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Considerations in the Diagnosis and Treatment of Morton’s Entrapment: A Review

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DOI: 10.31038/IJOT.2020331

Introduction

Intermetatarsal neuromas, known by their eponym as Morton’s neuromas, are a common painful forefoot pathology seen in the foot and ankle clinic. The nomenclature of this condition is misleading. The term “neuroma” refers to a non-degenerative nerve injury. The condition clinicians most often describe in a “Morton’s neuroma” is more accurately described as a perineural fibrosis of the plantar interdigital nerve leading to entrapment of this nerve [1]. Surgical treatment varies from entrapment release to full neurectomy [2]. Post-operative pathology review of neurectomized tissue rarely demonstrates axonal degeneration and collagen proliferation [3]. Those changes are the pathophysiological markers associated with nerve injury that lead to true neuroma formation. The authors, therefore, recommend changing the common name of the condition from “intermetatarsal neuroma” to interdigital nerve entrapment to better define the disease. The aim of this review is to present treatment schemes seen in “Morton’s” diagnosis, and to suggest an algorithm which may improve patient outcome.

Anatomy and Biomechanics

Intermetatarsal nerve entrapment is classically found in the third intermetatarsal space, but this condition can affect any of the four intermetatarsal nerves in the foot [4]. The rate of occurrence in the third metatarsal space is higher due to the anatomy of the foot [5]. First, the innervation of the foot begins with the tibial and common fibular (peroneal) nerves [6]. As the tibial nerve courses distally past the knee joint, its motor fibers to the posterior compartment of the leg and enters the tarsal tunnel at the level of the medial malleolus [7]. The tibial nerve then typically bifurcates just distal to the laciniate ligament at the tarsal tunnel to form both the medial and lateral plantar nerves [8]. Those two nerves work in tandem to provide sensation to the plantar aspect of the foot form their proper digital branches distally. At the most common area between the medial and lateral plantar nerves, there is a medial communicating branch between them at the level of the third intermetatarsal space. This is the actual nerve which becomes entrapped and that causes the clinical signs and symptoms for this condition [9].

There are certain foot types which are more likely to become entrapped. The medial longitudinal arch height typically defines whether a foot is in pes planus or pes cavus, clinically [10]. As the medial longitudinal arch is depressed, this is usually in compensation for a rearfoot valgus [11]. There is increased congruity of the three facets of the subtalar joint with rearfoot valgus positioning. This in turn increases the flexibility of all joints about the midfoot. The increase in flexibility is an evolutionary advantage for the foot so it may adapt against uneven terrain. There is an unfortunate consequence for this adaptability. There is increased motion in-between the medial and lateral columns of the foot.

The medial column of the foot is defined as the combination of the medial, intermediate and lateral cuneiform bones and their associated first, second and third rays of the forefoot. The lateral column of the foot is defined as the cuboid bone and its articulation with the fourth and fifth rays of the forefoot. In flexible pes planus conditions, there is an increase in motion in-between the third and fourth metatarsals [12]. This motion becomes pathological when the medial communicating branch between the medial and lateral plantar nerves becomes entrapped. The entrapment results in perineural fibrosis as compensation to prevent axonal damage [13]. Due to the nature of the pathological mechanics and the common occurrence of pes planus, it is more common to see third intermetatarsal nerve incarceration versus the surrounding intermetatarsal spaces.

Physical Examination of Intermetatarsal Nerve Entrapment

Third intermetatarsal space nerve entrapment is known to be found in 50-87 out 100,000 people, and women are more commonly affected versus men [14]. Typical symptoms the patient may present in cases of Morton’s intermetatarsal/ interdigital nerve entrapment are often described by the patient as a burning, shooting pain or numbness/ paresthesia between the third and fourth metatarsal heads that may radiate distally toward the corresponding toes in up to 60% of cases and may also radiate proximally [15]. The patient may also be described as one feeling as though they are stepping on a pebble or have the sensation of a “rolled up sock” in the proximal forefoot area.

As with diagnosis of other nerve entrapments, Morton’s intermetatarsal nerve entrapment is largely clinically based. The high variability of presentation between patients encourages a clinical diagnosis based on symptoms and physical examination findings, rather than staunch guidelines. Symptoms may include focal tenderness and tinel’s sign. The presence of Mulder’s sign clicking (compression of forefoot while plantar interspace is palpated) and pain with interspace compression while performing this test are often positive findings [16]. A Lachman’s test is often used for evaluation of the differential diagnoses of capsulitis and plantar plate rupture versus intermetatarsal nerve entrapment [17].

A thorough biomechanical evaluation and physical examination are warranted with presence of Morton entrapment symptoms to help identify biomechanical influences as well as elucidate other pathologies that may be unrecognized yet contributing to symptoms, such as tarsal tunnel syndrome. As with any pathology, complete diagnosis and treatment of underlying conditions will help to prevent unnecessary recurrence. Radiographic evaluation with particular emphasis of weightbearing views of the foot should be utilized to further rule out other pathologies contributing towards metatarsalgia, such as an abnormal elongated metatarsal parabola or possible contribution of cavus foot and equinus deformity. Varying options have been noted on the effectiveness of MRI findings in symptomatic patients. Ultrasound is highly recommended and may be optimal for diagnosis of neuromas smaller than 5mm [18], however it is noted that this imaging technique is operator dependent. A recent meta-analysis has concluded that ultrasonography has been found equivalent to MRI for diagnostic value in Morton’s intermetatarsal entrapments [19]. Although these visual modalities have been advocated, one study comparing preoperative imaging with surgical findings noted approximately half of the neuromas were missed by ultrasound and MRI.

Differentials to consider may include degenerative changes to the metatarsal phalangeal joint, plantar pad, Metatarsal stress fracture, Freiberg’s infarction, other foot nerve pathologies, such as lateral or medial plantar nerve lesions and tarsal tunnel syndrome as well as presence of soft tissue masses, tumors and cystic changes.

Conservative Treatment for Morton’s Entrapment

Conservative (non-surgical) interventions for treatment of Morton’s entrapment include orthoses and shoe gear modification, corticosteroid and alcohol injection, extracorporeal shockwave therapy, radiofrequency ablation, cryoablation, capsaicin injection, botulinum toxin, and laser therapy [20]. A systematic review for treatment of Morton’s neuroma reveals conservative treatment can be effective. Use of orthoses leads to improvement in nearly 50% of patients. Radiofrequency ablation was found to be more effective as well as associated with less frequent complications compared to injections including alcohol and corticosteroids. This review concluded however, that most successful treatments included operative treatment [21].

Injection efforts are often utilized when the patient presents with high levels of pain and symptoms and may help relieve symptoms temporarily and are quite effective in the short term. The most common utilized agents include alcohol and corticosteroids. Injectables have been described as particularly useful while concomitantly addressing biomechanical contributions, which includes shoe gear modification and use of custom orthoses. The use of corticosteroids is associated with plantar plate rupture as well as deterioration of the joint capsule and is typically recommended to have a limitation of three treatments per year. Ethanol injection has poor success rates reported and has even been determined as not an effective treatment for interdigital neuroma but has the noted advantage of available repetition of procedure when compared to corticosteroid [22].

Morton’s intermetatarsal nerve entrapment has been likened to carpal tunnel syndrome in the upper extremity, a similar nerve entrapment condition of the median nerve. Conservative efforts for treatment of carpal tunnel syndrome with wrist splinting and steroid injections are effective in the short term and recommended if symptom duration is less than 3 months with absence of sensory impairment, but only 10% remain asymptomatic within one year [23]. Additionally, a retrospective study has demonstrated that increased utilization of corticosteroid application has led to worse long-term outcome in surgical carpal tunnel release [24,25]. Controversy remains in direct to surgery vs local corticosteroid injection with multiple elements to consider [26].

Surgical Approaches and Considerations for Morton’s Entrapment

Surgical treatment for intermetatarsal nerve entrapment should be considered when painful symptoms have not been adequately relieved by conservative methods. The underlying pathologic etiology contributing to developed condition must be considered for optimal outcome. Of particular note, the forefoot loading effects of equinus as well as the influence of the metatarsal parabola potential for increased plantar pressures should be evaluated for potential effects leading to chronic repetitive microtrauma to the forefoot. Bauer has been previously advocated for adjunctive metatarsal osteotomies to be performed with release of deep transverse intermetatarsal ligament, however this should only be performed as necessary and in some cases peak plantar forefoot pressures and contact time remain unaffected and are not elevated [27].

Surgical external neurolysis of the common plantar interdigital nerve (decompression of nerve) should be considered following correction of biomechanics. This procedure has a noted high success and low complication rate. This has been described in both open and endoscopic release techniques. The endoscopic approach results with 86% of patients having excellent or good results and allows for the advantage of minimal tissue disruption and possible earlier return to activity as demonstrated by Barrett and Walsh [28]. The approach to an open external neurolysis of the intermetatarsal nerve will be discussed further. Plantar and dorsal incisions have been described, with the dorsal linear approach providing the advantage of decreased painful scar formation as well as early ambulation of the patient. The plantar approach can be performed in a transverse or longitudinal incision. The plantar transverse may be performed on the non-weightbearing aspect of the foot, allowing for ideal visualization for nerve identification, exposure for adjacent intermetatarsal nerve procedures, and allows for immediate weightbearing.

This procedure should be performed under loupe magnification to allow for optimal visualization of nerve tissue. The patient is placed on the operative room table in a supine position with placement of a well-padded ankle tourniquet. Utilizing aseptic technique, the lower extremity is scrubbed, prepared and draped. Next, topographic anatomic landmarks are drawn including the heads of the third and fourth metatarsals at the metatarsal phalangeal joint and their respective metatarsal shafts. The surgical incisional site should be planned midline between these structures, extended distally to the corresponding webspace. Utilizing a #15 blade, the longitudinal incision is performed to the level of dermis, and next tenotomy scissors with blunted tips are utilized with careful dissection utilizing atraumatic technique is performed with care to avoid injury to superficial nerve branches and vascular structures. Bipolar electrocautery is utilized as necessary to assist with hemostasis to help reduce hematoma formation, as well as provides a more controlled and limited destruction of tissue with cauterization. Retraction to obtain optimal surgical field visualization should be performed by an assistant or with an atraumatic Weitlander or lamina spreader placed deep to the metatarsal heads. The dorsal fascia is then incised, and deeper dissection is performed until the transverse intermetatarsal ligament is identified. This structure is then isolated and elevated with assistance of placing a curved hemostat or Senn retractor deep to this structure, which is then incised along its entire length, in an effort to protect deeper structures. The intermetatarsal nerve lies deep to the transverse intermetatarsal ligament. Other constricting structures should be evaluated visually as well as palpated digitally, and the nerve should be freed from adhesions both distally as well as proximally to the bifurcation with careful blunt dissection efforts. This is continued throughout the entire surgical field to maximally reduce contributing factors of nerve entrapment. The surgical site is re-evaluated to ensure all constricting elements have been removed, and then irrigated with normal sterile saline. If biological adjunctive products, such as amniotic membrane, are utilized they should be placed along the released structure. Minimal subcutaneous tissue closure with an absorbable suture should be performed and primary skin closure is then performed with nonabsorbable suture and dry sterile dressing is then applied. Of note, in the event of suboptimal patient satisfaction with use of neurolysis (decompression) as a first line of surgical treatment, excisional neurectomy should be considered in subsequent treatment of the surgical algorithm.

Excisional neurectomy (denervation) proximal to the deep transverse intermetatarsal ligament has been well described and it is the authors’ opinion that this procedure should be considered following the decompression efforts. Wolfort and Dellon have advocated for treatment with nerve resection in combination with the implantation of the proximal end of the intermetatarsal nerve into muscle belly, reporting 80% excellent relief of symptoms29. This is most often performed with the dorsal longitudinal incisional approach. A lazy S type incision may be considered for cases with adjacent identified nerve entrapment, in an effort to increase exposure of surgical sites with a single incision. Layered anatomic dissection should be performed in a similar manner as described for neurolysis. Upon freeing the nerve, attention is directed to the proximal portion of the operative site. Mild tension is placed distally and at this point is excised just proximal to the metatarsal head utilizing a sterile tongue depressor cut in a transverse/perpendicular manner with a new blade to ensure sharp and clean transection of nerve with the goal of limiting axonal growth. Next, the freed proximal portion of the intermetatarsal nerve is then transposed proximally and placed into adjacent intrinsic muscle belly with minimal tension. The nerve is then loosely affixed via a windowing technique into the muscle created with hemostats and secured via an epineurial stitch. Excision may lead to formation of a true “stump neuroma”. Nerve excision has varying success reported up to 85%, however good or excellent long term results have been noted in only 50% of patients in a large retrospective cohort study by Womack, and 40% of patients obtaining poor results [29,30].

Revisional Surgical Approaches

Revisional surgeries often have less than optimal results; consideration of contributing factors to symptoms should be considered. These symptoms can take up to one year following surgical excision. There is a high prevalence of tarsal tunnel syndrome in conjunction with painful recurrent interdigital neuromas [29], and through physical examination is warranted when addressing recurrent neuromas.

Due to the increased likelihood of suboptimal results in cases of recurrence, in cases of poor surgical candidates, a less invasive approach to consider may be use of radiofrequency ablation. This destructive process includes use of radiofrequency energy which provides thermic electrocoagulation to the tissue surrounding the tip of the probe. Three cycles of treatment is advocated to increase efficacy when compared to two [30].

Surgical intervention, which may be selected often, includes the plantar approach surgical neurectomy of the intermetatarsal nerve. In this procedure, care should be taken to ensure eversion of incisional closure to minimize painful scarring with delayed weight bearing to avoid dehiscence. The use advanced techniques and modalities include nerve capping with the goal to reduced size and number of axons sprouting from transection of nerve, nerve transposition and implantation into muscle, nerve grafting, peripheral nerve stimulator with possible use of amniotic products.

Conclusion

Interdigital/intermetatarsal nerve entrapment or Morton’s neuromas are common forefoot pathologies that are most often attributed to an underlying entrapment condition of the nerve. This can be described as interdigital /intermetatarsal nerve neuralgia secondary to perineural fibrosis. Persisting symptoms warrant through physical examination, with emphasis on biomechanical contribution. Imaging may be helpful in diagnosis, particularly the use of radiographs and ultrasonography. Both conservative and surgical means of treatment have been recommended for the treatment of intermetatarsal/ interdigital entrapment, which remains somewhat controversial. Multiple studies have been conducted to ascertain the effectiveness of non-surgical versus surgical treatment of this condition [1,3,7]. Many studies have demonstrated improvement in symptoms over 80% with surgical intervention. Non-surgical efforts should be attempted prior to any surgical intervention to avoid possible complications, with surgery to be attempted upon failure of non-surgical intervention.

Excision remains the most common surgical management in treatment of Morton’s intermetatarsal nerve entrapment [31]. Due to the true nature of this condition having an underlying compression syndrome, neurolysis efforts are warranted and should strongly be considered in the first line of surgical procedures to address this issue. Similar outcomes have been established with both neurolysis and excisional efforts.

References

    1. Matthews BG, Hurn SE, Harding MP, Henry RA, Ware RS (2019) The effectiveness of non-surgical interventions for common plantar digital compressive neuropathy (Morton’s neuroma): A systematic review and meta-analysis. J Foot Ankle Res 12: 12. [crossref]
    2. Kasparek M, Schneider W (2016) Transection of the deep metatarsal transverse ligament in Morton’s neuroma surgery does not increase risk of splayfoot development. International Orthopaedics (SICOT) 40: 953-957. [crossref]
    3. Bhatia M, Thomson L (2020) Morton’s neuroma-Current concepts review. Journal of Clinical Orthopaedics and Trauma 11: 406-409. [crossref]
    4. Levitsky KA, Alman BA, Jevsevar DS, Morehead J (1993) Digital nerves of the foot: Anatomic variations and implications regarding the pathogenesis of interdigital neuroma. Foot & Ankle 14: 208-214. [crossref]
    5. Matsumoto T, Chang SH, Izawa N, Ohshiro Y, Tanaka S (2016) Interdigital neuroma in the second intermetatarsal space associated with metatarsophalangeal joint instability. Case Reports in Orthopedics 2016: 1-6. [crossref]
    6. Andreasen Struijk LNS, Birn H, Teglbjærg PS, Haase J, Struijk JJ (2010) Size and separability of the calcaneal and the medial and lateral plantar nerves in the distal tibial nerve. Anat Sci Int 85: 13-22.
    7. Meares C, Dusseldorp J (2020) Review of the efficacy of tibial nerve decompression in the management of diabetic feet. Clinical Neurophysiology 131: 1-2.
    8. Iborra A, Villanueva M, Sanz-Ruiz P (2020) Results of ultrasound-guided release of tarsal tunnel syndrome: A review of 81 cases with a minimum follow-up of 18 months. J Orthop Surg Res 15: 30. [crossref]
    9. Govsa F, Bilge O, Ozer MA (2005) Anatomical study of the communicating branches between the medial and lateral plantar nerves. Surg Radiol Anat 27: 377-381. [crossref]
    10. Lee JH, Cynn HS, Yoon TL, Choi SA, Kang TW (2016) Differences in the angle of the medial longitudinal arch and muscle activity of the abductor hallucis and tibialis anterior during sitting short-foot exercises between subjects with pes planus and subjects with neutral foot. BMR 29: 809-815. [crossref]
    11. Tang SFT, Chen CH, Wu CK, Hong WH, Chen KJ, et al., (2015) The effects of total contact insole with forefoot medial posting on rearfoot movement and foot pressure distributions in patients with flexible flatfoot. Clinical Neurology and Neurosurgery. 129: 8-11. [crossref]
    12. Gougoulias N, Lampridis V, Sakellariou A (2019) Morton’s interdigital neuroma: Instructional review. EFORT Open Reviews 4: 14-24. [crossref]
    13. Wang ML, Rivlin M, Graham JG, Beredjiklian PK (2019) Peripheral nerve injury, scarring, and recovery. Connective Tissue Research 60: 3-9. [crossref]
    14. DeHeer PA, Nanrhe AP, Michael SR, Standish SN, Bhinder CD, et al., (2020) Gender correlation to the prevalence of pedal neuromas in various interspaces-a retrospective study. Journal of the American Podiatric Medical Association. [crossref]
    15. Owens R, Gougoulias N, Guthrie H, Sakellariou A (2011) Morton’s neuroma: Clinical testing and imaging in 76 feet, compared to a control group. Foot and Ankle Surgery 17: 197-200. [crossref]
    16. Cloke DJ, Greiss ME (2006) The digital nerve stretch test: A sensitive indicator of Morton’s neuroma and neuritis. Foot and Ankle Surgery 12: 201-203.
    17. Bergeron MC, Ferland J, Malay DS, Lewis SE, Burkmar JA, et al., (2019) Use of metatarsophalangeal joint dorsal subluxation in the diagnosis of plantar plate rupture. The Journal of Foot and Ankle Surgery 58: 27-33.
    18. Fazal MA, Khan I, Thomas C (2012) Ultrasonography and magnetic resonance imaging in the diagnosis of morton’s neuroma. Journal of the American Podiatric Medical Association 102: 184-186.
    19. Bignotti B, Signori A, Sormani MP, Molfetta L, Martinoli C, et al., (2015) Ultrasound versus magnetic resonance imaging for Morton neuroma: Systematic review and meta-analysis. Eur Radiol 25: 2254-2262. [crossref]
    20. Thomson L, Aujla RS, Divall P, Bhatia M (2020) Non-surgical treatments for Morton’s neuroma: A systematic review. Foot and Ankle Surgery 26: 736-743. [crossref]
    21. Valisena S, Petri GJ, Ferrero A (2018) Treatment of Morton’s neuroma: A systematic review. Foot and Ankle Surgery 24: 271-281. [crossref]
    22. Espinosa N, Seybold JD, Jankauskas L, Erschbamer M (2011) Alcohol sclerosing therapy is not an effective treatment for interdigital neuroma. Foot Ankle Int 32:  576-580 [crossref]
    23. Graham RG, Hudson DA, Solomons M, Singer M (2004) A prospective study to assess the outcome of steroid injections and wrist splinting for the treatment of carpal tunnel syndrome. Plastic and Reconstructive Surgery 113: 550-556. [crossref]
    24. Vahi PS, Kals M, Kõiv L, Braschinsky M (2014) Preoperative corticosteroid injections are associated with worse long-term outcome of surgical carpal tunnel release: A retrospective study of 174 hands with a mean follow-up of 5.5 years. Acta Orthopaedica 85: 102-106. [crossref]
    25. Bland JDP, Ashworth NL (2016) Does prior local corticosteroid injection prejudice the outcome of subsequent carpal tunnel decompression? J Hand Surg Eur Vol 41: 130-136. [crossref]
    26. Naraghi R, Slack-Smith L, Bryant A (2018) Plantar pressure measurements and geometric analysis of patients with and without morton’s neuroma. Foot Ankle Int 39: 829-835. [crossref]
    27. Barrett SL, Walsh AS (2006) Endoscopic decompression of intermetatarsal nerve entrapment. Journal of the American Podiatric Medical Association 96: 19-23.
    28. Womack JW, Richardson DR, Murphy GA, Richardson EG, Ishikawa SN (2008) Long-Term evaluation of interdigital neuroma treated by surgical excision. Foot Ankle Int 29: 574-577. [crossref]
    29. Wolfort SF, Lee Dellon A (2001) Treatment of recurrent neuroma of the interdigital nerve by implantation of the proximal nerve into muscle in the arch of the foot. The Journal of Foot and Ankle Surgery 40: 404-410. [crossref]
    30. Brooks D, Parr A, Bryceson W (2018) Three cycles of radiofrequency ablation are more efficacious than two in the management of morton’s neuroma. Foot & Ankle Specialist 11: 107-111. [crossref]
    31. Villas C, Florez B, Alfonso M (2008) Neurectomy versus Neurolysis for Morton’s Neuroma. Foot Ankle Int 29: 578-580. [crossref]

Narrative Communication Messaging in Raising Public Awareness of Type 2 Diabetes Risk – A Multi-Perspective Cartography

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DOI: 10.31038/EDMJ.2020441

Abstract

Objectives: Type 2 diabetes is the seventh leading cause of death and disability worldwide. Estimates suggest that by 2035, 642 million people worldwide will suffer from diabetes. Higher awareness of risks of type 2 diabetes is a prerequisite to prevent or delay the onset of diabetes but, little attention has been paid to identifying effective communication messages to raise public awareness of risks of this disease and this is the focus of this study.

Methods: A conjoint based procedure facilitated an experimental design testing the power of narrative persuasion messages as driving awareness of risks of type 2 diabetes based on stability of utilities. The sample comprised 50 Americans recruited by Luc.id, Inc.

Results: Similarity in response patterns to messages uncovered three mindsets, each responsive to different messages. We identified effective messages for each mindset and developed a prediction tool assigning a person/group in the population to a sample mindset.

Discussion: Members of Mindset1 respond to empowering messages depicting members as having control, as able to modify their behaviors. Members of Mindset2 respond to messages presenting doctors as enhancing the health literacy of members and informing them of ways to prevent diabetes. Members of Mindset3 respond to messages presenting patients as a resource for learning, information, and support. Messages used in campaigns emerged as ineffective across mindsets

Conclusion: The prediction tool assigning people to mindsets may enable professionals to detect the psychological mind-set of an individual and drive health behavior changes using effective messaging.

Keywords

Awareness, Communication, Diabetes, Narrative-Messaging, Public, Mindsets

Type 2 diabetes is a major cause of increasing mortality incurring vast expenditures. Direct costs of type 2 diabetes account for $1.31 trillion and additional indirect costs account for 35% of the total burden [1]. Type 2 diabetes is one of five leading causes of premature death in high-income countries [2]. In 2017, around 415 million adults suffered from Type 2 diabetes [2]. Estimates suggest that over the next decade, 642 million adults will suffer from type 2 diabetes [2]. Moreover, type 2 diabetes, thus far diagnosed among adults, is now expanding to adolescents and children, making it THE epidemic of the 21st century [3]. So far, all interventions to maintain Glycemic control achieved sub-optimal outcomes [3-7]. Lack of Glycemic control leads to progress of type 2 diabetes resulting in a range of health complications, morbidity and disability [2].

Tremendous efforts to halt the expansion of type 2 diabetes involved: behavior-modification programs, pharmacological interventions and educational interventions. Whereas policy makers viewed these efforts as promising means to affect modifiable determinants of type 2 diabetes (i.e., obesity, sedentary lifestyles, smoking, stress), research evidence remains inconsistent [6-8]. Moreover, most interventions failed as program-compliance challenged patients and due to the global shortage in clinicians which limited program accessibility [9-14]. Research on pharmacological interventions suggests that lifestyle modifications, are, in fact, more efficacious [15]. No findings of other specific pharmacological interventions were published in papers. Last, research on educational interventions demonstrated contradictory results exposing provision barriers which inhibited intervention deployment [16,17]. In sum, to date, hypotheses of evaluation studies for interventions for control, prevention, and delay of the onset of type 2 diabetes, have not been corroborated. The prevalence of diabetes and the per capita expenditures of diabetes (direct and indirect costs) are rising and while they may be grounds for diabetes prevention, the awareness level among prediabetes and the rate of preventing interventions are low and of great concern [18].

Two recent studies that tested awareness among high risk British adults and among Americans, reported that half of participants demonstrated gaps in awareness of risks, symptoms and related behaviors [19,20]. Researchers recently acknowledged that individual-level prevention approaches are inadequate and thus unable to reverse epidemic trends, costly, and not scalable for targeting the healthy population [21]. Since lack of public information is a major barrier to risk awareness, researchers suggest the importance of increasing vigilance in reducing risks of type 2 diabetes by addressing gaps in public awareness [2,3,15,19,22,23].

Numerous institutions, including the World Health Organization, have recommended mass communication messaging to improve public awareness [22]. Studies in medicine, public health, and health communication, however, targeted patients rather than the healthy population [20-22]. Creating public awareness of the healthy population was thus far seen as less important than improving practices of patients [22]. The few studies that tested communication messaging for public awareness regarding general health issues, featured linkages among awareness behavior and health outcomes [23,24]. While research on communication messaging in general health topics is growing, the topic of communication messaging to the healthy population in type 2 diabetes, is unexplored [21,23-25].

One study presented a successful communication messaging campaign on determinants of type 2 diabetes but its reach was limited as it only engaged youth [21]. Another study on communication messaging in type 2 diabetes revealed that awareness of risks increased in the one Indian city where it was conducted [26]. Whereas studies on communication messaging in type 2 diabetes are scarce, findings of these two studies suggest that public campaigns may effectively raise awareness among many different segments of the healthy population and may reverse current concerning paths of behavioral trends in modifiable drivers of type 2 diabetes [21]. Since all groups in the population suffer from the burden of type 2 diabetes, this epidemic should be addressed, as other healthy issues, by effective communication messaging. An alternative as yet unexplored way to respond to previous calls to reduce risks of type 2 diabetes is to test and optimize messaging among healthy people. A systematic examination of effective campaigns indicates that in health disparities narrative messages have a persuasive impact on attitude change and behavioral modifications [27,28]. Also, facets that draw on the narrative persuasion theory, have been reported to bring individuals in the population to accept greater responsibility for their health [28]. In this study we draw on the theory of narrative persuasion in the daily life experiences of healthy people touching on risk awareness of Type 2 diabetes.

The Theoretical Framework and Hypotheses Development

A narrative comprises cohesive and coherent statements that may make up a story with an identifiable beginning, middle, and end and provide information about a daily phenomenon [29]. Narratives entail an integration of attention, imagery, and feelings [30]. Narrative communication messages either convey a point to another party or receive information from another party [31]. Narratives are a scientific way of relying on empirical and experimental methods to discover, describe, or elucidate some domain of interest through which we develop our understanding of the world and the distinctive ways of constructing reality [29,32]. One’s engagement with a narrative may result in one’s endorsement of modified attitudes and behaviors [33]. Engagement is affected by the attentional focus and one’s identification with the narrative [34]. Prior studies that tested the effect of narrative persuasion, however, did not focus on health [35,36]. Narrative messages may be effective in the health-behavior context, as they are the basic mode of human interaction that we use in our day-to-day lives to influence others [32].

Narrative messages in health communication entail anecdotes, testimonials, and stories [33]. In health communication several moderators were found to shape the narrative’s extent of persuasion: the health behavior, the delivery channel, the research design and the sample characteristics [35]. Previous studies tested the effect of narratives on health-related attitudes and intentions which were strongly associated with health behaviors [37-42].

Previous studies relied on behavioral modeling of exemplars with whom the audience identified [43,44]. Identification with an exemplar was key in the persuasion effect the narrative yielded [38,40,45-47]. Narratives of an exemplar delivered via audio and video which aimed at prevention, had a greater persuasion effect than did print-based narratives aiming at cessation [35]. Crafting engaging narratives, however, requires lengthy stories which are hard to apply in public health communication [43]. Some brief print-based narrative messages regarding risks of type 2 diabetes may have a stronger effect than will others.

Hypothesis 1

Different narrative communication messaging will have a different effect on perceived risks of Type 2 diabetes. Since the narrative persuasion theory is interpretive, it explores the impact of each message asking: for whom; under what circumstances; how; and when does each message achieve optimum effects [48,49]. The extent to which narrative messages regarding risks of type 2 diabetes will influence individuals may, therefore, differ among them. Narrative messages that are employed specifically for type 2 diabetes, could be more effective than general health related messaging because they touch on well-known determinants of type 2 diabetes. We hypothesize that the ability of narrative messages to raise awareness of type 2 diabetes risks, may depend, in part, on the extent to which people “identify” with the different narrative messages [31]. Narrative messaging, therefore, may carry a different appeal to homogeneous groups of people who are defined by similarity in their pattern of responses to narrative persuasion messages (i.e. mindset-segments) regarding risks in type 2 diabetes.

Hypothesis 2

Different narrative communication messages regarding risk of type 2 diabetes will carry a different appeal for different people by mindset segments. Narrative messages may also impact beliefs of healthy individuals about who is responsible for addressing and engaging in health behaviors, thereby, shaping their perceptions about their risks of type 2 diabetes [50].

Hypothesis 3

Different narrative communication messages will have a greater impact on perceived responsibility for health behaviors to avoid risks of type 2 diabetes.

The Current Study

Studies that tested the effect of specific print-based narrative messaging on identification and on attitudes towards the messaging by mindset-segmentation regarding urgent health problems are scant [35]. This study is in response to previous calls to explore under what condition a print-based narrative messaging may influence attitudes [35]. This study attempts to explore the effect of various elements of narrative messaging on the identification with the message and on risk awareness. While previous studies mostly included lab experiments or field experiments, this study employs an experimental research design [35]. This study is an important step in beginning to close the literature gap by testing specific brief narrative messaging for awareness of type 2 diabetes risk among healthy people. The aim of this study was to fill the above theoretical, methodological and practical gaps in the state of the art. Theoretically, to best of our knowledge, studies that tested specific narrative messaging for healthy populations regarding risks of type 2 diabetes are scant [29]. Also, the application of the narrative persuasion theory in the context of diabetes prevention while measuring one’s identification with elements of the message is an underutilized and underexplored research area [43]. Methodologically, we test unexplored communication messages among healthy individuals through a multi-disciplinary view, examining narrative messaging from different perspectives. In terms of practice, this research project assesses the impact of a variety of narrative messages as drivers of perceived risk of type 2 diabetes and proses to apply the knowledge by a classification tool developed based on the impact of the narrative communication messages.

Research Design and Methods

Conjoint measurement refers to a class of research procedures in which the respondent is provided with a set of systematically varied combinations of features (questions and answers) and rates the combination, providing an estimate for the part-worth utility of each answer [51]. Since our objective is to develop a model of messaging for each respondent, the question of sample size devolves into a question of the number of respondents needed before the average model across respondents becomes stable [52]. Whereas sociologists study behaviors of large groups of people and deal with the percent of people who achieve a given score, experimental psychologists deal with individual behavior focusing on the magnitude of a response and looking at means, and the stability of the mean as a predictor of the performance of the dependent variable. Thus, in Mind-Genomics, since results are based upon the average rating assigned to a narrative statement, the size of the sample is not a question of the stability of the average rating, but rather the stability of the model averaged across the different respondents. Data on utilities from several conjoint measurement samples confirm previous observations on base size studies and indicates that much of the information can be obtained with lower bases than the typical base size and the same conclusions can be made with base sizes around 50 [53]. Therefore, the sample comprised 50 respondents, healthy American adults with 25 females and 25 males, ages 31-44 (n=12); 45-55 (n=18) and 56+ (n=18). Respondents were selected by Luc.id, Inc., a panel provider of on-line samples. Respondents represent a cross-section of the typical respondent.

We structured messages that tell a story and attend to coherent statements with a clear beginning, middle, and end [54,55]. We designed the narrative messages and shaped the rating question to influence cognitive attention, thereby, mediating between the content and the intention. Since narrative communication messaging that relates to only one perspective, may carry bias, reducing the complexity in our world and inhibiting effective awareness for different target audiences, this study combines among narrative persuasion messages from several perspectives: the psychological perspective (individual’s behavior), the sociological perspective (perceived contextual factors), the economics perspective (social structural elements and costs) and the health management perspective (health services). We structure messages by an experimental design guided by Mind-Genomics®, a new conjoint based scientific approach, best described a ‘cartography of the mind.’ Mind-Genomics® examines responses of people to different stimuli in daily life [56]. Mind-Genomics maps an experience by identifying its different facets, determining to what facets the person attends, and how important each facet is for each person. Mind-Genomics® reveals how people react to the specifics of the messaging, looking at the nuances, whereas accounting for the richness of the experience. Mind-Genomics® segments different groups of people by their different viewpoints, so-called mindsets.

Outcome and Independent Variables

The dependent variable is perceived risks of type 2 diabetes, measured by the extent of importance each respondent attributes to each driver of risk on a 1-9 rating scale. Four categories of narrative statements: determinants of type 2 diabetes, healthcare needs, expectations and support and responsibility. Each category comprised four narrative messages about type 2 diabetes, each from different disciplines. Each respondent evaluated a unique set of 24 combinations of narrative messages that are each independent of all other messages by experimental design, with each category comprising a minimum of two statements, or a maximum of four statements. By virtue of the Mind-Genomics® experimental design, the 16 messages are statistically independent of each other. The structure of the 24 combinations remained the same, ensuring statistical independence of the predictor variables for subsequent regression. Effective messages regarding risks of type 2 diabetes need not only proper framing, but also avoiding the activation of negative attitudes and resistance to the message itself [57]. The specific combinations changed, however, due to a permutation scheme allowing the experiment to cover many more of the possible combinations of messages using today’s standard experimental designs [57,58].

With 50 respondents, the researcher covers 1200 messages (50×24), rather than repeating the same 24 messages 50 times. Table 1 presents categories and messages per category. Respondents rated the importance of each message in shaping their perceived risk of type 2 diabetes on a 1-9 rating scale. Response biases were overcome by presenting the respondent with combinations of messages assembled by an experimental design, which mixes and matches different types of ideas to test combinations of messages by categories that drive the perceived risk of type 2 diabetes [20,31]. To test the instrument, reliability was established by the split-half method. The entire data set was divided into two equal groups, with each respondent contributing data equal to both groups. Each group is used to estimate the coefficient of the messages. Three sets of coefficients were created: from the total panel, and from each half-set. The two half sets of data were highly correlated with data for the total panel (0.90 for group 1; 0.87 for group 2).

Table 1: The Four Categories and the Four Narrative Messages in Each Category.

Question A: type 2 diabetes determinants
A1 By living longer there is a greater chance of suffering from type 2 Diabetes
A2 Type 2 diabetes is dangerous without treatment
A3 Diet and exercise are key to type 2 Diabetes prevention
A4 Type 2 Diabetes is the most profound disease of this century
Question B: Healthcare Needs
B1 It’s OK to self-manage type 2 diabetes
B2 People with type 2 diabetes use a lot of health services
B3 Frequent doctor promote medication-adherence
B4 Type 2 diabetes requires a lot of medications
Question C: Expectations
C1 It’s a doctor’s role to educate patients about type 2 diabetes
C2 The internet is all you need to learn about type 2 diabetes
C3 A doctor should refer people to reliable educational materials about type 2 diabetes
C4 People should know all the possible treatments of type 2 diabetes
Question D: Support
D1 Family support is important to manage diabetes
D2 Learning how others cope with challenges is beneficial
D3 Participation in workshops helps prevent type 2 diabetes
D4 Belonging to a community helps maintain health behaviors that prevent type 2 diabetes

Statistical Analysis

The experimental design ensures that an individual-level regression model can be run on the data. The original 9-point rating scale, anchored at both ends, was transformed to a binary scale (i.e., Ratings of 1-6 were considered ‘not important,’ and transformed to 0. Ratings of 7-9 were transformed to 100), to denote that these were important. The data were then subject to Ordinary Least-Squares regression (OLS). The regression equation was run for total panel and for each key subgroup (total, gender, age), incorporating all relevant data into one regression model for the group. Whereas the regression model suggests that a standard error around 4.0 or so characterizes the different coefficients, as a rule of thumb in conjoint coefficients of 8 or higher tend to be statistically significant and to co-vary with measurable external behavior which might serve as a validation.

In conjoint analysis, regression coefficients reveal the impact (degree of agreement) of communications of messages. The pattern of strong performing (positive) coefficients across different subgroups, suggest the nature of what is important for the respondents who are assigned to a mindset which is created by clustering the coefficients across all of the messages. There is no need for Beta values for the coefficient because in the modeling the messages are represented as either 0 (absent from the combination) or 1 (present in the combination) [57].

Results

The rated importance of the information presented by the narrative message on type 2 diabetes varied across groups. Respondents in the youngest group rated information as unimportant. Members of the other age groups rated the information as moderately important and very important. Males had a higher additive constant indicating that they will require less specific information to reach risk awareness than will females. The differences in response patterns of different groups showed that there are three distinct mind-sets. Table 2 presents the coefficients for the total panel and for the three mind-set segments reflecting different patterns of responses to the importance of each narrative statement contributing to the perceived risk as emerged from Mathematical K-clustering analysis. Figure 1 presents sample distribution by mind-set segments and Figure 2 presents sample distribution into mindset-segments by age group.

Table 2: Coefficients for total panel and the three emergent mindsets based upon the patterns of coefficients of narrative messages.

Total Mindset 1 Mindset 2 Mindset 3
Base 50 18 13 19
Additive constant 59 62 43 67
Mind-Set 1 – The patient is in control, and must take responsibility (psychology)
A3 Diet and exercise are key to type 2 Diabetes prevention 8 17 4 3
A2 TYPE 2 DIABETES is dangerous without treatment 7 14 8 -1
Mind-Set 2 – The doctor is very important (sociology)
C3 A doctor should refer patients to educational materials about type 2 Diabetes -3 -13 20 -11
C1 It’s a doctor’s role to educate patients about type 2 Diabetes -4 -13 16 -9
C4 A patient should know all the possible treatments of Type 2 Diabetes 0 -3 12 -7
Mind-Set 3 – Help from others is important (Social structure & Services)
D3 Participation in workshops for patients helps manage Type 2 Diabetes 2 -12 -2 19
D1 Family support is important to manage type 2 Diabetes 5 0 0 16
D4 Belonging to a community of patients helps support others with type 2 Diabetes 1 -10 -3 15
B3 Frequent doctor visits help adherence to type 2 Diabetes treatment 4 4 -8 11
D2 Learning how others cope with type 2 Diabetes is beneficial 3 -5 4 8
Elements which are not key to any mind-set (Cost & Health services)
B2 People with type 2 Diabetes use a lot of health services -3 -4 -13 2
B4 Type 2 Diabetes requires a lot of medications -5 5 -22 -4
A4 Type 2 Diabetes is the most profound disease of this century -3 4 0 -10
B1 It’s OK to self-manage the type 2 Diabetes -17 -14 -27 -13
A1 By living longer there is a greater chance of suffering from Type 2 Diabetes -9 1 -5 -20
C2 The internet is all you need to learn about diabetes -26 -24 -4 -42

fig 1

Figure 1: Risk Awareness of Type 2 Diabetes in Healthy Individuals.

fig 2

Figure 2: Distribution into Mindsets by Age.

Applying Narrative Communication Messaging for Raising Awareness to Type 2 Diabetes

To identify which communication messaging should be used in practice, we applied the personal viewpoint identifier (PVI) which is created a new for each study and in this case revealed the mind-set of an individual through a simple, 30-second interaction. The respondent completed a short, 6-question evaluation, with the pattern of the responses linked to membership in one of the three mind-sets. The six most discriminating narrative messages were chosen to create the PVI which then created a binary scale on which new participants may rapidly indicate their answers. Based on these answers, the Mind-Genomics system instantly presents the sample mind-set membership for the individual in the population, who can then be given the most effective messaging for the mind-set to which the individual appears to belong. The PVI is available at: http://162.243.165.37:3838/TT37

Discussion

This study tested narrative persuasion messages as drivers of public awareness of risks of type 2 diabetes. This study makes theoretically, methodologically and practical contribution. Theoretically, this study extended the narrative persuasion theory testing narrative communication messaging in the health context, focusing on risk awareness in type 2 diabetes among healthy people. Methodologically, this study explored narrative communication messaging through a multi-disciplinary view, from different perspectives applying an innovative conjoint-analysis procedure. Practically, findings direct professionals on a local level and on a national health policy level to use narrative communication messaging that impact the risk perception of healthy people, by mind-set segments, regarding type 2 diabetes. Findings show that all study hypotheses were corroborated and also suggest that just as narrative messaging was effective in public campaigns on general health issues, it can be effective for public campaigns targeting awareness of risks in type 2 diabetes for the healthy population [21].

As for hypothesis 1, stating that different narrative communication messaging will have a different effect on perceived risks of type 2 diabetes, findings suggest that a number of narrative messages, that may be used on local level by professionals appear to be ineffective, and may create antagonism and anxiety, rather than raise public awareness of risks of type 2 diabetes and navigate individuals towards the adoption of healthy behaviors. Such messages are: People with type 2 diabetes use a lot of health services; Type 2 diabetes requires lots of medications; Type 2 diabetes is the most profound disease of this century and; living longer raises the risk of suffering from Type 2 diabetes. This finding may be attributed to the underlying communication orientation in these narrative messages. Ineffective messages fall under the category of content-oriented messaging which focuses on ‘what the public should know about type 2 diabetes’. Whereas content-oriented messaging is popular, it does not promote behavioral change, particularly compared to change-process oriented communication which was found to be a ‘make or break’ factor in behavioral modifications, including in type 2 diabetes [56,57].

As for hypothesis 2 stating that different narrative communication messages regarding risk of type 2 diabetes will carry a different appeal for different people by mindset segments, data show that response patterns to narrative messages differed among groups of people, differentiating them by mindset segments. People who are members of mind-set1 will react to messages depicting individuals as having control and able to take responsibility for their health stressing the psychology view (e.g., Diet and exercise are key to type 2 diabetes prevention; Type 2 diabetes is dangerous without treatment). This finding supports previous findings on the role of communication in promoting perceived control in behavioral modifications [56,57]. Outreach to people belonging to mindset l should entail information on: steps in the behavioral change process; what may assist them throughout the change process; what internal and external resources they may use; and how they may overcome barriers [58].

Messaging is to be inspirational and hopeful enhancing self-efficacy [57,58]. People who belong to Mindset2, the smallest mindset segment, will positively react to narrative messages depicting the doctor as a resource stressing the sociological view (e.g., A doctor should refer patients to educational materials about type 2 diabetes; It’s the doctor’s role to educate patients about type 2 diabetes; A patient should know all the possible treatments of type 2 diabetes). This finding supports previous studies on the sociological role of trust in physicians and the public expectation from physician to inspire them in adopting healthy behaviors [57,59].

People who are members of Mindset 3, will positively react to narrative messages depicting help from others stressing the economics and health management view (e.g., Participation in workshops helps prevent type 2 diabetes; Belonging to a community helps maintain healthy behaviors to prevent type 2 diabetes; learning how others cope with challenges is beneficial), focusing on community and available supporting health services. These findings support previous studies that claimed that communication messaging in national public campaigns may improve awareness of type 2 diabetes risks in healthy populations and among different segments of the population [23,29]. Study findings echo previous findings on the strong impact that narrative messaging may have on attitude change and behavioral modifications [29,31]. As for hypothesis 3, stating that different narrative communication messages will have a greater impact on perceived responsibility of individuals to modify their health behaviors and avoid risks of type 2 diabetes, the membership of people to mindset-segments entailed differences in their perceived responsibility. Perceived responsibility for reducing risks of type 2 diabetes ranged from self- responsibility (segment 1) to doctor’s responsibility (segment 2) and to community as having a role in helping its healthy members prevent risks of type 2 diabetes. Findings support previous studies stating that narrative messaging may play an important role in health communication campaigns to influence attitudes, intentions, and health behaviors [35].

Practice Implications

The knowledge derived from this research enables policy makers to accord the most effective narrative communication messaging to each person and group in the population, by the mind-set segmentation, in the sample. The segmentation by mindset suggests that a public communication campaign with the same messages for all, will be futile. When designing campaigns to raise public awareness of risks of type 2 diabetes, content-oriented messages should be omitted. Figures 1 and 2 indicate that segments of mindsets1 and 3 are about the same size but as age increases, on one hand the perceived importance of this information increases but perceived individual’s responsibility to modify risk behaviors decreases. People in the oldest group (56+) who are under the highest risk of type 2 diabetes, attribute the highest authority to doctors compared to people in other age groups and expect support of doctors, the community and health services (i.e. workshops) in behavior modification to prevent type 2 diabetes. These data suggest that in campaigns targeting people who are older than 45 years old, messaging is to be based on the change-process orientation rather than content-oriented. Last, three campaigns are to be designed, each targeting people in a different mindset segments and each focusing on a different perspective. One campaign entailing messages of perceived control over health (psychology), another campaign entailing messages of advice from trusted professionals (sociology) and the third campaign offering health-services (i.e., workshops and mentorship of supporting individuals) (health management) for maintaining healthy behaviors.

Future Studies

Future studies may continue to test unique features of brief printed-based narrative messaging and their effect on health attitudes and intentions. Future studies may also broaden our knowledge as to the effect of culturally tailored messaging on risk awareness in urgent health problems.

Conclusion

To sum, this study closed a knowledge gap in the state of the art examining multi-perspective narrative persuasive messaging as means to raise awareness of type 2 diabetes in healthy populations. This study presents a new approach to raise public awareness of risks of type 2 diabetes through narrative messaging by mindset segmentation. To enhance effectiveness in raising awareness of type 2 diabetes risks and to wisely allocate budgets, health professionals, policy makers and public campaign designers, are urgently called upon to use the VPI, ask the right few questions to identify the belonging of each individual in the healthy population to a mindset segment in the sample and use the appropriate narrative communication messaging per segment in raising awareness. The theoretical, methodological and practical knowledge derived from this study will enable policy makers and professionals to accord the most effective narrative communication messaging to each person and group in the population, by the mindset segmentation, in a cost-effective manner.

References

    1. Bommer C, Heesemann E, Sagalova V, Manne-Goehler J, Atun R, et al. (2017) The global economic burden of diabetes in adults aged 20-79 years: a cost-of-illness study. The Lancet Diabetes & Endocrinology 5: 423-430.
    2. Gregg EW (2017) The changing tides of the type 2 diabetes epidemic-smooth sailing or troubled waters ahead? Kelly West Award Lecture 2016. Diabetes Care 40: 1289-1297. [crossref]
    3. Rubin RR, Peyrot M, Siminerio LM (2006) Health care and patient-reported outcomes: results of the cross-national Diabetes Attitudes, Wishes and Needs (DAWN) study. Diabetes Care 29: 1249-1255. [crossref]
    4. Tiv M, Viel JF, Mauny F, Eschwege E, Weill A, et al. (2012) Medication adherence in type 2 diabetes: the ENTRED study 2007, a French population-based study. PLoS One 7: e32412.
    5. Carratalá‐Munuera FMC, Gil‐Guillen VF, Orozco‐Beltran D, Navarro‐Pérez J, Caballero‐Martínez F, et al. (2013) Barriers associated with poor control in S panish diabetic patients. A consensus study. International Journal of Clinical Practice 67: 888-894.
    6. Shadi F, Mohammad AS, Amir HZ, Amini M (2011) Effect of pharmacist-led patient education on glycemic control of type 2 diabetics: a randomized controlled trial. Journal of Research in Medical Sciences 16: 43-49. [crossref]
    7. Walker EA, Shmukler C, Ullman R, Blanco E, Scollan-Koliopoulus M, et al. (2011) Results of a successful telephonic intervention to improve diabetes control in urban adults: a randomized trial. Diabetes Care 34: 2-7. [crossref]
    8. American Diabetes Association (2013) Standards of medical care in diabetes. Diabetes Care 36: S11-S66.
    9. Atlas, Diabetes (2015) International diabetes federation. IDF diabetes atlas. Brussels: International Diabetes Federation.
    10. Guangwei L, Zhang P, Wang J, Gregg EW, Yang W, et al. (2008) The long-term effect of lifestyle interventions to prevent diabetes in the China Da Qing Diabetes Prevention Study: a 20-year follow-up study. The Lancet 371: 1783-1789.
    11. Diabetes Prevention Program Research Group (2009) 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. The Lancet 374: 1677-1686.
    12. Diabetes Prevention Program (DPP) Research Group (2002) The Diabetes Prevention Program (DPP): description of lifestyle intervention. Diabetes Care 25: 2165-2171.
    13. Sepah S, Cameron LJ, Peters AL (2015) Long-term outcomes of a Web-based diabetes prevention program: 2-year results of a single-arm longitudinal study. Journal of Medical Internet Research 17: e92. [crossref]
    14. Subramanian K, Inuka M, Chellapilla V (2017) Overcoming the challenges in implementing type 2 diabetes mellitus prevention programs can decrease the burden on healthcare costs in the United States. Journal of Diabetes Research. [crossref]
    15. Diabetes Prevention Program Research Group (2013) The 10-year cost-effectiveness of lifestyle intervention or metformin for diabetes prevention: an intent-to-treat analysis of the DPP/DPPOS. Diabetes Care 36: 4172-4175. [crossref]
    16. Butcher MK, Karl K, Vanderwood TO, Hall D, Helgerson GSD, et al. (2011) Capacity of diabetes education programs to provide both diabetes self-management education and to implement diabetes prevention services. Journal of Public Health Management and Practice 17: 242-247. [crossref]
    17. Bloomfield HE, Greer N, Kane R, Wilt JT (2017) Effects on health outcomes of a Mediterranean diet with no restriction on fat intake. Annals of Internal Medicine 166: 378-379.
    18. Riddle MC, Herman WH (2018) The cost of diabetes care-an elephant in the room. Diabetes Care 41: 929-932. [crossref]
    19. Reem K, Slater N, Sahi A, Mepani D, Lalji K, et al. (2019) Type 2 Diabetes: how informed are the general public? A cross-sectional study investigating disease awareness and barriers to communicating knowledge in high-risk populations in London. BMC Public Health 19: 138. [crossref]
    20. Okosun IS, Davis-Smith M, Seale JP (2012) Awareness of diabetes risks is associated with healthy lifestyle behavior in diabetes free American adults: evidence from a nationally representative sample. Primary Care Diabetes 6: 87-94. [crossref]
    21. Rogers EA, Fine S, Handley MA, Davis H, Kass J, et al. (2014) Development and early implementation of the bigger picture, a youth-targeted public health literacy campaign to prevent type 2 diabetes. Journal of Health Communication 19: 144-160. [crossref]
    22. Niederdeppe JQ, Bu L, Porismita B, Kindig DA, Robert SA (2008) Message design strategies to raise public awareness of social determinants of health and population health disparities. The Milbank Quarterly 86: 481-513. [crossref]
    23. Randolph KA, Whitaker P, Arellano A (2012) The unique effects of environmental strategies in health promotion campaigns: a review. Evaluation and Program Planning 35: 344-353.
    24. Robert SA, Booske BC (2011) US opinions on health determinants and social policy as health policy. American Journal of Public Health 101: 1655-1663. [crossref]
    25. Clarke CE, Niederdeppe J, Lundell HC (2012) Narratives and images used by public communication campaigns addressing social determinants of health and health disparities. International Journal of Environmental Research and Public Health 9: 4254-4277. [crossref]
    26. Siegel K, Venkat Narayan (2008) The Unite for Diabetes campaign: overcoming constraints to find a global policy solution. Globalization and Health 4: 1-8. [crossref]
    27. Somannavar S, Lanthorn H, Deepa MR, Pradeepa MR, Mohan V (2008) Increased awareness about diabetes and its complications in a whole city: Effectiveness of the “prevention, awareness, counselling and evaluation [PACE] Diabetes Project [PACE-6]. Journal of the Association of Physicians of India 56: 495-502. [crossref]
    28. Lundell HC, Niederdeppe J, Clarke CE (2013) Exploring interpretation of complexity and typicality in narratives and statistical images about the social determinants of health. Health Communication 28: 486-498. [crossref]
    29. Hinyard LJ, Kreuter MW (2007) Using narrative communication as a tool for health behavior change: a conceptual, theoretical, and empirical overview. Health Education and Behavior 34: 777-792. [crossref]
    30. Moyer-Gusé E (2008) Toward a theory of entertainment persuasion: Explaining the persuasive effects of entertainment-education messages. Communication Theory 18: 407-425.
    31. Schank R, Berman T (2002) The pervasive role of stories in knowledge and action.
    32. Gabay G (2019) Patient self-worth and communication barriers to trust of Israeli patients in acute-care physicians at public general hospitals. Qualitative Health Research 29: 1954-1966. [crossref]
    33. Bilandzic H, Busselle RW (2011) Enjoyment of films as a function of narrative experience, perceived realism and transportability. Communications 36: 29-50.
    34. Busselle R, Bilandzic H (2009) Measuring narrative engagement. Media Psychology 12: 321-347.
    35. Shen F, Sheer VC, Li R (2015) Impact of narratives on persuasion in health communication: A meta-analysis. Journal of Advertising 44: 105-113.
    36. Van Laer T, De Ruyter K, Visconti LM, Wetzels M (2014) The extended transportation-imagery model: A meta-analysis of the antecedents and consequences of consumers’ narrative transportation. Journal of Consumer Research 40: 797-817.
    37. Morgan SE, Movius L, Cody MJ (2009) The power of narratives: The effect of entertainment television organ donation storylines on the attitudes, knowledge, and behaviors of donors and non-donors. Journal of Communication 59: 135-151.
    38. Moyer-Gusé E, Chung AH, Jain P (2011) Identification with characters and discussion of taboo topics after exposure to an entertainment narrative about sexual health. Journal of Communication 61: 387-406.
    39. Moyer-Gusé E, Nabi RL (2010) Explaining the effects of narrative in an entertainment television program: Overcoming resistance to persuasion. Human Communication Research 36: 26-52.
    40. Murphy ST, Frank LB, Chatterjee JS, Baezconde-Garbanati L (2013) Narrative versus non-narrative: The role of identification, transportation, and emotion in reducing health disparities. Journal of Communication 63: 116-137. [crossref]
    41. Van Leeuwen L, Renes RJ, Leeuwis C (2013) Televised entertainment-education to prevent adolescent alcohol use: Perceived realism, enjoyment, and impact. Health Education & Behavior 40: 193-205. [crossref]
    42. Fishbein M, Ajzen I (2010) Prediction and change of behavior: The reasoned action approach. Taylor and Francis Publishing, New York.
    43. Kim HS, Bigman CA, Leader AE, Lerman C, Cappella JN (2012) Narrative health communication and behavior change: The influence of exemplars in the news on intention to quit smoking. Journal of Communication 62: 473-492. [crossref]
    44. Tal-Or N, Cohen J (2010) Understanding audience involvement: Conceptualizing and manipulating identification and transportation. Poetics 38: 402-418.
    45. Graaf DA, Hoeken H, Sanders J, Beentjes JW (2012) Identification as a mechanism of narrative persuasion. Communication Research 39: 802-823.
    46. Slater MD, Rouner D (2012) Entertainment-education and elaboration likelihood: Understanding the processing of narrative persuasion. Communication Theory 12: 173-191.
    47. Banerjee SC, Greene K (2012) Role of transportation in the persuasion process: Cognitive and affective responses to antidrug narratives. Journal of Health Communication 17: 564-581. [crossref]
    48. Gollust SE, Lantz PM, Ubel PA (2009) The polarizing effect of news media messages about the social determinants of health. American Journal of Public Health 99: 2160-2167. [crossref]
    49. Schank RC, Berman T (2006) Living stories: Designing story-based educational experiences. Narrative Inquiry 16: 220-228.
    50. Gabay G (2020) From the crisis in acute care to post-discharge resilience-The communication experience of Geriatric patients: A qualitative study. Scandinavian Journal of Caring Sciences.
    51. Green PJ, Douglas C, Goldberg SA (1981) General approach to product design optimization via conjoint analysis. Journal of Marketing 45: 17-37.
    52. Gofman A, Moskowitz HR (2010) Isomorphic permuted experimental designs and their application in conjoint analysis. Journal of Sensory Studies 25: 127-145.
    53. Moskowitz HR (1997) Base size in product testing: A psychophysical viewpoint and analysis. Food Quality and Preference 8: 247-255.
    54. Gabay G, Gere A, Stanley J, Habsburg-Lothringen C, Moskowitz HR (2019) Health threats awareness–responses to warning messages about Cancer and smartphone usage. Cancer Studies Therapeutics Journal 1-10.
    55. Orme B (2010) Getting started with conjoint analysis: strategies for product design and pricing research second edition. Madison: Research Publishers LLC.
    56. Ratanawongsa N, Karter AJ, Parker M, Heisler LM, Moffet HH, et al. (2013) Communication and medication refill adherence: the diabetes study of northern California. JAMA Internal Medicine 173: 210-218. [crossref]
    57. Gabay G (2015) Perceived control over health, communication and patient–physician trust. Patient Education and Counseling 98: 1550-1557. [crossref]
    58. Gabay G (2016) Exploring perceived control and self-rated health in re-admissions among younger adults: A retrospective study. Patient Education and Counseling 99: 800-806. [crossref]
    59. Gabay G, Moskowitz HR (2012) The algebra of health concerns: implications of consumer perception of health loss, illness and the breakdown of the health system on anxiety. International Journal of Consumer Studies 36: 635-646.

To What Extent do Fracture Clinic Patients use Smart Mobile Technology and What are Their Specific Educational and Rehabilitee Needs that can be Addressed

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DOI: 10.31038/IJOT.2020324

Abstract

Introduction: The fracture burden of the UK utilises a vast proportion of National Health Service (NHS) resources. Subsequent complications in healing result in poor patient outcomes (indirect costs) and increased demand on healthcare services (direct costs). Inadequate education regarding risk factors for poor outcomes provides a target for intervention. The increasing proportion of smartphone users makes smartphone applications (apps) a viable platform from which to distribute educational resources and conduct research.

Methods: A questionnaire was distributed randomly to 100 patients attending fracture clinic at the Queen Elizabeth Hospital in Birmingham over a twelve-week period. The mean age was 46 years (range 19 to 78), 52% female and a third were aged over 60 years. Primary questions determined the proportion of smartphone users, specifically those willing to utilise apps as an educational resource. Secondary information collected included patients’ concerns, smoking status, interest in smoking cessation and awareness of the risk factors affecting fracture healing.

Results: Almost 72% of responders used a smartphone, 71% would use an app for education and 74% would allow their data to be utilised for research. Some 60% of smokers would engage with cessation therapy through an app. The two greatest concerns identified were healing time (46%) and the long-term consequences of a fracture (46%). NSAID use was reported in 30%, however only 20% identified these as risk factor.

Conclusion: he majority of fracture clinic patients use smartphones and are were willing to utilise apps for both healthcare education and research. This could provide a cost-effective solution to an existing void in patient awareness. Developing an out-patient data collection tool offers new opportunities to epidemiological researchers.

Keywords

Fracture, Smartphone, Non-union, Education; Virtual clinic

Introduction

The incidence rate of fractures in the United Kingdom is approximated at 3.6 per 100 people per year [1]. According to recent statistics from Public Health England, the number of people aged 65 and over will increase by 40% over the next 17 years. In any year, 35% of these individuals will have a fall, and 5% of these falls will result in a fracture [2]. Fractures however, are not unique to the elderly; evidence suggests that almost one third of children will experience at least one fracture before the age of 17 [3]. This rising burden presents an immense challenge to existing NHS services striving to deliver urgent, definitive and complete follow-up care [4].

The impact on healthcare services is further increased by complications of fracture treatment, which require extended periods of follow-up and in some cases, readmission (direct costs). These complications affect up to 10% of patients within the two years of the initial injury [5]. Patients affected by complications have reported a reduction in their quality of life and a failure to return to their premorbid activity levels (indirect costs) [5,6]. Increased risk of delayed union and non-union has been associated with multiple risk factors. Whilst some, such as age, ethnicity and gender are non-modifiable, others, including prolonged NSAID use, smoking and poorly regulated diabetes management are potentially modifiable. These modifiable factors provide therapeutic targets for intervention [7-9].

Increasingly busy fracture clinics impede clinician’s ability to deliver information on fracture rehabilitation and meaningful dialogue on modifiable risk factors. This setting hinders the clinician’s ability to address patient concerns, such as answering individualised questions on healing times and functional impairment. As fracture clinics evolve, we see reduced face to face encounters with patients, the introduction of physician assistants and virtual clinics. Improved self-management following a fracture has the potential to improve patient outcomes and reduce the strain on healthcare services. Whilst there is extensive evidence for the relationship between modifiable risk factors and fracture healing, there is limited evidence surrounding public awareness of these. Without first establishing and improving public awareness, it follows that limited progress will be made in reducing the number of poor outcomes following acute fractures.

Over recent years, the number of individuals with access to a smartphones has risen exponentially [10]. A recent systematic review investigated the use of healthcare related smartphone applications by both medical professionals and patients. Findings suggested that these applications had a vital role to play in patient education, disease management and the remote monitoring of patients [11]. Considering the incidence of fractures within the UK population and the ability to therapeutically target modifiable risk factors, it is therefore surprising that to date, no smartphone application exists to educate the public on these risk factors and to give advice about fracture management. As a result, we hypothesise that current patient education regarding risk factors may be improved via education delivered through a smartphone application.

This study therefore aims to quantify the possession of smartphones in patients attending fracture clinic, and secondarily, report awareness of risk factors for fracture healing and attitudes towards the use of smartphone applications in acute fracture management.

Method

Over a twelve-week period, from June to August 2017, 144 patients attending fracture clinic at the Queen Elizabeth Hospital in Birmingham were asked to complete a questionnaire regarding their acute fracture in the waiting room. Of those approached, 100 voluntarily returned the completed forms. All patients seen in the fracture clinic for a first or follow-up appointment following both surgical and conservative management were included. The host hospital is a major trauma centre treating skeletally mature patients and comprises a limb reconstruction service. Patients not admitted via the emergency department are seen within 24 to 48 hours of their injury in fracture clinic. Skeletally immature patients were excluded as they are assessed at the regional Children’s’ Hospital.

The questionnaire was designed with an ethos of simplicity to encourage compliance and precise questions to reduce data collection bias [12]. Prior to distribution, the questionnaire was peer reviewed by senior orthopaedic clinicians and amendments made. A pilot study was also conducted on a smaller number of patients, to assess feasibility of circulation and the willingness of patients to participate. An adverse event pathway developed in case of any incidents. The final questionnaire comprised of closed and open questions to provide quantitative and qualitative information. The questionnaire included questions relating to patients’ concerns about their fracture, smoking status, interest in smoking cessation and understating of the risk factors affecting bone healing. It also recorded their level of smartphone use and willingness to engage with smartphone application in relation to their healthcare (Appendix I).

Data was collated using Microsoft Excel (Office 2016) and statistical analysis was performed using IBM SPSS Statistics 23. The trusts ethical review board deemed the study to be a service evaluation. No funding was received for this study.

Results

A total of 100 fracture clinic patients competed the questionnaire over a six-week period. The mean age of participants was 46 years (SD 16.7, range 19 to 78 years). Of the patients who completed the questionnaire 29% were over 60 years of age and of the responders 52% were female.

Smartphone Use

Of the patients who completed the questionnaire, 72% used a smartphone, of which 52% owned Apple iPhones© with IOS Software. Non-smartphone users were predominantly female (n=26, 92%) and older (mean age 62, range 45 to 76). With regards to the role of smartphone application in patient education, 71% of participants would use an application to educate themselves and support their healing journey, 15 would not and 14 patients did not respond to the question. Similarly, 74% of participants would be happy for their information to contribute towards research.

Patient Concerns

The two greatest concerns affecting patients were the time taken for the fracture to heal (46%) and the long-term consequences of an acute fracture (46%). Other concerns included functional aspects of the injury such as returning to work, driving and sport. Several patients also commented in free text box worries about the possibility of a recurrent fracture. Figure 1 below details patient concerns following an acute fracture.

fig 1

Figure 1: Patient concerns following an acute fracture.

Smoking

Of the 25 (25%) patients who admitted to smoking at the time of being interviewed 60% stated that they would engage with smoking cessation therapy via a smartphone application. Five respondents would not use smartphone applications to stop smoking and the remainder did not answer (n=5).

Analgesia

Of the patients who completed the questionnaire, 30% admitted to regular use of NSAIDs such as ibuprofen for analgesia. The most commonly used analgesic was paracetamol. Figure 2 shows the analgesia use following acute fracture.

fig 2

Figure 2: Patient analgesia use following acute fracture.

Perceived Risk Factors to Fracture Healing

There was a wide variety of responses regarding the risk factors associated with poor outcomes following a fracture. There was an increased tendency for the patients to highlight lifestyle factors such as alcohol consumption, smoking, poor diet and obesity, all of which are modifiable. The most commonly recognised risk factor was age (74%). Other factors such as ibuprofen use (20%) and diabetes (39%), were less frequently identified, despite their recognised detrimental effects on fracture healing amongst medical professionals. Interestingly, a select number of participants attributed the use of paracetamol, vegetarian diet and hypertension as risk factors, despite the lack of evidence to substantiate these. Figure 3 below represents the commonly identified risk factors to fracture healing.

fig 3

Figure 3: Perceived risk factors to fracture healing.

Discussion

This study highlights the wide demographics of patients attending fracture clinic who could benefit from personalised management via smartphone applications, with over three quarters of those questioned having access to such devices. This provides a valuable platform from which to target a large population and opens the door to health interventions delivered via mobile application and web-based tools. Smartphone use was lower in older patients, particularly females, but we anticipate this to increase over the next decade. Correspondingly, 72% of participants were happy for their anonymised data to be used in research, which could facilitate the development of large, multi-centre databases via mobile applications to be used in epidemiological research. Investment by technology industries to create clinician and patient faced applications has increased. There are already devices to help patients regulate blood glucose levels, aid smoking caseation (QuitMedGuide, University of Texas, America) and help treat dementia. Primary care is being delivered remotely via face-to-face mobile platforms (GPatHand, Babylon, London) and clinicians are increasing using smartphones to transfer images, communicate and monitor patient care.

Despite follow-up in fracture clinic, where patient education should be incorporated into the consultation, it is concerning that patient’s still lack knowledge of less publicised risk factors such as the prolonged use of NSAIDs and optimising management of chronic diseases. The disparity of the results reinforces our hypothesis that patients lack understanding and need further education to encourage favourable behaviour and promote healing. We have not investigated the causality of poor information delivery but suggest it is sequelae of limited contact time with patients in fracture clinic as clinic sizes increase and resources decrease.

The proportion of smokers within the sample size is representative of the national average of 19%. The latter percentage decreased dramatically from an all-time high of 46% in 1974 [13]. Despite this relative decrease, smoking remains a considerable factor in non-union [9,14,15]. As of 2012, Abroms et al. identified 252 smoking cessation smartphone applications for iPhone and android devices [16]. They suggested that adherence with the applications was poor overall, despite a high download rate. Similar experiences have been reported when modifying other additive behaviours, such as alcoholism, where significant decreases in risky drinking behaviour in alcoholic patients were observed following the use of an application compared to controls [17]. We hypothesise that an acute fracture may provide an opportune moment for successful lifestyle modifications.

Interestingly, patient recognition of risk factors affecting fracture healing demonstrated a trend to identify modifiable lifestyle risk factors such as smoking, obesity and alcohol consumption. These risk factors are in general well publicised by prominent public health campaigns. Established In 2012, the ‘Stoptober’ campaign has been very successful in raising awareness of the association between smoking and lung cancer [18]. Smoking was identified as a risk factor for poor fracture healing by 53% of the population questioned, however evidence suggests that smoking is more commonly identified by the population as a risk factor for cancer [19]. These findings highlight the power of patient education and the ability to target vast numbers of people with the aim of improving their self-care. On the other hand, the discrepancy between the public awareness of the effects of smoking on cancer compared to fracture healing suggests that further information must be provided to fracture patients in order for them to make adequate lifestyle modifications.

Introduced in 2009, the NHS campaign ‘Change4Life’ was targeted specifically at dietary modification to reduce childhood obesity and subsequently promote a healthier nation. A year after its launch, over 400,000 families were participating with an awareness rate of 87% amongst parents with children in the target age range [20]. Since its development, the campaign has both expanded to incorporate adult health and modernised to utilise a smartphone application providing information on food groups, exercise and recipes. The success of these public health campaigns highlights the scalability of mobile devices and reinforces the importance of patient education as the key to reducing the burden of modifiable risk factors and their consequences on NHS services.

In addition to patient identified risk factors, primary patient concerns included the time taken for the fracture to heal, as well as long term consequences of a fracture. As these figures will vary according between individuals, providing tailored information to patients about appointments, long term follow up and recovery milestones would be of benefit. Utilising the smartphone platform to engage patients would enable them to record their past and upcoming appointments whilst gaining access to information regarding cast care, return to driving and physiotherapy exercises designed to promote rapid return of function. Access to all the necessary resources in one application would act as both a source of information and a method of alleviating patient concerns.

Limitations

Although a small study, the data collected from this population is consistent with national statistics. However, it is more challenging to compare subjective measures such as level of education and understanding. The sample tested did not include children with skeletally immature fractures. The rate of non-union in children is low and many do not have behaviours that require modification [21]. Considering the lower reading age of children and diminished understanding, they were excluded from the study and the application was tailored towards adults.

Those who failed to return a completed questionnaire were not included in the study, this may constitute an element of selection bias. Conversely, it may be that patients who were more technologically aware were more inclined to complete questionnaire. It would not be able to eliminate this source of bias this unless completion was mandatory. Factors such as reporting and recall bias are also valid considerations. Although the proportion of smokers identified was in keeping with the expected level, some patients may not have reported their smoking habits truthfully.

Conclusion

Overall, this preliminary research has demonstrated the widespread use of smartphones within the patient population attending fracture and the willingness of patients to engage with healthcare information using this platform. It has also confirmed that the majority of patients would accept having their anonymised data utilised for research purposes, which could facilitate the development of large, multi-centre databases via mobile applications.

A large proportion of patients were unaware of behaviours that impaired fracture healing and focused their concerns on finite endpoints, time to healing, ability to drive and long-term morbidity. Reinforcing the need for a more targeted approach to patient management following a fracture, to address these specific agendas. This study provides evidence to support the development of software that will improve overall treatment satisfaction, educate patients and modify behaviour that may in term improve fracture care outcomes. For example, mobile devices can play a vital role in appointment planning, information on cast care, basic physiotherapy exercises and fracture healing.

References

    1. Donaldson LJ, Reckless IP, Scholes S, Mindell JS, Shelton NJ (2208) The epidemiology of fractures in England. Journal of Epidemiology and Community Health 62: 174. [crossref]
    2. England PH. Falls and fracture consensus satement: Supporting commissioning for prevention. 2017.
    3. Cooper C, Dennison EM, Leufkens HG, Bishop N, van Staa TP (2004) Epidemiology of childhood fractures in Britain: a study using the general practice research database. Journal of Bone and Mineral Research 19: 1976-1981. [crossref]
    4. (NHFD) NHFD (2016) National Hip Fracture Database (NHFD).
    5. Ekegren CL, Gabbe BJ, Edwards ER, Steiger Rd, Page R (2016) 791 Incidence, costs and outcomes of non-union, delayed union and mal-union following long bone fracture. Injury Prevention.
    6. Court-Brown CM, McQueen MM (2008) Nonunions of the proximal humerus: their prevalence and functional outcome. The Journal of Trauma 64: 1517-1521. [crossref]
    7. Hernandez RK, Do TP, Critchlow CW, Dent RE, Jick SS (2012) Patient-related risk factors for fracture-healing complications in the United Kingdom general practice research database. Acta Orthopaedica 83: 653-660. [crossref]
    8. Jiao H, Xiao E, Graves DT (2015) Diabetes and its effect on bone and fracture healing. Current Osteoporosis Reports 13: 327-335. [crossref]
    9. Patel RA, Wilson RF, Patel PA, Palmer RM (2013) The effect of smoking on bone healing: A systematic review. Bone & Joint Research 2: 102-111. [crossref]
    10. The UK is now a smartphone society The communications market report 2015: Ofcom; 2015
    11. Mosa ASM, Yoo I, Sheets L (2012) A Systematic review of healthcare applications for smartphones. BMC Medical Informatics and Decision Making 12: 67. [crossref]
    12. Edwards P (2010) Questionnaires in clinical trials: Guidelines for optimal design and administration. Trials 11: 2. [crossref]
    13. (HSCIC) HaSCIC (2016) Statistics on Smoking, Englang.
    14. Sloan A, Hussain I, Maqsood M, Eremin O, El-Sheemy M (2010) The effects of smoking on fracture healing. The surgeon: Journal of the Royal Colleges of Surgeons of Edinburgh and Ireland 8: 111-116. [crossref]
    15. Castillo RC, Bosse MJ, MacKenzie EJ, Patterson BM (2005) Impact of smoking on fracture healing and risk of complications in limb-threatening open tibia fractures. Journal of Orthopaedic Trauma 19: 151-157. [crossref]
    16. Abroms LC, Westmaas JL, Bontemps-Jones J, Ramani R, Mellerson J (2013) A content analysis of popular smartphone apps for smoking cessation. American Journal of Preventive Medicine [crossref]
    17. Gustafson DH, McTavish FM, Chih MY, Atwood AK, Johnson RA, et al. (2014) A smartphone application to support recovery from alcoholism: A randomized clinical trial. JAMA Psychiatry 71: 566-572. [crossref]
    18. Stoptober Public Health England 2012.
    19. Sanderson SC, Waller J, Jarvis MJ, Humphries SE, Wardle J (2009) Awareness of lifestyle risk factors for cancer and heart disease among adults in the UK. Patient Education and Counselling 74: 221-227. [crossref]
    20. (BHFNC) TBHFNCfPAaH. Change4Life one year on. 2010.
    21. Mills LA, Simpson AH (2013) The risk of non-union per fracture in children. Journal of Children’s Orthopaedics 7: 317-322. [crossref]

Appendix I – Unify Questionnaire

The University of Birmingham and Queen Elizabeth Hospital are designing a smartphone app for people with fractures. This app will be called MyFracture and will be tailored to each specific patient and their injury. Please could you help us by answering a few questions? Thank you.

Appendix fig 1

Appendix fig 2

Appendix fig 3

Neuroinvasive Action of SARS-CoV-2 in Coronavirus Disease (COVID-19): A Review

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DOI: 10.31038/JNNC.2020324

Abstract

Background: SARS-CoV-2 can affect different organ systems, causing a range of symptoms that include fever, cough, myalgia, fatigue, headache, diarrhea and dyspnoea; in more severe cases acute respiratory distress, acute cardiac injury and secondary infection can develop and result in death. Skin lesions, ophthalmic changes and anosmia may also occur, which may be related to the effects of the virus on the central nervous system. Because it is an emerging virus, it is not yet known precisely how the virus can affect the human brain. The aim of the present study is therefore to investigate the causal relationship between SARS-CoV-2 infection and neurological manifestations, through scientific evidence.

Methods: A systematic search was carried out in the databases SciELO, Web of Science, Science Direct, PubMed, Embase and Scopus. Initially, 912 articles were identified; at the end of the selection process and after applying the inclusion and exclusion criteria, 18 articles were selected for this review.

Results: Of the selected articles, two did not associate the neurological symptoms with the new coronavirus; despite this, both did not exclude the possibility that COVID-19 actually has neuroinvasive potential. The remaining articles attributed the neurological changes evaluated to COVID-19.

Discussion: It was reported that COVID-19 manifests itself neurologically in different ways, including stroke, Guillan-Barré syndrome, encephalopathy, convulsion, dizziness and altered consciousness.

Conclusion: Neurological symptoms that compromise the central nervous system should not be ruled out in the diagnosis of the new coronavirus. It is important to investigate neurological changes, with or without the presence of respiratory changes, as these changes may appear as the initial symptoms of COVID-19.

Keywords

COVID-19, Neuroinvasive action, Neurological changes, SARS-CoV-2

Introduction

In recent decades, a number of coronaviruses with different characteristics have appeared. Due to their capacity for mutation, recombination and infection, there is a possibility that new coronavirus variations will continue to appear [1]. Recently, a new coronavirus called SARS-CoV-2, which causes the disease COVID-19, appeared. It started in Wuhan, China, in December 2019, but quickly reached the level of a pandemic disease [2,3]. The initial reports of the infection characterized the condition as pneumonia of unknown origin; however, it has been observed that COVID-19 can affect different organ systems, causing a range of symptoms that include fever, cough, myalgia, fatigue, headache, diarrhea and dyspnoea. In more severe cases, acute respiratory distress, acute cardiac injury and secondary infection can develop which may result in death [4]. Some studies describe other clinical pictures that seem to be associated with the new disease, with symptoms such as skin lesions, ophthalmic changes and anosmia – manifestations that may be associated with the Central Nervous System (CNS) [5-7]. Since SARS-CoV-2 is an emerging virus, it is not yet known to what extent the virus can affect the human brain; therefore, the present study aims to investigate the causal relationship between SARS-CoV-2 infection and neurological manifestations, through scientific evidence.

Methods

This article is a systematic review based on the following guiding question: “Is there a causal relationship between COVID-19 and neurological manifestations?”

Search Strategy for the Identification of Studies

A search of the literature was undertaken in six databases: ScIELO, Web of Science, Science Direct, PubMed, Embase and Scopus; the descriptors (“COVID-19” OR “CORONAVIRUS” OR “SarS-CoV-2” OR “Coronavirus infections”) AND (“Neurological” OR “Nerve” OR “Brain” OR “Convulsion” OR “Nervous system”) were used. Two reviewers independently participated in each review phase (screening, eligibility and inclusion) and a third independent reviewer was invited to resolve any conflicts in the selection process.

Inclusion and Exclusion Criteria

As an inclusion criterion, articles were selected that were available in full and free of charge in the databases, written in English, Portuguese or Spanish, and published in the period between 2019 and May 2020. The exclusion criterion were: systematic reviews, meta-analyses, letters to the editor, brief communications, perspective, editorials, studies addressing psychological problems, and articles that, after reading the title and abstract, could not identified as being relevant to the proposed theme. The first search of the databases identified 10,412 articles. After applying the inclusion criteria, 912 articles were selected, of which 317 were excluded because they were duplicate texts, leaving 595 articles to be analyzed from reading the title and abstract; after this reading, 556 articles that did not fit the study criteria were eliminated and the remaining 39 articles were selected for reading in full. After reading the full texts, 21 were excluded because they did not meet the criteria previously established, leaving 18 articles to be included in the review. Figure 1 shows the systematic search strategy used to select articles for this review.

Capture

Figure 1: Flowchart of search and selection of articles.

Results

The data were organized according to the title, authorship, country, correlation between the new coronavirus and neurological changes and which neurological changes were mentioned in the articles. Table 1 shows the general characteristics of the articles identified by our systematic review.

Table 1: Details of articles included in the review.

Title Author

Year

(Country)

 Correlation Neurological manifestations
SARS-CoV-2 can induce brain and spine demyelinating lesions (Zanin et al., 2020) 2020

(Italy)

 Yes ·         Anosmia

·         Ageusia

·         Convulsion
Neurological Complications of Coronavirus Disease (COVID-19): Encephalopathy, MRI Brain and Cerebrospinal Fluid Findings: Case 2 (Espinosa et al., 2020) 2020

(USA)

 No ·         Encephalopathy

·         Altered mental state
Basal Ganglia Involvement and Altered Mental Status: A Unique Neurological Manifestation of Coronavirus Disease 2019 (Haddadi, Ghasemian and Shafizad, 2020) 2020

(Iran)

 Yes ·         Encephalopathy

 
2019 novel coronavirus pneumonia with onset of dizziness: a case report (Kong et al., 2020) 2020

(China)

 Yes ·         Dizziness
Neurological Complications of Coronavirus Disease (COVID-19): Encephalopathy (Filatov et al., 2020) 2020

(USA)

 No ·         Encephalopathy

·         Severe change in                      mental status
COVID-19 and anosmia in Tehran, Iran (Gilani, Roditi and Naraghi, 2020) 2020

(Iran)

 Yes ·         Hyposmia

·         Anosmia

·         Ageusia
Lessons of the month 1: A case of rhombencephalitis as a rare complication of acute COVID-19 infection (Wong et al., 2020) 2020

(England)

 Yes ·         Encephalopathy

·         Rhomboencephalitis
A first case of meningitis/encephalitis associated with SARS-Coronavirus-2 (Moriguchiet al., 2020) 2020

(Yamanashi)

 Yes ·         Encephalitis

·         Meningitis

·         Convulsion

·         Epileptic crisis
COVID-19 Presenting with Seizures (Sohal and Mansur, 2020) 2020

(USA)

 Yes ·         Convulsion

·         Altered mental state
Early Guillain-Barré syndrome in coronavirus disease 2019 (COVID-19): a case report from an Italian COVID-hospital (Ottaviani et al., 2020) 2020

(Italy)

 Yes ·         Guillain Barré Syndrome

·         Flaccid paralysis

·         Unilateral facial                        neuropathy
COVID-19 presenting as stroke (Avula et al., 2020) 2020

(USA)

 Yes ·         Stroke
Facial diplegia, a possible atypical variant of Guillain-Barré Syndrome as a rare neurological complication of SARS-CoV-2 (Juliao Caamaño and Alonso Beato, 2020) 2020

(Spain)

 Yes ·         Guillain Barré Syndrome

·         Facial nerve palsy
Guillain-Barré syndrome related to COVID-19 infection (Alberti et al., 2020) 2020

(Italy)

 Yes ·         Guillain Barré Syndrome

·         Paresthesia

·         Severe flaccid                          tetraparesis
Two patients with acute meningo-encephalitis concomitant to SARS-CoV-2 infection (Bernard-Valnet et al., 2020) 2020

(Switzerland)

 Yes ·         Non-convulsive                        epileptic focal status

·         Viral                                        meningoencephalitis

·         Tonic-clonic convulsion

·         Aseptic encephalitis
Plasmapheresis treatment in COVID-19-related autoimmune meningoencephalitis: Case series (Dogan et al., 2020) 2020

(Turkey)

 Yes ·         Autoimmune                            meningoencephalitis
A Case of Coronavirus Disease 2019 With Concomitant Acute Cerebral Infarction and Deep Vein Thrombosis (Zhou, B. et al., 2020) 2020

(China)

 Yes ·         Acute Cerebral Infarction
Coexistence of COVID-19 and acute ischemic stroke report of four cases (TUNÇ et al., 2020) 2020

(Turkey)

 Yes ·         Acute ischemic stroke
 

 

 

Neurologic Manifestations of Hospitalized Patients with Coronavirus Disease 2019 in Wuhan, China

  

 

 

(Mao, Jin, et al., 2020)

  

 

 

2020

(China)

  

 

 

Yes

 ·         Ischemic stroke

·         Acute                                      cerebrovascular                        disease

·         Convulsion

·         Change in sense of taste

·         Change insenseofsmell

·         Dizziness

·         Change in the level of              consciousness

·         Muscle alteration

Cerebrovascular Accident (CVA)

It is believed that COVID-19, in addition to invading the respiratory system, also causes negative effects on the nervous systems of people who are affected by this disease. Four of the studies identified in the review presented evidence of a relationship between COVID-19 infection and the development of cerebrovascular accident (CVA). A study carried out in Turkey discussed the clinical status of four patients aged between 45 and 77 years diagnosed with COVID-19 and who had acute ischemic CVA. Three of the four patients had high levels of D-dimer, and two of them had high levels of C-reactive protein (CRP); these increases may have played a considerable role in the formation of ischemia. From these findings, the authors suggested that there may be a relationship between COVID-19 and the development of ischemic cerebrovascular diseases, independently of the critical disease process [8].

Similar evidence was found in a study in the USA, in which four patients, still in the early stages of COVID-19 infection, were also diagnosed simultaneously with acute ischemic CVA. The four patients were over 70 years old and had altered mental status, weakness on either side of the body, as well as difficulty in finding words. The authors suggested that the CVA may have occurred due to hypercoagulability, which is a pathophysiology directly related to the COVID-19 infection [9]. Another study reported a case in which a 75-year-old patient, who was being treated for COVID-19, suddenly had neurological symptoms, with changes in muscle strength. Computed tomography findings of the head showed that the patient had suffered cerebral infarction and had high levels of D-dimer, suggesting hypercoagulability [10]. Corroborating the findings from the aforementioned studies, a larger study conducted with 214 patients in China reported that there were strong indications that SARS-CoV-2 can infect the nervous system and skeletal muscle, in addition to the respiratory system. Clinical data showed that just over 35% of the study patients had neurological manifestations due to the infection. In people with severe infection, neurological involvement is greater, which includes ischemic or hemorrhagic CVA, acute cerebrovascular diseases, impaired consciousness and skeletal muscle damage [6].

Guillain-Barré Syndrome

Studies show that the development of Guillan Barré Syndrome (GBS) is associated with COVID-19. A study [11] reported on a 71-year-old patient who had an acute and severe peripheral nervous system disorder, manifested by the subacute onset of paresthesia in the extremities of the limbs, followed by distal weakness that quickly evolved into severe flaccid tetraparesis. In general, these clinical findings were interpreted as a severe form of acute polyradiculoneuritis with prominent demyelinating characteristics, thus diagnosing GBS associated with COVID-19 [11]. Another case occurred in Spain, where a 61-year-old patient infected with COVID-19 was diagnosed with paralysis of the right peripheral facial nerve with an eye reflex that did not respond to the stimulus, but without other neurological symptoms. Due to facial diplegia, the authors believe that this neurological disorder is a rare variant of GBS directly related to COVID-19 infection [12]. Similarly, in Italy, a 66-year-old patient diagnosed with COVID-19 infection presented a clinical picture consistent with GBS, which started with progressive difficulty in walking and acute fatigue, initial distal weakness in the upper limbs, diffuse areflexia, but without any clear sensory deficits. The patient progressively developed proximal weakness in all limbs, dysesthesias and unilateral facial paralysis, with increasing flaccid weakness of the limbs [13].

Encephalopathy

There were two cases of encephalopathy and COVID-19 in the same center, in very close periods. In the first case, a 72-year-old man hospitalized due to COVID-19 infection, did not show neurological improvement after sedation, did not respond to verbal commands, and did not show any reaction to noxious painful stimuli. For diagnostic clarification, an electroencephalogram (EEG) was performed after the patient had been sedated for 72 hours and showed only bilateral deceleration consistent with encephalopathy; however, when a puncture was performed with analysis of cerebrospinal fluid, no evidence was found to suggest meningitis or encephalitis. Thus, the authors concluded that the virus does not appear to cross the blood-brain barrier, even if patients with COVID-19 develop encephalopathy. In this case, the authors believe that the cause of encephalopathy was multifactorial, but stressed that the virus may have contributed to the encephalopathy [14]. In the second case at the same center [15] reported on a 74-year-old patient who presented encephalopathy with severe mental status changes, without verbal communication and unable to follow any command, but without motor changes. The study reported that patients with COVID-19 may have encephalopathy; however, the authors did not attribute the neurological complications to COVID-19, and did not consider encephalopathy to be a symptom or complication of COVID-19 in this case.

In a similar study in Iran, the authors reported that a 54-year-old patient diagnosed with COVID-19 presented disorders related to encephalopathy, manifesting severe changes in mental status, without verbal communication and unable to follow any order; however, he did not present any motor alteration, being able to move all of his extremities. Therefore, the authors emphasized the importance of considering neurological manifestations as a consequence of COVID-19, and stressed that it is necessary to understand the pathways of viral neuroinvasion in order to improve the fight against the new coronavirus [16]. Unlike the previously mentioned cases, in a study from the United Kingdom the authors attributed neurological changes to COVID-19 infection, in a case report in which a 40-year-old man developed acute brain stem dysfunction after being infected with COVID-19. Magnetic resonance imaging of the brain and cervical spine showed inflammation of the brain stem and upper cervical cord, leading to a diagnosis of inflammatory rhombencephalitis/myelitis, with the authors concluding that rhombencephalitis is a complication of COVID-19 infection [17].

A case of encephalitis as a result of COVID-19 was described by a study [18] in which a 24-year-old patient, hospitalized with a diagnosis of COVID-19, underwent an MRI scan that demonstrated abnormal findings in the temporal lobe, including in the hippocampus, suggesting encephalitis. The authors emphasized the importance of paying attention to the symptoms of encephalitis or cerebropathy, as these, in addition to respiratory symptoms, may be the first indication of SARS-CoV-2. A study [19] reported the case of two patients who developed autoimmune meningoencephalitis a few days after a diagnosis of mild COVID-19 infection. The patients developed severe neuropsychological symptoms suddenly and after specific exams, the hypothesis was that meningoencephalitis was derived from COVID-19; thus, the authors made the temporal association between acute SARS-CoV-2 infection and aseptic encephalitis with focal neurological symptoms and signs [19]. Finally, the study [20] reported on a series of cases in which the involvement of COVID-19 in the CNS was diagnosed in 6 of 29 intubated patients. A neurological investigation was carried out by means of specific tests, as some patients were unable to regain consciousness or developed agitated delirium during the weaning period, and found evidence that was compatible with autoimmune meningoencephalitis. The authors hypothesized that the neurological changes in the CNS were associated with COVID-19 [20].

Convulsions

In a case report, a 64-year-old patient with a positive result for COVID-19 infection presented with tonic-clonic seizure after being hospitalized with acute psychotic symptoms; he also had disorientation, strong attention deficit and psychotic symptoms. A routine electroencephalogram revealed non-convulsive epileptic focal status, which contributed to the association between acute COVID-19 infection and the neurological symptom [19]. In another study, a 54-year-old patient was admitted to hospital after being found unconscious at home; after a brief neurological examination the patient did not present any focal sensorimotor deficits. However, she presented disturbances of consciousness and convulsions, these symptoms being consistent with neurological involvement resulting from infection by SARS-CoV-2. The authors pointed out that sudden neurological impairment with convulsions in COVID-19 patients may occur due to CNS involvement and demyelinating lesions [21]. In agreement with the previous cases, another study reported a case of convulsion associated with COVID-19, in which a 24-year-old patient was transported to hospital following a convulsion and unconsciousness. In the ambulance, the patient had a transient generalized convulsion that lasted for about a minute. After arriving at hospital, the patient needed mechanical ventilation due to multiple epileptic convulsions. The differential diagnosis was post-convulsive encephalopathy [18].

A study in China reported the case of a patient who had a seizure characterized by the sudden onset of limb spasms, foaming at the mouth and loss of consciousness, which lasted for three minutes. The authors concluded that SARS-CoV-2 may infect the nervous system and cause several neurological changes [6]. Similarly, a case was presented in which a 72-year-old patient, with no previous history of convulsion, developed several convulsive episodes after being transferred to the intensive treatment unit due to complications derived from COVID-19. The causal relationship between COVID-19 and neurological manifestations, such as the appearance of convulsion, was highlighted [22].

Dizziness

A study carried out in China highlighted the presence of dizziness as an initial symptom of COVID-19 infection. A 53-year-old patient complained of sudden dizziness for three days, with no apparent cause. He did not show any other neurological symptoms, and had a normal MRI result. However, he presented the characteristic symptoms of the infection and tested positive for COVID-19. From these findings, the authors concluded that COVID-19 can manifest itself in the nervous system, and suggest that greater attention should be paid to complaints of dizziness by patients, as it may be an early symptom of COVID-19 [23]. In a series of retrospective and observational cases that included 214 hospitalized patients with a confirmed diagnosis in the laboratory of infection with the new coronavirus, in patients who manifested changes in the central nervous system, dizziness was the most common symptom, being reported by 36 of the patients. The authors concluded that the more severe the patient’s clinical condition, the worse the neurological manifestation associated with COVID-19 infection can be [6].

Other Neurological Manifestations

Studies cite other neurological changes, but not all discussed in detail how the changes occurred and how they were associated with COVID-19. Table 2 describes other manifestations mentioned in the studies selected by this review.

Table 2: Other manifestations described in the articles.

Neurological Alteration

References
Change in Taste/Ageusia (GILANI, RODITI AND NARAGHI, 2020; MAO et al., 2020a)
Smell Change/Anosmia/Hypogeusia (GILANI, RODITI AND NARAGHI, 2020; MAO et al., 2020a; ZANIN et al., 2020)
Change in mental status (ESPINOSA et al., 2020; FILATOV et al., 2020; Mao et al., 2020a; SOHAL E MANSUR, 2020)
Muscle alteration (ALBERTI et al., 2020; MAO et al., 2020a)

Most of the selected articles were case reports and some of them discussed more than one neurological disorder, not being restricted to just one symptom, as can be seen in Figure 2.

fig 2

Figure 2: Symptoms cited in articles.

Discussion

COVID-19 is a relatively new disease, and it is not yet known how it behaves neurologically. Of the articles in this review, only two of the studies did not associate the neurological symptoms described with the new coronavirus, although neither excluded the possibility that COVID-19 has neuroinvasive potential. The number of studies that aim to explore the virus’s action in the brain is growing, and there are several that have already shown neurological changes due to SARS-CoV-2 infection [24-28]. Current evidence, therefore, suggests that there is a risk of developing neurological diseases as a result of COVID-19, but it is not yet known what the possible long-term neurological sequelae might be [29]. In respect of this emerging evidence suggesting that SARS-CoV-2 is associated with neurological changes in patients with COVID-19, particularly in those with severe clinical manifestations, there are three feasible scenarios: the first is that the impact of SARS-CoV-2 on the CNS could lead to neurological changes directly; the second is that it could aggravate pre-existing neurological conditions; and the third is that it could increase susceptibility to the infection, or aggravate the damage it causes [30,31]. It is believed that, together with the host’s immunological mechanisms, SARS-CoV-2 can cause infections to result in neurological diseases [28].

A recent study highlighted the possibility that SARS-CoV-2 reaches the central nervous system through the olfactory bulb and infects the olfactory nerve; from there, it would spread to various parts of the brain via trans-synaptic transmission and infect the PreBotzinger complex (PBC) in the brain stem, the brain’s respiratory center that controls the lungs, shutting off breathing and potentially causing death [30]. Olfactory and gustatory disorders have been found as prevalent symptoms among infected patients, and studies have stressed the importance of recognizing anosmia and ageusia as relevant symptoms in the diagnosis of COVID-19 [32,33]. Hyposmia and hypogeusia, together with dizziness, headaches and stroke have all been widely reported in patients with COVID-19, and could all be associated with neurological changes that affect the central nervous system [31]. Among the various neurological changes described in the articles in this review, the most prevalent was encephalopathy and similar changes, also with the presence of seizures, data that corroborates other studies which discuss the presence of encephalopathy associated with the new coronavirus [34,35]. The presence of necrotizing encephalitis associated with COVID-19 was also seen, but without evidence of viral isolation from cerebrospinal fluid. This neurological change can lead to brain dysfunction caused by the virus, which results in seizures and mental disorientation after infection [36]. The presence of seizures in the clinical picture calls attention to the possible involvement of SARS-CoV-2 in the neurological system. They can occur as a result of infection, an acute systemic disease, a primary neurological disease, or the adverse effect of medication on critically ill patients, and can present a variety of symptoms, ranging from seizure activity, subtle spasms and even lethargy [36,37]. In a number of studies identified in the review, Guillain-Barré syndrome was considered by the authors to be a possible important neurological complication of COVID-19 infection. It is imperative that medical teams pay attention to the presence of this syndrome, as it can lead to admission to the intensive care unit (ICU) and needs to be differentiated from a possible weakness acquired in the ICU after treatment [38-40].

Studies carried out recently have observed that patients with COVID-19 have an increased risk of cerebrovascular disease the incidence is similar to other critical illnesses. This has been widely reported as causing cytokine storm syndromes that may be one of the factors that leads to stroke [37,41]. Ischemic stroke associated with COVID-19 infection can occur in the context of a highly prothrombotic systemic state, and it is necessary to pay extra attention to the signs, as there is a strong association between SARS-CoV-2 and the development of systemic thromboembolisms due to a hypercoagulable state. This possibility, regardless of the patient’s age, makes it necessary to increase the awareness of the health team about severe forms of ischemia and systemic stroke in patients with signs of COVID infection, in order to provide all patients with the best possible care [42-44]. In view of the severity of the neurological changes that can occur in infected patients, early assessments of neurological symptoms are necessary. The assessment should investigate headaches, disturbances in consciousness, paresthesia, ageusia, paralysis, among other factors. Timely cerebrospinal fluid analysis, and awareness and management of infection-related neurological complications are critical to improving the prognosis of critically ill patients [28].

Conclusion

The new coronavirus manifests itself neurologically in different ways, including headache, paraesthesia, encephalopathy, altered consciousness, Guillain-Barré syndrome, dizziness, seizure, stroke, among other conditions. These different neurological symptoms that affect patients and compromise the central nervous system should not be ruled out in the differential diagnosis of the new coronavirus. The health professional needs to be aware of these symptoms and request an evaluation from a neurologist to confirm the clinical suspicions; close attention should be paid to possible neurological conditions in patients who are suspected of having COVID-19 infection. The respiratory changes caused by COVID-19 infection are well documented, but it is important that attention is also focused on neurological changes, as they can cause serious damage to patients affected by the infection. This is particularly the case with patients who have comorbidities or are part of the risk group with previous diseases, as they are more susceptible to developing complications.

It is not yet known with certainty whether the neurological damage is temporary or permanent after the patient has recovered from COVID-19. Studies that aim to verify the presence of neurological damage in patients previously affected by the new coronavirus are necessary, so that the extent of any damage can be scientifically assessed. As the disease only emerged relatively recently, there is still a lack of knowledge in the scientific community regarding the subjects addressed here. Finally, the importance of investigating neurological changes is emphasized, with or without the presence of respiratory changes, as these changes may appear as the initial symptoms of COVID-19, thus being able to help in a faster and more accurate diagnosis, in order to provide better treatment for the patient.

Acknowledgments

The authors dedicate this article to all health professionals who are facing COVID-19. We are eternally grateful to them, and hope that our article can contribute to reducing the number of deaths.

Author contributions: All authors have read and agreed to the published version of the manuscript.

Funding: This research was not funded. The authors themselves financed it.

Conflicts of interest: The authors have declared that there is no conflict of interest.

References

    1. Fehr AR, Perlman S (2015) Coronaviruses: An Overview of Their Replication and Pathogenesis. Coronaviruses: Methods and Protocols 1282: 1-282. [crossref]
    2. Zhu N, Zhang D, Wang W, Li X, Yang B, et al. (2020) A Novel Coronavirus from Patients with Pneumonia in China, 2019. New England Journal of Medicine 382: 727-733. [crossref]
    3. World Health Organization (2020) Coronavirus disease (COVID-19) pandemic. Geneva: WHO. URL: htps://www.who.int/emergencies/diseases/novel-coronavirus-2019.
    4. HUANG C, WANG Y, LI X, REN L, ZHAO J, et al. (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet 395: 497-506. [crossref]
    5. GALVÁN CC, CATALÀ A, CARRETERO HG, RODRÍGUEZ JP, FERNÁNDEZ ND, et al. (2020) Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases. British Journal of Dermatology 183: 71-77. [crossref]
    6. MAO L, JIN H, WANG M, HU Y, CHEN S, et al. (2020) Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China. Jama Neurology 77: 683-690. [crossref]
    7. ZHOU B, SHE J, WANG Y, MA X (2020) A Case of Coronavirus Disease 2019 with Concomitant Acute Cerebral Infarction and Deep Vein Thrombosis. Frontiers in Neurology 11: 2-5. [crossref]
    8. TUNÇ A, ÜNLÜBAŞ Y, ALEMDAR M, AKYÜZ E (2020) Coexistence of COVID-19 and acute ischemic stroke report of four cases. Journal of Clinical Neuroscience 77: 227-229. [crossref]
    9. AVULA A, NALLEBALLE K, NARULA N, SAPOZHNIKOV S, DANDU V, et al. (2020) COVID-19 presenting as stroke. Brain, Behavior, and Immunity 87: 115-119. [crossref]
    10. ZHOU Y, LI W, WANG D, MAO L, JIN H, et al. (2020) Clinical time course of COVID-19, its neurological manifestation and some thoughts on its management. Stroke and Vascular Neurology 5: 177-179. [crossref]
    11. ALBERTI P, BERETTA S, PIATTI M, KARANTZOULIS A, PIATTI ML, et al. (2020) Guillain-Barré syndrome related to COVID-19 infection. Neurology: Neuroimmunology and NeuroInflammation 7: 1-4. [crossref]
    12. CAAMAÑO DSJ, BEATO RA (2020) Facial diplegia, a possible atypical variant of Guillain-Barré Syndrome as a rare neurological complication of SARS-CoV-2. Journal of Clinical Neuroscience 77: 230-232. [crossref]
    13. OTTAVIANI D, BOSO F, TRANQUILLINI E, GAPENI I, PEDROTTI G, et al. (2020) Early Guillain-Barré syndrome in coronavirus disease 2019 (COVID-19): a case report from an Italian COVID-hospital. Neurological Sciences 41: 1351-1354.
    14. ESPINOSA PS, RIZVI Z, SHARMA P, HINDI F, FILATOV A (2020) Neurological Complications of Coronavirus Disease (COVID-19): Encephalopathy, MRI Brain and Cerebrospinal Fluid Findings: Case 2. Cureus [crossref]
    15. FILATOV A, SHARMA P, HINDI F, ESPINOSA PS (2020) Neurological Complications of Coronavirus Disease (COVID-19): Encephalopathy. Cureus [crossref]
    16. HADDADI K, GHASEMIAN R, SHAFIZAD M (2020) Basal Ganglia Involvement and Altered Mental Status: A Unique Neurological Manifestation of Coronavirus Disease 2019. Cureus [crossref]
    17. WONG PF, CRAIK S, NEWMAN P, MAKAN A, SRINIVASAN K, et al. (2020) Lessons of the month 1: a case of rhombencephalitis as a rare complication of acute covid-19 infection. Clinical Medicine 20: 293-294. [crossref]
    18. MORIGUCHI T, HARII N, GOTO J, HARADA D, SUGAWARA H, et al. (2020) A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. International Journal of Infectious Diseases 94: 55-58. [crossref]
    19. BERNARD-VALNET R, PIZZAROTTI B, ANICHINI A, DEMARS Y, RUSSO E, et al. (2020) Two patients with acute meningo-encephalitis concomitant to SARS-CoV-2 infection. European Journal of Neurology, 2020. doi:10.1111/ene.14298
    20. DOGAN L, KAYA D, SARIKAYA T, ZENGIN R, DINCER A, et al. (2020) Plasmapheresis treatment in COVID-19-related autoimmune meningoencephalitis: Case series. Brain, Behavior, and Immunity 155-158. [crossref]
    21. ZANIN L, SARACENO G, PANCIANI PP, RENISI G, SIGNORINI L, et al. (2020) SARS-CoV-2 can induce brain and spine demyelinating lesions. Acta Neurochirurgica 162: 1491-1494. [crossref]
    22. SOHAL S, MANSUR M (2020) COVID-19 Presenting with Seizures. ID Cases 20: e00782. [crossref]
    23. KONG Z, WANG J, LI T, ZHANG Z, JIAN J (2020) 2019 Novel Coronavirus Pneumonia With Onset of Dizziness: a Case Report. Annals of Translational Medicine 8: 506-506. [crossref]
    24. GILANI S, RODITI R, NARAGHI M (2020) COVID-19 and anosmia in Tehran, Iran. Medical Hypotheses 141: 109757. [crossref]
    25. AZIM D, NASIM S, KUMAR S, HUSSAIN A, PATEL S (2020) Neurological Consequences of 2019-nCoV Infection : A Comprehensive Literature Review. Cureus
    26. SANTOS MF, DEVALLE S, ARAN V, CAPRA D, ROQUE NR, et al. (2020)Neuromechanisms of SARS-CoV-2: A Review. Frontiers in Neuroanatomy 14: 1-12. [crossref]
    27. MUNHOZ RP, PEDROSO JL, NASCIMENTO FA, ALMEIDA SM DE, BARSOTTINI OGP, et al. (2020) Neurological complications in patients with SARS-CoV-2 infection: a systematic review. Arquivos de neuro-psiquiatria 78: 290-300. [crossref]
    28. WU Y, XU X, CHEN Z, DUAN J, HASHIMOTO K, et al. (2020) Nervous system involvement after infection with COVID-19 and other coronaviruses. Brain, Behavior and Immunity 87: 18-22. [crossref]
    29. HENEKA MT, GOLENBOCK D, LATZ E, MORGAN D, BROWN R (2020) Immediate and long-term consequences of COVID-19 infections for the development of neurological disease. Alzheimer’s research & therapy 12: 69.
    30. FELICE FG, TOVAR-MOLL F, MOLL J, MUNOZ DP, FERREIRA ST (2020) Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the Central Nervous System. Trends in Neurosciences 43: 355-357. [crossref]
    31. MAO L, WANG M, CHEN S, HE Q, CHANG J, et al. (2020) Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: a retrospective case series study. Med Rxiv 77:683-690. [crossref]
    32. GIACOMELLI A, PEZZATI L, CONTI F, BERNACCHIA D, SIANO M, et al. (2020) Self-reported olfactory and taste disorders in SARS-CoV-2 patients: a cross-sectional study. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 2-3. [crossref]
    33. LECHIEN JR, ESTOMBA CMC, SIATI DR, HOROI M, BON SDL, et al. (2020) Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. European Archives of Oto-Rhino-Laryngology 277: 2251-2261. [crossref]
    34. ASADI-POOYA AA (2020) Seizures associated with coronavirus infections. Seizure: European Journal of Epilepsy 79: 49-52. [crossref]
    35. YE M, REN Y, LV T (2020) Encephalitis as a clinical manifestation of COVID-19. Brain, Behavior, and Immunity 88: 945-946. [crossref]
    36. POYIADJI N, SHAHIN G, NOUJAIM D, STONE M, PATEL S, et al. (2020) COVID-19–associated Acute Hemorrhagic Necrotizing Encephalopathy: imaging features. Radiology 296: 119-120. [crossref]
    37. LI YC, BAI WZ, HASHIKAWA T (2020) Theneuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. Journal of Medical Virology 92: 552-555. [crossref]
    38. CAMDESSANCHE JP, MOREL J, POZZETTO B, PAUL S, THOLANCE Y, et al. (2020) COVID-19 may induce Guillain–Barré syndrome. Revue Neurologique 176: 516-518. [crossref]
    39. SEDAGHAT Z, KARIMI N (2020) GuillainBarresyndrome associated with COVID-19 infection: A case report. Journal of Clinical Neuroscience 76: 233-235. [crossref]
    40. ZHAO H, SHEN D, ZHOU H, LIU J, CHEN S (2020) Guillain-Barré syndrome associated with SARS-CoV-2 infection: causality or coincidence? The Lancet Neurology 19: 383-384. [crossref]
    41. MEHTA P, MCAULEY DF, BROWN M, SANCHEZ E, TATTERSALL RS, et al. (2020) COVID-19: consider cytokine storm syndromes and immunosuppression. The Lancet 395: 1033-1034. [crossref]
    42. BEYROUTI R, ADAMS ME, BENJAMIN L, COHEN H, FARMER SF, et al. (2020) Characteristics of ischaemic stroke associated with COVID-19. Journal of Neurology, Neurosurgery and Psychiatry 8-11. [crossref]
    43. GONZÁLEZ-PINTO T, LUNA-RODRÍGUEZ A, MORENO-ESTÉBANEZ A, AGIRRE-BEITIA G, RODRÍGUEZ-ANTIGÜEDAD A, et al. (2020) Emergency Room Neurology in times of COVID-19: Malignant Ischemic Stroke and SARS-COV2. Infection. European Journal of Neurology 1: 1-2. [crossref]
    44. SAIEGH FA, GHOSH R, LEIBOLD A, AVERY MB, SCHMIDT RF, et al. (2020) Status of SARS-CoV-2 in cerebrospinal fluid of patients with COVID-19 and stroke. Journal of Neurology, Neurosurgery & Psychiatry 91: 846-848. [crossref]

When two pandemics meet

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Abstract

The COVID-19 pandemic has emerged in the middle of another pandemic which is far from under control: the cardiometabolic syndrome pandemic. Recently published data suggests patients with obesity are at a higher risk of being hospitalized and placed on a mechanical ventilator for COVID-19 than patients with a normal body weight. We discuss the pathophysiology behind this relationship and the implications in the global fight against COVID-19.

Keywords

COVID-19; coronavirus; obesity; cardiometabolic syndrome.

No one single mechanism is responsible for disease progression into severity in COVID-19 cases as in almost all diseases -chronic or not, transmissible or not-. We as scientists are trained to observe, identify differences and similarities between cases and arrive at possible explanations called hypothesis that can help the scientific community to develop effective strategies to combat the illness.

To this day several factors have been identified and when put together they tell a storyline that sums up the pathophysiology of severity in COVID-19 shown in Figure 1.

EDMJ-4-2-405-g001

Figure 1. Schematic representation of shared pathophysiology in COVID-19 cases with underlying metabolic illness. [1]. DIC: Disseminated Intravascular Coagulation.

But how does this scenario come to be? The answer comes from a previous pandemic that has been around for many years: the Cardiometabolic Syndrome (CMS) pandemic. CMS is defined by a combination of metabolic disorders that include diabetes mellitus, systemic arterial hypertension, central obesity, and dyslipidemia. All these conditions lead to elevated heart disease risk, which in turn is the leading cause of death in first world countries and doesn´t fall far behind in the rest of the world as well. This global epidemic to some doesn´t seem so scary being that it cannot be transmitted through droplets or by touching “infected” surfaces. Thisidea, however, isn´t completely true. The first risk factor for this group of diseases is being overweight or obesity, and this is in a sense “transmitted”. Eating habits are a cultural phenomenon, and from one generation to the next, families and communities pass on grocery lists, recipes and pantry contents. As of 2019 the global mean prevalence of obesity was measured at 19.5%. This number has almost tripled since 1975 and is currently the number one risk factor associated with premature death. Obesity as a risk factor for disease usually means it leads to chronic diseases such as the ones previously mentioned, but nowadays we are observing a different consequence of being overweight. An elevated body mass index has become a high-risk factor for severity in COVID-19 cases. [2]

Table 1 shows the evidence on the previous statement. A study by Zheng et al of 214 patients in Wuhan, China with laboratory confirmed COVID-19 showed that the presence of a Body Mass Index (BMI) >25 kg/m2 was associated with a near-6 fold increased risk of severe illness, even after adjusting for age and other comorbidities. [3] Of 4,103 COVID-19 cases in New York City the chronic condition which conferred the strongest association with critical illness was obesity, with 39.8% of hospitalized patients having obesity. [4]

Table 1. Epidemiological studies on COVID-19 outcomes and obesity related risk-factors

Author, Region and Date

Subjects

Findings

Z. Wu [7]
Mainland China
Updated Feb 11, 2020

72,314 suspicious cases of COVID-19
44,672 lab-confirmed cases

2.3% Case-Fatality Rate
Mild cases 81%
Severe cases 14%
Critical cases 5%

S. Garg [8]
USA (COVID-NET)
March 1-30, 2020

1,482 hospitalized patients

89% of patients had one or more underlying conditions:
Hypertension 49.7%
Obesity 48.3%
Chronic lung disease 34.6%
Diabetes Mellitus 28.3%
Cardiovascular disease 27.88%

Among patients 18-49 years-old obesity was the most prevalent underlying condition (59%).

P. Goyal [9]
New York City, US
Mar 3-27, 2020

First 393 cases of COVID-19 adults hospitalized in New York

Patients who required invasive mechanical ventilation were more likely to be male, have obesity and elevated liver-function and inflammatory markers.

S. Richardson [10]
New York, USA
Mar 1 – Apr 4, 2020

5,700 hospitalized patients

Most common comorbidities among hospitalized patients:
Hypertension 56.6%
Obesity 41.7% – (Morbid obesity 19%)
Diabetes Mellitus 33.8%

G. Grasselli [11]
Milan, Italy
Feb 20 – Mar 18, 2020

73 patients in intensive care unit

Over 80% of patients in ICU were overweight or had obesity.
Normal weight – 19%
Overweight – 51.9%
Obesity 1 – 15.4%
Obesity 2 – 11.5%
Obesity 3 – 1.9%

Zheng [3]
Wenzhou, China
Jan 1 – Feb 29, 2020

214 patients with lab confirmed COVID-19
Ages 18-75

A BMI equal to or greater than 25 kg/m2 was associated with a 6-fold increased risk of severe illness.
This risk remained significant even after adjusting for age and other comorbidities.

Petrilli [4]
New York
Mar 1 – Apr 7, 2020

4,103 cases of COVID-19
1,999 hospitalized

The chronic condition with the strongest association to critical illness was obesity.
39.8% of hospitalized patients had obesity.

Qingxian [12]
Mainland China
Jan 11 – Feb 16, 2020

383 patients admitted to a hospital in Shenzen

After adjusting for age, sex, disease history and treatment the overweight group was 2.42 times more likely to develop severe pneumonia.

A. Simonnet [5]
Lille, France
Feb 27 – Apr 5, 2020

124 patients admitted to ICU for COVID-19.
Compared to control group from 2019

Obesity was significantly more frequent among cases of COVID-19 (47.6%) compared to control group (25.2%).
The median BMI of patients requiring intubation was 31.1 kg/m2 compared to 27 kg/m2 in the patients who did not require intubation.
In individuals with a BMI ³35 kg/m2 the odds ratio for intubation was 7.36 compared to individuals with a normal BMI.

Among 124 patients admitted for COVID-19 to a hospital in Lille, France 47.6% had obesity. Patients with a BMI of greater than 35 kg/m2 were 7.36 times more likely to require a ventilator than patients with a BMI of less than 25 kg/m2. [5] In Milan more than 80% of 73 patients treated in an ICU were overweight or had obesity, when the rates of overweigh and obesity in Italy are only 35.4% of the population. [6]

Two main explanations play a role in this complicated infectious disease in association with weight problems. The first one is the chronic inflammatory state it conveys. Recent studies have found that adipose tissue secretes extracellular vesicles that function as vectors which can modify cellular function in the recipient through the information they carry. Data suggests that this mechanism is used by fat to induce monocyte differentiation into active macrophages and high secretion of IL-1 and TNF-α among other cytokines. [13] The second one is the fact that patients with obesity have been found to have higher concentrations of pro-thrombotic factors as compared to normal-weight controls. Some of these altered parameters include higher D-dimer, fibrinogen and factor VII; as well as lower fibrinolysis because of higher plasminogen activator inhibitor-1. [14]

Besides increased inflammatory cytokines, obesity englobes several pathophysiological factors which affect the risk and outcomes of patients with COVID-19. In the respiratory tract obesity may cause pulmonary restriction, decreased pulmonary volumes and ventilation-perfusion mismatching. Patients with obesity are more likely to present diabetes mellitus and atherosclerosis which may be complicated by COVID-19. Additionally, there is limited data on the right dosing of antimicrobials in obesity and bioavailability of drugs used to treat patients with this disease may be affected by altered protein binding, metabolism and volume of distribution. [15]

On the other hand, new information is developing every day concerning COVID-19 cases and more data is suggesting that bad prognosis is linked to thromboembolic events caused by inflammation, hypoxia and coagulation abnormalities. One study by Klok et alstudied 184 Intensive Care Unit (ICU) patients with confirmed COVID-19, and found that 31% showed thrombotic complications, of which 81% was due to pulmonary embolism. [16] When we put two and two together, the relationship becomes apparent. Obesity is a clear catalyzer for severe COVID-19 cases. In a country like Mexico, where the prevalence for overweight and obesity in over 20-year-olds is 75.2%, this relationship is very threatening. [17]

It seems that the best way to prevent bad outcomes from this novel disease (as well as from infectious diseases in general) is to be in good health prior to contracting it in the first place. As for those patients who already suffer from CMS or one of its components, preventive treatment is our main recommendation. These patients should be at optimal glycemic, systemic arterial pressure and cholesterol level goals. A study by Carter et al also suggests that vitamin D deficiencies (also more common in patients with obesity) have been linked to worse cytokine storms. To this end, physical activity as well as sun exposure is effective ways to boost vitamin D levels. [18]

This sound reasonable, right? Well, reasonable doesn´t always mean achievable in all populations. Vulnerable communities around the world are struggling every day just to have access to general medical attention. These communities are also at an increased risk of exposure to COVID-19. Working from home is a privilege that is unavailable for many people from a lower socio-economic status. Social distancing is considerably more difficult for people living in overcrowded neighborhoods. Emerging epidemiological studies in the U.S. suggest a disproportionate burden of illness and higher death rates among minority groups. [9]

Currently there is no gold standard treatment for COVID-19, however, all this data suggests that global efforts need to be directed towards prevention and education. Pre-existing conditions need to be under control and lifestyle habits should be aimed towards getting enough exercise and a proper nutrition. [19,20]

References

  1. Xiong M, Liang X, Wei YD (2020) Changes in Blood Coagulation in Patients with Severe Coronavirus Disease 2019 (COVID‐19): A Meta‐Analysis. Br J Haematol.[crossref]
  2. Blüher M (2019)Obesity: global epidemiology and pathogenesis. Nat Rev Endocrinol15:288-298.
  3. Zhou F, Yu T, Du R, Fan G, Liu Y et al. (2020) Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet.395: 1054-1062. [crossref]
  4. Petrilli CM, Jones SA, Yang J, Rajagopalan H, O’Donnell LF, Chernyak Y, Horwitz LI (2020) Factors associated with hospitalization and critical illness among 4,103 patients with COVID-19 disease in New York City. medRxiv.
  5. Simonnet A, Chetboun M, Poissy J, Raverdy V, Noulette J et al. (2020) Intensive Care COVID‐19 and Obesity study group. High prevalence of obesity in severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) requiring invasive mechanical ventilation. Obesity.[crossref]
  6. Zangrillo A, Beretta L, Scandroglio AM, Monti G, Fominskiy E (2020) Characteristics, treatment, outcomes and cause of death of invasively ventilated patients with COVID-19 ARDS in Milan, Italy. Crit Care Resusc.[crossref]
  7. Wu Z, McGoogan JM (2020) Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention. Jama.[crossref]
  8. Garg S (2020) Hospitalization rates and characteristics of patients hospitalized with laboratory-confirmed coronavirus disease 2019—COVID-NET, 14 States, March 1–30, 2020. MMWR. Morbidity and Mortality Weekly Report 69.
  9. Goyal P, Choi JJ, Pinheiro LC, Schenck EJ, Chen R, Jabri A, Hoffman KL (2020) Clinical Characteristics of Covid-19 in New York City. New England Journal of Medicine..[crossref]
  10. Richardson S, Hirsch JS, Narasimhan M, Crawford JM, McGinn T et al. (2020) Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area. JAMA.[crossref]
  11. Grasselli G, Zangrillo A, Zanella A, Antonelli M, Cabrini L et al. (2020) Baseline characteristics and outcomes of 1591 patients infected with SARS-CoV-2 admitted to ICUs of the Lombardy Region, Italy. Jama. [crossref]
  12. Qingxian C, Fengjuan C, Fang L, Xiaohui L, Tao W et al. (2020) Obesity and COVID-19 severity in a designated hospital in Shenzhen, China. China.
  13. Kim A, Shah AS, Nakamura T (2018) Extracellular Vesicles: A Potential Novel Regulator of Obesity and Its Associated Complications. Children 5: 152.[crossref]
  14. De Pergola G, Pannacciulli N (2002) Coagulation and fibrinolysis abnormalities in obesity. J Endocrinol Invest25: 899-904.[crossref]
  15. R Huttunen, J Syrja¨nen (2013) Obesity and the risk and outcome of infection. International Journal of Obesity37: 333-340.[crossref]
  16. Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, GommersDAMPJ et al. (2020) Incidence of thrombotic complications in critically ill ICU patients with COVID-19. ThrombosisResearch.[crossref]
  17. Romero-Martínez M, Shamah-Levy T, Vielma-Orozco E, Heredia-Hernández O, Mojica-Cuevas J et al. (2019) Encuesta Nacional de Salud y Nutrición (Ensanut 2018): metodología y perspectivas. salud pública de México 61: 917-923.
  18. Carter SJ, Baranauskas MN, Fly AD (2020) Considerations for obesity, vitamin D, and physical activity amidst the COVID‐19 pandemic. Obesity.
  19. Smith JA, Judd J (2020) COVID‐19: Vulnerability and the power of privilege in a pandemic. Health Promotion Journal of Australia 31: 158.[crossref]
  20. Ahmed F, Ahmed NE, Pissarides C, Stiglitz J (2020) Why inequality could spread COVID-19. The Lancet Public Health5: 240.[crossref]

Effects of Intermittent Exercise during Initial Rainbow Trout Oncorhynchus mykiss Rearing in Tanks Containing Vertically-Suspended Environmental Enrichment

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DOI: 10.31038/AFS.2020222

Abstract

This study evaluated the effect of an exercise routine on the hatchery rearing performance of juvenile rainbow trout (Oncorhynchus mykiss) reared in circular tanks containing vertically-suspended environmental enrichment. This experiment occurred in two sequential trials, with fish remaining in the same treatment group in each trial. The first trial began upon initial feeding and lasted for 47 days with velocities in the exercised tanks alternated bi-weekly between 5 cm s-1 and 8 cm s-1. The second trial began the day after the first trial ended and lasted for 98 days, with velocities in the exercised tanks alternating between 5 cm s-1 and 11 cm s-1. Velocities in the unexercised tanks stayed constant at 5 cm s-1 throughout the study. No significant differences in final tank weight, gain, percent gain, individual weight, individual length, feed conversion ratio, specific growth rate, or condition factor were found between the two treatments in either trial. These results indicate that an intermittent exercise regime does not improve the hatchery rearing performance of juvenile rainbow trout grown in circular tanks with vertically-suspended enrichment.

Keywords

Exercise, Structure, Enrichment, Rainbow trout, Oncorhynchus mykiss

Introduction

Modifications to fish rearing units to encourage natural behaviors or mimic natural habitats have been studied with many different fish species [1-4]. Different forms of environmental enrichment have been shown to increase growth and post-stocking survival of fish raised in hatcheries [5]. Environmental enrichment research has particularly focused on salmonids during hatchery rearing [6-10].

Occupational enrichment is a category of environmental enrichment including exercise [5]. Fish are typically forced to exercise by increasing water velocities [9-11], which has generally been associated with increased fish growth. However, when fish are over-exercised, fatigue and reduced rearing performance can occur [12,13]. Most exercise studies start with relatively larger and older salmonids [2,3,9,14-16]. Beginning an exercise routine at initial feeding has not occurred.

Physical structure has been added to fish rearing tanks as a form of environmental enrichment [17-24]. Vertically-suspended structures were developed to add enrichment but still maintain circular tank hydraulic self-cleaning. Kientz and Barnes [25] and Kientz et al. [26] reported an increase in rainbow trout (Oncorhynchus mykiss) growth using suspended aluminum rods and suspended strings of plastic spheres. Positive results using a variety of vertically-suspended structures with a variety of salmonid species have been reported [27-33].

Voorhees et al. [16] evaluated the combination of vertically-suspended structure and an exercise routine during juvenile rainbow trout rearing and found no significant interaction between structure and exercise. Given the lack of paucity of information on exercise in conjunction with vertically-suspended structure, and exercise in general with small salmonids, the objective of this study was to evaluate the effects of an exercise routine, beginning at initial feeding, on the rearing performance of rainbow trout reared in circular tanks containing vertically-suspended environmental enrichment.

Methods

This experiment was conducted at McNenny State Fish Hatchery, rural Spearfish, South Dakota, USA, using degassed and aerated well-water (constant temperature 11°C; total hardness as CaCO3, 360 mg L-1; alkalinity as CaCO3, 210 mg L-1; pH, 7.6; total dissolved solids, 390 mg L-1) using 2,000-L circular tanks (1.8 m diameter x 0.6 m deep; 0.4 m water depth). This experiment used Arlee strain rainbow trout in two sequential trials.

All tanks contained vertically-suspended environmental enrichment, which consisted of an array of four suspended aluminum angles (2.5-cm wide on each angle side x 57.15-cm long) [27] suspended from a corrugated plastic cover [34]. The angles were placed so the peak of the angle faced into the water current.

Fish were fed every 15 minutes during daylight hours using automatic feeders. Feeding rates were determined by the hatchery constant method [35], with an expected feed conversion ratio of 1.1. Total feed fed was 116.7 kg per tank throughout the entire experiment.

The experimental design for each trial was similar, with treatments being either unexercised (control) or exercise. Velocities in the control tanks were maintained at 5 cm s-1, the minimum velocity required for hydraulic self-cleaning. Exercise occurred by changing the angle of the incoming water (spray bar) to increase in-tank water velocities; incoming water flows were not changed. The exercise regime was alternating every 84 hours (3.5 days) between velocities of 5 cm s-1 and higher velocities of 8 to 11 cm s-1 depending on the trial. The exercise regime started after one week of acclimation to the lower velocity of 5 cm s-1. Velocities were measured using a flowmeter (JDC Electronics Flowatch Flowmeter, JDC, Yverdon-les-Bains, Switzerland), with all readings taken directly across from the incoming water spray bar approximately 20 cm deep (halfway from water surface).

The first trial began on January 14, 2020 and lasted until March 2, 2020, for a total of 47 days. Each of eight tanks received 1.2 kg (approximately 6,600 fish) of trout (individual mean ± SE, weight = 0.2 ± 0.0 g, total length 26.8 ± 0.4 mm, n = 30). Feeding rates were projected at 0.08 cm day-1, a rate at or slightly above satiation. Fish were fed #1 granules (Fry, Skretting USA, Tooele, Utah, USA) until February 4, when feed was switched to #2 granules (Fry, Skretting USA, Tooele, Utah, USA). Four tanks received the control velocity and four tanks received the exercise regime (n = 4). The higher velocity used in the exercise regime was 8 cm s-1. At the end of the trial, total tank weight was obtained by weighing all fish in each tank to the nearest 0.1 kg. In addition, ten individual fish from each tank were weighed to the nearest 0.1 g and total length measured to the nearest 1.0 mm.

The second trial used the fish from the first trial and began on March 3, 2020, immediately after cessation of the first trial. The second trial lasted for 98 days until June 9, 2020, with the trout from the first trial subjected to the same treatment (control or exercised). Fish in the control treatment for the first trial were pooled (combined into one tank) and split into seven tanks, with each tank receiving 9.1 kg (approximately 3,600 fish). Initial mean ± SE weights and total lengths were 2.5 ± 0.1 g and 61 ± 1 mm (n = 40) respectively. The exercised fish from the first trial were also pooled and split into seven tanks, with each tank receiving 9.3 kg (mean ± SE, weight = 2.7 ± 0.1 g, total length 61 ± 1 mm, n = 40). Feeding rates were based on a projected growth of 0.075 cm day-1. Fish were fed #2 granules (Fry, Skretting USA, Tooele, Utah, USA) until March 26, when the fish received 1.5 mm extruded floating pellets (Protec Trout, Skretting USA, Tooele, Utah, USA). The higher velocity used in the exercise regime was 11 cm s-1. At the end of the trial, total tank and individual fish data was recorded as in the first trial.

The following formulas were used:

formula final

Data were analyzed using SPSS (24.0) statistical program (IBM Corporation, Armonk, New York, USA). T-tests were used with significance was predetermined at p < 0.05. This experiment was carried out within the American Fisheries Society “Guidelines for the Use of Fishes in Research” [36] and within the guidelines of the Aquatics Section Research Ethics Committee of the South Dakota Department of Game, Fish and Parks, USA.

Results

In both trials, no significant differences were found in final tank weight, gain, percent gain, feed conversion ratio, or percent mortality (Table 1). In the first trial, mean feed conversion ratios were relatively low at 0.75 in the control and 0.77 in those tanks of fish that were exercised. Feed conversion ratios were higher in the second trial and nearly identical between the groups at 1.12 in the control and 1.11 in the exercised treatment. Overall feed conversion for both trials combined was identical between the control and exercised groups. Mortality was relatively low and did not exceed 1.2% in either trial.

Table 1: Mean (± SE) final tank weight, gain, percent gain, feed conversion ratio (FCRa), and percent mortality of rainbow trout reared with or without exercise.

Unexercised Exercised
Trial 1 n 4 4
Initial weight (kg) 1.2 1.2
Final weight (kg) 16.0 ± 0.8 16.3 ± 0.3
Gain (kg) 14.7 ± 0.8 15.0 ± 0.3
Gain (%) 1,207 ± 64 1,232 ± 22
FCR 0.75 ± 0.04 0.77 ± 0.01
Mortality (%) 1.2 ± 0.3 1.0 ± 0.1
Trial 2 n 7 7
Initial weight (kg) 9.1 9.3
Final weight (kg) 118.3 ± 2.6 116.7 ± 1.9
Gain (kg) 109.2 ± 2.6 107.6 ± 1.9
Gain (%) 1,200 ± 28 1,183 ± 21
FCR 1.12 ± 0.03 1.11 ± 0.02
Mortality (%) 0.8 ± 0.1 0.6 ± 0.1
Overall FCR 0.94 0.94

a FCR = Food fed/gain.

Individual total length, weight, specific growth rate, and condition factor were also not significantly different between the two groups in either trial (Table 2). Specific growth rate decreased from 5.59 and 5.73 in the control and exercised groups in the first trial respectively, to 2.81 and 2.70 in the second trial.

Table 2: Individual fish mean (±SE) total length, weight, specific growth rate (SGRa), and condition factor (Kb) of rainbow trout reared with or without exercise.

Unexercised Exercised
Trial 1 Length (mm) 60 ± 2 61 ± 1
Weight (g) 2.5 ± 0.2 2.7 ± 0.2
SGR 5.59 ± 0.19 5.73 ± 0.16
K 1.14 ± 0.05 1.16 ± 0.01
Trial 2 Length (mm) 146 ± 2 143 ± 2
Weight (g) 38.5 ± 1.6 37.2 ± 2.1
SGR 2.81 ± 0.04 2.70 ± 0.05
K 1.24 ± 0.01 1.26 ± 0.02

aSGR = 100 * (ln (end weight) – ln (start weight))/(number of days).
bK = 105 * [(fish weight)/(fish length)3].

Discussion

The results of this study indicate that exercise beginning with initial feeding does not improve the growth of rainbow trout during hatchery rearing. This study is unique because it used small rainbow trout, which were only 27 mm long at the start of the experiment. Most research using exercise in juvenile salmonids begins when the fish are larger. For example, Parker and Barnes [37] found positive effects of exercise in a trial using 72 mm long rainbow trout. Voorhees et al. [16] conducted an exercise study with 69 mm rainbow trout and Reiser et al. [11] used rainbow trout that were 409 mm long. Exercise studies using other salmonid species have also used larger fish, such as the 130 mm Arctic charr (Salvelinus alpinus) used by Christiansen and Jobling [12].

The lack of difference in growth between the control and exercise regime tanks in this study support the observations of Voorhees et al. [16] that a combination of both physical and occupational enrichment was not necessary to improve the hatchery rearing performance of rainbow trout. Voorhees et al. [16] reported that either exercise or vertically-suspended structures increased trout growth, but that no further improvements were realized when both forms of environmental enrichment were combined. The lack of any improvement in growth observed using exercise in this study was likely due to the presence of vertically-suspended structures in both the exercise and non-exercise tanks.

The water velocities used for exercise in this experiment may have affected the results. At the start of the first trial, the exercise velocities were 5 cm s-1, which based on fish size was approximately 3.1 body lengths per second. By the end of the second trial, relative velocities in the exercised fish had decreased to approximately 0.9 body lengths per second. The preferred relative velocity for optimal exercise in salmonids has been reported to be between 1.5 and 2.0 body lengths per second [6,37,38]. The relatively high velocities used for exercise at the start of the trial may have been particularly deleterious. Exercising Chinook salmon (Oncorhynchus tshawytscha) at 3.0 body lengths per second resulted in poorer feed conversion ratios compared to those exercised at 1.5 body lengths per second [37].

The feed conversion ratios obtained in this study are consistent with the observations of Huysman et al. [29] and Voorhees et al. [16]. They are also similar to studies using similarly sized rainbow trout in environmental enrichment studies [15,25,27]. The decreased feed conversion ratio in the first trial compared to the second trial was likely due to the smaller size of the fish [39].

It is possible that the high rearing densities encountered at the end of the second trial may have influenced trout growth [40-42]. It is possible, as suggested by Huysman et al. [29], that the trout in the exercised tanks initially grew more rapidly, with growth slowing as they achieved relatively high densities faster than the unexercised tanks. In other words, the fish in the control tanks may have grown more slowly throughout the course of the second trial and only achieved the high final densities because of the long duration of the experiment. Interestingly, the final tank densities observed in this study were higher than those reported by Huysman et al. [29].

The specific growth rates of this study are consistent with those of similarly-sized rainbow trout reared using vertically-suspended enrichment [15,16,29]. However, Gregory and Wood [7] reported a much lower specific growth rate for juvenile rainbow trout of similar size who were exercised intermittently than was observed in this experiment. The difference may be because of the inclusion of vertically-suspended enrichment, which has been shown to improve specific growth rate [25,27]. It may also be due to differences in fish size, water temperature, water chemistry, diet, or the genetic strain used, though the results are similar to other non-enriched salmonid exercise studies [7,15,43].

In conclusion, the results of this study indicate no significant improvement in the rearing performance of rainbow trout when exercised in the presence of vertically-suspended environmental enrichment. Further research should examine the interaction of exercise routines and vertically-suspended enrichment, including evaluating exercise routines designed to minimize the risk of exercise fatigue.

Acknowledgements

We thank Lynn Slama, Joshua Caasi, and Michael Robidoux for their assistance with this study.

References

    1. Li XM, Yu LJ, Wang C, Zeng LQ, Cao ZD, et al. (2013) The effect of aerobic exercise training on growth performance, digestive enzyme activities and postprandial metabolic response in juvenile qingbo (Spinibarbus sinensis). Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology 166: 8-16. [crossref]
    2. Liu G, Wu Y, Qin X, Shi X, Wang X (2018) The effect of aerobic exercise training on growth performance, innate immune response and disease resistance in juvenile Schizothorax prenanti. Aquaculture 486: 18-25.
    3. Martin-Perez M, Fernandez-Borras J, Ibarz A, Millan-Cubillo A, Felip O, et al. (2012) New insights into fish swimming: a proteomic and isotopic approach in gilthead sea bream. Journal of Proteome Research 11: 3533-3547.
    4. Shrivastava J, Rašković B, Blust R, De Boeck G (2018) Exercise improves growth, alters physiological performance and gene expression in common carp (Cyprinus carpio). Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology 226: 38-48. [crossref]
    5. Gerber B, Stamer A, Stadtlander T (2015) Environmental enrichment and its effects on welfare in fish. Review. Research Institute of Organic Agriculture (FiBL) CH-Frick.
    6. Christiansen JS, Ringø E, Jobling M (1989) Effects of sustained exercise on growth and body composition of first-feeding fry of Arctic charr, Salvelinus alpinus (L.). Aquaculture 79: 329-335.
    7. Gregory TR, Wood CM (1998) Individual variation and interrelationships between swimming performance, growth rate, and feeding in juvenile rainbow trout (Oncorhynchus mykiss). Canadian Journal of Fisheries and Aquatic Sciences 55: 1583-1590.
    8. Houlihan DF, Laurent P (1987) Effects of exercise training on the performance, growth, and protein turnover of rainbow trout (Salmo gairdneri). Canadian Journal of Fisheries and Aquatic Sciences 44: 1614-1621.
    9. Lagasse JP, Leith DA, Romey DB, Dahrens OF (1980) Stamina and survival of Coho salmon reared in rectangular circulating ponds and conventional raceways. The Progressive Fish-Culturist 42: 153-156.
    10. Voorhees JM, Barnes ME, Chipps SR, Brown ML (2018) Rearing performance of juvenile brown trout (Salmo trutta) subjected to exercise and dietary bioprocessed soybean meal. Open Journal of Animal Sciences 8: 303-328.
    11. Reiser S, Sähn N, Pohlmann DM, Willenberg M, Focken U (2019) Rearing juvenile brown Salmo trutta (L.), and rainbow trout Oncorhynchus mykiss (Walbaum), in earthen ponds with and without an induced current. Journal of Applied Aquaculture 31: 1-21.
    12. Christiansen JS, Jobling M (1990) The behaviour and the relationship between food intake and growth of juvenile Arctic charr, Salvelinus alpinus L., subjected to sustained exercise. Canadian Journal of Zoology 68: 2185-2191.
    13. Davison W, Goldspink G (1977) The effect of prolonged exercise on the lateral musculature of the brown trout (Salmo trutta). Journal of Experimental Biology 70: 1-12.
    14. Brown EJ, Bruce M, Pether S, Herbert NA (2011) Do swimming fish always grow fast? Investigating the magnitude and physiological basis of exercise-induced growth in juvenile New Zealand yellowtail kingfish, Seriola lalandi. Fish Physiology and Biochemistry 37: 327-336. [crossref]
    15. Voorhees JM, Barnes ME, Chipps SR, Brown ML (2019) Effects of Exercise and Bioprocessed Soybean Meal Diets during Rainbow Trout Rearing. The Open Biology Journal 7: 1-13.
    16. Voorhees JM, Huysman N, Krebs E, Barnes ME (2020) Use of Exercise and Structure during Rainbow Trout Rearing. Open Journal of Applied Sciences 10: 258-269.
    17. Bosakowski T, Wagner EJ (1995) Experimental use of cobble substrates in concrete raceways for improving fin condition of cutthroat (Oncorhynchus clarki) and rainbow trout (O. mykiss). Aquaculture 130: 159-165.
    18. Berejikian BA, Tezak EP, Flagg TA, LaRae AL, Kummerow E, et al. (2000) Social dominance, growth, and habitat use of age-0 steelhead (Oncorhynchus mykiss) grown in enriched and conventional hatchery rearing environments. Canadian Journal of Fisheries and Aquatic Sciences 57: 628-636.
    19. Berejikian BA (2005) Rearing in enriched hatchery tanks improves dorsal fin quality of juvenile steelhead. North American Journal of Aquaculture 67: 289-293.
    20. Näslund J, Rosengren M, Del Villar D, Gansel L, Norrgard JR, et al. (2013) Hatchery tank enrichment affects cortisol levels and shelter-seeking in Atlantic salmon (Salmo salar). Canadian Journal of Fisheries and Aquatic Sciences 70: 585-590.
    21. Salvanes AGV, Moberg O, Ebberson LOE, Nilsen TO, Jensen KH et al. (2013) Environmental enrichment promotes neural plasticity and cognitive ability in fish. Proceedings of the Royal Society B 280.
    22. Roberts LJ, Taylor J, Gough PJ, Forman DW, Leaniz CG (2014) Silver spoon in the rough: can environmental enrichment improve survival of hatchery Atlantic salmon Salmo salar in the wild? Journal of Fish Biology 85: 1972-1991.
    23. Bergendahl IA, Salvanes AGV, Braithwaite VA (2016) Determining the effects of duration and recency of exposure to environmental enrichment. Applied Animal Behaviour Science 176: 163-169.
    24. Cogliati KM, Herron CL, Noakes DLG, Schreck CB (2019) Reduced stress response in juvenile Chinook salmon reared with structure. Aquaculture 504: 96-101.
    25. Kientz JL, Barnes ME (2016) Structural complexity improves the rearing performance of rainbow trout in circular tanks. North American Journal of Aquaculture 78: 203-207.
    26. Kientz JL, Crank KM, Barnes ME (2018) Enrichment of circular tanks with vertically suspended strings of colored balls improves rainbow trout rearing performance. North American Journal of Aquaculture 80: 162-167.
    27. Krebs E, Huysman N, Voorhees JM, Barnes ME (2018) Suspended arrays improve rainbow trout growth during hatchery rearing in circular tanks. International Journal of Aquaculture and Fishery Sciences 4: 27-30.
    28. Crank KM, Kientz JL, Barnes ME (2019) An evaluation of vertically suspended environmental enrichment structures during rainbow trout rearing. North American Journal of Aquaculture 81: 94-100.
    29. Huysman N, Krebs E, Voorhees JM, Barnes ME (2019) Use of large vertically-suspended rod array in circular tanks during juvenile rainbow trout rearing. International Journal of Marine Biology and Research 4: 1-5.
    30. Huysman N, Krebs E, Voorhees JM, Barnes ME (2019) Use of two vertically-suspended environmental enrichment arrays during rainbow trout rearing in circular tanks. International Journal of Innovative Studies in Aquatic Biology and Fisheries 5: 25-30.
    31. Rosburg AJ, Fletcher BL, Barnes ME, Treft CE, Bursell BR (2019) Vertically-suspended environmental enrichment structures improve the growth of juvenile landlocked fall Chinook salmon. International Journal of Innovative Studies in Aquatic Biology and Fisheries 5: 17-24.
    32. White SC, Krebs E, Huysman N, Voorhees JM, Barnes ME (2019) Use of suspended plastic conduit arrays during brown trout and rainbow trout rearing in circulars. North American Journal of Aquaculture 81: 101-106.
    33. Jones MD, Krebs E, Huysman N, Voorhees JM, Barnes ME (2019) Rearing performance of Atlantic salmon grown in circular tanks with vertically-suspended environmental enrichment. Open Journal of Animal Science 9: 249-257.
    34. Walker LM, Parker TM, Barnes ME (2016) Full and partial overhead tank cover improves rainbow trout rearing performance. North American Journal of Aquaculture 78: 20-24.
    35. Buterbaugh GL, Willoughby H (1967) A feeding guide for brook, brown, and rainbow trout. The Progressive Fish-Culturist 29: 210-215.
    36. American Fisheries Society (AFS) (2014) Guidelines for the Use of Fishes in Research. Bethesda, MD: American Fisheries Society.
    37. Parker TM, Barnes ME (2014) Rearing velocity impacts on landlocked fall Chinook salmon (Oncorhynchus tshawytscha) growth, condition, and survival. Open Journal of Animal Sciences 4: 244-252.
    38. Parker TM, Barnes ME (2015) Effects of different water velocities on the hatchery rearing performance and recovery from transportation of rainbow trout fed two different rations. Transactions of the American Fisheries Society 144: 882-890.
    39. Handeland SO, Imsland AK, Stefansson SO (2008) The effect of temperature and fish size on growth, feed intake, food conversion efficiency and stomach evacuation rate of Atlantic salmon post-smolts. Aquaculture 283: 36-42.
    40. Holm JC, Refstie T, Bø S (1990) The effect of fish density and feeding regimes on individual growth rate and mortality in rainbow trout (Oncorhynchus mykiss). Aquaculture 89: 225-232.
    41. Procarione LS, Barry TP, Malison JA (1999) Effects of high rearing densities and loading rates on the growth and stress responses of juvenile rainbow trout. North American Jounral of Aquaculture 61: 91-96.
    42. Ellis T, North B, Scott AP, Bromage NR, Porter M, et al. (2002) The relationships between stocking density and welfare in farmed rainbow trout. Journal of Fish Biology 61: 493-531.
    43. Jørgensen EH, Jobling M (1993) The effects of exercise on growth, food utilisation and osmoregulatory capacity of juvenile Atlantic salmon, Salmo salar. Aquaculture 116: 233-246.