, n (%)

Females

176 (82.6%)

Males

37 (17.4%)

Race/Ethnicity, n (%)

Caucasian

 38 (17.8%)

African American

117 (54.9%)

Hispanic/Latino

35 (16.4%)

Asian/Pacific Islander

15 (7.04%)

Other

8 (3.8%)

Type of insurance, n (%)

MassHealth

174 (81.7%)

Other

 39 (18.3%)

History of previous dental radiographs for participants’ child/children, n (%)

Yes

159 (74.7%)

No

54 (25.4%)

In the pre-intervention, more than half the study population (59%) reported that they were either not comfortable or somewhat comfortable in allowing dental radiographs for their children (S2 Table). However following the educational intervention, in the post-intervention, a significant majority (66%) reported being very comfortable (p<0.001).

In the post-intervention analysis regarding the helpfulness of the educational materials, the great majority (94%) had a positive response (S4 Figure). Eighty two percent reported no concerns with dental radiographs after reviewing the materials during the educational intervention (S2 Table). When evaluating the preferred method of communication of health information, interestingly the responses were almost equally distributed. As mentioned previously, this question was initially not included in the post-intervention questionnaire and was added after our pilot exploration. Therefore, the complete sample population was not included in the comparison of preferred method of communication. Among 147 parents or caregivers 53% reported that they preferred the printed handout versus 47% reported that they preferred the mobile phone application (S5 Figure). No significant differences by gender, race/ethnicity and insurance type was observed as the majority of the participants in this study was women, African-American and had Medicaid insurance (S1 Table). Hence due to the lack of variability by demographic characteristics we did not observe statistically significant differences by these characteristics and were unable to explore potential confounding by these factors in multivariate analyses.

JDMR-19-124-Jayapriyaa R. Shanmugham_USA_F5

S4 Figure. Helpfulness of the educational materials in understanding of pediatric radiation imaging (post-intervention) N = 213.

JDMR-19-124-Jayapriyaa R. Shanmugham_USA_F6

S5 Figure. Preference for receiving health information (post-intervention) N= 147.

S2 Table. Evaluation of parental knowledge and attitudes of radiation imaging among pediatric caregivers at the Pediatric Oral Health Center (N = 213)

Radiation Imaging

Pre-test questionnaire

n (%)

Post-test questionnaire

n (%)

p-value

Level of confidence in knowledge about benefits

Not confident

52 (24.4)

2 (0.94)

Somewhat confident

105 (49.3)

72 (33.8)

Very confident

56 (26.3)

139 (65.3)

<0.0001*

Level of confidence in knowledge about risks

Not confident

38 (17.8)

9 (4.2)

Somewhat confident

109 (51.2)

80 (37.6)

Very confident

66 (31.0)

124 (58.2)

<0.0001*

Level of comfort in allowing the use of dental radiographs

Not comfortable

28 (13.2)

11 (5.2)

Somewhat comfortable

98 (46.0)

61 (28.6)

Very comfortable

87 (40.8)

141 (66.2)

<0.0001*

Reported understanding of radiation from electronic devices

Yes

140 (65.7)

162 (76.1)

No

73 (34.3)

51 (23.9)

<0.0001*

Level of comfort in using dental radiographs by race/ethnicity before intervention

Not comfortable

Somewhat comfortable

Very comfortable

White

7 (25)

21 (21.4)

10 (11.5)

African-American

15 (53.6)

50 (51.0)

52 (59.8)

Hispanic/Latino

6 (21.4)

17 (17.4)

12 (13.8)

Pacific Islander

0 (0)

6 (6.1)

9 (10.3)

Other

0 (0)

4 (4.1)

4 (4.6)

0.29†

Level of comfort in using dental radiographs by race/ethnicity after intervention

White

3 (27.3)

12 (19.7)

23 (16.3)

African-American

5 (45.5)

32 (52.5)

80 (56.7)

Hispanic/Latino

2 (18.2)

14 (22.9)

19 (13.5)

Pacific Islander

1 (9.1)

1 (1.6)

13 (9.2)

Other

0 (0)

2 (3.3)

6 (4.3)

0.47

Concerns regarding dental radiographs (post-intervention)

n (%)

Yes

174 (81.7)

No

39 (18.3)

*Results from Pearson Chi-square analysis.
†Based on results from Fisher’s Exact analysis;
‡Post-intervention question

Discussion

Overall the results from our study indicate that a simple brief educational intervention in the dental office can not only improve parental the level of knowledge but can also increase their level of confidence and comfort thus enabling them to be more accepting and comfortable with radiation imaging procedures for their child/children. Our study also explored the preferred mode of communication among parents and we observed that the majority preferred the printed informational handout over the mobile application.

Communication of health risks and benefits is an important step towards better provider-patient relationship. Particularly in pediatric dentistry the level of anxiety among children and their parents are high due to mainly lack of knowledge among patients and parents, which may be as a result of failing to receive adequate information prior to dental procedures. While dental providers showed an acceptable level of knowledge on radiation risks, evidence from one study reported that the patients’ knowledge was inadequate [17]. Similar findings were reported in another study conducted in Australia where among 309 parents there was a low level of knowledge [18]. In our study, in the pre-intervention questionnaire, parents reported a lower level of confidence in knowledge of risks and benefits of radiation however this significantly improved in the post-intervention following the educational intervention and discussion using the mobile application. This was also observed in the previously mentioned study in Australia where the investigators reported that parents with higher level of education appeared to have not only higher knowledge of radiation risks but were more likely to accept radiation imaging as ‘safe’ and ‘beneficial’. A study in Malaysia among patients reported that insufficient knowledge was associated with higher level of disapproval of the use of dental imaging among children [13]. In our study in the post-intervention when parents were asked if they still had concerns and if they comfortable in allowing their children to undergo imaging procedures, the majority reported that they did not have concerns and that they were very comfortable.

The risk-benefit dialogue is an important component of patient care in the current practice of dentistry and can aid in lowering the level of fear anxiety towards radiation [3,19]. This dialogue should be designed based on individual patient needs. The providers should also keep in mind that each patient and family differ in terms of their social and cultural background, medical and dental history, and access to care, especially given the growing diversity of the demographics in the US [20]. The risk communication strategy should be developed keeping in mind the prominent role of the parents in clinical decision making of dental treatment for their children. Dental practitioners should be aware that parents’ risk perception is often influenced by social factors, personal belief systems, previous health experiences, socio-economic factors and level of education [20]. Therefore, when communicating health information it is vital that dental practitioners take these factors into account and communicate information to the parents and children in a way that is easy for them to comprehend. In our study as we did not collect information on level of education and socio-economic factors. We collected information on insurance type which can be a proxy for economic level however the majority of the participants in our study since the majority reported Medicaid as their insurance we were unable to evaluate differences by economic level of the participants. The demographic characteristics observed in our study are however reflective of the patient population at the Boston University’s Goldman School of Dental Medicine.

Our educational intervention used a brief two-sided printed informational handout and a mobile application. The informational handout included content in simple easy to understand 8th grade level of English language as is the standard when preparing consent forms in English. The mobile application MIR, which was used in our study intervention was also simple user-friendly application. The preference for material used in health communication was distributed almost equally with slightly higher preference for the printed handout. This clearly points to the need to have various types of parental educational aids available in the dental clinic as individuals tend to have diverse learning styles and preferences. A recent study collected data on patient perspectives on how physicians should communicate information on radiation risks to patients and the results suggest that there was equal preference for both oral and written information [19]. Previous studies that used multi-media educational materials for dental procedures have reported successful improvement in knowledge [21,22]. Another study reported that text-messaging was more effective than printed pamphlets when educating mothers. These methods of communicating health information should also be considered for future long-term studies.

Graphic display and visually appealing text play an important role in enhancing health communication and improving knowledge [1]. Our educational handout with information on radiation risks and benefits was colorful with visual images and tables with clear breakdown of details on radiation dosages. As a result, the parents in our study may have preferred the printed handout a little more than the mobile application for the ease of information description and availability of the handout on hand. However, almost half the population preferred the mobile application MIR which may have been for those who prefer the portability and availability of information in their personal devices.

Limitations of our study include the short follow-up time following the intervention as the post-intervention questionnaire was handed out to the parents immediately after the intervention. Parents’ knowledge of risks and benefits may be higher as a result of this short follow-up time. Future studies should consider a longer follow-up period to evaluate long term retention of knowledge. Also, in our study while we described the availability of the mobile application MIR, there is no information about whether parents who preferred the use of the app downloaded the app and whether they continued to use it. Again, a study with longer follow-up period will be able to determine the frequency of use and the long-term benefits of the mobile application.

According to the policy statement published by the American Academy of Pediatrics (AAP), in the field of medical practice, key elements in improving physician-parent-child communications are  (adapted from Levetown MaCob 2008 AAP policy statement) [24]:

  • Informativeness: Quantity and quality of health information provided by physicians.
  • Interpersonal sensitivity: Behavior of the physician that reflects his or her attention to or interest in parents’ and child’ feelings or concerns.
  • Partnership building: Extent to which the physician opens a dialogue that allows the parents or children to share their perspectives and suggestions.

These concepts can be applied in the field of dentistry as well to improve dentist-parent-child communications which in turn will improve the overall treatment and management thus resulting in improved oral and systemic health of the child. In our study we demonstrated that even a simple brief educational intervention during a child’s dental care visit can significantly improve the level of comfort and confidence among parents and caregivers. Future research can utilize our study model to design larger studies with longer follow-up and more detailed information on patient and parent background. This can lead to better understanding on parental and patient preferences and perspectives that will in turn help practitioners to design more effective health communication strategies.

Acknowledgement

The authors would like to acknowledge and thank the parents who participated in this study.

References

  1. Dauer L, Thornton R, Hay J, Balter R, et al. (2011) Fears, feelings, and facts: Interactively communicating benefits and risks of medical radiation with patients. American Journal of Roentgenology 196: 756–61.
  2. Thornton R, Dauer L, Shuk E, Bylund C, et al. (2015) Patient perspectives and preferences for communication of medical imaging risks in a cancer care setting. Radiology 275: 545–52.
  3. WHO, World Health Organization (2015) Communicating radiation risks in paediatric imaging: Information to support healthcare discussions about benefit and risk. Geneva 2016.
  4. Madan K, Baliga S, Thosar N, Rathi N (2015) Recent advances in dental radiography for pediatric patients. Journal of Medicine, Radiology, Pathology & Surgery 1: 21–5.
  5. Linton O, Mettler Jr. F (2003) National council on radiation protection and measurements. In National conference on dose reduction in CT, with an emphasis on pediatric patients. American Journal of Roentgenology 181: 321–9.
  6. White S, Scarfe W, Schulze R, Lurie A, et al. (2014) The Image Gently in Dentistry Campaign: promotion of responsible use of maxillofacial radiology in dentistry for children. Journal of Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology 118: 257–61.
  7. ADA, American Dental Association: Image Gently Alliance. [Internet]. 2007 [cited August 26, 2019]. Available from: https://www.imagegently.org/About-Us/The-Alliance.
  8. Aanenson J, Till J, Grogan H (2018) Understanding and communicating radiation dose and risk from cone beam computed tomography in dentistry. The Journal of Prosthetic Dentistry 120: 353–60.
  9. Brody A, Frush D, Huda W, Brent R (2007) Radiation risk to children from computed tomography. Pediatrics 120: 677–82.
  10. Chiri R, Awan S, Archibald S, Abbott P (2013) Parental knowledge and attitudes towards dental radiography for children. Australian Dental Journal 58: 163–9.
  11. Lee C, Haims A, Monico E, Brink J, Forman H (2004) Assessment of patient, physician, and radiologist awareness of radiation dose and possible risks. Radiology 231: 393–8.
  12. Ludwig R, Turner L (2002) Effective patient education in medical imaging: public perceptions of radiation exposure. Journal of Allied Health 31: 159–64.
  13. Purmal K, Alam M, Nambiar P (2013) Patients’ perception on dental radiographs. International Medical Journal 20: 235–8.
  14. Friedberg W, Copeland K, Duke F, O’Brien III K, Darden Jr. E (2000) Radiation exposure during air travel: guidance provided by the Federal Aviation Administration for air carrier crews. Health Physics 79: 591–5.
  15. Hwang H. Knowledge, attitude and perception on radiation imaging among children’s caregivers in pediatric dental clinic.: Boston University; 2017.
  16. Zavras J, Hwang H, Murray G, Zletni A, Shanmugham J (2018) Educational intervention to increase parental knowledge and acceptance of pediatric imaging. Journal of Pediatrics and Neonatal Care 8: 1–7.
  17. Aravind B, Joy E, Kiran M, Shrubin J, et al. Attitude and awareness of general dental practitioners toward radiation hazards and safety. Journal of Pharmacy and Bioallied Sciences. 2016;8(1):553–8.
  18. Chiri R, Awan S, Archibald S, Abbott P (2013) Parental knowledge and attitudes towards dental radiography for children. Australian Dental Journal 58: 163–9.
  19. Lumbreras B, Vilar J, Gonzalez-Alvarez I, Guilabert M, et al. (2017) Avoiding fears and promoting shared decision-making: How should physicians inform patients about radiation exposure from imaging tests? PLoS One 12: 1–14.
  20. Garcia R, Cadoret C, Henshaw M (2008) Multicultural issues in oral health. Dental Clinics of North America 52.
  21. Pei D, Liang B, Du W, Wang P, et al. (2017) Multimedia patient education to assist oral impression taking during dental treatment: A pilot study. International Journal of Medical Informatics 102: 150–5.
  22. Kazancioglu H-O, Dahhan A-S, Acar A-H (2017) How could multimedia information about dental implant surgery effects patients’ anxiety level? Medicina Oral, Patologia Oral y Cirugia Bucal 22: 102–7.
  23. Sharma R, Hebbal M, Ankola A, Murugabupathy V (2011) Mobile phone text messaging (SMS) for providing oral health education to mothers of preschool children in Belgaum city. Journal of Telemedicine and Telecare 17: 432–6.
  24. Levetown MaCoB (2008) Communicating with children and families: From everyday interactions to skill in conveying distressing information. American Association of Pediatrics 2008.

Maternal nutrition, social correlates and obstetric outcomes in northern Mymensingh, Bangladesh

DOI: 10.31038/AWHC.2019246

Abstract

National indices of maternal health have improved in Bangladesh, but no data is available from rural Mymensingh where two non-government aid agencies have been working for years. Surveys were held to inform their planning.

Methods: In November 2018, aided by a research team from Western Sydney University, Australia, anthropometric, mortality and socioeconomic data was compiled from 25 sites around Haluaghat and Dhobaura, and compared with national figures.

Results: Of 1982 mothers surveyed: 15.5% were ‘stunted’(<145 cm) vs 15.7% in Sylhet, and 13.3% in Dhaka, correlating with poverty, reduced education, and stunting of offspring. 13% were underweight (BMI <18.5 kg/m2) vs 29.8% in Sylhet and 18.2% in Dhaka. Conversely, overweight was common. Of stunted mothers 14.4% were ‘at risk’, 26.1% overweight and 4.2% obese. 29.7% consumed betel nut. Stillbirth, Perinatal, Neonatal and Child Mortality rates were very high: 89.8, 108.8, 27.45, and 61.3 respectively. 63.5% of births occurred at home with untrained assistance. 33.2% of mothers were married < 16 years, and suffered higher Neonatal and Child Mortality Rates.

Conclusion: Rates of undernutrition and child mortality are very high. The dyad of stunting and obesity portends the metabolic syndrome.

Key words

Child Mortality Rates, Dyad of Stunting and Obesity, Home Births, Maternal Health, Stunting, Underage Marriage, Underweigth

Introduction

Although the maternal mortality rate in Bangladesh declined significantly from 322 per 100,000 live births in 1998–2001 to 194 in 2007–2010, it stalled at that level in 2016, despite an increase in deliveries attended by medically trained personnel and an increase in a continuum of care from before to after the birth. The reasons for this stalling are not clear, but the Bangladesh Maternal Morbidity Survey (BMMS) regrets ‘the quality of health care is generally poor in Bangladesh’ and ‘most facilities…are not fully ready to provide quality maternity care [1].

In a similar period, however, maternal nutrition is reported to have improved. The national rate of Body Mass Indices (BMI) <18.5 fell from 34 to 19% from 2004 to 2014, though 31% of ‘ever married women age 15–19’ were ‘undernourished’ with BMI <18.5 in 2014 [2].

Bangladesh Demographic and Health Surveys (BDHS) report periodically on Maternal and Newborn Health, and on Nutrition of Children and Women. They present data from representative sites throughout Bangladesh, but these have not included the rural region in the north of Mymensingh District where, for many years, two non-government organisations, Symbiosis International and the Mennonite Central Committee, have sought to improve women’s and children’s health. To review progress and assist planning, a survey was undertaken in November 2018 of indices of maternal and child health in 25 sites in an around the region of activity of the NGOs. The aim was to capture a ‘moment in time’ of major anthropometric data, clinical and historical status and social correlates of health, and to compare the findings with national data as found in BDHS. This report will concentrate on aspects of maternal health. Other reports will concentrate on children. The surveyed sites are on flat agricultural land along the border with India, with two commercial and administrative centres: Haluaghat and Dhobaura. Local roads are of poor quality, particularly in the rainy season, and transportation of women to the main birthing centre in Joyramkura Hospital may be delayed. Rice is the staple crop and most villagers are involved in agricultural labour. Ethnicity is predominantly Bengladeshi with a Garo minority.

Methods

The surveys were organised by two non-government aid organisations, Symbiosis International and Mennonite Central Committee, with assistance of a research group of senior medical students and supervisors associated with the School of Paediatrics, Western Sydney University, Australia. In preliminary visits to the villages, the aims and the process of the surveys were explained and participation invited. Surveyors were divided into two teams, each visiting one village a day where a line of ‘booths’ were established, first, to elicit historical data from the mother on her age, age at marriage, numbers of still and live births, numbers of childhood deaths, ages of children, participation in programmes of vaccination and worming, and social correlates including mothers’ education and family income, sanitation, and water supply. Then, heights and weights of the mothers and lightly dressed children were measured, and children were examined physically. Information regarding maternal deaths was not sought. Data was recorded on paper and later transcribed into a computer for analysis.

All participants did so voluntarily. Information was encoded by numbers but a master list was kept, in confidence, in case health reasons mandated subsequent contact. Maternal stunting was defined as height <145 cm. Maternal ‘underweight’ was defined as Body Mass Index (BMI) <18.5 Kg/m2. A BMI from 18.6 and 22.9 Kg/m2 was defined as normal: from 23–24.9 as ‘at risk for overweight’; from 25–29.9 Kg/m2 as ‘overweight’ and >30 Kg/m2 as obese [3]. Maternal anthropometry was compared with data contained in Bangladesh Maternal Morbidity Surveys (BMMS) and BDHS reports. Family income was graded into four categories: Band 1 had a monthly income of <5000 Taka; Band 2 between 5001–10,000; Band 3 between 10,001–15000 and Band 4 had>15,000. (US $1 = 84 Taka) Sanitation was categorised into open and closed latrines with the former discharging untreated effluent upon surrounding ground or water.

The Stillbirth Rate (SBR) was defined as the rate of deaths in utero after 28 weeks of gestation: The Perinatal Mortality Rate (PMR) as the number of Stillbirths plus deaths in the first week of life per 1000 total births; The Neonatal Mortality Rate (NMR) as the number of deaths in the first 28 days of life per 1,000 live births:; the Infant Mortality Rate (IMR) as the number of deaths in the first year of life per 1,000 live births; the Child Mortality Rate (CMR) as the number of deaths < 5 years of age per 1000 live births. Ethnicity was denoted by the mother: Bangladeshi or Garo.

Statistics

Data was cleansed and imported into a relational database enabling cross correlating queries to be executed. WHO anthropometric factors of Height vs Age (HAZ), Weight vs Age (WAZ), Weight vs Height (WHZ) were calculated using the WHO published mathematical algorithms.[1]

Outliers were identified according to WHO statements of limits and discarded as per WHO stated process. Data was converted to Z Scores and expressed as the standard deviation (SD) from the mean of the WHO reference standard population for both male and female.[2]

Continuous unpaired data was analysed using zTest,. Count data was analysed using Chi-Squared Best Fit assuming equal proportions and trend data analysed using Chi-Squared Tend Analysis. Correlations were performed using Pearson’s correlation. In all tests sample size was > 30 and the null hypothesis rejected for results > 95% confidence, resultant P-Values are reported. We perform all comparisons against the combined male-female scores, unless otherwise stated. We used Minitab Express for all statistical analysis.

Ethics

The surveys were approved by governance of both Symbiosis International and Mennonite Central Committees as quality assurance of current programmes and preparation for future activity. Representatives of those NGOs visited the sites in advance, explained the aims and the process, and invited participation. Mothers and their children attended voluntarily. Data was de-identified for analysis but a list was kept in confidence in case of need to contact the parents eg with regard to medical concerns.

Results

In the 25 sites, 1982 mothers were interviewed and measured, and 2987 children were measured and examined.

  1. Maternal Anthropometry

    Overall, 15.4% of mothers in northern Mymensingh were ‘stunted’, with height <145 cm, similar to the rate of 15.7% in rural Sylhet, the highest in the country, and greater than the 13.3% in Dhaka [2]. The overall rate in northern Mymensingh has stalled near the national rate of 16% reported in BDHS 2004, but the rate is rising within families. Of the 15.4% of stunted mothers, the rate in their children aged from 5–14 years increased to 25.6% and in those <5 years to 36.2%.

    Maternal stunting was greatest in the lowest Income Band (18.0%) from which it remained around 13% through higher Bands. These rates are worse than reported nationally in both the lowest (16%) and highest Income Bands (9%) [2]. Maternal stunting was associated with adverse outcome in offspring. First, it was strongly associated with stunting in the offspring: 47.9% compared to 33.2% from non-stunted mothers (PValue 0.0007). This effect was significant for female children (PValue 0.0013), but weaker for male children (PValue 0.1053). Second, the <5 CMR was increased in stunted mothers (74.0 vs 57.1 per 1,000, (PValue 0.0183). The CMR was higher in stunted mothers who were also overweight and obese (130.4 vs 64.4) compared with stunted mothers who were not (PValue 0.00394).

    As well as stunting, maternal underweight was common (12.7%), though less than in rural Sylhet (29.8%) and Dhaka. (18.2%) [2]. The rate decreased with rising income. Contemporaneous with maternal underweight in northern Mymensingh is a high rate of overweight: 23.7% of women had BMI> 25 kg/m2 and 5.6% a BMI >30 kg/m2, similar to those of Chittagong (27 and 5.6%), reported as the highest in the nation [2].

    Overall, the rates of maternal underweight decreased and the rates of overweight increased through rising Income Bands. See Figure 1. In all 25 sites, there were both underweight and overweight mothers. In 16 villages, more than 20% of mothers were overweight: in six, more than 40% were overweight.

    AWHC-19-138- John S Whitehall_ Australia_f1

    Figure 1. Bar graph revealing decreasing rates of underweight and increasing rates of overweight through increasing Income Bands.

    Many stunted mothers were overweight: though 12.9% were also underweight and 42.4% were appropriately weighted, 14.4% are ‘at risk’ of overweight, 26.1% were overweight and 4.2% obese Figure 2.

    AWHC-19-138- John S Whitehall_ Australia_f2

    Figure 2. Bar graph revealing high rate of association between stunting and overweight.

  2. Mothers’ fertility and income: The numbers of live births fell progressively through the income bands, from a mean of 2.63 per mother in the lowest to 1.97 in the highest.
  3. Child Mortality rates: The mothers reported 435 still and 4408 live births, of whom 275 children had died: 93 in the first week of life, 122 within the first month, giving an SBR of 89.8, a PMR of 109.0, an NMR of 27.7, and an <5 CMR of 62.4. The SBR in northern Mymensingh is almost four times higher than the national rate (89.8 vs 20.4) [4]4, and over twice that of the hitherto highest, Sylhet, (89.8 vs 36.3) [5]. PMR is over twice the national rate (109.0 vs 44), while NMR (27.7 vs 28) is comparable, and CMR is much higher (62.4 vs 46) [2].
  4. Site of birth: 63.2% of surveyed births occurred at home, revealing no improvement from the national rate of 63% reported in 2014 [2]. Overall, 56.3% occurred under the care of a family member or traditional birth attendant. Attendance by a ‘professional’ increased through the income bands from 37% in the lowest to 72% in the highest.

Breast Feeding

Overall, 96.9% of mothers initiated breastfeeding immediately after birth. Of those who did not, 47.8% were clustered in 3 of the poorest sites. The offspring of the mothers who did not breast feed immediately after birth were significantly more stunted (p-value 0.0304). Across all incomes, 14.1% of mothers breast fed for < 6 months, or not at all. Overall, 81% of mothers in the higher income Bands ceased feeding in the sixth or seventh month, compared with 11% in the lowest income Band. Most notably, 51% of mothers in Band 1 continued to feed beyond 12 months, with a large proportion (32%) continuing beyond 2 years. This conflicts sharply with the length of breastfeeding in all higher Bands in which only 6% continued beyond 1 year, and 3% beyond 2 years. In all income bands, the rate of breastfeeding was higher in Garo mothers (p-value 0.0001). Children in Income Band 1 who were breast fed for longer than 6 months were more stunted (PValue 0.0048) than those who were not. This association between prolonged breast feeding and stunting was not, however, observed in higher Income Bands.

Latrines

44.6% of families used an ‘open latrine’ compared with the national rate of 36%2. Their use was strongly associated with the lowest Income Band, and thus correlated with stunting of both mothers and children. Controlling for income within that Band, the rate of childhood stunting was much greater in families with open rather than sanitary latrines (40.8 vs 27%. P Value 0.0227). The effect was not seen in Band 2 and the number of open latrines sampled in Band 3 and 4 was too low for meaningful analysis.

Underage marriage of females

The mean reported age of marriage was 17.92 (SDev 3.48, n 1816). Overall, 42.5% were married <18 years, with 33.2% at or below 16 years, of whom 38.0% were Bangladeshi compared with 9.5% Garo. Bangladeshi youths are 3.98 times more likely to be married < 16 years than Garos. The youngest bride was 7. The percentage of child brides differed markedly by village, from 79% to 23%, with prevalence inversely correlating with household income (Pearson’s correlation = -0.17017, PValue <0.0001). Though BDHS 2014 reported 71% of girls were married <18 years, it claimed a substantial, and accelerating decrease in underage marriage in recent years. Our overall rate of 42.5%, together with a mean age of 17.92 and median of 18 years, might reflect that decline, but our data is skewed to a younger age, with an exceptional, outlying rate at exactly 18 years which may be misleading. See Figure 3.

AWHC-19-138- John S Whitehall_ Australia_f3

Figure 3. Histogram of ages of marriage, revealing a curve skewed to the left and a marked outlier at 18 years.

Overall, the proportion of younger age marriage was higher in families with the lowest income but, even within the income Bands, underage marriage was associated with specific disadvantage. Girls married at or before 16 years were 4.42 times less likely to obtain a basic education defined as Year 10 school certificate (10.33% vs 43.65% of their cohort, Chi Squared 202.46, PValue < 0.0001). They are 5.12 times less likely to obtain a Year 12 Higher School Certificate (2.2% vs 11.2% of their cohort, Chi Squared 42.282, PValue < 0.0001), and 16.3 times less likely to obtain a bachelor’s degree (0.7% vs 10.9% of their cohort, (Chi Squared 60.279, PValue <0.0001). Expressed differently, when controlled for income, for every 8.15 brides in the poorest income Band who obtains at least a basic school certificate, only 1 will have been married at or before 16 years.

Girls married at or under 16 years experienced higher rates of reproductive adversity: CMR was 1.4 times (78.2 vs 54.8, PValue 0.0008), and NMR 1.7 times higher (23.7 vs 13.7, PValue 0.0002) than those with older mothers. Offspring of under-aged mothers in income Band 1 were more frequently stunted (44.8% PValue 0.0204) than children of older brides in the same Band (34.9%) (PValue 0.0204). This effect was not seen in higher Bands.

Betel nut

28.6% of mothers declared they chewed betel nut during pregnancy. Consumption was more common in the lowest income group (37.7%), falling progressively to 1% in the highest.

Discussion

Compared to national data published by BDHS many aspects of maternal health have stalled in rural northern Mymensingh District. Our survey did not examine rates of maternal mortality but maternal stunting, underweight, overweight, home births, reproductive adversity, and underage marriage rival the highest in the country. The burden of maternal adversity is thus a major challenge in the region. The rate of maternal stunting in northern Mymensingh (mean of 15.4%) rivals that reported from Sylhet (15.7%), the highest recorded in BDHS 2014. Maternal stunting is a recognised risk factor for foetal growth restriction and adverse perinatal outcome [6] and for increased morbidity, mortality, underweight and stunting in offspring [7]. Foetal growth restriction is also known to predispose to the metabolic syndrome in adulthood, particularly when food intake is enhanced. Childhood stunting increases mortality rates in children and reduces their human capital and, thus, their ultimate contribution to national development. Maternal undernutrition confirmed by BMI <18.5 has similar adverse effects as stunting6 and was common in surveyed areas, but not as common as reported from rural Sylhet (13 vs 29.8%), though stunting rates are similar [2].

Our contemporaneous rates of overweight are remarkably high: with 14.4% of mothers at risk, 26.1% overweight and 4.2% obese, nearly half the female population is affected. Though ‘at risk’ pertains to BMI as low as 23 kg/m2, Asian populations have been reported susceptible to the development of cardiovascular disease and diabetes from that level, perhaps because of a higher percentage of body fat [3]. This propensity to being overweight may explain the lower rates of underweight between Mymensingh and Sylhet, despite similar rates of stunting. Thus, the higher rates of BMI (dependent on weight vs height) in Mymensingh confirm the unreliability of BMI as an index of healthy nutrition, especially in Asian populations [3]. Being overweight is associated with obstetric adversity [8] but the dyad of stunting and obesity compounds problems. Described as ‘The new obstetrical dilemma’ [9], the risk of cephalo-pelvic disproportion is increased when a small pelvis is presented with a macrosomic baby in a stunted but obese mother. Also described as a ‘double burden’ of malnutrition, the dyad is being recognised with increasing frequency in many developing countries, but causes remain debated [10–12]. Perhaps it is related to increasing wealth and, therefore, family consumption of high-density caloric foods which fatten the stunted mother but do not promote linear growth in the offspring. ‘Food consumption’ by itself, however, was not found to account for higher obesity in a poor region of Brazil [13]: reduction in urbanised maternal activity was considered contributory. Given the overlap of the high prevalence of both stunting and obesity, its correlation has even been dismissed as a statistical artefact, not a distinct entity [14].

Whatever the association, given the predisposition of stunting with overweight to the metabolic syndrome according to the Barker Hypothesis, increasing problems of cardiovascular disease and diabetes may be expected in northern Mymensingh. At present, however, only 10 cases of gestational diabetes and 15 cases of hypertension were associated with the 2532 births in 2018 in Joyramkura Hospital [15]. Doubtless, in-utero growth restriction contributed to the high rate of stunting but birth weights were unknown to most mothers in our survey. The 9% rate of babies born <2,500 gm in the private Joyramkura Hospital is much less than the national rate of 20% [16], and may reflect difficulty in attendance by the poorest, undernourished and stunted mothers.

Perinatal death rates appear to result from the lethal combination of vulnerable mothers undergoing home births with untrained attendants. The high rate of children living with cerebral palsy (11.8 per 1000 live births) found in the 25 sites (and reported elsewhere) [17] would confirm problems in labour and neonatal care. The high CMR probably reflects their later deaths. Childhood stunting was associated with prolonged breast feeding, especially in low income households, and appears associated with failure of diversification of diet from six months of age (personal communication). Further research is being undertaken but breast milk and unpolished rice appear fundamental. That the prevalence of stunting increased from mother to older and then younger child is hard to explain. There have been no financial or natural disasters in the region that could account for such a dramatic increase in childhood under-nutrition. Perhaps the prevalence of maternal obesity is related to the phenomenon: mothers are now consuming new foods whose density of calories causes them to gain weight, but whose sparsity of protein prevents linear growth in offspring. Perhaps, this diet explains the increased CMR in children of stunted and overweight mothers, whose stillbirth rate is not significantly increased.

Open latrines predispose to recurrent intestinal infection and infestation, and malabsorptive enteropathy. Our survey revealed childhood stunting to be related to their use in the poorest income Band. That many mothers will have grown up in those sites suggests open latrines contribute to inter-generational stunting. Marriage before the age of 18 is often considered a breach of human rights [18]18 but is common in many developing countries [19] especially in Asia [20,21], Its risks are publicised: mental, sexual and reproductive problems, violence, reduced education and sustained poverty [22]; as well as a higher risk of stunting, developmental delay18 and mortality in offspring [23]. Socio-cultural and financial factors are reported causative [24]. Our study did not pursue such factors, but noted the frequency of under-age marriage in northern Mymensingh and its association with poverty, reduced education and reproductive adversity. We relied on maternal reporting for age of marriage and did not distinguish between betrothal and co-habitation.

The actual rate is likely to be much greater than suggested by our survey. The great outlier of professed marriage at 18 years may suggest an awareness of its illegality at a younger age. Alternatively, girls could be waiting to be married at 18, but if that were case, there would be fewer marriages at 16 and 17 years, contrary to the expected distribution as revealed in Figure 3. Education programmes fostering female empowerment are claimed effective in reducing child marriage [25]. Consumption of ‘betel nuts’ ranks fourth in the world’s consumption of addictive substances, after alcohol, tobacco and caffeine [26]. Our survey revealed 29% of mothers, particularly the poorest, consumed it in pregnancy. The seeds of the Areca palm (Arecha catechu) are consumed in a ‘quid’ with tobacco leaf, to which calcium hydroxide has been added to promote extraction of alkaloids. Effects on the autonomic system as well as endothelial cell growth in the placenta [27] may contribute to intra-uterine growth restriction [28–30].

Our study cross sectional study has limitations. The birth dates, weights and gestations were rarely recorded in home births. As warned in BDHS 2014, memory of ages and causes of death, even of stillbirths themselves, dims with passing years in retrospective, cross sectional studies. Lack of memory predisposes to the next problem in data collection: the ‘heaping up’ of estimates to intervals of significance eg to one year of age. Third, information was gathered by several translators without calibration of skill. Our study reveals the need for further investigation. ‘Verbal’ post-mortems should probe the high rates of death. Practical issues need to be examined: how can traditional birth attendants be educated to recognise complications in the mother and care for the baby. What transportation is possible for a mother in difficulty? What obstetric facilities are available? Why is a population of over half a million not seeking help in the regional centres of Dhobaura and Haluaghat? In 2018, together, those hospitals reported 809 deliveries, 788 live births, 21 stillbirths and 62 neonatal deaths, with no Caesarian sections [31].

Conclusion

Our broad brush, cross-sectional survey reveals, for the first time, major problems in mothers’ health in northern Mymensigh. It emphasises the need for education on nutrition, early recognition of obstetric complications, neonatal care, disposal of sewage, betel nut consumption, under-age marriage and empowerment of women. It emphasises the need for improved obstetric care: from more and better trained attendants, to adequate transportation, to the ability to intervene when things go wrong. The scarcity of Caesarian sections in the regional government hospitals substantiates the introductory lament of BMMS that ‘most facilities…are not fully ready to provide quality maternity care’.

References

  1. Ahsan KZ, Ahmed S, Angeles G, Benson A, Chakraborty N, et al. (2017) (National Institute of Population Research and Training, International Centre for Diarrhoeal Disease Research, Bangladesh, MEASURE Evaluation). Bangladesh maternal mortality and health care survey 2016. Preliminary report. Dhaka (BD): Government of the People’s Republic of Bangladesh; 106 p. Report No.: TR-17–218.
  2. Ministry of Health and Family Welfare (2016) National Institute of Population Research and Training; Mitra and Associates; ICF International, DHS Program. Bangladesh demographic and health survey 2014. Dhaka (BD): Ministry of Health and Family Welfare, National Institute of Population Research and Training, Pg No: 328.
  3. WHO Expert Consultation (2004) Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 363: 157–163.
  4. Halim A, Aminu M, Dewez JE, Biswas A, et al. (2018) Stillbirth surveillance and review in rural districts in Bangladesh. BMC Pregnancy Childbirth 18: 224. [crossref]
  5. Baqui AH, Choi Y, Williams EK, Arifeen SE, Mannan I, et al. (2011) Levels, timing, and etiology of stillbirths in Sylhet district of Bangladesh. BMC Pregnancy Childbirth 11: 25. [crossref]
  6. Black RE, Victora CG, Walker SP, Bhutta ZA, Christian P, et al. (2013) Maternal and child undernutrition and overweight in low-income and middle-income countries. Lancet 382: 427–451.
  7. Ozaltin E, Hill K, Subramanian SV (2010) Association of maternal stature with offspring mortality, underweight, and stunting in low- to middle-income countries. JAMA 303: 1507–1516.
  8. Black M, Bhattacharya S (2013) Maternal Obesity and the Risk of Stillbirth. In: Mahmood T, Arulkumaran S, (eds). Obesity. Oxford: Elsevier; Pg No: 371–382.
  9. Wells JC (2017) The New “Obstetrical Dilemma”: Stunting, Obesity and the Risk of Obstructed Labour. Anat Rec (Hoboken) 300: 716–731.
  10. Jehn M, Brewis A (2009) Paradoxical malnutrition in mother-child pairs: untangling the phenomenon of over- and under-nutrition in underdeveloped economies. Econ Hum Biol 7: 28–35.
  11. Lee J, Houser RF, Must A, de Fulladolsa PP, Bermudez OI (2010) Disentangling nutritional factors and household characteristics related to child stunting and maternal overweight in Guatemala. Econ Hum Biol 8: 188–196. [crossref]
  12. Lee J, Houser RF, Must A, de Fulladolsa PP, Bermudez OI (2012) Socioeconomic disparities and the familial coexistence of child stunting and maternal overweight in Guatemala. Econ Hum Biol 10: 232–241. [crossref]
  13. Florêncio TT, Ferreira HS, Cavalcante JC, Luciano SM, Sawaya AL (2003) Food consumed does not account for the higher prevalence of obesity among stunted adults in a very-low-income population in the Northeast of Brazil (Maceió, Alagoas). Eur J Clin Nutr 57: 1437–1446. [crossref]
  14. Dieffenbach S, Stein AD (2012) Stunted child/overweight mother pairs represent a statistical artifact, not a distinct entity. J Nutr 142: 771–773.
  15. Samper-González J, Burgos N, Bottani S, Fontanella S, Lu P, et al. (2018) Reproducible evaluation of classification methods in Alzheimer’s disease: Framework and application to MRI and PET data. Neuroimage 183: 504–521. [crossref]
  16. Khan JR, Islam MM, Awan N, Muurlink O (2018) Analysis of low birth weight and its co-variants in Bangladesh based on a sub-sample from nationally representative survey. BMC Pediatr 18: 100.
  17. Authors (2019) Child mortality, nutrition and cerebral palsy: a cross sectional survey in northern Bangladesh. Nutrients 2019.
  18. Efevbera Y, Bhabha J, Farmer PE, Fink G (2017) Girl child marriage as a risk factor for early childhood development and stunting. Soc Sci Med 185: 91–101. [crossref]
  19. Nour NM (2009) Child marriage: a silent health and human rights issue. Rev Obstet Gynecol 2: 51–56. [crossref]
  20. Raj A (2010) When the mother is a child: the impact of child marriage on the health and human rights of girls. Arch Dis Child 95: 931–935. [crossref]
  21. UNICEF (2011) Working towards a common goal: ending child marriage [Internet]. [2019 Jun 6]. Available from: https://www.unicefusa.org/stories/working-towards-common-goal-ending-child-marriage/7086.
  22. Parsons J, Edmeades J, Kes A, Petroni S, Sexton M, et al. (2015) Economic impacts of child marriage: A review of the literature. The Review of Faith & International Affairs 13: 12–22.
  23. Adhikari R (2003) Early marriage and childbearing: risks and consequences. In: Bott S, Jejeebhoy S, Shah I, Puriet C, editors. Towards adulthood: Exploring the sexual and reproductive health of adolescents in South Asia; 2000; Mumbai, India. Geneva: World Health Organization Pg No: 62–66.
  24. Chowdhury FD (2014) The socio-cultural context of child marriage in a Bangladeshi village. Int J Soc Welf 13: 244–253.
  25. Lee-Rife S, Malhotra A, Warner A, Glinski AM (2012) What works to prevent child marriage: a review of the evidence. Stud Fam Plann 43: 287–303. [crossref]
  26. Gupta PC, Ray CS (2004) Epidemiology of betel quid usage. Ann Acad Med Singapore 33: 31–36. [crossref]
  27. Kuo FC, Wu DC, Yuan SS, Hsiao KM, Wang YY, et al. (2005) Effects of arecoline in relaxing human umbilical vessels and inhibiting endothelial cell growth. J Perinat Med 33: 399–405. [crossref]
  28. Garcia-Algar O, Vall O, Alameda F, Puig C, Pellegrini M, et al. (2005) Prenatal exposure to arecoline (areca nut alkaloid) and birth outcomes. Arch Dis Child Fetal Neonatal Ed 90: 276–277.
  29. Senn M, Baiwog F, Winmai J, Mueller I, Rogerson S, et al. (2009) Betel nut chewing during pregnancy, Madang province, Papua New Guinea. Drug Alcohol Depend 105: 126–131.
  30. Yang MS, Lee CH, Chang SJ, Chung TC, Tsai EM, et al. (2008) The effect of maternal betel quid exposure during pregnancy on adverse birth outcomes among aborigines in Taiwan. Drug Alcohol Depend 95:134–139.
  31. Government of the People’s Republic of Bangladesh, Ministry of Health and Family Welfare. Dhubaura Upazila Health Complex Health Bulletin 2015 [Internet]. [Mohakhali, Dhaka]: Government of the People’s Republic of Bangladesh, Ministry of Health and Family Welfare; 2015 [cited 2019 Jun 6].

[1] de Onis M, et al. (2012) Worldwide implementation of the WHO Child Growth Standards. Public Health Nutrition 15: 1603–1610.

[2] de Onis M (2006) Reliability of anthropometric measurements in the WHO Multicentre Growth Reference Study. Acta Pædiatrica 95: 8–46.

Making Smiles in the Community

DOI: 10.31038/JDMR.2019231

 

The Riser School Based Dental Hygiene Clinic was started in March 2006 with a grant from the Kellogg Foundation in association with the Glenwood School Based Health Clinic and the University of Louisiana at Monroe Dental Hygiene Program on the campus of Riser Elementary and Middle Schools in West Monroe, Louisiana. Initial funding paid for the renovation of a school building and purchasing of equipment and supplies. There are three dental hygiene operatories and one x-ray operatory with a panorex machine located at the Riser School Based Dental clinic. Since 2009, the Living Well Foundation has awarded the necessary funds for project supplies and supervision to operate the Riser School Based Dental Clinic.  Riser school is located in an underserved area in the West Monroe community. Above 80% of the students at Riser School are eligible for Medicaid and the free or reduced lunch program.  The fall semester of 2019 will signify the beginning of University of Louisiana of Monroe’s 13th year on the Riser campus. Approximately 30 ULM Dental Hygiene students, supervised by a licensed dental hygienist, provide preventive oral health services the equivalent of 2 days a week throughout the academic year.  In the past thirteen years, there have been more that 3000 dental visits at the Riser SBDHC to children ages 4-16 years old.  Services provided are: x-rays, fluoride treatments, prophylaxis, sealants, nutritional counseling, and oral health education.  Each student leaves with a goody bag filled with a toothbrush, toothpaste, floss, and a prize they get to pick out of the treasure chest.  For some students this is the first toothbrush they have received for their own personal use. Many times they ask for extras for their siblings or parents.

A visit to our clinic is an opportunity to change patients’ views of dentistry.  So many have had bad experiences because of decay and disease in their mouths that the only time they go to the dentist is when something hurts. Provision of these services meets a significant need as access to routine healthcare is limited for most of these children who may not understand the importance of good oral hygiene.   In addition to seeing patients in the clinic, the ULM Dental Hygiene students go into the classrooms and conduct oral health education. Our goal is to provide a positive environment focusing on the patient individually, satisfying their oral health needs and showing them how to prevent dental diseases. Provision of these services at Riser school has several benefits: underserved children receive clinical and educational services; oral health awareness is created for the entire family; and dental hygiene students receive valuable clinical experience.

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Public Health Responding to the Epidemic of Alzheimers Disease

DOI: 10.31038/ASMHS.2019334

 

In the course of my career I’ve written frequently about the needs of caregivers of people with dementia and the urgency for public health to address their health and stress issues to avoid a human and health crisis in our culture. Recent publications by the Centers for Disease Control and the Alzheimers Association highlight that these issues are even more critical [1,2]. The stress of caring for a vulnerable person with dementia, or other person with special needs is a major risk factor for developing numerous physical and emotional chronic conditions.

Let’s be clear, we’re experiencing an aging population trend and commensurate increase in age related conditions. Chief among these are the various forms of dementia that constitute the epidemic I reference above. Alzheimers disease is the most common form of dementia, and we now recognize it often appears along with other forms of dementia and related conditions. During the course of these diseases one aspect we humans lose is independence, this leads to the necessity of persons to care for those with dementia for their health, well-being and everyday needs. Much has been written about the empathy of these people; sometimes referring to them as “angels”, what I want to focus on today is the very real risk to their health and mental health that comes with the role of caregiver. The nature of this role often leads to risky health behaviors such as sedentary lifestyle, poor nutrition, social isolation, and overuse and abuse of substances such as alcohol or prescription drugs. Additionally, economic strain frequently occurs with the all too common absenteeism or presenteeism at/from work, additional costs related to obtaining healthcare for the patient with dementia, and selfless acts of putting the patient before the caregiver’s own needs. These stresses can also complicate otherwise strained relationships and result in increasing risks to health and mental health.

This important public health issue cuts both ways. First the person with needs who requires care is at risk, and second the role of caregiver causes risk as well. Given that this phenomenon relates to millions of Americans alone, the impact around the globe is multiples of the recently published data. In the US health and well-being of informal caregivers is in many ways the backbone of the system of long-term care. This includes the healthcare system and what serves as the system of long-term care services and supports. The everyday needs of those requiring care become dependent on a population at high risk of chronic conditions both physical and emotional [3].

Recent CDC data highlight that over 40% of caregivers report having two or more chronic diseases; 14.5% of caregivers report experiencing 14 or more mentally unhealthy days in the last month; and 36.7% report getting insufficient sleep. Given that these are self-reported statistics, arguably the actual numbers may be higher [1]. As I have frequently stated in the past [4–7], those of us in caring professions have a moral and ethical responsibility to find ways to support these hardworking caregivers and policy-makers must act on their responsibility to create policies and systems that enable caregivers to perform their duties without compromising their own health and economic well-being.

We know that caregivers with knowledge, access to support systems, ability to engage socially, and resources to make healthy choices live healthier and more fulfilling lives. They are also more likely to have the energy to continue caring for their vulnerable loved one, manage other family responsibilities (i.e., sandwich generation members — those caring for children and an aging parent), and maintain their occupation, thus limiting collateral impacts across families and communities.

One key element to ensuring that a caregiver has the information and access to support is an actively engaged health care provider — either the caregiver’s health care provider or the provider for the person receiving care. It should be both, but either should take some responsibility as a preventive measure. Today some practical suggestions for consideration include:

  1. In clinical and human service encounters we have a professional responsibility to tune in to the well-being of people who are caregivers. This tuning in can and should happen both informally (“So how are you doing today?”) and formally (“Let’s check your vital signs while you are here.”). These vital signs should include assessing the caregiver’s sleep, nutrition, physical activity, work/life balance, use of alcohol, and access to support services, including respite.
  2. Assessing knowledge and coping skills to reduce caregiving burden on multiple fronts. In the case of progressive disease like dementia, for instance, we can assess whether there is a plan for how to manage the increasing physical demands of that role.
  3. Plain language resources on respite and other resources should be repetitively available (in healthcare offices, social service settings, religious communities).
  4. Tips for caregivers should be similarly available (how to communicate, coping with common challenges such as hearing loss and limited mobility. Tips on managing common costs and available discounts and supports (for phone, cable, trash removal, food delivery).
  5. Expand proven strategies such as the New York State program referenced below and Naturally Occurring Retirement Communities that can provide formal and informal supports – and the key service of having multiple sources of “checking in” to reduce the feeling of isolation [4].

These are just a few suggestions, the critical issue today is the need for action on this challenge, especially where other additional challenges are present. In previous articles there have been many calls for action on these questions [6], including a call for a national plan. Today my call is for a systemic approach to address the health of vulnerable members of society who require care and the integral informal caregivers who attempt to address these needs in every community across the country. In my former role, with support of advocates like the Alzheimers Association and key policymakers, New York State invested significantly in both Centers of Excellence to educate professionals and provide high quality clinical services across the state and various Caregiver Support Programs strategically located to be accessible statewide. This program was built because using data like that from CDC referenced below, we were able to show that early diagnosis, aggressive quality clinical care and an array of proven caregiver support activities in addition to being lifesaving to patients and caregivers could also be cost effective. I recognize this doesn’t solve all the issues raised here, but this huge step forward can provide lessons for nations, states and other jurisdictions. Evaluation data on the program prepared by NYSDOH with a team at the Albany School of Public Health led by Dr. Mary Gallant can be reached at: https://www.health.ny.gov/health_care/medicaid/redesign/mrt_8004.htm

A new set of materials and data I reference above from the Centers for Disease Control and Prevention related to Alzheimer’s disease, including background information as well as additional suggested action steps for a variety of audiences can be found here:

References

  1. https://www.cdc.gov/aging/caregiving/caregiver-brief.html
  2. Alzheimer’s Association (2019) Alzheimer’s Disease Facts and Figures. Alzheimers Dement 2019 15: 321–387.
  3. Hoffman D, Zucker H (2016) A Call to Preventive Action by Health Care Providers and Policy Makers to Support Caregivers. Prev Chronic Dis 13: 160233. [crossref]
  4. Masotti PJ, Fick R, Johnson-Masotti A, MacLeod S (2006) Healthy Naturally Occurring Retirement Communities: A Low-Cost Approach to Facilitating Healthy Aging.  Am J Public Health 96: 1164–1170. [crossref]
  5. Hoffman D (2014) Alzheimers Disease Legislation and Policy, Now and in the Future. Health Aff (Millwood) 3: 561–565. [crossref]
  6. Khachaturian AS, Hoffman DP, Frank L, Petersen R, Carson BR, et al. (2017) Zeroing out preventable disability: Daring to dream the impossible dream for dementia care: Recommendations for a national plan to advance dementia care and maximize functioning. Alzheimer’s Dement 13: 1077–1080. [crossref]
  7. Hoffman D (2015) Looking at The Future of Alzheimers Disease Policy. Health Affairs Health Policy Lab JULY 14, 2015.10.1377/hblog20150714.049333

Is there a Role for Complementary Medicine in the Management of Patients with Breast Cancer?

DOI: 10.31038/IGOJ.2019236

Editorial

Breast cancer is the most frequent cancer among women and one of the three most common cancers worldwide, along with lung and colon cancer [1]. The survival of patients with breast cancer has increased in recent years due to earlier diagnosis and also due to advances in the treatment of this common disease [2]. However, half of million patients die each year from breast cancer, highlighting the need for further improvements in the management of these patients [3]. Moreover, survivors of breast cancer often exhibit poor quality of life as a result of the complications of treatment [4].

In this context, complementary medicine might be a useful option is selected patients with breast cancer as an addition to the established treatment options. Complementary medicine includes 5 major categories of treatment: a) traditional medical practices, such as whole medical systems, b) mind-body interventions, c) biological substance–based practices, d) manipulative and body-based practices, and e) energy medicine [5]. Several preclinical studies showed that various herbs used in complementary medicine, including turmeric and black cumin, inhibit breast cancer cell proliferation and induce apoptosis [6, 7]. A number of traditional Chinese medications, including Xihuang, shikonin and bakuchiol, also showed anticancer potential in in vitro studies [8, 9]. However, there are no clinical studies that evaluated the safety and efficacy of these traditional herbs and medications in patients with breast cancer.

Complementary medicine might also have a role in the management of complications of breast cancer treatment. In a randomized, controlled study in 30 patients with breast cancer-related chronic lymphedema, warm acupuncture improved lymphedema, range of motion and quality of life more than placebo treatment and had no adverse effects [10]. In another uncontrolled, pilot study (n = 9), Saam acupuncture, a Korean variation of acupuncture, also improved lymphedema [11]. In a meta-analysis of 9 randomized controlled trials (n = 322), tai chi improved handgrip strength and elbow mobility in patients with breast cancer but had no effect on pain, physical, social or emotional well-being or on general health-related quality of life [12]. In another meta-analysis of 13 studies (n = 606), arts therapy, including music therapy interventions, various types of art therapy, and dance/movement therapies, improved anxiety but had no effect on depression or quality of life in patients with breast cancer [13]. Several studies also showed that yoga improves anxiety, depression, perceived stress, psychological distress, fatigue, functional, social and spiritual well-being as well as global health-related quality of life in this population [14, 15].

In conclusion, complementary medicine appears to be useful for the improvement of well-being in patients with breast cancer. In addition, preclinical data suggest that several traditional herbs might exert antiproliferative and proapoptotic effects on breast cancer cells. However, randomized clinical trials are needed to establish the safety and efficacy of these herbs.

References

  1. Ferlay J, Soerjomataram I, Dikshit R, et al. (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 36: 359–86.
  2. Malvezzi M, Carioli G, Bertuccio P, et al (2016) European cancer mortality predictions for the year 2016 with focus on leukemias. Ann Oncol 27: 725–31.
  3. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2012) Global cancer statistics, 2012. CA Cancer J Clin 65: 87–108.
  4. Edward KL, Chipman M, Giandinoto JA, Robinson K (2019) Quality of life and personal resilience in the first two years after breast cancer diagnosis: systematic integrative review. Br J Nurs 28: S4-S14.
  5. Saquib J, Madlensky L, Kealey S, et al (2011) Classification of CAM use and its correlates in patients with early-stage breast cancer. Integr Cancer Ther 10: 138–47.
  6. Sun XD, Liu XE, Huang DS (2012) Curcumin induces apoptosis of triple-negative breast cancer cells by inhibition of EGFR expression. Mol Med Rep 6: 1267–70.
  7. Sutton KM, Doucette CD, Hoskin DW (2012) NADPH quinone oxidoreductase 1 mediates breast cancer cell resistance to thymoquinone-induced apoptosis. Biochem Biophys Res Commun 426: 421–6.
  8. Zheng W, Han S, Jiang S, et al (2016) Multiple effects of Xihuang pill aqueous extract on the Hs578T triple-negative breast cancer cell line. Biomed Rep 5: 559–66.
  9. Li L, Chen X, Liu CC, Lee LS, Man C, Cheng SH (2016) Phytoestrogen bakuchiol exhibits in vitro and in vivo anti-breast cancer effects by inducing S phase arrest and apoptosis. Front Pharmacol 7: 128.
  10. Yao C, Xu Y, Chen L, et al (2016) Effects of warm acupuncture on breast cancer-related chronic lymphedema: a randomized controlled trial. Curr Oncol 23: 27–34.
  11. Jeong YJ, Kwon HJ, Park YS, Kwon OC, Shin IH, et al (2015) Treatment of lymphedema with Saam acupuncture in patients with breast cancer: a pilot study. Med Acupunct 27: 206–15.
  12. Pan Y, Yang K, Shi X, Liang H, Zhang F, Lv Q. Tai chi chuan exercise for patients with breast cancer: a systematic review and meta-analysis. Evid Based Complement Alternat Med 2015: 535237.
  13. Boehm K, Cramer H, Staroszynski T, Ostermann T (2014) Arts therapies for anxiety, depression, and quality of life in breast cancer patients: a systematic review and meta-analysis. Evid Based Complement Alternat Med 2014: 103297.
  14. Cramer H, Lange S, Klose P, Paul A, Dobos G. Can yoga improve fatigue in breast cancer patients? A systematic review. Acta Oncol 51: 559–60.
  15. Cramer H, Lange S, Klose P, Paul A, Dobos G (2012) Yoga for breast cancer patients and survivors: a systematic review and meta-analysis. BMC Cancer 12:412.

Impact on Bones and Joint during Pregnancy and Breastfeeding: A Short Note

DOI: 10.31038/IGOJ.2019235

Short Commentary

Bone is the name given to hard extremely dense connective tissue that forms the human skeleton. Individual bones may be classed as long, short, flat or irregular. Bones not only form the skeleton but also act as stores for mineral salts and play an important part in the formation of blood cells. Haematopoiesis is the process of production of blood cells and platelets which continues throughout life, replacing aged cells (which are removed from the circulation). In healthy adults, haematopoiesis is confined to the bone marrow, but in embryonic life and in early infancy, as well as in certain diseases, it may occur in other sites (extramedullary haematopoiesis). Joint is the point when two or more bones are connected. The opposing surfaces of bone are lined with cartilaginous fibrous or soft (synovial) tissue. The three main classes of joint are diarthrosis (freely movable), amphiarthrosis (slightly movable) and synarthrosis (unmovable). Between the causes that can damage the bones and joints are: (i) pregnancy; and (ii) breastfeeding. Here, our objective is: 1- summarized (presents) those causes and their effects based on publications that we consider relevant, for divulgation of the impact on bones and joints during pregnancy and breastfeeding, for physicians and other health personnel to bear in mind this when assisting mothers of babies and infants.

In [1] the authors have” identified 35 women who have developed osteoporosis during or shortly after pregnancy and in only six of them could a recognized underlying cause be suggested. These findings would suggest that idiopathic osteoporosis associated with pregnancy may be more common than the current literature suggests”.

In [2] the authors suggest “that calcium needed for fetal skeletal growth during pregnancy was gained from maternal trabecular and cortical sites and that calcium needed for infant growth during lactation was drawn mainly from the maternal trabecular skeleton in our patients. The effect of pregnancy and lactation on the maternal bone mass was spontaneously compensated after weaning”.

In [3], the authors, in their investigation, have “evaluated (1997–1999) a total of 193 Mexican women, in the first, second and third trimesters of pregnancy, to test the hypothesis that maternal bone lead burden is associated with increasing maternal whole blood and plasma lead levels over the course of pregnancy and that this association is modified by rates of maternal bone resorption.

The results confirm previous evidence that bone resorption increases during pregnancy, with consequential significant release of lead fromda bone, constituting an endogenous source of prenatal exposure”.

In [4], it is indicated -1- in pregnancy and bone health, that: (i) “pregnant women absorb calcium from food and supplements better than women who are not pregnant. This is especially true  during the last half of pregnancy, when the baby is growing quickly and had the greatest need for calcium”; (ii) “during pregnancy, women produce more estrogen, a hormone that protects bones; (iii) “any bone mass lost during pregnancy is typically restored within several months after the baby’s delivery (or several months after breastfeeding has stopped); -2- in breastfeeding and bone health, that: “studies have shown that women often lose 3 to 5 percent of their bone mass during breastfeeding, although they recover it rapidly after weaning. This bone loss may be caused by the growing baby’s increased need for calcium, which is drawn from the mother’s bones. Women also may lose bone mass during breastfeeding because they are producing less estrogen, which is the hormone that protects bones”.

In [5], we have, in our opinion, an excellent revision on “the influence of pregnancy and lactation on maternal bone health” where are considered several topics including each one of them a conclusion. Here, we indicate the title of some of these topics and respective conclusions: (i) – Bone metabolism during pregnancy and lactation – high calcium demand and estrogen deficiency stimulate bone metabolism during pregnancy and lactation; (ii) – Pregnancy, lactation and bone – because of a potent correlation between lactation and pregnancy, both are considered as a combined risk factor; (iii) –Parity and bone – several investigations showed log-term supportive effect of parity on bone. For example, it was observed less bone mineral density decrement in multiparous women compared with primiparous; (iv) – Lactation and bone – bone metabolism is higher in lactating mothers with longer period of breastfeeding than that of non-lactating mothers [6]; “it is hypothesized that after discontinuing breast feeding bone resorption returns to normal while bone formation continues [7]; (v) – Pregnancy, lactation and risk of fracture – “bone loss predisposes patients to bone fractures which may cause disabilities, and work loss and imposes high cost to the society [5].

In conclusion, we are in agreement with authors [5]:” it seems that pregnancy itself may lead to bone loss but if followed by lactation, it will have a protective effect on bone density while the duration of lactation and parity may modulate its effects. Further investigation on this topic by considering the study limitations, contributory factors and using new safe techniques such as quantative ultrasometry is highly recommended.”

Key words

Pregnancy; Breastfeeding; Gynecology; Obstetrics; Bones and Joint

References

  1. Dunne F, Walters B, Marshall T, Health DA (1993) Pregnancy associated osteoporosis. Clinical Endocrinology 1993: 487–490.
  2. More C, Bettembuk P, Bhattoa HP, Balogh A (2001) The effects of pregnancy and lactation on bone mineral density. Osteoporos Int 12: 732.
  3. Téllez-Rojo MM, Hernández-Avila M, Lamadric-Figueroa et al (2004) Impact of bone lead and bone resorption on plasma and whole blood lead levels during pregnancy. American Journal of Epidemiology 160: 668–678.
  4. Pregnancy, breastfeeding and bone health/NIH Osteoporosis and related bone diseases National Resource Center. WWW.bones.nih.gov
  5. Salari P,  Abdollahi M (2014) The influence of pregnancy and lactation on maternal bone health: a systematic review.  J Family Reprod Health 8: 135–148
  6. Holmberg-Marttila D, Leino A, Sievânen H (2003) Bone turnover markers during lactation postpartum amenorrhea and resumption of menses. Osteoporos Int 14: 103–109
  7. Sowers M, Eyre D, Hollis B, Randolph JF, Shapiro B Jannaush ML et al (1995) Biochemical markers of bone tumover in lacting and nonlacting potpartum women, J Clin Endocrinol Metab 80: 2210–6.

Relationship between Melatonergic and Thyroid Systems in Depression

DOI: 10.31038/EDMJ.2019351

Summary

Although melatonergic and thyroid system dysregulations are often observed in depression, it remains largely unknown whether these abnormalities are interrelated. Plasma melatonin concentrations were evaluated between 2100 h and 0800 h in 12 DSM-5 major depressed euthyroid inpatients; light (2,000 lux) was administered at midnight for one hour with a portable light device. On the following day, thyrotropin (TSH) responses to 0800 h and 2300 h protirelin (TRH) tests were measured.  Melatonin profiles exhibited a wide interindividual variability. Light induced a reduction in melatonin concentrations. Melatonin suppression (MEL-S) values (expressed as percentage of change between concentration at midnight and lowest concentration after light) were correlated with 2300 h TRH-TSH responses (∆TSH) and ∆∆TSH values (difference between 2300h-∆TSH and 0800h-∆TSH). Post-light rise in melatonin (MEL-PLR) values (expressed as percentage of change between lowest concentration after light and concentration at 0400 h) were correlated with 2300 h-∆TSH and ∆∆TSH values. Moreover, patients with reduced ∆∆TSH values (< 2.5 mU/L) showed a trend toward lower MEL-S and MEL-PLR values than patients with normal thyroid function. Together, our results suggest close functional relationships between melatonergic and thyroid systems in depression.

Keywords:

Depression, melatonin, light, Hypothalamic-Pituitary-Thyroid (HPT) axis, Thyrotropin-Releasing Hormone (TRH) test, thyrotropin (TSH).

Introduction

Depression is often associated with disrupted circadian rhythms. The neurohormone melatonin, synthesized by methylation of serotonin in the pineal gland, provides a robust circadian message to the organism (for review see Pevet, 2014) [1]. Given an inhibitory effect of light, melatonin secretion increases after dusk and terminates by dawn. It has been previously reported in healthy humans that melatonin secretion is suppressed at night with light of 500 lux or greater [2,3]. In depression it was found, but not unanimously, abnormalities of circadian rhythm of melatonin with advanced phases and/or decrease in nocturnal amplitude [4–6], and increased, decreased, or normal sensitivity to light [2].

On the other hand, while the vast majority of depressed patients have thyroid function tests within the euthyroid range, most inpatients exhibit a chronobiological Hypothalamic-Pituitary-Thyroid (HPT) axis dysregulation. Indeed, it has been consistently found that circadian thyrotropin (TSH) secretion is altered in depression (i.e., failure of the normal nocturnal surge of TSH, and lower and less variable 24-hour TSH levels compared to controls [5]) associated with blunted TSH response to protirelin (TRH) and reduced difference in TSH response between 2300 h and 0800 h TRH tests (∆∆TSH) (for review see Duval and Mokrani, 2018) [7]. In depression, the ∆∆TSH test represents a very sensitive chronobiological index since it is reduced in about 70% of inpatients [7].

Preclinical studies have demonstrated complex interactions between melatonergic and HPT systems. Different experimental models suggest inhibitory effects of melatonin on thyroid secretion [8,9]. In humans, it has been hypothesized that melatonin could act on the HPT axis by a “feed-sideward” effect that diminishes or increases responses when stimuli are respectively too high or too low [10]. To date, very few studies have focused on the links between melatonergic and HPT systems in depressed patients. Souêtre et al. [5] reported a positive correlation between amplitudes of melatonin and TSH circadian rhythms. Kjellmann et al. [11] found no significant correlation between nocturnal melatonin and morning ∆TSH levels.

The main goal of our exploratory pilot study was to investigate the possible pineal-thyroid functional relationship in euthyroid depressed inpatients, by examining in the same subjects the melatonin response to light administered at midnight, and the TSH response to TRH challenge at 0800 and 2300 h, performed on the following day.

Methods and Material

Subjects

Twelve inpatients (5 male and 7 female; aged 38 to 58 years; mean age ± SD, 50.6 ± 6.2 years) meeting DSM-5 criteria for major depressive disorder participated in this study. They were recruited from the inpatient units of the Pole 8/9, Psychiatric Hospital of Rouffach (France). None had a history of recent suicidal behavior (in 5 patients the last suicide attempt occurred > 1 year prior to evaluation). They were free of all drugs for a minimum of 1 week; this washout was supervised in hospital. Patients were evaluated by means of at least two unstructured clinical interviews conducted by an experienced research psychiatrist (F.G.L., or V.D.) and a structured interview (Schedule for Affective Disorders and Schizophrenia—Lifetime Version)—conducted by a separate psychiatrist (A.E). The final diagnoses were made by consensus of two psychiatrists blind to endocrine results. Severity of depression was measured with the 17-item Hamilton Rating Scale for Depression (HAM-D); inclusion in the study required a baseline HAM-D of 18 or greater (mean ± SD, 23.5 ± 4.0).

The protocol was approved by the local ethical committee (Comité de Protection des Personnes Est IV, Hôpital Civil Strasbourg) and performed according to the Declaration of Helsinki. All participants gave their informed and written consent.  Routine blood tests and physical examination excluded subjects with medical illnesses. All patients had normal basal thyroid hormone values (TSH, free T4 [FT4] and free T3 [FT3]), and normal body mass index (18.5< BMI <24.9 kg/m2). Subjects with a history of thyroid or other endocrine diseases; alcoholism or drug abuse; previous treatment with lithium salts, carbamazepine, long-acting neuroleptics, fluvoxamine, monoamine oxidase inhibitors or electroconvulsive therapy within one year of testing; and women taking oral contraceptives were excluded. We also excluded from the study patients with ocular disease, including cataract, glaucoma, retinitis pigmentosa, diabetic retinopathy, macular degeneration, or Stargardt disease.

All subjects were on a caffeine-restricted diet for at least three days before testing and their environment was synchronized, with diurnal activity from 0800 h to 2300 h, and nocturnal rest (sleep).

Procedures and Measurements

Light was administered with Luminettes® (Lucimed Company, Villers-le-Bouillet, Belgium). This portable LED device precisely focuses the light rays onto the lower half of the retina no matter the incline angle of the eye. During the session, performed in a room lighted below 50 lux, subjects were sitting in their bed. Light (2000 lux) was administered at midnight for one hour using Luminettes®. Subjects could sleep after light administration, but only in a sitting position to eliminate the influence of posture on melatonin levels. The intensity of 2000 lux and the duration of light exposure (one hour) were chosen to obtain a significant degree of melatonin suppression [3]. An indwelling cannula was inserted at 2000 h into a forearm vein and kept open with a slow drip of heparinized saline (5,000 IU heparin/l). Blood was sampled for melatonin determination at 2100h, and then every 20 minutes between 2320 h and 0500 h, a last sample was taken at 0800 h.

On the following day, the first TRH stimulation test was carried out at 0800 h—blood was drawn for assay of TSH at -15, 0, 15, 30, 60 minutes after injection of 200 µg TRH intravenously (TRH Ferring®, Ferring Pharmaceuticals, Kiel, Germany)—and the second TRH test was performed at 2300 h, on the same day, using the same previously depicted procedure [12].  Given that high cortisol secretion could decrease melatonin production, a Dexamethasone Suppression Test (DST) was carried out at midnight with oral ingestion of 1 mg of dexamethasone (Dectancyl, Laboratoires Roussel, Paris, France) followed by the assay of plasma cortisol at 0800 h, 1600 h and 2300 h on the next day. After the tests, blood samples were immediately centrifuged at 3000 rpm and 4°C; plasma samples were then stored at -20°C until assay.

Hormonal concentrations were determined by Radioimmunoassay (RIA) techniques (melatonin) and immunometric techniques based on enhanced luminescence (TSH, cortisol). Average intra-assay and inter-assay coefficients of variation were respectively: melatonin: <7%-8/3%, sensitivity < 3 ng/L [3,4]; TSH: 3.4 % – 4.8 %, sensitivity < 0.01 mU/L (Access Hypersensitive hTSH Assay, Beckman Coulter, Inc., Fullerton, CA, USA); Cortisol: 5.1 – 6.8%, sensitivity < 11 nmol/L (Access Cortisol Assay, same supplier).

Results

Melatonin profiles exhibited a wide interindividual variability. Light induced a reduction in melatonin concentrations and lowest values were observed at 0113 h ± 30 minutes (mean ± SD). Melatonin suppression (MEL-S) to light was expressed as percentage of change between concentration at midnight and lowest concentration after light according to the formula: MEL-S = ([melatonin concentration at 2400 h (immediately prior to phototherapy; i.e., baseline) – minimum melatonin concentration after light]/melatonin concentration at 2400 h) × – 100; mean ± SD, 31.9 ± 23.5 %. Post-light rise in melatonin (MEL-PLR) was expressed as percentage of change between lowest concentration after light and melatonin value at 0400 h according to the formula: MEL-PRL = ([minimum melatonin concentration after light (i.e., baseline) – melatonin concentration at 0400 h]/ minimum melatonin concentration after light) × 100; mean ± SD, 102 ± 103 %. The calculation of the percentage of melatonin changes (during and after light exposure) eliminated the baseline effect, although the inter-subject variations remained very large.

MEL-S and MEL-PLR values were not significantly correlated (rs [Spearman] = 0.43, n = 12, p = 0.16). However, there was a positive relationship between MEL-S and MEL-PLR values and evening TSH responses to TRH (Figure 1)—expressed as the maximum increment above the baseline value after TRH injection (2300h-∆TSH), and the difference between 2300 h-∆TSH values and 0800 h-∆TSH (∆∆TSH). Correlations between MEL-S and MEL-PLR and 0800h-∆TSH values were not significant. In our population, MEL-S, MEL-PLR, and TSH (baseline, ∆TSH, and ∆∆TSH) values were unrelated to age, gender, severity of depression and post-DST cortisol values.

EDMJ 2019-120 - Fabrice Duval France_F1

Figure 1. Relationships between maximum increment in plasma TSH level above baseline (∆TSH) after TRH injection at 2300h, and difference between 2300 h-∆TSH and 0800 h-∆TSH values (∆∆TSH), and (A) melatonin suppression (MEL-S) to light, expressed as percentage of change between concentration at midnight and lowest concentration after light, and (B) post-light rise in melatonin (MEL-PLR), expressed as percentage of change between lowest concentration after light and melatonin value at 0400 h, in 12 depressed patients. rs: Spearman rank coefficient.

We further classified the patients on the basis of their ∆∆TSH test status, since reduced ∆∆TSH values reflect chronobiological HPT axis alterations (for review see Duval and Mokrani, 2018) [7]. The first group showed reduced ∆∆TSH values (i.e. less than 2.5 mU/L [Duval et al. 2015]) (n=5; 3 male and 2 female; mean age, 51.6 ± 3.1 years). The second group showed normal ∆∆TSH values (n=7; 2 male and 5 female; mean age, 49.9 ± 7.9 years). Statistical analysis employing generalized Friedman rank sum test for rough melatonin data (sampled between 2320 h and 0500 h) showed a significant time effect in patients with normal ∆∆ TSH values (p < 0.9 10–7), but not in patients with reduced ∆∆TSH values  (p = 0.11). MEL-S and MEL-PLR values tended to be lower in patients with reduced ∆∆TSH values compared to patients with normal HPT activity (Figure 2).

EDMJ 2019-120 - Fabrice Duval France_F2

Figure 2. Nocturnal melatonin profiles (A) and responses to light (B) in 12 depressed patients classified according to the presence (∆TSH < 2.5 mU/L, n=5) or absence (∆∆TSH ≥ 2.5 mU/L, n=7) of HPT dysregulation. Raw data are expressed as mean ± SEM. The histograms (±SEM) represent the mean melatonin suppression (MEL-S) and post-light rise in melatonin (MEL-PLR). P values are obtained by Mann-Whitney two-tailed test.

Discussion

The main findings of this study are as follows: (1) light-induced melatonin amplitude suppression and post-light rise in melatonin are positively correlated to nocturnal TRH-TSH responses (i.e, 2300h-∆TSH and ∆∆TSH) in depressed patients; and (2) patients with HPT axis dyregulation show a trend toward decreased melatonin responses to light. The present results provide some evidence that melatonergic and thyroid systems are interrelated, suggesting the involvement of common mechanisms.

Pineal and thyroid activity follows a circadian rhythm closely connected to the hypothalamic Suprachiasmatic Nuclei (SCN), which house the master circadian clock. In preclinical studies SCN ablation resulted in marked alteration in both melatonin and HPT axis hormones rhythms. Thus, a downward trend in nocturnal responses of melatonin (to light) and TSH (to TRH) could possibly result from a weakened output of the SCN in depression. Moreover, since reduced ∆∆TSH values may reflect altered TRH receptor chronesthesy on pituitary thyrotrophs secondary to endogenous TRH hypersecretion (for review see Duval and Mokrani, 2018) [7], our findings could also suggest that decreased melatonin function may act at the hypothalamus by disinhibiting TRH release. Indeed, some animal studies reported that decreased pineal activity enhanced secretion of TRH, while injected melatonin altered the secretion and production of TRH [13,14].  Conversely, in vitro studies demonstrated that TRH could antagonize the effects of melatonin [15]. Therefore, another intriguing possibility is that increased TRH secretion in depression could lead to altered melatonin functionality. These latter two hypotheses are not mutually exclusive. However, future studies are needed to confirm these assumptions.

Limitations of the Present Study

Some shortcomings in our study require discussion. Firstly, owing to the lack of healthy comparison subjects we cannot demonstrate that plasma melatonin levels before and after light exposure are abnormal in depression. However, it is noteworthy that we used the same melatonin radioimmunoassay as Claustrat et al. [3] who administered light with eyeglass LED delivery systems (Somnavue® and Lumino®) in 10 healthy individuals; in comparison, the mean melatonin profile of our patients appears diminished. Secondly, given the exploratory nature of our research we studied a rather small sample of depressed inpatients. This may have reduced the statistical power of our analyses (performed with nonparametric methods) since results, although suggestive of an impaired functionality of the melatonergic system in patients with abnormal HPT axis activity, did not achieve statistical significance. Thus, our findings must be considered preliminary until replicated in a larger patient population.

In conclusion, our pilot study suggests that pineal and thyroid systems exert mutual interregulation. In the future, it will be important to understand the mechanisms underlying links between melatonin, HPT axis, circadian rhythms, and sleep-wake regulation in order to provide novel insight into the pathophysiology of affective disorders.

Aknowledgment

The authors express their gratitude to the nurses of the pole 8/9, Centre Hospitalier, Rouffach, France

Role of the Funding Source

Funding of this study was provided by inner sources (Association Pour la Formation et la Recherche de Rouffach [APF2R], Centre Hospitalier, Rouffach). No outside parties had any role in study design; in the collection, analysis, and interpretation of data; in the writing of the report and in the decision to submit the paper for publication.

References

  1. Pévet P (2014) the internal time-giver role of melatonin. A key for our health. Rev Neurol (Paris) 170: 646–652.
  2. Nurnberger JI, Adkins S, Lahiri DK, Mayeda A, Hu K, Lewy A, et al (2000) Melatonin suppression by light in euthymic bipolar and unipolar patients. Arch Gen Psychiatry 57: 572–579.
  3. Claustrat B, Brun J, Borson-Chazot F, Cohen-Tannoudji D, Claustrat F, et al (2010) Suppression of melatonin secretion in healthy subjects with eyeglass LED delivery system. Neuro Endocrinol Lett 31, 330–335.
  4. Claustrat B, Chazot G, Brun J, Jordan D, Sassolas G (1984) A chronobiological study of melatonin and cortisol secretion in depressed subjects: plasma melatonin, a biochemical marker in major depression. Biol Psychiatry 19: 1215–1228.
  5. Souêtre E, Salvati E, Belugou JL, Pringuey D, Candito M, et al (1989) Circadian rhythm in depression and recovery: evidence for blunted amplitude as the main chronbiological abnormality. Psychiatry Res 20: 263–278.
  6. Crasson M, Kjiri S, Colin A, Kjiri K, L’Hermite-Baleriaux M, et al (2004) Serum melatonin and urinary 6-sulfatoxymelatonin in major depression. Psychoneuroendocrinology 29: 1–12.
  7. Duval F, Mokrani MC (2018) Thyroid axis activity in depression. Ann Thyroid Res 4: 166–171.
  8. Wright ML, Cuthbert KL, Donohue MJ, Solano SD, Proctor KL (2000) Direct influence of melatonin on the thyroid and comparison with prolactin. J Exp Zool 286: 625–631.
  9. Prendergast BJ, Pyter LM, Kampf-Lassin A, Patel PN, Stevenson TJ (2013) Rapid induction of hypothalamic iodothyronine deiodinase expression by photoperiod and melatonin in juvenile Siberian hamsters (Phodopus sungorus). Endocrinology 154: 831–841.
  10. Mazzoccoli G, Giuliani A, Carughi S, De Cata A, Puzzolante F (2004)The hypothalamic-pituitary-thyroid axis and melatonin in humans: possible interactions in the control of body temperature. Neuro Endocrinol Lett 25: 368–372.
  11. Kjellman BF, Ljunggren JG, Beck-Friis J, Wetterberg L (1985) Effect of TRH on TSH and prolactin levels in affective disorders. Psychiatry Research 14: 353–363.
  12. Duval F, Mokrani MC, Erb A, Gonzalez Lopera F, Alexa C, et al (2015) Chronobiological hypothalamic-pituitary-thyroid axis status and antidepressant outcome in major depression. Psychoneuroendocrinology 59: 71–80.
  13. Relkin R (1978) Use of melatonin and synthetic TRH to determine site of pineal inhibition of TSH secretion. Neuroendocrinology 25: 310–318.
  14. Mitsuma T, Nogimori T (1985) Effects of various drugs on thyrotropin secretion in rats. Horm Metab Res 17: 337–341.
  15. Naftalin RJ, Cunningham P, Afzal-Ahmed I (2004) Piracetam and TRH analogues antagonise inhibition by barbiturates, diazepam, melatonin and galanin of human erythrocyte D-glucose transport. Br J Pharmacol 142: 594–608.