View of Management of shoulder pain in the emergency room: a narrative review

Introduction

It is estimated that shoulder pain represents the third most common cause of musculoskeletal consultation in primary care and emergency departments [1]. The majority of shoulder problems are arthritis, soft tissue or intra-articular injury, and instability. The majority of patients seen in the ER following shoulder trauma are investigated using plain radiographs and, in some cases, with ultrasounds. Many different treatments can be proposed, with differences regarding hospital guide-lines and common practice, available devices, and costs. This literature review aims to propose what authors consider the most effective approach for the treatment of some of the most common shoulder pathologies in the emergency department.

Materials and method

A review of scientific studies was performed in November 2020. The following keywords were used: “Acute shoulder pain”, “shoulder traumatology”, “shoulder emergencies”, “painful shoulder”. Inclusion criteria were reviews, case report or retrospective studies concerning shoulder’s emergencies. We analyzed 34 published articles from the most updated literature focused on the management of shoulder emergencies. Titles and abstracts were screened and the full text was retrieved when a study seemed appropriate to be included in our review. The search was restricted to the English language literature. Results:

GLENOHUMERAL DISLOCATION - ANTERIOR Abstract

Introduction: The frequency of Emergency Room (ER) accesses for shoulder pain is constantly increasing. The presenting symptoms are similar across the various pathological conditions, therefore an appropriate focus on the pathogenetic mechanism (traumatic or not-traumatic) and the correct imaging choice is of extreme importance. The correct treatment strategy is fundamental. The aim of this study is to provide a simple and straightforward guide toward the correct treatment when facing a painful shoulder in ER.

Methods: We performed a narrative review analyzing 34 published articles from the most updated literature focused on the management of shoulder emergencies. The most significant data were collected to propose a document suggesting the most effective treatments in this group of patients.

Results: Authors developed a guide that could help clinicians to propose the correct treatment when dealing with patients with acute shoulder pain in ER.

Conclusions: Shoulder emergencies are frequent and different possible treatments can be proposed to the patients, as a consequence of local guidelines and hospital habits. This narrative review could help clinicians in the emergency room to propose an effective treatment in some of the most common situations.

Level of evidence: V - Narrative review

Keywords: Acute shoulder pain, shoulder traumatology, shoulder emergencies, painful shoulder

Management of shoulder pain

in the emergency room: a narrative review

Riccardo Compagnoni

_{, Alfonso Liccardi}

_{, Chiara Fossati}

_,

Pietro Randelli

_.

1) Laboratory of Applied Biomechanics, Department of Biomedical Sciences for Health, Università degli Studi di Milano, Via Mangiagalli 31, 20133 Milan, Italy; 2) 1° Clinica Ortopedica, ASST Centro Specialistico Ortopedico Traumatologico Gaetano Pini-CTO, Piazza Cardinal Ferrari 1, 20122 Milan, Italy.

Corresponding author: Riccardo Compagnoni - Via Pini,3 20122 Milano - [email protected]

Archivesof MedicineAnd surgery ofthe universityof Mil An Attribution-NonCommercial-NoDerivatives 4.0

(FIRSTEPISODE)

Anterior glenohumeral dislocations are frequently-seen events during ER practice, and treatment objectives must include a correct diagnosis, which excludes concurrent vascular, nervous or bony lesions, a safe reduction, and exact discharge indications. The first episode is often caused by medium-high-energy trauma during physical activity on the affected shoulder. Clinical examination has to be accompanied by a radiographic exam of the shoulder in two projections (anteroposterior and trans-thoracic view), aiming to both confirm dislocation and exclude associated fractures. The reduction maneuver should be preferably performed under sedation, to avoid further trauma that could lead to new glenoid and humeral lesions. After the reduction maneuver, a new radiographic evaluation is required to confirm the reestablished relationship between articular surfaces and the absence of fractures. If a glenoid bone lesion is suspected, a shoulder CT-scan can better evaluate the extension of the lesion. If the bone loss goes beyond 25% of the surface of the glenoid, a hospitalization for surgical stabilization could prove beneficial; otherwise, the patient can follow standard protocol: discharge at home with sling arm support for about 7-10 days, then removal and orthopedic evaluation with initial active and passive mobilization. [1,2,3]

GLENOHUMERAL DISLOCATION - ANTERIOR (RECURRENT)

Anterior glenohumeral instability is a frequent event during First Aid practice, and treatment goals must include a correct diagnosis, which excludes concurrent vascular, nervous or bony lesions, a safe reduction, and exact discharge indications. In patients with a recurrent event of shoulder dislocation, a high energy trauma is uncommon, and the patient is usually capable of counting previous events.

Clinical examination has to be associated with a radiographic exam of the shoulder in two projections (anteroposterior and trans-thoracic view), aiming to both confirm dislocation and exclude associated fractures. The joint reduction is frequently less difficult compared with a first episode, and can thus be attempted gently without sedation but at the first difficulty, sedation shall be carried out. Post-reduction treatment includes a new radiographic evaluation to confirm reestablished relationships between articular surfaces and absence of fractures. If a glenoid bone lesion is suspected, a shoulder CT-scan can better evaluate the extension of the lesion. If the bone loss goes beyond 25% of the surface of the glenoid, a hospitalization for surgical stabilization is mandatory. When fractures are excluded, then patient can be discharged at home with a sling for 7 days. The patient who suffers from recurrent dislocations should be informed that the risk of new episodes is high, in particular in patients younger than 30 years old, and a surgical treatment should be proposed. In order to correctly plan the surgical treatment of shoulder stabilization, an arthro-MRI can be useful followed by a consultation with orthopedic surgeon ultra-specialized in shoulder surgery. [1,4,5] Shoulder dislocation - Posterior Posterior glenohumeral dislocations represent about 4% of all shoulder dislocations, but play a significant role in fist aid practice because they are often unrecognized, with subsequent and frequently disabling bone damage. The patient usually reports a high-energy trauma followed by functional impairment and pain. Clinical examination is often diriment, showing the deformity of the shoulder profile and the block of external rotation. When the clinical examination does not lead to diagnosis, a shoulder CT-scan is mandatory. The reduction should be performed under sedation. Control x-ray is mandatory after reduction maneuver

and followed by immobilization in a sling with external-rotating cushion for 14 days. Afterwards, the patient starts to mobilize the limb assisted by the physiotherapist or autonomously, either passively or actively. [6,7]

Acromionclavicular joint dislocation Acromioclavicular joint dislocations are often the result of a direct trauma of medium-high energy on the affected shoulder. In order to be able to make the correct diagnosis it’s mandatory to analyze the symptoms and to request a x-ray in two projections (anteroposterior for the acromioclavicular joint - Zanca - and axillary view). According to Rockwood classification there are six grades of acromion-clavicular joint dislocations: - In grade I and II the main symptom is pain localized at the acromioclavicular joint. In some cases a slight local swelling and joint instability is reported when the shoulder is stressed in adduction and flexion. In grade 1 there is no variation in the relationship between articular surfaces, while in grade 2 an elevation of the lateral extremity of the clavicle of less than 5mm is observed. Treatment is conservative with ice, painkillers and use of a sling for 2 weeks. It is useful to re-evaluate the patient in 2 weeks in a specialized shoulder ambulatorial service. [8]

- In a grade III, it is possible to find a prominence at the lateral extremity of the collarbone, mobile at digital pressure and during mobilization of the shoulder. The acromioclavicular joint appears swollen, with frequent presence of local hematoma and antalgic limitation of the shoulder’s mobility. The treatment is still controversial, but recent meta-analysis support a conservative approach. A subdivision in two groups, based on radiographic stability of joint dislocation in abduction, was proposed in order to help surgeons in the choice of the best therapeutic approach. Stable dislocations are treated conservatively with a Kenny-Howard

brace for 4 weeks, painkillers and ice; brace removal is planned in a shoulder-specialized ambulatorial setting. Unstable dislocations deserve surgical stabilization and different surgical techniques are described to treat this pathology. [8,9,10]

- A grade IV of acromioclavicular dislocation is characterized by a posterior dislocation of the lateral extremity of the clavicle. Pain and mobilization of the joint at digital pressure is always present. Diagnosis can be difficult with radiographic examination, since the posterior translation minimally alters the image in anteroposterior view, and axillary view may be hard to obtain because of the severe pain. If a case of type 4 dislocation is suspected, a CT-scan can be helpful to confirm the diagnosis. The treatment of these intrinsically unstable and painful dislocations is surgical. The patient needs to be hospitalized, to wear a wide-band brace and to receive an appropriate analgesic pharmacological therapy. Finally, a surgical procedure of stabilization should be planned, based on the preferences of the surgeon. [8,11] - In a grade V, an evident prominence at the lateral extremity of the collarbone, mobile at digital pressure and during shoulder mobilization, is present. The swelling of acromioclavicular joint is frequently associated with local hematoma and antalgic limitation of the shoulder’s mobility. This type of dislocation is unstable so it requires a surgical stabilization. The patient needs to be hospitalized and to wear a sling brace while waiting for surgery. [8,11]

- In a VI grade dislocation the lateral extremity of the clavicle is displaced below the coracoid process. Clinically, the patient shows an alteration of the collarbone’s lateral anatomic profile, not mobile by digital pressure, but very painful when the shoulder is mobilized. Clinical examination must focus on excluding vascular and nervous damages and deficits. This grade of dislocation is very painful and cause serious functional limitation, therefore, the treatment is surgical. The patient needs to

be hospitalized with a wide-band brace, set an analgesic pharmacological therapy, and plan the surgeon’s favourite surgical procedure which should be performed in the following days. [8,11]

Greater tuberosity detachment Isolated greater tuberosity (GT) fractures represent 20% of all proximal humerus fractures. The displacement of the GT can be caused by an impact against the inferior surface of the acromion, resulting from a glenohumeral dislocation or, rarely, an avulsion of the supraspinatus tendon. The diagnosis is based on radiographic imaging. Anteroposterior, axial and trans-scapular view must be requested. GT fractures are not or minimally displaced in 85-95% of cases. When fragments show a < 5 mm diastasis, conservative treatment is indicated. In a First Aid setting, a Desault-type brace or bandaging positioned in abduction (20°) and slight external-rotation of the limb is applied, and kept for 3 weeks. The splint can be provided with a cushion or not. Clinical and radiographic control should be planned after three-weeks. GT fractures are considered displaced when fragments show a diastasis >5mm, which represent 5 to 15% of cases. Treatment of these fractures is surgical. In ER, the patient has to wear a Desault bandage in order to keep the limb in abduction and external-rotation, pending surgery. Surgical treatment includes osteosynthesis with screws and washer, usually with transdeltoid approach, paying attention to not damage the circumflex axillary nerve. [12,13,14]

Proximal humerus fracture

Proximal humerus fractures can be caused by both high-energy trauma in young patients and low-energy trauma in osteoporotic patients. The patients show an absolute functional limitation of the shoulder, local

swelling and ecchymosis and painful passive mobilization. The evaluation of possible vascular or nervous lesions is mandatory. The diagnosis is based on radiographic imaging. Anteroposterior, axial and trans-scapular view must be requested. These fractures are classified based on the displacement of the main fragments involved (humeral head and shaft, greater and lesser tubercles). A fracture is considered “displaced” when the fragments show an angulation >45° or a diastasis >1cm. The treatment of non-displaced fractures (85% of cases) is conservative. The patient must be immobilized with a Desault bandage for three weeks. A radiographic control should be planned in 7-10 days in order to exclude secondary displacements. After three weeks, after a new radiographic evaluation, the brace is removed and the patient can start a cautious mobilization. Even though proximal humerus has a good restorative capacity, the treatment for displaced fractures and comminuted fractures is usually surgical. The patient must be immobilized with a Desault bandage or a wide-band sling and hospitalized for further instrumental examination (CT scan); surgery has to be planned in the following days. [15,16] Clavicle fracture

Clavicle fractures are often the result of a direct trauma (e.g. falling) on the shoulder, whereas forces transfer throughout the axis of the collarbone itself, from the acromioclavicular joint to the sternoclavicular joint. Clinically, a deformation of the anatomical profile, swelling, local ecchymosis, and pain-induced limitation of movement can all be observed. Since the majority of the fractures affect the middle third, possible vascular lesions must be carefully evaluated. Diagnosis is based on radiographic imaging (anteroposterior and craniocaudal views). Edimburgh classification is the most used one, it is based on the location of the fracture (proximal, middle or distal third of the clavicle). Traditionally, these fractures

are treated conservatively with a figure-of-eight bandage, even in the presence of a discrete displacement. The presence of a third fragment and a severe displacement represent indications for surgical treatment; particular attention must be paid to the fractures that affect the third lateral of the clavicle, due to their intrinsic unstable nature, these types of fractures often require a surgical solution. In these situations the patient can be hospitalized with a wide-band brace in order to plan surgery in the following days. [17,18,19]

Clavicle fracture - floating shoulder A “Floating shoulder” is defined as a clavicle fracture combined with a fracture of the glenoidal neck, which are consequence of a high energy trauma and determine instability of the shoulder girdle. Clinically, pain at the level of the affected clavicle, swelling, local ecchymosis, and pain-induced limitation of movement can all be observed. A CT scan of the shoulder must be performed urgently for a correct diagnosis. In an ER setting it is essential to exclude vascular and nervous lesions related to the trauma, since combined shoulder and thoracic lesions have been described. Surgery is mandatory because these fractures are inherently unstable. In ER the patient must be immobilized with a Desault bandage and hospitalized to perform surgery in the following days. [20,21,22]

Coracoid fractures

Coracoid fractures are rare and often associated with glenohumeral and acromioclavicular dislocations or fractures of the scapular body. The specific symptoms consist in pain at the level of the coracoid process, local swelling, and pain during active flexion and abduction of the shoulder. The diagnosis is based on radiographic imaging, even though non-displaced fracture can be difficult to diagnose. The treatment for non-displaced or minimally

displaced fractures is conservative, with a sling brace worn for at least 3 weeks. A follow-up examination and x-ray should be planned at 3-weeks for brace removal and specialistic outpatient evaluation. Surgery is reserved to severely displaced fractures (>1cm diastasis) or evolution with nonunion. [23,24,25,26] Scapular body fracture

Scapular body fractures represent about 5% of all shoulder girdle fractures and are often a direct consequence of a medium-high energy traumatism. The patient may refer posterior pain, painful shoulder mobilization, and functional impairment of the shoulder. Since high energy traumas are often involved, a thoracic evaluation can be useful in order to exclude scapular-thoracic dissociations and potential lesions of the subclavian vessels or the brachial plexus. The diagnosis is based on radiographic imaging. Anteroposterior, axillar, and axial scapular view must be requested. A CT-scan allows to better evaluate the extension of the rim of fracture, the number of fragments, and involvement of scapular neck. The exam should be programmed as urgent, so that final treatment can be set and adjusted. In the majority of patients, this fracture can be treated conservatively with a brace for 1 month, followed by radiographic and clinical control. Hospitalization for surgery is recommended for fractures compromising scapular neck and/ or displaced glenoid fractures. [27,28]

Acromion fracture

Acromion fractures are rare and often associated with other fractures. The patient may report a direct trauma to the shoulder and complains pain in acromial margin and painful abduction of the shoulder. Diagnosis relies on radiographic imaging, including anteroposterior and trans-thoracic views of the shoulder. In doubtful cases, a CT-scan can be useful to detect the fracture. Non or

minimally-displaced fractures can be treated conservatively, with a wide-band brace for 4 weeks, followed by radiographic and clinical evaluation. Surgical treatment is rarely required and reserved to fractures with significant displacement of the residual fragments. In this case, after positioning a sling brace in the ER, the patient is hospitalized and a surgical osteosynthesis is organized in the following days. [29,30]

Adhesive capsulitis

Adhesive capsulitis is a form of shoulder stiffness that affects between 2 and 5% of general population, more frequently in women between 40 and 50 years old. Adhesive capsulitis has multiple phases (4), with different pain levels and limitation of mobility. Stage 1 is characterized by normal ROM and slight pain; stage 2, minimal limitation of ROM and severe pain; stage 3, severe stiffness and minimal pain; stage 4 recovery of normal ROM and minimal pain. The diagnosis is clinical, although in ER a x-ray is recommended in order to exclude calcific tendinitis, fractures, glenohumeral dislocations and osteoarthritis. In the following weeks an MRI could be a good choice for furtherly study the case as a second-level exam, since in some cases it highlights a thickened coraco-humeral ligament, joint’s capsule and rotator interval. Treatment is conservative and surgery is reserved to refractory cases where functional limitation lasts for several months after the start of therapy. Initial treatment (in stage 1) includes NSAIDs. Good results have been reported using oral corticosteroids (e.g. Prednisolone) in the short term. Intra-articular injections of corticosteroids have shown effectiveness in pain-relief and a faster recovery of the normal ROM. Furthermore when the patient’s free of pain, physiotherapy becomes essential in order to restore normal range of motion. [31,32]

Calcific Tendinitis

Calcific tendinitis typically affects women between the age of 30 and 50 years old. Diagnosis is based on clinical examination and imaging. The patient usually refers acute pain, exacerbated by shoulder movement, and functional limitation. In the ER, a shoulder x-ray in two views is mandatory, and an ultrasound is recommended. These exams allow to detect the presence of the calcification and its dimensions, exact localization and texture. Since in many cases symptoms and calcification disappear spontaneously, the first line of treatment is conservative and includes NSAIDs, physiotherapy, shockwave and subacromial injection of corticosteroid. A recent alternative is represented by ultrasound-guided lavage, which consists, under local anesthesia, in a percutaneous injection of saline solution in order to dissolve the calcification and promote tissue healing. At the moment, there is no evidence for superiority of a singular treatment, although ultrasound-guided lavage seems to be more effective in pain relief. [33,34]

Conclusion

Shoulder emergencies are frequent and different possible treatments can be proposed to the patients, as a consequence of local guidelines and hospital habits. This narrative review could help clinicians in the emergency room to propose an effective treatment in some of the most common situations of acute shoulder pain.

Declaration of interests: None declared. Funding: No funding to declare.

References

1. Braun C, McRobert CJ. (2019) Conservative management following closed reduction of traumatic

anterior dislocation of the shoulder. Cochrane Database Syst Rev. 10;5:CD004962.

2. Kane P, Bifano SM, Dodson CC, Freedman KB (2015) Approach to the treatment of primary anterior shoulder dislocation: A review. Phys Sportsmed. 43(1):54-64.

3. Paterson WH, Throckmorton TW, Koester M, Azar FM, Kuhn JE (2010) Position and duration of immobilization after primary anterior shoulder dislocation: a systematic review and meta-analysis of the literature. J Bone Joint Surg Am. 92(18):2924-33. 4. Balg F, Boileau P (2007) The instability severity index score. A simple pre-operative score to select patients for arthroscopic or open shoulder stabilisation. J Bone Joint Surg Br. 89(11):1470-7.

5. Steinbach LS (2008) MRI of shoulder instability. Eur J Radiol;68(1):57-71.

6. Paul J, Buchmann S, Beitzel K, Solovyova O, Imhoff AB (2011) Posterior shoulder dislocation: systematic review and treatment algorithm. Arthroscopy. ;27(11):1562-72.

7. Brelin A, Dickens JF. Posterior Shoulder Instability (2017) Sports Med Arthrosc Rev. ;25(3):136-143. 8. Beitzel K, Mazzocca AD, Bak K, Itoi E, Kibler WB, Mirzayan R, Imhoff AB, Calvo E, Arce G, Shea K (2014) Upper Extremity Committee of ISAKOS. ISAKOS upper extremity committee consensus statement on the need for diversification of the Rockwood classification for acromioclavicular joint injuries. Arthroscopy. 30(2):271-8.

9. Tang G, Zhang Y, Liu Y, Qin X, Hu J, Li X (2018) Comparison of surgical and conservative treatment of Rockwood type-III acromioclavicular dislocation: A meta-analysis. Medicine (Baltimore) ;97(4):e9690. 10. Schlegel TF, Burks RT, Marcus RL, Dunn HK (2001) A prospective evaluation of untreated acute grade III acromioclavicular separations. Am J Sports Med ;29(6):699-703.

11. Søndergård-Petersen P, Mikkelsen P (1982) Posterior acromioclavicular dislocation. J Bone Joint Surg Br ;64(1):52-3.

12. Gruson K I, Ruchelsman D E, Tejwani N C (2008) Isolated tuberosity fractures of the proximal humeral: current concepts. Injury; 39: 284-98.

13. Stefan G Mattyasovszky, Klaus J Burkhart, Christopher Ahlers, Dirk Proschek, Sven-Oliver Dietz, Inma Becker, Stephan Müller-Haberstock1, Lars P

Müller and Pol M Rommens (2011) Isolated fractures of the greater tuberosity of the proximal humerus. A long-term retrospective study of 30 patients. Acta Orthopaedica; 82 (5): 714–720

14. George M S. (2007) Fractures of the greater tuberosity of the humerus. J Am Acad Orthop Surg; 15: 607-13.

15. Neer CS. (1970) 2nd Displaced proximal humeral fractures: I. Classification and evaluation. J Bone Joint Surg Am ;52:1077–1089.

16. Handoll HHG, Brorson S (2015) Interventions for treating proximal humeral fractures in adults. Cochrane Database of Systematic Reviews, Issue 11. Art. No.: CD000434.

17. Stanley D, Trowbridge EA, Norris SH (1988) The mechanism of clavicular fracture: a clinical and biomechanical analysis. J Bone Joint Surg Br; 70:461-4. 18. Robinson CM (1988) Fractures of the clavicle in the adult. Epidemiology and classification. J Bone Joint Surg Br; 80:476-84.

19. Burnham JM, Kim DC, Kamineni S (2016) Midshaft Clavicle Fractures: A Critical review. Orthopedics; 39(5):e814-21.

20. Herscovici D Jr, Fiennes AG, Allgöwer M, Rüedi TP (1992) The floating shoulder: ipsilateral clavicle and scapular neck fractures. J Bone Joint Surg Br;74(3):362-4.

21. Kani KK, Porrino JA, Mulcahy H, Chew FS (2019) The floating shoulder. Emerg Radiol (4):459-464. 22. Owens BD, Goss TP (2006) The floating shoulder. J Bone Joint Surg Br; 88(11):1419-24

23. K. Ogawa, A. Yoshida, M. Takahashi, and M. UI (1997) Fractures of the coracoid process. Journal of Bone and Joint Surgery B, vol. 79, no. 1, pp. 17–19. 24. E. Vaienti, F. Pogliacomi (2012) Delayed diagnosis of isolated coracoid process fractures: results of 9 cases treated conservatively. Acta Biomedica, vol. 83, no. 2, pp. 138–146. 25. R. Botchu, K. J. Lee, and S. Bianchi (2012) Radiographically undetected coracoid fractures diagnosed by sonography. Report of seven cases. Skeletal Radiology, vol. 41, no. 6, pp. 693–698. 26. T. P. Goss (1996) The scapula: coracoid, acromial, and avulsion fractures. American Journal of Orthopedics, vol. 25, no. 2, pp. 106–115.

27. Baldwin KD, Ohman-Strickland P, Mehta S, Hume E (2008) Scapula fractures: a marker for concomitant

injury? A retrospective review of data in the National Trauma Database. J Trauma; 65(2):430-5. 28. Zlowodzki M, Bhandari M, Zelle BA, Kregor PJ, Cole PA (2006) Treatment of scapula fractures: systematic review of 520 fractures in 22 case series. J Orthop Trauma; 20(3):230-3.

29. Hess F, Zettl R, Welter J, Smolen D, Knoth C (2019) The traumatic acromion fracture: review of the literature, clinical examples and proposal of a treatment algorithm. Arch Orthop Trauma Surg; 139(5):651-658. 30. Çiçekli Ö, Akar A, Topçu HN (2017) Displaced acromion fracture: A rare injury, case report. Int J Surg Case Rep; 39:313–316.

31. Gordon JA, Breitbart E, Austin DC, Photopoulos CD, Kelly JD (2016) Adhesive capsulitis: diagnosis, etiology, and treatment strategies. In: Kelly JD IV, ed. Elite techniques in shoulder arthroscopy: newfrontiers in shoulder preservation. Cham: Springer:149–168. 32. Le HV, Lee SJ, Nazarian A, Rodriguez EK (2017) Adhesive capsulitis ofthe shoulder: review of pathophysiology and current clinical treatments. Shoulder Elbow; 9(2):75–84.

33. Merolla G, Singh S, Paladini P, Porcellini G (2016) Calcific tendinitis of the rotator cuff: state of the art in diagnosis and treatment. J Orthop Traumatol; 17(1):7-14. 34. Lafrance S, Doiron-Cadrin P, Saulnier M, Lamontagne M, Bureau NJ, Dyer JO, Roy JS, Desmeules F (2019) Is ultrasound-guided lavage an effective intervention for rotator cuff calcific tendinopathy? A systematic review with a meta-analysis of randomised controlled trials. BMJ Open Sport Exerc Med; 5(1):e000506.