AMSJ Volume 10, Issue 2 2021 by Australian Medical Student Journal

Australian Medical Student Journal Volume 10, Issue 2 2021

www.amsj.org

Volume 10 Issue 2 2021

Design and layout © 2021, Australian Medical Student Journal Australian Medical Student Journal, PO Box 2119, Carlington Court, Carlington NSW 2118 enquiries@amsj.org www.amsj.org Content © 2021, the authors ISSN (Print): 1837-171X ISSN (Online): 1837-1728 Editor-in-chief Mabel Leow Typesetting Isabel Lee The Australian Medical Student Journal is an independent not-for-profit organisation. The Australian Medical Student Journal can be found on the EBSCOhost databases. Responsibility for article content rests with the respective authors. Any views contained within articles are those of the authors and do not necessarily reflect the views of the Australian Medical Student Journal.

Australian Medical Student Journal Volume 10, Issue 2

CALL FOR SUBMISSIONS • Original Research • • Review Articles • • Research Articles • • Case Reports • • Letters • • Book Reports • The AMSJ accepts submissions from all medical students in Australia. What makes the AMSJ unique is that it provides the opportunity to show-case your work within the academic rigours of a peer-reviewed biomedical journal whilst sharing your ideas with thousands of students and professionals across the country. Whether your passions lie in advocacy, education or research, you can submit to the AMSJ today.

2 Editor’s welcome Mabel Leow Original research

54 Welcome to the wards: Pilot study on microbial contamination of medical students during initial clinical rotations Yanning Elisabeth Xu, Despina Kotsanas, A/Prof. Rhonda L. Stuart, A/Prof. Ian Woolley Reviews

39 Musculoskeletal Disorders in Surgeons Xiang Ron Sim, Alex Ades, Shane Nanayakkara, Pavitra Nanayakkara 61 Do medical students practice what they preach? A review of their dietary patterns over the last decade. Sara Hussain, Zaynab Gerashi, Kosar Hussain, Sahar Hussain 72 Experimental pharmacotherapy approaches to prevention of alcohol dependency Chelsea Linda Smith Case reports

3 A multidisciplinary approach in diagnosing children 9

13 18 24

Submissions open now! AMSJ.ORG

with autistic traits and multiple behavioural issues Ying Hoong Yong Continuous positive airway pressure for obstructive sleep apnoea improved oculogyric crises as well as psychotic symptoms in a woman with schizophrenia and developmental disability Joseph Rizzuto A case of postoperative pericardial effusion progressing to tamponade Richard Zhang, Dr George Wen-Gin Tang, Dr Vincent Chow Aicardi-Goutières Syndrome: A Case Report Jack P. Archer Oxygen delivery: A case-based approach Ryan Teo Xuan Wei, A/Prof Christopher Wright Feature Article

31 Exchange Experiences: Exploring Chinese Healthcare as Australian Medical Students Shivangi Gupta, Lachlan Hou, Dr Gill Cowen Covid-19 discussions

81 The impact of COVID-19 on the mental health of medical students in Australia Madeleine J. Cox 83 How COVID-19 has changed my medical experience Pabasha Savindi Nanayakkara 85 Where in the world is the COVID-19 Vaccine? Clara Dahlenburg 90 Medicine in the age of COVID-19: considerations for the ongoing use and development of telehealth Jaidyn Muhandiramge, Hannah Matthiesson

Editor’s Welcome Dr Mabel Leow MD, PhD Editor-in-Chief, AMSJ Welcome to Volume 10, Issue 2 of the Australian Medical Student Journal.

This has been and unprecedented year with Covid-19. In this issue, we have included a Covid-19 section for medical students to share their thoughts on issues associated with the pandemic. This is in addition to our usual wide range of medical and surgical topics. Of mention are two papers which will be relevant to all medical students. One is a case-based discussion on oxygen delivery, as it is commonly prescribed therapy. The second is a research study on microbial contamination in medical students, a problem which all of us face with in our everyday work. Over the last 12 months, the AMSJ has taken steps to raise the standards of our editorial team to ensure that we publish quality studies. We have started an Understudy team to provide a platform to train pre-clinical medical students with minimal research experience, but aspire to be editors. As part of being a student journal, it is our mission to train medical students. Hence, if you have an interest in being an editor but lack the experience, please do join our team! Last but not least, I would like to express my gratitude to various parties who have made this issue possible. First, the editorial team is grateful to the authors who have chosen to publish their work to AMSJ. We are privileged to be part of your research journey, in which you have put in many hours and months of hard work. At a personal level, I am thankful to my entire editorial and proofreading team who have been the backstage workers making this issue possible. To acknowledge their work this year, we have included the names of the editors and proofreaders who have been working on the manuscripts. Moving forward, we want to increase the visibility of AMSJ. This would take in the form of advertising our manuscripts on Facebook and Twitter. We would greatly appreciate if authors and readers could also share your articles with your friends and colleagues. Correspondence: mabelleowqihe@yahoo.com

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A multidisciplinary approach in diagnosing children with autistic traits and multiple behavioural issues Date of submission: 2 September 2018 Date of acceptance: 13 April 2020 Date of online publication: 18 April 2020 Ying Hoong Yong BBiomedSci Final year MBBS (Hons) Student (Graduated in Dec 2018) Monash University I am a final year medical student in Monash University. Before pursuing my medical degree, I have completed an undergraduate Biomedical Science degree, minoring in Psychology. I have a great interest in child psychiatry and paediatric developmental medicine. Abstract The diagnosis of autism spectrum disorder (ASD) among children with suspected autistic traits and behavioural problems is increasingly common. Due to the common features of ASD and other psychological and behavioural disorders, health professionals are faced with complex diagnostic challenges when outlining the clinical history behind a child’s presenting symptoms. To accurately exclude potential differential diagnoses, health professionals are required to consider a myriad of underlying factors. Parental stress and psychosocial issues can lead to autistic-like behavioural problems in children, and vice versa. This report presents a case of an eight-year-old girl who presented with long-standing anxiety and multiple behavioural issues, which were suspected to be related to ASD. She was referred to the developmental clinic for an integrated multidisciplinary diagnostic workup and assessment to determine if she fulfilled the criteria for ASD. With a detailed review and appropriate assessments, her overall symptoms did not meet the Diagnostic and Statistical Manual of Mental Disorders 5 diagnostic criteria of ASD. In fact, the multidisciplinary team came to a joint conclusion that parental stress and social isolation were the leading causes of the child’s presenting issues. This case emphasises that a single consultation is usually insufficient for health professionals to reach the conclusion of ASD. By highlighting specific screening and diagnostics tests focusing on speech, social interaction, and cognition, this case report underlines the importance of these valuable tools in excluding differential diagnoses and detecting underlying factors that could mimic ASD-related symptoms.

Key learning points 1. ASD is not a straightforward diagnosis that can be simplified by a set of symptoms; a multidisciplinary approach is the future direction in assessing children with suspected ASD. 2. Specific screening and diagnostics tests focusing on speech, social interaction, and cognition, are valuable tools in excluding differential diagnoses and detecting underlying factors that could mimic ASD-related symptoms. 3. The integrated multidisciplinary approach is crucial in providing an appropriate long term management plan, even for children who not qualify for the ASD diagnosis. Introduction Diagnosing autistic spectrum disorder (ASD) is a challenging task for health professionals as the diagnostic approach is mainly based on a constellation of symptoms, including reciprocal social communication deficits, and restrictive and repetitive behaviours [1,2]. The prevalence of ASD has risen since the introduction of the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) criteria, which has raised concerns of overdiagnosis and misdiagnosis of ASD from several studies [1-3]. While a diagnosis of ASD is necessary for government subsidies for autism-related services, the social stigma attached to a misdiagnosis may negatively impact the children and their families [1-2,6-10].

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Furthermore, a misdiagnosis will result in unnecessary therapies for the child, while a missed diagnosis will lead to a suboptimal follow-up and management for the child’s behaviour. Thus, it is important to improve the accuracy of ASD diagnoses by taking a multi-disciplinary approach. Integrating inputs from different disciplines, including developmental paediatrics, psychology, and speech therapy, may provide a more thorough understanding of why a child presents with ASD-like symptoms to inform an effective management plan [9]. Case report May* was an 8-year old girl who presented with long-standing anxiety, multiple autistic traits, and behavioural issues, including temper tantrums and pica (rock-eating behaviour). May’s paediatrician referred her to the developmental paediatric clinic for an assessment of ASD-related concerns. An integrated multidisciplinary diagnostic approach was conducted, which includes a comprehensive medical review completed by a developmental paediatrician and several assessments conducted by allied health professionals, including a child psychologist, occupational therapist, social worker, and case manager. Background May lived with her biological parents, Sophie* and John*, one elder half-sibling, and four younger siblings in regional Victoria. As the family recently moved from a metropolitan suburb in Melbourne earlier this year, there were some delays in May attending her new school in regional Victoria. Her parents had not had a stable income since relocating. John was not present throughout the interviews due to his new job, while Sophie was still looking for job opportunities. Sophie explained that their home situation was challenging due to the lack of childcare support. Presenting issues 1. Anxiety and pica behaviour May had a history of anxiety from the age of two. May had always been anxious and easily distressed by normal daily activities, in particular, getting changed to leave home, having breakfast before going to school, and playing with toys with siblings or similarly-age friends. According to Sophie, May soothed her distress by sucking on her pacifier until the age of five. When May turned five, Sophie started noticing May’s rock-eating behaviour whenever May got highly anxious during social activities. She found rocks in May’s stools on several occasions when May complained of abdominal pain.

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2. ASD-related concerns: social communication deficits and restrictive repetitive behaviours, interests or activities (RRBIs) From a young age, May preferred to be alone and liked to stay in her room even during family gatherings. According to her mother, she was deemed to be ‘rude’ by relatives because she had difficulty understanding social cues and manners. However, May was able to maintain good eye contact and non-verbal communication. May did not have difficulty developing new relationships and had started making friends at her new school. During an individual interview with Sophie, she reported May had shown characteristics related to sensory processing abnormalities, including sensory avoidance and seeking behaviours that had persisted from a young age. May’s parents had made a great effort to adapt the family’s routines to accommodate her hyper-reactivity to smell and taste stimuli. May had a heavily restricted diet, which mainly included olives and frozen peas while avoiding all other food. Since early childhood, May had had temper tantrum that lasted for hours when there was a change in her daily routine, her diet, or her possessions. Family history There is a strong maternal and paternal family history of anxiety and depression. Sophie had a history of anxiety, depression, and bipolar disorder since her teenage years. John also had long-standing anxiety that was mostly related to financial stress and lack of social support. May’s elder half-sibling was diagnosed with oppositional defiant disorder at the age of five. Birth history With a psychiatrist’s advice, Sophie took risperidone throughout her pregnancy with May. She had never been a smoker or a drinker, and her antenatal history was otherwise unremarkable. May was born at 41 weeks gestation and needed brief respiratory support at birth without special nursery admission. She was otherwise healthy. Developmental history May achieved all her developmental milestones at age-appropriate times.

Diet and bowel habits Due to her sensory processing issues, May had a restricted diet that mainly consisted of milk, frozen peas, and olives. The main issue was rock-eating behaviour, as described previously. May had a regular bowel action on a daily basis and no soiling issues were reported. Sleep May did not have issues falling asleep. However, she woke up almost every night to sleep in her parents’ bed. Medication May had been on iron supplement tablets for three years due to her poor diet. However, her mother reported that she refused to take them regularly.

Examination and assessment May was polite and cooperative during the physical examination and all the assessments. Through several interviews with May, the child psychologist and occupational therapist completed several diagnostic assessments, including the Autism Diagnostics Observation Schedule 2nd edition (ADOS-2), and a speech assessment – Clinical Evaluation of Language Fundamentals 4 (CELF4) and Pragmatics. The Childhood Autism Rating Scale (CARS) questionnaire was completed, with a final score of 23 out of 60, as a part of the screening assessment. The results of the physical examinations and assessments are listed in Table 1 and Table 2, respectively.

Table 1. Physical examination findings. NAD: no abnormality detected

Examination

Results

Weight

37.8 kg

Height

129 cm

Head circumference Skin examination Neurological examination Respiratory examination Cardiovascular examination Thyroid examination

Developmental examinations

53.5 cm A 1 x 2 cm cafe-au-lait macule on her right scapular region NAD. Normal coordination, able to hop on one leg NAD NAD NAD Gross motor – Upon current examination, May was able to stand on one leg and hop on a single leg Fine motor - May had good fine motor skills, she showed tripod pencil grip in her drawing and writing Speech and language – May’s receptive speech was very literal and she did not understand simple jokes, she was able to elaborate on her statements, understand instructions, and hold conversations. Social – Although May was not socially proactive, she could maintain a reciprocal conversation once the interviewer had initiated it. May had good eye contact and non-verbal communication.

Audiology test

NAD. Test completed one week prior to the assessment

Vision test

NAD. Test completed one week prior to the assessment

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Table 2. Assessment results

Assessment types

Results

Autism Diagnostics Observation Schedule 2nd edition (ADOS-2), Module 3

Minimal features of ASD. Final ADOS score of 2: does not satisfy the criteria of ASD as per DSM-V. No concerns in communication reciprocity, non-verbal communication, and understanding relationships. No current evidence of stereotyped or repetitive movements. Moderate concerns in hyper-reactivity to sensory input.

Speech assessment – Clinical Evaluation of Language Fundamentals 4 (CELF4) and Pragmatics

Normally developed receptive (122, 93rd percentile) and expressive (116, 86th percentile) language.

Cognitive assessment - Wechsler Intelligence Scale for Children 5th edition (WISC5)

Full Scale Intelligence Quotient (FSIQ) was 115, classified as high average range.

Childhood Autism Rating Scale (CARS)

23/60. Total score of less than 30: not suggestive of ASD

Diagnosis After vigorous discussion and assessments among the multidisciplinary team, they concluded that May did not have Autism Spectrum Disorder (as per ADOS-2, CARS, CELF4 and Pragmatics, and her developmental paediatric assessment). Through thorough interviews and assessments, the team concluded that her social interaction was adequate and appropriate for her age. Her behavioural difficulties could be attributed to anxiety, complicated by parental stresses and family dynamics. Although some of her presenting characteristics were highly suggestive of ASD based on the DSM-5 criteria on both the social communication domain and RRB domain, the team argued that May’s individual level of functioning was not significantly impacted. Therefore, she did not fulfil the DSM-5 criteria for ASD. May’s mother was given the joint feedback and explanation of the final diagnosis by the developmental paediatrician and psychologist. The paediatrician made a referral to the local family support services and discussed recommendations of constructive parenting strategies to improve May’s anxiety and behavioural problems. The case manager arranged follow-up appointments and meetings with May’s new school teacher for another review and observed for new developments in her anxiety and behavioural issues.

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Discussion Diagnostic criteria of ASD in DSM-5 The current DSM-5 diagnostic criteria are classified into two domains – social communication deficits and restrictive repetitive behaviours (RRB) [1,2]. To fulfil the DSM-5 criteria, a child has to present with all symptoms in the interactive social domain and two out of four symptoms listed under the RRB domain [1,5]. Furthermore, these symptoms have to cause a significant impact on the child across different contexts from early childhood [1,2,6]. When comparing DSM-4 and DSM-5 criteria, DSM-5 was found to have higher specificity but lower sensitivity in detecting children with ASD [4,6]. Therefore, paediatricians can more confidently rule out ASD in children, but may miss the higher functioning subtypes, such as Asperger’s syndrome, that were previously included in DSM-4 [1-3,6]. Dilemma of ASD diagnosis Paediatricians face dilemmas when making an ASD diagnosis due to its significant impact – a misdiagnosis will result in unnecessary therapies for the child, while a missed diagnosis will lead to suboptimal management of the child’s behaviour. According to several studies, children diagnosed with ASD are more likely to get government-funded coordinated care that targets their needs, and the parents are more proactive in managing their children’s behavioural difficulties [1,3,6,7]. However, with the increasing demand for autism-related services, access to government funding is becoming limited, and the healthcare system is increasingly burdened by the long waiting lists [7-9]. According to several studies, other consequences following ASD diagnosis include parental stress, social stigma, and devaluation [7-9].

Furthermore, a misdiagnosis may divert health professionals towards the wrong path of management strategies when addressing the child’s behaviour. Therefore, paediatricians are increasingly vigilant of the consequences of overdiagnosis and misdiagnosis. Benefits of an integrated multidisciplinary diagnostic approach Some studies have raised concerns about overdiagnosis and misdiagnosis after the introduction of DSM-5 [1-4,9]. Although the DSM-5 raises the threshold to potentially exclude higher functioning individuals, more children are diagnosed with ASD than 20 years ago, predominantly due to oversimplification of the criteria [3,4,10]. With discussion from different disciplines, paediatricians can avoid misdiagnosis and provide an effective management plan for the family [6,8,9]. The benefits of a multidisciplinary approach are supported by Austin et al. [9] who showed dramatic improvements in ruling out children without ASD, reducing the length of appointment waiting lists and offloading the overburdened autism-related services. May’s case portrays the importance of a holistic approach in accurately diagnosing children with ambiguous ASD traits. It raises awareness among medical students by familiarising clues and signs of ASD through different screening and diagnostic tools. ADOS-2, CARS, WISC5, CELF4, and Pragmatics are particularly useful to detect and quantify the severity of the impairment from several aspects [6,10,11]. Cognitive assessment, WISC5, is utilised to screen for intellectual disability (ID), which can be an isolated diagnosis or may co-exist with ASD and anxiety [6,10]. By using speech assessment CELF4, paediatricians can isolate receptive and expressive language disorders, which can lead to behavioural issues and communication difficulties [11]. Both ID and speech disorders may also be contributing factors for behavioural dysregulations and social interaction deficits [6, 10].

Relating diagnosis to May’s presenting symptoms Although May’s primary referral raised the suspicion of ASD, her overall symptoms did not justify an ASD diagnosis after the detailed review and appropriate assessments. When the multidisciplinary team investigated the underlying factors for different aspects, parental stress and social isolation became the collective answer to May’s presenting issues. Recent studies emphasise that the relationship between parental stress and children’s behavioural problems is bidirectional and is often confounded by financial difficulties and social isolation [10,12,13]. While the on-site case manager arranged a six-month review with May’s parents, May was linked in with her new school’s counsellor and a child psychologist to manage her behaviours. Furthermore, May’s mother was introduced to the local parental and community support services, who offer financial and social support. For children who do not qualify the ASD diagnosis, the National Institute for Health and Care Excellence (NICE) guidelines also suggest keeping the child under review, in order to take into account any new information that could alter the diagnosis [2]. Unfortunately, May was lost to follow up as her family moved to another state shortly after the assessment. Conclusion This case conveys two important messages to healthcare professionals and the public. Firstly, ASD is not a straightforward diagnosis that can be simplified by a set of symptoms. Therefore, a multidisciplinary approach is the future direction in assessing children with suspected ASD. Contributions from different disciplines can offer a collective insight into the reasons behind the child’s presenting symptoms. With a clearer picture of the underlying factors, the child can receive appropriate services and support targeting the right issue. Secondly, an integrated multidisciplinary approach provides appropriate ongoing management planning even for children who do not qualify for the ASD diagnosis. May’s case raised the importance of post-diagnosis follow-up in providing parental support and ongoing advice on behavioural management. For children who do not qualify for the ASD diagnosis but continue to have behavioural issues, they can be referred to a psychologist for family therapy, cognitive-behavioural therapy, and school aid for behavioural management.

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Acknowledgements I would like to thank Dr Sarah Woodall, one of the registrars from Developmental Paediatrics at Monash Children’s Hospital, for her advice and discussion in this case report. Conflict of interest None declared. *Name has been changed for confidentiality.

References [1]

manual of mental disorders. BMC Med. 2013;17:133-7. [2]

Consent Declaration Informed consent was obtained from the patient and patient’s next-of-kin for publication of this case report.

UK NICE Guideline Updates Team. Autism spectrum disorder in under 19s: recognition, referral and diagnosis.

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Lobar SL. DSM-V changes for autism spectrum disorder (ASD): implications for diagnosis, management, and care coordination for children with ASDs. J Pediatr Health Care. 2016;30(4):359-65.

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Funding This case report is not funded by any party. Author’s contribution This case report was selected, recorded, and written by YH. Yong.

American Psychiatric Association. Diagnostic and statistical

McPartland JC, Reichow B, Volkmar FR. Sensitivity and specificity of proposed DSM-5 diagnostic criteria for autism spectrum disorder. J Am Acad Child Adolesc Psychiatry. 2012;51(4):368-83.

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Volkmar FR, McPartland JC. From Kanner to DSM-5: autism as an evolving diagnostic concept. Annu Rev Clin Psychol. 2014;28(10):193-212.

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Kaland N. Brief report: Should Asperger syndrome be excluded from the forthcoming DSM-V? Research in Autism Spectrum

[8]

Abstract

tion: Parental perspectives on the diagnosis of autism spectrum

Introduction This report highlights the risk factors and complexities of schizophrenia as well as the adverse effects of treatment. Obstructive sleep apnoea (OSA) has a notorious history of under-diagnosis in both the general population as well as those suffering from mental health disorders, particularly schizophrenia. Antipsychotics have life altering side effects contributing both to a decrease in quality of life as well as increasing morbidity and mortality.

Johnson TD, Joshi A. Dark clouds or silver linings? A stigma workplace well-being. J Appl Psychol. 2016;101(3):430-49.

[9]

Austin J, Manning-Courtney P, Johnson ML, Weber R, Johnson H, Murray D et al. Improving access to care at autism treatment centers: a system analysis approach. Pediatrics. 2016;137:S149-57.

[10]

Autism and Developmental Disabilities Monitoring Network Surveillance Year 2010 Principal Investigators. Prevalence of autism spectrum disorder among children aged 8 years—autism and developmental disabilities monitoring network, 11 sites, United States, 2010. Morbidity and Mortality Weekly Report: Surveillance Summaries. 2014 ;28;63(2):1-21.

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Condouris K, Meyer E, Tager-Flusberg H. The relationship between standardized measures of language and measures of spontaneous speech in children with autism. Am J Speech Lang Pathol. 2003;12(3):349-58.

[12]

Baker BL, McIntyre LL, Blacher J, Crnic K, Edelbrock C, Low C. Pre-school children with and without developmental delay: behaviour problems and parenting stress over time. J Intellect Disabil Res. 2003;47(4-5):217-30.

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Valicenti-McDermott M, Lawson K, Hottinger K, Seijo R, Schechtman M, Shulman L et al. Parental stress in families of children with autism and other developmental disabilities. J Child Neurol. 2015;30(13):1728-35. spontaneous speech in children with autism. Am J Speech Lang Pathol. 2003;12(3):349-58.

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Joseph Rizzuto Candidate MD, University of Wollongong Graduate School of Medicine MS 4 (4 year degree) Joe is an avid surfer, sailor, and diver with a particular interest in psychiatry and oncology. He is passionate about delving into the psyche of the mentally handicapped and those from disadvantaged backgrounds both domestically and abroad.

Russell G, Norwich B. Dilemmas, diagnosis and de-stigmatiza-

threat perspective on the implications of an autism diagnosis for

Section Editor Subhashaan Sreedharan Proofreader Emily Feng-Gu

Date of submission: 9 March 2019 Date of acceptance: 5 March 2020 Date of online publication: 7 March 2020

Disorders. 2001;5(3): 984-9. [7]

disorders. Clin Child Psychol Psychiatry. 2012;17(2):229-45.

Associate Editor Simran Dahiya

Continuous positive airway pressure for obstructive sleep apnoea improved oculogyric crises as well as psychotic symptoms in a woman with schizophrenia and developmental disability

Case overview This case report presents a 61-year-old female with diagnoses of schizophrenia, frontal lobe epilepsy, a developmental disability, oculogyric crises (OGC), and obstructive sleep apnoea. Discussion overview Early intervention with continuous positive airway pressure (CPAP) in those suffering from OSA can have dramatic effects decreasing the burden of concurrent disease. This report showcases that treatment of OSA with CPAP increased patient wellbeing, allowing down-titration of risperidone, and thereby ameliorating the drug-induced OGC in this patient.

Key learning points 1. Management considerations for the adverse effects of high dose risperidone treatment in those suffering from schizophrenia and concurrent developmental disability 2. Obstructive sleep apnoea is notoriously under diagnosed in both the general population as well as those suffering from mental health disorders, particularly schizophrenia 3. Treatment of obstructive sleep apnoea with continuous positive airway pressure increased patient wellbeing, allowing down-titration of risperidone thereby ameliorating the drug-induced oculogyric crises in the case patient Introduction Individuals suffering long-term from schizophrenia experience broad functional deficits negatively impacting clinical outcome [1]. This case report presents a 61-year-old female with schizophrenia receiving long-term treatment with risperidone. She has a complex background with concurrent diagnoses of frontal lobe epilepsy, a developmental disability, and obstructive sleep apnoea (OSA). This report elucidates some of the risk factors and complexities of schizophrenia as well as highlighting some adverse effects of treatment. Lastly, concerning the long-term management, continuous positive airway pressure (CPAP) is presented as a novel consideration to reduce the burden of disease in those suffering from schizophrenia with concurrent OSA.

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Case A 61-year-old female, PB, presented for a routine follow-up appointment in August 2018 at a private psychiatric hospital. PB was accompanied by a carer as she is intellectually disabled and residing in an assisted living facility. PB has a complex history of schizophrenia, frontal lobe epilepsy, and obstructive sleep apnoea. Detailed medical records have been kept throughout the patient’s lifetime. The patient’s medical history can be followed back to 1961, when she was admitted to hospital for a frontal lobe abscess of unknown aetiology. An exploratory craniotomy revealed a space occupying lesion and subsequently the pus was drained. During the first post-operative week, additional aspirations were performed via a frontal burr hole. The patient’s medical records detailed the presence of a frontal lobe scar following the abscess drainage. Later medical records describe developmental disabilities following the abscess removal. A gradual cognitive decline is noted along with the progression of “aggressive outbursts” and reported “social isolation”. Over time she became further withdrawn, demonstrating a lack of interest in social engagement, poverty of speech, and apathy. She was diagnosed with paranoid schizophrenia and started on risperidone 1 mg BD in 2003. However, this dose of risperidone was ineffective as PB was reported to be “talking to herself,” and assaulted a staff member at her group home. Subsequently, her risperidone was increased to 2 mg BD. Records then show the addition of chlorpromazine 200 mg BD in 2004 which resulted in a reduction of her symptoms. Seizures were reported in 2006 and valproate 500 mg was prescribed to control epileptic episodes. PB remained on this treatment regime for her psychiatric issues. Irritability and psychotic exacerbations were noted, but she remained relatively stable on this treatment plan. In 2011, the presence of oculogyric crises (OGC) was noted. This was attributed to risperidone and the dose was lowered to 1 mg BD. The lower dose lead to an alleviation of her oculogyric crises, however there was a re-emergence of paranoia. Subsequently, her risperidone was up-titrated back to 2 mg BD. This process of down- and up-titration suggests a direct causal relationship between risperidone and oculogyric crises.

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At an appointment with the patient’s general practitioner (GP) in February 2018, PB’s carer described episodes of unpleasant loud snoring along with a perceived overall decline in quality of sleep noted by daytime lethargy. These symptoms were attributed to obstructive sleep apnoea and the patient was prescribed CPAP. Three weeks after initiating CPAP, an improvement in PB’s overall mood and energy was noted by the GP. Risperidone and chlorpromazine were reduced to 1 mg nocte, and 100 mg BD, respectively, in early March. This reduction in medication lead to the first remission of her oculogyric crises since it began in 2011. Additionally, carers at her assisted living facility reported less irritability and fewer signs of paranoia in PB. PB’s story demonstrates that treating comorbidities, such as OSA, in individuals with a psychotic illness may reduce their reliance on high-dose polypharmacy and consequently reduce the burdensome adverse effects that these medications have on day-today functioning. Discussion Current approaches towards the phenomenology of schizophrenia emphasize its complex biopsychosocial aetiologies [2]. It is important to note that because of the high prevalence of comorbid disorders among people with schizophrenia, most studies have been inconclusive in determining whether or not specific comorbidities are a consequence of pre-existing psychotic symptoms rather than a cause [3]. Pertinent to this case, a recent study in Western Australia found that of people with an intellectual disability, nearly 5% had co-occurring schizophrenia [4]. Additionally, functional imaging scans of patients with schizophrenia showed the presence of altered prefrontal fibers along with decreased frontal white matter mass [5]. When looking at patient PB; it is difficult to ascertain whether or not either the frontal lobe abscess, craniotomy, or intellectual disability were a root cause or independent factors from her schizophrenia. Regardless, these factors play into the broader context of current approaches to schizophrenia by revealing the absence of a specific cause to be adjusted. There is, rather, a necessity to holistically manage not just the positive or negative symptoms of schizophrenia, but the individual patient [6]. Oculogyric crisis is a dystonic reaction consisting of spastic deviations of the eyes, most commonly upward, lasting for a few minutes to many hours [7]. OGC is a rare, but severe adverse effect of antipsychotics [8].

Once classically associated with first generation antipsychotics, recent literature has revealed a greater number of cases of patients on second generation antipsychotics experiencing extrapyramidal side effects than anticipated [8,9]. In line with the case of patient PB, a previous study found the emergence of OGC in those with developmental disabilities [10]. In the study of forty participants, two had experienced OGC while another two developed dyskinetic movements; it is worth noting that both side effects ceased with the withdrawal of risperidone [10]. Despite this adverse effect, risperidone has still been proven to be one of the most effective treatments for those with developmental disabilities, especially those displaying aberrant behaviors [11]. Obstructive sleep apnoea is a chronic condition characterized by recurrent episodes of upper airway collapse leading to a reduction in airflow and gas exchange during sleep [12,13]. The prevalence of OSA has proven to be difficult to calculate due to underdiagnosis in community-based psychiatric patients [14]. Despite this limitation, it has been estimated that the co-occurrence of OSA in people with schizophrenia is particularly high, with one study finding that among those with severe sleep apnoea, 31% had schizophrenia compared with 19% in the general population [15]. Further, those with schizophrenia are estimated to have a 16-18 year reduction in life expectancy due to cardiovascular disease, with OSA being a risk factor for hypertension, diabetes, stroke, and heart failure [16,17]. Additionally, the high rates of obesity, tobacco smoking, alcohol consumption, and the use of antipsychotic medications among people with schizophrenia are believed to pose an increased risk for OSA [18-21]. A pilot study of 104 patients, found that the treatment of OSA with CPAP in patients with schizophrenia led to an improvement in quality of life [22]. Leading hypotheses surrounding the phenomenology of this correlation point towards the multifactorial benefits of CPAP: after six months of treatment the study showed improvements in cognition, weight loss, reduction in blood pressure, and increased rapid eye movement (REM) sleep [22]. It is believed that CPAP causes these myriad effects by reducing daytime lethargy and improving cognitive function, giving individuals the energy to live a more active and healthier lifestyle [23]. This becomes ever more important in people with schizophrenia as cognitive impairment is a hallmark of schizophrenia

and neurodevelopmental changes are present, further debilitating sufferers from their premorbid condition [1]. Therefore, this improvement in cognitive function may lead to higher overall function, lessening the burden of disease. A retrospective cohort study of 284 patients showed that there were not any statistical differences (33.6% v. 33.3% p=0.82) among patients with psychiatric illness and those without regarding their ability to tolerate CPAP titration in the treatment of OSA [24]. While the preceding studies demonstrated the efficacy of CPAP treatment, this study shows the lack of precluding factors that would prevent using CPAP treatment in those with a concurrent psychiatric illness [22,23,24]. With treatment of their OSA, our patient displayed a reduction in psychotic symptoms and remission of adverse effects of risperidone, namely OGC. OSA may be potentially under-recognized in people with schizophrenia and further research is necessary to determine the relationships between antipsychotic medications and OSA. Clinicians should consider exploring the presence of OSA in their patients with schizophrenia, as treating OSA may reduce their dependence on high-dose medication and thus reduce the risk of extra-pyramidal side effects. Furthermore, this report highlights the need to consider the patient more holistically, taking into account broader biopsychosocial factors in treatment. Acknowledgements The author would like to acknowledge Dr. Warren Rich from the University of Wollongong for his assistance and enthusiasm for medical student research. Conflicts of Interest None declared. Funding No outside funding was received for the development of this article. Authors Contribution Project design, synthesis of data and publication. Consent Declaration Informed consent was obtained from the patient for publication of this case report. Senior Editor Subhashaan Sreedharan Mabel Leow Proofreaders Ivy Jiang Margaret Hezkial

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Dr Vincent Chow, BSc (Med) MBBS (Hons) PhD FRACP FCSANZ Staff Specialist Cardiologist, Concord Hospital Clinical Senior Lecturer, Macquarie University Senior Lecturer, Sydney Medical School, University of Sydney Dr Vincent Chow is a staff specialist Cardiologist at Concord Hospital and a senior lecturer at the Faculty of Medicine at University of Sydney. He has an interest in clinical medicine, medical education of medical students and junior doctors as well as ongoing postdoctoral medical research.

Manjunath S, Yataco J, Murillo L. Psychiatric disorder does not

Abstract Introduction: Pericardial effusions often occur after cardiac surgery, but are usually asymptomatically. However, large postoperative effusions may cause cardiac tamponade, which is a medical emergency.

Zarcone JR, Hellings JA, Crandall K, Reese RM, Marquis J,

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Dr George Wen-Gin Tang, Conjoint Senior Lecturer (UNSW) B. Med, Grad. Dip. HPEd., MHA, FRACGP Dr Tang is a GP who is passionate about education, and is heavily involved with teaching and assessing medical students and GP registrars, as well as supervising their clinical research. In addition to above, he is also a clinical supervisor in GP Synergy, examiner of RACGP and senior examiner for the Australian Medical Council.

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persons with developmental disabilities: I. A double-blind

[14]

Richard Zhang Third year medical student, BMed/MD (expected date of graduation 2023) University of New South Wales Richard is a third year medical student with a passion for global health and a keen interest in all things cardiology. He has enjoyed his experiences with international medical volunteering and clinical cardiology research, and hopes to gain further involvement with both.

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Date of submission: 15 September 2019 Date of acceptance: 27 June 2020 Date of online publication: 4 July 2020

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12 Australian Medical Student Journal

Case overview: We report a case of a 62-year-old businessman who presented with worsening paroxysmal nocturnal dyspnoea, orthopnoea, and an episode of near-syncope. Echocardiography revealed evidence of cardiac tamponade, most likely due to recent coronary artery bypass graft and aortic valve replacement surgery. He was treated with pericardiocentesis and ongoing review revealed no recurrence of the effusion.

Key learning points 1. It is important to monitor for pericardial effusion post-cardiac surgery, as large effusions can lead to cardiac tamponade. 2. Cardiac tamponade is largely a clinical diagnosis with Beck’s Triad as the common clinical sign, even though echocardiography is useful when evaluating a patient with suspected tamponade. 3. Cardiac tamponade is best treated by ultrasound-guided percutaneous pericardiocentesis, which can be performed quickly and at bedside, though more invasive pericardial window surgery may be indicated in cases of active bleeding and recurrent fluid accumulation.

Discussion overview: We discuss the incidence and risk factors for postoperative pericardial effusion and the possibility of tamponade after cardiac surgery. Though rare, recognising tamponade after cardiac surgery is vital and a thorough understanding of the treatment of tamponade is necessary.

Australian Medical Student Journal

Introduction Pericardial effusion occurs when excess fluid accumulates between the visceral and parietal layers of the pericardium. There are many causes of pericardial effusion, including post-surgery, viral illness, direct injury to the pericardium, malignancy, but it can also be idiopathic [1]. Pericardial effusions are common after cardiac surgeries, with a prevalence of up to 84% in cardiac surgery patients [2]. Though most are small and non-life threatening, larger effusions can compress the heart and prevent proper ventricular filling, causing cardiac tamponade in 4.1% of these patients [2]. Management of postoperative pericardial effusion (PPE) varies based on the size and location of the effusion, and whether there is evidence of cardiac tamponade. This case highlights the need to be acutely aware of clinical and echocardiographic features of cardiac tamponade, and the need for urgent intervention in life-threatening cardiac tamponade. The Case Assessment at cardiology clinic A 62-year-old retired businessman presented to his cardiologist for assessment a week after discharge from hospital, after undergoing coronary artery bypass graft and metallic mechanical aortic valve replacement for presumed infective endocarditis (IE) and ischaemic heart disease. He reported worsening paroxysmal nocturnal dyspnoea, orthopnoea, and an episode of near syncope since discharge. The patient had known hypertension and a 30 pack-year history of smoking but had no other cardiovascular risk factors and no other previous surgeries. During his earlier admission, he was treated for presumed IE with a six-week course of antibiotics. On physical examination, the patient’s blood pressure was 105/70 mmHg, and heart rate was regular at 90 bpm. Respiratory rate was 20 breaths per minute. He appeared diaphoretic. Heart sounds were muffled, no murmurs were appreciated. The jugular venous pressure (JVP) could not be assessed accurately, as he was tachypnoeic with shallow breathing. Chest auscultation revealed reduced air entry bilaterally. Electrocardiogram revealed sinus rhythm with low electrical voltages in all leads with no ischaemic changes or changes consistent with pericarditis.

14 Australian Medical Student Journal

He underwent an urgent echocardiogram revealing a mildly dilated left ventricle with an ejection fraction of 30-35%. Most remarkably, there was a large pericardial effusion measuring up to 30 mm (Figure 1). There was significant mitral inflow variation of 34% and tricuspid inflow variation of 48%.

Figure 2. A4C view of patient’s heart two weeks after drainage of pericardial effusion revealing no re-accumulation of fluid and no evidence of cardiac tamponade on echocardiogram. RA = right atrium, LA = left atrium, RV = right ventricle, LV = left ventricle, black arrows indicate absence of pathological effusion

Discussion Figure 1. An echocardiographic apical four-chamber (A4C) view of the patient’s heart, which shows the large effusion and diastolic collapse of the left and right atria, demonstrating severe haemodynamic compromise and cardiac tamponade. A4C view of patient’s heart. RA = right atrium, LA = left atrium, RV = right ventricle, LV = left ventricle, PE = pericardial effusion.

Upon admission to hospital He was urgently readmitted to hospital and was promptly assessed by the cardiothoracic surgical team, who immediately decided an urgent chest ultrasound-guided percutaneous drainage was most appropriate. Approximately 800 mL of blood-stained fluid was drained which led to immediate improvement in his symptoms and haemodynamic status. A drain was placed for 48 hours. The pericardial fluid was sent to microbiology and cytology, where no evidence of infection or malignancy was found. The patient was reviewed by the infectious disease team and recommenced on a short course of intravenous antibiotics. Echocardiography performed post-pericardial drain removal revealed only a trivial effusion. He was discharged home three days later for ongoing cardiology review. After discharge Upon review with his cardiologist four weeks after discharge, the patient felt well with no recurrence of dyspnoea or syncope. Follow-up echocardiography revealed no re-accumulation of his pericardial effusion and there were no signs of cardiac tamponade (Figure 2). He was also reviewed by the infectious disease team four weeks after discharge, where no further antibiotics were recommended, and the patient was discharged from the clinic.

Pericardial effusion after cardiac surgery A pericardial effusion constitutes any fluid in excess of 50 mL in the pericardial sac [1]. Pericardial effusion can occur in any disease affecting the pericardium, after injury to the pericardium, or due to obstruction of the lymphatics draining the pericardial fluid. In the context of cardiac surgery, as with our patient, PPE can occur due to any of postoperative impairment of lymphatic drainage, pericardial inflammation in response to injury during the surgery, and post-pericardiotomy syndrome [3,4]. A chest tube is usually inserted after cardiac surgery to drain fluid in the mediastinum, but a pericardial drain is not routinely placed unless there is evidence of cardiac effusion [1]. Pericardial effusion is often asymptomatic, especially for small or moderate effusions. In symptomatic cases, dyspnoea and malaise occur most frequently. Some features of tamponade, such as hypotension and tachycardia due to decreased cardiac output, can manifest in large effusions [1].

Diagnosis of pericardial effusion is most commonly done by echocardiography, which allows for real-time assessment of the pericardial effusion size, location, and possible haemodynamic effects, from which it can be classified as shown in Table 1 [6]. Since transthoracic echocardiography is routine after cardiac surgeries, PPE is often picked up, and can be monitored. Effusions are visualised as anechoic separation of the visceral and parietal layers of the pericardium and are best detected from parasternal short and long-axis and sub-xyphoid views [5]. Electrocardiography may demonstrate low voltages in large effusions, which occurred with our patient. It may also reveal electrical alternans, characterised by alternating QRS amplitude, due to the anterior-posterior swinging of the heart with each contraction in the fluid-filled pericardium. Risk factors for PPE Risk factors for PPE include type of surgery, urgency of operation, larger body surface area, pulmonary thromboembolism, hypertension, renal failure, and immunosuppression [7]. Early chest tube removal after cardiac surgery is also associated with PPE requiring invasive treatment [8]. The problem of tamponade As discussed, though rare, the most feared complication of a large PPE is cardiac tamponade. If fluid accumulates rapidly, as is the case in PPE, the pericardium has low compliance and intrapericardial pressure rises rapidly. This compresses the heart, impairing ventricular filling and ultimately decreasing cardiac output. If fluid accumulates slowly, the parietal pericardium can stretch and can hold larger volumes of fluid before compressing the heart [9]. Haemodynamic tamponade occurs when right atrial pressures are affected by the effusion but can have no echocardiographic or clinical significance [10].

Table 1. Classifications of pericardial effusions [7]

Size (mm)

Composition

Onset (weeks)

Distribution

Definition

Small (<10mm)

Transudative

Acute (<1 week)

Circumferential/ generalised

Simple

Moderate (10-20mm)

Exudative

Subacute (<12 weeks)

Focal/loculated

Complex

Large (>20mm)

—

Chronic (>12 weeks)

—

Australian Medical Student Journal

Cardiac tamponade is a clinical diagnosis, though echocardiography is useful when evaluating a patient with suspected tamponade. Classically, the clinical signs of tamponade are described by Beck’s Triad, which consists of hypotension, elevated JVP, and muffled heart sounds. Pulsus paradoxus, defined as a decrease of > 10 mmHg in systolic blood pressure on inspiration, can also be a common clinical finding. Early echocardiographic signs of tamponade include a dilated inferior vena cava and increased respiratory variation in mitral (> 25%) and tricuspid (> 40%) inflows. Late signs include collapse of the cardiac chambers. However, loculated effusions, which are more common after cardiac surgery, may compress select chambers causing regional tamponade, and may require additional imaging such as transoesophageal echocardiography or computed tomography [11]. The incidence of late tamponade after cardiac surgery is 4.1% [2,12]. Moreover, tamponade is more common in patients receiving oral anticoagulants (8%) than in those without anticoagulants (2%) [12]. Treatment of PPE Treatment of PPE depends on the size and location of the effusion. Small and most moderate effusions are generally asymptomatic and require no treatment. Tamponade requires immediate drainage. However, large effusions can be asymptomatic but can progress to tamponade. Treatment is less clear in these cases, with no existing guidelines for treating PPE [10]. Colchicine, a nonsteroidal anti-inflammatory drug (NSAID), can be effective in preventing post-surgical pericardial effusion and some surgical units routinely commence patients on a six-week course of colchicine post-operatively to help reduce the incidence of postoperative pericarditis and pericardial effusion. However, recent evidence shows NSAIDs do not reduce either the size of the effusion or the incidence of late tamponade [13-15]. Drainage of excess fluid in PPE can be accomplished by pericardiocentesis, where a needle is used to aspirate the excess fluid, or pericardial window surgery, where an excision of part of the pericardium allows fluid to drain into another body cavity. For PPE, percutaneous pericardiocentesis is preferred as it can be performed expeditiously at bedside, avoiding the need for general anaesthesia which can be risky in the case of cardiac tamponade. Ultrasound-guided pericardiocentesis is the traditional gold standard for treatment. Loculated effusions must be

16 Australian Medical Student Journal

treated differently and may require pericardiocentesis at nonstandard entry sites. Traditional sub-xyphoid pericardiocentesis is most effective in circumferential effusion or if the effusion is inferior or anterior to the heart [16]. However, pericardiocentesis does not control continuous fluid accumulation in the pericardium. Therefore, the surgical window is preferred in traumatic hemopericardium, where there may be active bleeding, and aortic dissection or myocardial rupture, where relief of the tamponade may lead to increased bleeding. Moreover, in cases of recurrence, posteriorly located effusions, or when biopsy material is required, more invasive strategies such as pericardial window are preferred [11]. It has not been formally studied whether IE changes the management of PPE, as was the case in our patient, but in general, pericardiocentesis is done in all pericardial effusions which have a background of bacterial infection for diagnostic purposes. The pericardial fluid drained is then sent for fluid analysis and microscopy, culture, and sensitivity to determine the infective aetiology, which will dictate the treatment.

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Conclusion PPE is a common complication after cardiac surgery and, though usually asymptomatic, can progress to tamponade. It is, therefore, essential to recognise features of clinical cardiac Consent Declaration Informed consent was obtained from the patient for publication of this case report and accompanying figures.

2010;89(1):112-8. doi:10.1016/j.athoracsur.2009.09.026. [8]

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Acknowledgements None. Conflicts of interest None.

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Funding None.

and management of pericardial diseases of the European

Authors’ Contributions RZ wrote the manuscript. GWT and VC collected the patient data and supervised RZ in writing the manuscript. All authors revised the final manuscript.

Association for Cardio-Thoracic Surgery (EACTS). Eur Heart J.

Society of Cardiology (ESC) Endorsed by: The European 2015;36(42):2921-64.

Senior Editor Daniel Wong Mabel Leow Senior Proofreader Emily Feng-Gu Proofreader Ivy Jiang Australian Medical Student Journal

Aicardi-Goutières Syndrome: A Case Report Date of submission: 14 December 2019 Date of acceptance: 14 June 2020 Date of online publication: 20 June 2020 Dr. Jack P. Archer Medical Internship, Wagga Wagga Hospital, 2020. Doctor of Medicine, University of Wollongong, 2016-2019. Bachelor of Physiotherapy (Honours), Charles Sturt University, 2012-2015. Jack is an Intern at Wagga Wagga Base Hospital and graduated from the University of Wollongong in 2019. Jack has previously completed a bachelor’s degree with Honours in Physiotherapy. He has worked as a physiotherapist in acute and rehabilitation services. Jack has a personal interest in rural medicine and surgery. Abstract Background: Aicardi-Goutières Syndrome (AGS) is a rare genetic neurological disorder that presents as pseudo-TORCH syndrome. There are 350 confirmed cases worldwide. This case report describes a 22-month-old male with AicardiGoutières Syndrome who was diagnosed at four months of age. This paper seeks to highlight AGS as a differential for TORCH Syndrome, and to build on the limited knowledge from previous cases to identify key concepts and management strategies that may be of benefit to the medical community. Case overview: A four-month-old male was admitted to a New Zealand Hospital in status epilepticus. A history of inconsolable crying, subjective fevers and abnormal posturing was elicited. Examination found a spastic quadriplegic cerebral palsy. Investigation excluded infective causes. MRI and CT scans demonstrated atrophy of the cerebral cortex with calcification of the basal ganglia. CSF analysis showed elevated white cells and neopterin, and genetic analysis identified variants of unknown significance in the ADAR1 gene. A diagnosis of AGS was made. Treatment focused on managing complications including seizures, spasticity, and airway clearance. Discussion overview: This case highlights AGS as a differential for TORCH syndrome. Complication management forms the basis of care. Current literature is limited, and future research is needed to understand the pathophysiology of the disease to develop treatments and management strategies.

18 Australian Medical Student Journal

Key learning points 1. Aicardi-Goutières Syndrome is a rare differential for TORCH Syndrome and should be considered when TORCH infections have been excluded. 2. Key clinical findings that help distinguish Aicardi-Goutières Syndrome from TORCH Syndrome include onset at four months, vasculitic lesions, absence of ocular anatomical pathology, and absence of hearing impairment. 3. Complication management currently forms the basis of care. A balance between treatments, side effects, and patient goals is required to achieve optimal outcomes for the patient. 4. The understanding of the genetic processes in Aicardi-Goutières Syndrome has allowed the investigation of future therapeutic agents such as JAK inhibitors, antiretrovirals, anti-IFN-alpha and cGAS inhibitors, and introduction of genetic counselling.

Introduction Aicardi-Goutières Syndrome (AGS) is a rare genetic neurological condition first described in 1984 [1]. It is a Type 1 interferonopathy [2] and only 350 confirmed cases have been recorded worldwide by the International Aicardi-Goutières Syndrome Association [3]. Prior to its discovery, AGS was classified as pseudo-TORCH Syndrome due to the similar presentation to TORCH Syndrome in the absence of identifiable pathogens [4]. The disease typically begins in the fourth month of life with extreme irritability, disturbed sleep, feeding difficulties, and fever [5]. New research has enabled further understanding of the genetics and pathophysiology of AGS, contributing to the investigation of therapeutic agents and utilisation of genetic counselling [6, 7]. This study reports the hospital admission and diagnosis of a 22-month-old male with complications of Aicardi-Goutières Syndrome. A comprehensive history and retrospective analysis of patient notes was completed during this admission to obtain a clinical timeline of disease progression and the subsequent management from the initial presentation at the age of four months. The Case AA is a 22-month-old Caucasian male with a known diagnosis of AGS who was admitted to a New Zealand hospital. He was first diagnosed at four months of age after presenting to an emergency department with a generalised tonic-clonic seizure and status epilepticus. A detailed history on admission revealed daily episodes of inconsolable crying and the development of subjective febrile episodes.

He had adopted an abnormal posture with extension of the upper limb, lower limb, and spine. Pregnancy and birth were uneventful with normal growth and development. The family conscientiously objected to vaccinations. An older half-brother (paternal) had a diagnosis of epilepsy. Examination demonstrated hypertonia in the upper limbs, lower limbs, and postural muscles consistent with a spastic quadriplegic cerebral palsy. Head circumference, weight, and height were measured on the 25th, 50th, and 50th centiles respectively. The remainder of the examination was normal including the absence of hepatosplenomegaly. Blood tests showed elevated white cells and lymphocytes, with normal transaminases and platelets. The presence of seizures, extreme irritability, fevers, dystonia, and elevated white cells raised the possibility of an infective process involving the central nervous system. Therefore meningitis, encephalitis, and TORCH Syndrome were considered as possible causes in a patient of this age. However, after further investigation, both metabolic and infective causes including TORCH Syndrome and Human Immunodeficiency Virus (HIV) were excluded. It was decided computed tomography (CT) scan of the brain would be completed, which identified basal ganglia calcifications (Table 1). Subsequent magnetic resonance imaging (MRI) of the brain showed atrophy of the cerebral cortex with calcification of the basal ganglia and white matter (Table 1). Cerebrospinal fluid (CSF) analysis showed elevated white cells (24x106/L) and neopterin with the absence of infective aetiology.

Table 1. Key investigation results in AA.

Investigation

Findings

Computed Tomography (CT) Brain

No acute intracranial haemorrhage. Basal ganglia calcification and generalised parenchymal atrophy.

Magnetic Resonance Imaging (MRI) Brain

Bilateral calcifications of the putamen on CT correlates with diffuse high T2 signal on MRI. No focal lesion is identified throughout. No diffusion restriction/infarct or venous thrombosis. Appearances of the generalised mild atrophy and basal ganglia calcifications remain non-specific, the underlying cause/condition uncertain.

Electroencephalogram (EEG)

Abnormal EEG. The background is dominated by diffuse high amplitude delta slowing with some intermixed theta. The background is poorly organised but not consistent with hypsarrhythmia but rather a moderate diffuse encephalopathy. There are no epileptiform discharges. Throughout the recording there are multiple clinical annotations of “tensing” as well as tongue sticking out. These do not have abnormal EEG correlate. However, there is a clinical episode of the baby outstretching arms that is associated with a decremental response on EEG and consistent with seizure that is likely infantile spasm.

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20 Australian Medical Student Journal

Discussion

HSV 1 or 2 polymerase chain reaction (PCR) positive HSV1 or 2 serology positive CMV serology positive

Investigation Findings Suggestive of Diagnosis

Negative TORCH infection screen Elevated INF-alpha in the cerebrospinal fluid (CSF) Lymphocytosis in CSF Elevated neopterins and biopterins in CSF Positive genetic screen

Toxoplasmosis serology positive

Rubella serology positive

Hearing deficits Hearing deficits Hearing deficits

Hearing

Impaired vision Chorioretinitis Cataracts Impaired vision Chorioretinitis Impaired vision Chorioretinitis Impaired vision Nystagmus

Vision

Impaired vision Chorioretinitis Cataracts Microphthalmia

Petechiae Purpura Petechiae Purpura Petechiae Purpura Maculopapular rash

Skin

Musculoskeletal System

Petechiae Purpura Chilblain lesions Acrocyanosis Periungual erythema

Nervous System

Cleft lip/palate Micrognathia

Hydrocephalus Microcephaly Mental impairment Basal Ganglia calcifications Cerebral atrophy Microcephaly Seizures Mental impairment Tetraplegia Dystonia Hypo/hypertonia Extrapyramidal signs Pyramidal signs Developmental regression

Hydrocephalus Microcephaly Intracranial calcifications Seizures

Hypothyroidism Insulin dependent diabetes mellitus Hypothyroidism Insulin dependent diabetes mellitus Micropenis

Endocrine System

Microcephaly Periventricular calcifications Hypotonia Seizures

Petechiae Purpura Vesicles

Hydrocephalus Microcephaly Seizures Hypertonia

Hepatosplenomegaly Jaundice Oral ulcerations Hepatosplenomegaly Jaundice Hepatosplenomegaly Jaundice Hepatosplenomegaly Jaundice

Gastrointestinal System

Pneumonitis Pneumonitis Pneumonitis

Cardiac System

Respiratory System

Patent ductus arteriosus Pulmonary artery stenosis Coarctation of aorta Myocarditis Cardiomyopathy

Hepatosplenomegaly Jaundice

Myocarditis

Herpes Simplex Virus 2 Cytomegalovirus Rubella virus Toxoplasmosis gondii Autosomal dominant Autosomal recessive

Aetiology

Herpes Simplex Virus (HSV) Cytomegalovirus (CMV) Aicardi-Goutières Syndrome

Toxoplasmosis

Rubella

TORCH Syndrome

Aicardi-Goutières Syndrome AGS is an early onset encephalopathy resulting in severe intellectual and physical disability with symptoms including neurological impairment, seizures, acquired microcephaly, hepatosplenomegaly, abnormal liver function tests, and thrombocytopaenia [5]. Prior to its discovery, AGS was classified as pseudo-TORCH Syndrome due to its similar presentation with the absence of identifiable pathogens [4,8] (Table 2). Other differentials for AGS include mitochondrial cytopathies, Cockayne syndrome, organic acidurias, HIV, Zika virus, lupus erythematosus, microcephaly-intracranial calcification syndrome, and polymicrogyria [5,8,9]. There are two main subtypes of AGS, categorised as either early or late onset [10,11]. Late onset disease presents at the age of four months and is the most common presentation (80%), while early onset disease presents immediately after birth and comprises 20% of cases [10,11]. Disease progression is split into an initial acute phase of deterioration that lasts a few months, and a second long-term phase of disease stabilisation [5]. Life expectancy is variable with 25% of patients dying by the age of 17 years, with the remainder experiencing a considerable decrease in their quality of life [5,10]. A review of the literature by Orcesi et al. [5] highlighted that AGS typically begins in the fourth month of life with extreme irritability, disturbed sleep, feeding difficulties, and fever. The most common clinical features of the disease are mental impairment (92%), dystonia (75%), microcephaly (63%), seizures (50%), and chilblain lesions (42%) [12]. Clinical findings are similar between AGS and TORCH infections making it difficult to distinguish between them [5,13,14] (Table 2). In this case, the absence of anatomical ocular abnormalities suggested a central pathology [15]. This finding combined with the absence of hearing deficits made a diagnosis of TORCH Syndrome unlikely [5,13-15]. Although vasculitic lesions are common in AGS, they were not reported in this case [5].

Table 2. Key findings in Aicardi-Goutières Syndrome and TORCH Syndrome.

Pseudo-TORCH Syndrome

An electroencephalogram (EEG) was completed which was abnormal (Table 1). Genetic analysis identified two variants of unknown significance in the ADAR1 gene and a diagnosis of AGS was made. Management of seizures was initiated with levetiracetam, while spasticity was managed with clobazam and gabapentin. At eight months of age he developed further symptomatology. He failed to meet further developmental milestones and exhibited developmental regression, thereby impacting on motor function, communication, and eye contact. Anatomical ocular pathology and hearing deficits were excluded. He had further generalised tonic-clonic seizures. Multiple admissions for respiratory tract illnesses complicated by an inability to clear airway secretions were attributed to disease progression and the use of benzodiazepines. A nasogastric tube was inserted for feeding and prevention of aspiration. Allied health input was sought for secretion clearance in conjunction with hyoscine patches. Levetiracetam and clobazam doses were increased to manage seizures and baclofen was added to improve dystonia. At 12 months of age the care giver reported that there had been a reduction in seizure frequency. Examination showed a decline in head circumference, dropping to below the 3rd centile. Height and weight remained consistent, being maintained at the 50th centile. Further investigations showed that he had developed mild liver dysfunction with transaminitis. At 22 months the caregiver reported that the abnormal posturing and spasticity had improved along with the frequency and severity of seizures. It was reported that he had begun to groan when having his hips moved and there was ongoing difficulty with the management of upper airway secretions. An X-ray of the pelvis showed bilateral hip dislocations which were managed conservatively. Given the reduction in seizure frequency, the dose of clobazam was reduced to assist in the reduction of airway secretions.

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Findings on investigation include a negative TORCH screen, basal ganglia calcification (5070%), white matter abnormalities (75-100%), cerebral atrophy (94%), and CSF analysis showing lymphocytosis, elevated interferon alpha, and pterins [5]. Genetic abnormalities are identified in 83% of cases and include autosomal recessive (TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR) and autosomal dominant alleles (TREX, ADAR, IFIH1) [5,16]. In this case, the presence of both basal ganglia calcifications and ADAR1 variants were highly suggestive of AGS [16,17]. The current hypothesis is that a defect in the DNA damage response leads to an accumulation of endogenous DNA or DNA–RNA hybrids which trigger an interferon-alpha-mediated immune response similar to that which occurs during viral infections [5]. It is believed this malfunctioning of the interferon-alpha pathway is also responsible for the increased rate of autoimmune diseases in those with AGS [5]. Current treatments offer primarily symptomatic relief with the management of epilepsy, postural abnormalities, airway clearance techniques, and dietary intake comprising the primary longterm goals of treatment [11]. Screening for associated conditions including glaucoma, diabetes mellitus, and hypothyroidism should be considered [5]. Although no cure is currently available, corticosteroids may reduce the frequency of fevers and improve vasculitic skin lesions [7]. In addition, treatments targeting the interferon signalling pathways such as immune modulating therapies, JAK inhibitors, antiretrovirals, antiIFN-alpha and cGAS inhibitors are emerging as possible therapeutic agents for interferonopathies [6, 7]. Management strategies In the case presented it can be determined that AA had a late-onset form of AGS [18]. He exhibited a classical presentation of the disease with normal development followed by an acute phase of inconsolable crying, subjective febrile episodes, seizures, and dystonia [5,12].

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This was then followed by a phase of disease stabilisation. Access to new and novel medications for AGS in New Zealand is limited. The care in this case focused on managing complications of the disease rather than treating the disease itself and, as such, general paediatric guidelines from the New Zealand Starship Hospital were followed [19]. Seizures were managed according to generalised epilepsy guidelines with levetiracetam and clobazam, while spasticity was managed with baclofen and gabapentin as per cerebral palsy guidelines [19]. Clobazam, however, had the undesired effect of increasing oral secretions. Feeding and airway secretions were managed by allied health professionals to prevent malnourishment and reduce the risk of aspiration [19]. Hip dislocation in AGS is not well documented in the literature. Research suggests patients with spasticity are at risk of hip dysplasia due to abnormal force loading through the joints [20]. Surgical correction is an option for pain and impaired mobility [20], however after discussion with the family and an orthopaedic consultation, it was decided that surgical intervention would be unwarranted given the degree of functional impairment. This case highlights the balance between treatments, side effects, and patient goals to achieve optimal patient care. Future considerations Although a rare disorder, AGS should be considered in patients who present with the signs and symptoms of TORCH Syndrome in the absence of an identifiable pathogen [11]. The disease follows a distinct clinical progression and as such may be identifiable by the informed clinician allowing timely introduction of therapies used for interferonopathies. Key distinguishing factors include onset at four months of age, vasculitic lesions, absence of hearing deficits, absence of ocular anatomical pathology, acquired microcephaly in the first year of life, and a negative TORCH screen [5,13-15]. The rarity of the condition dictates that large-scale quality research papers are not feasible, therefore small cohort studies form the core of current research. Nevertheless, it is promising that novel treatments such as immune modulating therapies, JAK inhibitors, antiretrovirals, anti-IFN-alpha and cGAS inhibitors may be able to treat the disease itself [6,7]. Future research should focus on developing understanding of the pathophysiology, treatments for the disease, and management of disease complications.

Consent Declaration Informed consent was obtained from the patient’s family for publication of this case report and accompanying figures. Acknowledgements Thank you to the family who were willing to allow me to publish this case report of their child.

Editor Dhruv Jhunjhnuwala Senior Editor Daniel Wong Proofreaders Nadiah Binte Mohamad Shariff Ke Sun

Conflicts of Interest None.

Senior Proofreader Emily Feng-Gu

Funding None. Author Contributions Sole author. References [1]

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analysis of a family with Aicardi-Goutières syndrome and

I interferonopathies. Nat Rev: Immunol. 2015;15(7):429-40.

literature review. Chin J Paediatr. 2014;52(11):822-7. doi:10.3760/

The syndrome: who discovered it? [Internet]. Italy: International

cma.j.issn.0578-1310.2014.11.006 [13]

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Tonduti D, Fassi E, Badolato R, Orcesi, S. Novel and emerging

and literature review. J Clin Med. 2019;8(5):750. doi:10.3390/ jcm8050750 [17]

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syndrome. Dev Med Child Neurol. 2020;62(1):42-7. doi:10.1111/

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Al-Dabbous R, Sabry MA, Farah S, Al-Awadi SA,

doi:10.4103/aian.AIAN_12_18 [18]

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Simeonov S, Farag TI. The autosomal recessive congenital

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Australian Medical Student Journal 23

Oxygen delivery: a case-based approach Date of submission: 18 December 2019 Date of acceptance: 24 February 2020 Date of online publication: 8 March 2020 Ryan Teo Xuan Wei MBBS (Recently graduated in Dec 2019) Monash University, Melbourne Ryan is a final year medical student commencing internship in Singapore next year. He has interests in physiology and general medicine and enjoys it when clinical concepts are best understood with a healthy dose of the former. A/Prof Christopher Wright MBBS, FRACP, FCICM, GradDipSc (Physics) Academic Director, Clinical Programs, Monash University A/Prof Christopher Wright has a background as an intensive care specialist and was Director of the intensive care unit at Monash Health for many years. He is currently the Academic Coordinator for the clinical years of Monash University’s medical course. He enjoys medicine and physics,and takes pride in the education of the next generation of doctors. Abstract Introduction: Oxygen delivery to tissues is a vital physiological process in the human body and an essential topic for all medical practitioners. Studying the topic strengthens understanding about the vital signs, in particular heart rate, blood pressure, respiratory rate, and oxygen saturation. It further grants insight into common clinical interventions such as supplemental oxygen and intravenous fluids. However, oxygen delivery is a concept that often goes underappreciated by medical students and junior doctors. This is an educational article that seeks to improve understanding and clinical application around the topic. Case overview: We use six common clinical scenarios (gastroenteritis, haemorrhagic shock in trauma, reactive polycythaemia, sepsis, status epilepticus, and peripheral vascular disease) to present the causes and management of tissue hypoxia, as well as the body’s physiological responses. Discussion overview: Tissue hypoxia occurs when the whole body or a region of the body is deprived of adequate oxygen supply to meet tissue metabolic demands. There are four types of tissue hypoxia: hypoxic, stagnant, anaemic, and histotoxic hypoxia. Consideration of the underlying cause of a patient’s tissue hypoxia aids rapid assessment and targeted management of the patient.

Key learning points 1. Hypoxia and hypoxaemia are terms that should not be used interchangeably. Hypoxia refers to inadequate delivery of oxygen to tissues, while hypoxaemia refers to inadequate PaO2 in blood. 2. The causes of tissue hypoxia can be logically deduced from the Oxygen Delivery Equation and comprise reduced cardiac output or regional blood flow (‘stagnant hypoxia’), true or functional anaemia (‘anaemic hypoxia’), reduced PaO2/SaO2 (‘hypoxic hypoxia’) as well as histotoxic hypoxia. 3. Common interventions addressing specific mechanisms of tissue hypoxia include fluids and inotropes for reduced cardiac output, RBC transfusions for anaemia and supplemental oxygen and positive pressure ventilation for reduced PaO2/SaO2

Introduction Cells use oxygen to produce energy through aerobic respiration. Inadequate delivery of oxygen to tissues results in a cascade of complications: anaerobic respiration, lactic acidosis, cell death, and eventual organ dysfunction [1]. The term hypoxia should first be distinguished from hypoxaemia. Hypoxaemia refers to reduced arterial oxygen tension or partial pressure of oxygen in blood (PaO2) below normal values, which is positively related to the oxygen saturation (SaO2) by the oxygen-haemoglobin dissociation curve [2]. Hypoxia is a broader term that refers to inadequate oxygen delivery to tissues and can be affected by any factor contributing to oxygen delivery and consumption, as elaborated upon below [2]. Hypoxia can be classified as either localised (affecting a region of the body) or generalised (affecting the whole body). Global oxygen delivery to tissues (DO2) is the amount of oxygen delivered to tissues per minute. It is the product of cardiac output (volume of blood delivered to tissues per minute) and the arterial oxygen content (the amount of oxygen in that blood). Formally, it is expressed by the Oxygen Delivery Equation (ODE) as follows: DO2 = CO × [Hb × 1.34 × SaO2 + [0.003 × PaO2]], where: - DO2 = Delivery of oxygen, in ml/min, - CO = Cardiac output, in L/min, - Hb = Haemoglobin concentration, in g/L, - SaO2 = Arterial oxygen saturation, in %, - And PaO2 = Arterial partial pressure of oxygen, in mmHg [3]

Table 1. Causes, brief descriptions, and examples of tissue hypoxia.

Cause of hypoxia

Brief description

Examples

Stagnant hypoxia

Decreased blood flow to tissues, either from reduced cardiac output (resulting in global hypoxia) or reduced regional blood flow (resulting in local hypoxia)

Hypovolaemia Arrhythmias such as ventricular tachycardia, ventricular fibrillation, bradyarrhythmias Acute myocardial infarction Peripheral vascular disease Acute vessel embolisms

Anaemic hypoxia

Decreased ability to transport oxygen, either from reduced haemoglobin concentration or reduced functionality of haemoglobin

Anaemia, for example, iron deficiency anaemia, anaemia of chronic disease Carbon monoxide poisoning

Hypoxic hypoxia

Decreased PaO2 (hypoxaemia)

High altitude Hypoventilation Many respiratory conditions, for example, asthma, pulmonary embolism, pneumonia

Histotoxic hypoxia

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The (0.003 × PaO2) component represents the small amount of dissolved oxygen in blood not bound to haemoglobin. Due to the numerical insignificance of this value, the equation can be simplified to: DO2 ∝ CO × Hb × SaO2 That is, the global delivery of oxygen is proportional to the product of the cardiac output, haemoglobin concentration, and the arterial oxygen saturation. Cardiac output is the product of heart rate and cardiac stroke volume (CO = HR x SV) and is approximately equal to 5 L/min for a healthy person at rest. DO2 is approximately equal to 1000 ml O2/min for such a person. Accordingly, the causes of tissue hypoxia are either inadequacies in cardiac output, regional blood flow (‘stagnant hypoxia’), true or functional anaemia (‘anaemic hypoxia’), or reduced PaO2 (‘hypoxic hypoxia’). ‘Histotoxic hypoxia’ is an additional uncommon cause of tissue hypoxia where tissues are unable to utilise oxygen that is delivered, classically described in cyanide poisoning. Excessive tissue oxygen demands may also result in tissue hypoxia if oxygen delivery cannot be increased sufficiently, although it is not typically considered part of this classification. The types of hypoxia are summarised in Table 1 [5].

Decreased tissue ability to properly utilise oxygen that is delivered

Cyanide poisoning Tissue oedema

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Blood pressure is notably not a parameter included in the ODE. The mean arterial pressure (MAP) is the product of cardiac output and systemic vascular resistance (MAP = CO × SVR). MAP is commonly used in the clinical assessment of organ perfusion as a less-invasive surrogate measure of cardiac output. However, the relationship between MAP and cardiac output is altered and becomes difficult to interpret in conditions with large changes in the SVR, such as sepsis-induced vasodilation or severe vasoconstriction in haemorrhagic shock [4]. Six common clinical cases below apply these concepts to explain the body’s physiological responses to tissue hypoxia and how medical interventions might preserve oxygen delivery during these situations. Case 1 – Stagnant hypoxia (global) Consider the case of Daniel, a 34-year-old previously healthy male presenting with three days of acute diarrhoea. He has been passing watery stools 10 times a day with inadequate fluid replacement, and reports that he has not voided for 12 hours. On examination, he has dry mucous membranes and a low jugular venous pressure. He is tachycardic at 115 beats per minute (bpm) and his blood pressure is 120/80 mmHg. An electrocardiogram (ECG) shows sinus tachycardia. Question: What is the pathophysiology of Daniel’s tachycardia and what would be the appropriate treatment? Discussion Tachycardia can be understood as being a rise in heart rate either secondary to increased sympathetic outflow (producing sinus tachycardia) or a non-sinus tachyarrhythmia. An ECG differentiates between the two and is therefore a key investigation in the workup of tachycardia [6]. This patient has hypovolaemia secondary to acute gastroenteritis which has resulted in sinus tachycardia without compromising blood pressure. Recall that cardiac output is the product of heart rate and stroke volume (CO = HR × SV). In this case of an otherwise healthy young man, hypovolaemia results in reduced stroke volume and therefore cardiac output due to reduced venous return. Through baroreceptor-mediated reflex mechanisms, the body compensates by activating the sympathetic nervous system which raises the heart rate and contractility of the ventricles to maintain CO [7]. Caution is therefore advised in patients with cardiac disease or medications affecting heart rate, for example, beta-blockers, as such physiological compensation may be impeded.

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These physiological responses can be reasoned out using the ODE. Upon a transient decrease in cardiac output, global oxygen delivery is lowered. To avoid resultant tissue hypoxia, the body compensates by increasing the heart rate. Worsening hypovolaemia would have the potential to overwhelm this compensatory mechanism and cause tissue hypoxia. Acute viral gastroenteritis is usually self-limiting, and treatment is largely supportive with fluid repletion [8]. This maintains the patient’s stroke volume and thereby preserves cardiac output and oxygen delivery. A return of heart rate towards normal would constitute an appropriate response to fluid therapy and be a useful way to assess efficacy of treatment. Compare the treatment aims of gastroenteritis with that of Case 2:

However, there are factors apart from cardiac output that affect global oxygen delivery. Recalling the ODE (DO2 ∝ CO × Hb × SaO2), it can be observed that while the administration of intravenous fluids would preserve cardiac output, it would reduce the haemoglobin concentration in this actively bleeding patient, reducing oxygen delivery. This explains the adage “Replace blood with blood”, with the next appropriate step being the provision of packed red blood cell (PRBC) transfusions [9]. In emergency situations, type O negative blood may be used due to insufficient time for cross-matching donor and recipient blood. In Betty’s case, it is important to note that these are only temporising measures, with a laparotomy in theatre being the definitive treatment to control the source of bleeding.

Case 2 – Stagnant hypoxia (global) and anaemic hypoxia Betty, a 65-year-old female pedestrian, has been brought in by ambulance to the emergency department after being struck by a motor vehicle at a speed of 40 km/hr. She has a history of hypertension and hyperlipidaemia managed well with perindopril and atorvastatin. She is conscious and complaining of abdominal pain. On primary survey, her airway is patent and a cervical collar is in place. Her respiratory rate is 22 breaths per minute with SpO2 of 98% on room air. Her heart rate is 125 bpm and her blood pressure is 85/50 mmHg. Abdominal examination finds generalised tenderness with some guarding. A focused assessment with sonography for trauma (FAST) scan is performed which shows a large amount of intraperitoneal free fluid. Question: While awaiting a laparotomy in theatre, what would be the appropriate immediate management of this patient?

Case 3 – Hypoxic hypoxia The third case pertains to John, a 72-year-old male presenting to the emergency department with an infective exacerbation of chronic obstructive pulmonary disease (COPD), which he has had for the past 15 years. He responds well to salbutamol burst therapy and on review his vital signs have all returned to within normal limits apart from an SpO2 of 93% on room air. He is prepared for discharge to home with a short course of antibiotics and steroids. However, a full blood count (FBC) returns showing a polycythaemia with a haemoglobin concentration of 180 g/L. His other cell line counts are within normal limits and no previous records are available. He does not have hepatosplenomegaly and denies constitutional and hyperviscosity symptoms. Question: Would it be worthwhile to work John up for sinister causes of polycythaemia such as an erythropoietin (EPO) secreting tumour or haematological malignancy with serum EPO levels and JAK-2 mutations respectively?

Discussion This is a patient who most likely has stage 3 haemorrhagic shock secondary to trauma [9]. Both Betty’s heart rate and blood pressure are compromised, with her antihypertensive agent further impairing her ability to compensate for the blood loss. As with Daniel in Case 1, the goal of initial resuscitation would be to preserve Betty’s volume status via the rapid infusion of intravenous fluids, thereby preserving her stroke volume and cardiac output.

Discussion This case relates to the Hb and SaO2 components of the ODE. In states of chronic hypoxaemia, the body compensates for the reduced oxygen delivery by increasing the secretion of EPO which may result in polycythaemia [10]. Examples of such conditions include advanced COPD, sleep apnoea, and living at a high altitude. Polycythaemia is most commonly secondary to one of these hypoxaemia-associated conditions. Rarely, it can be the result of an EPO-secreting tumour or be the manifestation of a primary haematological malignancy such as polycythaemia vera (PV) or other myeloproliferative neoplasms [10]. In this scenario, where there is an obvious explanation for the polycythaemia and an absence of red flag signs or symptoms, it would likely not be worthwhile to work John up further for such rare causes [10]. It is worthwhile noting that reactive polycythaemia does not occur in acute hypoxic states, as the production of haemoglobin is a relatively slow process [10]. This explains why reactive polycythaemia was not present in Cases 1 and 2. Case 4 – Stagnant hypoxia (global) and hypoxic hypoxia The next patient is Diane, a 62-year-old previously well female presenting with four days of worsening fever, cough, and shortness of breath. She was brought to the hospital by her husband today after she developed rigors and appeared confused. Her airway is patent, respiratory rate is 32 breaths per minute with SpO2 of 86% on room air, her heart rate is 120 bpm and her initial blood pressure is 95/50 mmHg. Her temperature is 38.5 degrees Celsius, her Glasgow Coma Scale (GCS) score is E4V4M6 and her blood sugar level is within normal limits. A chest X-ray reveals right lower lobe consolidation. Question: What would be the appropriate management for this patient?

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Discussion This patient has sepsis likely secondary to a chest infection, with a qSOFA score of 3 [11]. Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection [11]. It causes tissue hypoxia, in part due to systemic arterial and venous dilatation that results in reduced preload, stroke volume, and cardiac output. According to the “sepsis bundle” [12], it is important that patients with sepsis are commenced on the following within the first hour of presentation: intravenous fluid resuscitation of 30 ml/kg, supplemental oxygen to keep SaO2 greater than 94%, as well as empiric intravenous antibiotics. The other recommendations are to obtain blood cultures and measure serum lactate. Failure of the patient to respond to these measures indicates the need for escalation of care and possible admission to an intensive care unit. These recommendations can be understood by considering the ODE. The administration of intravenous fluids raises cardiac output, while supplemental oxygen preserves SaO2. Empirical antibiotics treat the presumed bacterial infection to eventually halt the systemic vasodilatory and inflammatory response. Thus, these measures improve tissue oxygenation and limit organ dysfunction. Case 5 – Excessive oxygen consumption The next case pertains to James, a 30-year-old man brought in by ambulance to the emergency department for status epilepticus. He has had a generalised onset tonic-clonic seizure lasting 15 minutes which was eventually terminated by paramedic-administered benzodiazepines. His airway remained patent and oxygen saturations were adequate throughout the seizure. However, a severe lactic acidosis with a pH of 6.90 is noted on the venous blood gas performed after the seizure episode. Question: What is the cause of tissue hypoxia in this case?

Discussion This scenario of oxygen balance looks at global oxygen consumption – the amount of oxygen consumed by tissues per minute. Global oxygen delivery (DO2) in a normal person at rest is approximately 1000 ml O2/min, while oxygen consumption (VO2) for the same is approximately 250 ml O2/min. Tissues extract oxygen from incoming arterial flow while veins carry blood away from tissues, explaining why the typical mixed venous oxygen saturation is approximately 75% [13]. During periods of increased metabolic activity, such as during exercise or, as in this case, a seizure, tissue oxygen demands increase significantly to facilitate energy production through aerobic respiration. Hypoxia, anaerobic respiration, and lactic acidosis result when tissues are unable to extract enough oxygen from capillaries and have negative net oxygen balance [13]. Treatment involves maintaining a clear airway and breathing while preventing further seizures and looking for seizure precipitants. The tissue hypoxia should resolve with these definitive measures as metabolic demands return to normal. Case 6 – Stagnant hypoxia (local) The last case moves away from global oxygen balance and considers another factor that may affect oxygen balance of specific tissues. Shane is a 68-year-old male with a known history of poorly controlled type two diabetes mellitus, hypertension, hyperlipidaemia, and peripheral vascular disease. He presents to the emergency department with right lower limb claudication and pain at rest worsening over the past two weeks. On examination, his right lower limb is pale and cool distal to the knee joint. Popliteal, dorsalis pedis, and posterior tibial pulses are absent. The ankle-brachial index is 0.3, indicating critical limb ischaemia. An arterial Doppler ultrasound shows severe stenosis of the right femoral artery. Shane’s vital signs are all normal and he is not anaemic. Question: Given that Shane’s cardiac output (as inferred from blood pressure), haemoglobin concentration, and SaO2 are all unimpaired, what is the mechanism of his tissue ischaemia?

Discussion The ODE describes global oxygen delivery. However, for adequate oxygen delivery to specific tissues, there must be sufficiently patent local vasculature in addition to adequate global oxygen delivery [1]. In Shane’s case, management would focus on timely improvement of his right lower limb arterial supply before local tissue necrosis occurs, rather than correcting cardiac output, haemoglobin concentration, or the arterial oxygen saturation. This could be achieved using medical or surgical therapy. Local arterial insufficiency is the pathophysiological basis of many common clinical conditions with tissue hypoxia. Improving the vasculature is typically the most effective treatment, as seen from the following examples. Myocardial tissue hypoxia from type one acute myocardial infarction may be managed with percutaneous coronary intervention or thrombolysis. Brain parenchymal hypoxia from embolic ischaemic stroke may be treated with thrombolysis or removal of the clot by endovascular means. Patients with Raynaud’s phenomenon are managed with arterial vasodilating agents to restore perfusion to the fingers in addition to treating any underlying autoimmune disease. Summary of cases In summary, the four types of tissue hypoxia are stagnant hypoxia, anaemic hypoxia, hypoxic hypoxia, and histotoxic hypoxia. Histotoxic hypoxia has not been expounded on in this article due to its relative uncommonness.

Figure 1 summarises the causes and the commonly used directed management strategies of tissue hypoxia as described in this article. Note that this list of strategies is not exhaustive; for instance, it omits arrhythmia correction as a management strategy for low cardiac output. Limitations This article does not cover detailed guidelines about oxygen therapy, shock management, or other mentioned topics and should not be taken as such. It is intended for medical student education as a general approach to oxygen delivery and tissue hypoxia. Many research studies have looked at the potentially adverse effects of hyperoxia (excessively high PaO2) and supranormal oxygen delivery in various patient groups. This is beyond the scope of this paper. Conclusion It is our opinion that oxygen delivery is an essential medical topic that provides a structured framework to approach causes and management of tissue hypoxia. Medical students and junior doctors should actively engage the above framework in assessing the deteriorating patient. Consideration of the underlying cause of a patient’s tissue hypoxia aids rapid assessment and targeted management of the patient.

Figure 1: Causes of tissue hypoxia and their commonly used directed management strategies. Stagnant hypoxia globally (reduced cardiac output) is often treated with fluid administration or inotropes, while locally (reduced regional blood flow) is managed medically or procedurally depending on the cause. Anaemic hypoxia is typically managed with red cell transfusions. Hypoxic hypoxia is overcome with supplemental oxygen or positive pressure ventilation delivered through various oxygen delivery devices. Excessive tissue oxygen demands are managed according to the underlying cause.

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Acknowledgements The authors would like to thank A/Prof Geoffrey Parkin, Honorary Intensivist at Monash Health ICU, for his invaluable help with writing this article. Conflict of interest None Funding None Authors contributions R.T. conceived of the idea of the manuscript and was the primary author. C.W. provided revisions to scientific content and grammar of the manuscript. All authors read and approved the final manuscript.

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Date of submission: 10 September 2019 Date of acceptance: 2 February 2020 Date of online publication: 15 February 2020 Shivangi Gupta MBBS - 5 years 4th year Curtin University Student

Shivangi Gupta is a fourth-year medical student at Curtin University, who appreciates the holistic model of medicine and hopes to apply it into her learning and future practice. She has various interests in medicine, but counts research, neurology, and surgical skills among her favourites. Shivangi is the co-founder and Vice President of the Curtin Surgical Students’ Association, as well as a keen volunteer at the Future Doctors Workshop in partnership with Scitech.

Lachlan Hou MBBS - 5 years 4th year Curtin University Student

Lachlan is a fourth-year medical student at Curtin University with an interest in surgery and research. After going on exchange with the medical school and being exposed to the vast differences in health systems he was inspired to share his experiences. His keen interest in surgery lead Lachlan to establish the surgical society at his medical school and preside over it for two consecutive years. He has also been involved with several student medical bodies in various other capacities.

Supervisor- Dr Gill Cowen MBBS (Hons), MA(Oxon), FRACGP, MSportMed Senior Lecturer Curtin Medical School

Dr Cowen is a Senior Lecturer at Curtin Medical School. Having trained in the UK she moved to Australia in 2004 where she trained as a General Practitioner via the Rural and Remote GP pathway. She subsequently qualified as a Fellow of the Royal Australian College of General Practitioners and gained a Master of Sports Medicine from the University of Queensland. She is an EMST instructor for RACS and Chair of the RACGP Sports and Exercise Medicine Network. Her research interest is concussion and she also works as a Sports Doctor for the Western Australian Football Commission State Colts AFL team.

Gopinathannair R, Olshansky B. Management of tachycardia. F1000Prime Reports. 2015 May;7:60. doi:10.12703/P7-60

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Syper KM. Neural organisation and control of the baroreceptor reflex. Rev Physiol. Biochem. Pharmacol. 2005;88:23-124. doi:10.1007/BFb0034536

Associate editor Onur Tanglay

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Senior editor Justin Smith

[9]

Proofreader Emily Feng-Gu

Exchange Experiences: Exploring Chinese Healthcare as Australian Medical Students

Guerrant RL, Carneiro-Filho BA, Dillingham RA. Cholera, diarrhoea and oral rehydration therapy: triumph and indictment. Clin Infect Dis. 2003;37(3):398-405. doi:10.1086/376619 Gutierrez G, Reines DH, Wulf-Gutierrez ME. Clinical review: Hemorrhagic shock. Crit Care. 2004;8(5):373-81. doi:10.1186/ cc2851

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Keohane C, McMullin MF, Harrison C. The diagnosis and management of erythrocytosis. BMJ. 2013;347. doi:10.1136/bmj. f6667

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Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA. 2016;315(8):801-10. doi:10.1001/jama.2016.0287

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Levy MM, Evans LE, Rhodes A. The Surviving Sepsis Campaign Bundle: 2018 update. Intensive Care Med. 2018;44(6):925-8. doi:10.1007/s00134-018-5085-0

[13]

Walley KR. Use of Central Venous Oxygen Saturation to Guide Therapy. AJRCCM. 2011;184(5):514-20. doi:10.1164/ rccm.201010-1584CI

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Abstract This feature article explores the similarities and differences in the medical education and health care systems of modern China compared with those of the Western world. It explores how a system interacts with, and adapts to, the political and social structure of its population and the challenges that can arise from this. The authors were part of a medical school exchange program to the First Affiliated Hospital, Sun Yat-sen University Guangzhou where they observed the inner workings of the hospital. The authors have drawn their observations from their experiences attending lectures, taking patient histories and observing cases during their rotations through each department of the First Affiliated Hospital. The experience gave the authors insight into how healthcare and education can vary between each country and the factors controlling this.

Introduction A sprawling metropolitan city, with a population almost half that of Australia at 12.5 million, Guangzhou is the capital of the Guangdong Province in South East China. As third year medical students, we were fortunate enough to take part in a two-week exchange program with the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, in January 2019. Sun Yat-sen University was founded in 1924 by Dr Sun Yat-Sen, a democratic revolutionary leader of the 20th century. It is a top-tier university nationally and is renowned internationally, with many successful relations and exchange programs, including Harvard University. During the program, we rotated through different hospital departments each day, looking at their extensive facilities, discussing interesting cases, and receiving lectures from their esteemed clinicians.

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Having recently finished our second year of medical school, this was a fantastic opportunity to explore different clinical settings, learn firsthand from patients, and compare healthcare in China with that of our own country. During our stay, we also caught a glimpse of the city’s rich culture and history, and enjoyed its scrumptious food (Figure 1), stunning views of the Pearl River and the avant-garde architecture of the Canton Tower (Figure 2); the 4th tallest free-standing structure in the world. Throughout the course of the program, we observed many differences between the Chinese and Australian healthcare systems and their clinical settings. In this article, we will discuss these in relation to systemic and social features, referring to the population and the healthcare framework of China, as well as communitybased and cultural factors. Body This article discusses the differences between Australia and China (specifically Guangzhou) using the following sections: patient population, healthcare systems, family dynamics, doctorpatient relationships, and medical education. Table 1 summarises the observed similarities and differences between both countries.

Table 1. (Cont.) The similarities and differences between the Australian and Chinese medical systems

Patient population

Doctorpatient ratio

1.8 physicians per 1000 people

3.6 physicians per 1000 people

Healthcare system

Healthcare system structure

No GP system, patients arrive directly at ED. There are medical care centres in regional areas which mirror Australian GP practices.

GPs are usually the first point of contact.

Healthcare system

Variable public health insurance according to one’s place of residence and their employment status Urban Employee-Based Medical Insurance has more comprehensive packages and benefits than the other Medical (the rural New Cooperative Medical insurance two Scheme and the Urban Residencepolicies Based Medical Insurance) schemes, especially for outpatient services. Moreover, migrants from rural regions who are living or employed in urban regions are not eligible for the urban insurance schemes.

Figure 1. Food on offer in the vibrant city of Guangzhou

Rural vs. Urban Health care

Table 1. The similarities and differences between the Australian and Chinese medical systems

Guangzhou

Australia

Top three causes of mortality

1. 2. 3.

Cerebrovascular disease Cardiovascular disease Respiratory illness

1. 2. 3.

Coronary heart disease Dementia and Alzheimer’s disease Cerebrovascular disease

Ethical considerations

• •

Lack of confidentiality (e.g. patient details were discussed at the bedside in open rooms occupied by four patients and their carers) Lack of privacy (e.g. no curtains or partitions separating the patient beds, and physical examinations and investigations, such as ultrasounds, were conducted openly) Lack of patient autonomy (e.g. Most decisions made by elder family members or in consultation with family)

•

Privacy and confidentiality are fundamental to any doctor-patient interaction (e.g. strict rules to cover patients and use blinds even for the simplest procedures and examinations) All decisions are made by the patient themselves, provided they fulfil capacity criteria

• •

Patient population • •

Volume of patients

Roughly 20,000 patients per day pass through ED.

•

Only about 200 patients passing through an average ED per day.

Doctor-patient relationships

Medical Education

Much stronger ties in China, reflected by divorce rates of only 1.4 per thousand.

Comparative rates: divorce rates of 2 per thousand.

Elderly

Only 1.5% of people over 65 living in aged care homes.

6% of people over 65 living in aged care homes.

Hierarchy

A strong sense of duty in the older/ experienced individual is very evident especially in a medical situation.

Although a hierarchy often exists due to the innate nature of society, it is not as evident

Due to patient values, medical Nature of literacy rates, and volume of patients, Consultation consultations are often brief.

A larger emphasis on building rapport by doctors leads to a more thorough consultation.

Consultation seemed to have a larger Focus of focus on the biological aspects of Consultation disease due to the biomedical model of education in Chinese hospitals.

Consultations focus on holistic care reflected in the change of Western medical curriculum.

Assessment techniques

Doctors in both countries use similar verbal and non-verbal communication techniques during history and examination to come to a diagnosis.

Cultural Barriers

Both countries have patients where cultural barriers will need to be overcome. In China patients are often superstitious and can present dissociated from their care. In Australia however, due to the high levels of immigration along with the Indigenous and Torres Strait Islander population there is a vast number of cultures and they all come with their associated differences that all need to be approached accordingly.

Problem Based Learning

Our university utilizes Problem Based Learning as a core component of its curriculum. Sun Yat-sen seems to incorporate a similar system where Problem Based Learning is used to allow students to work collaboratively to discuss a case and its content.

Biopsycho- A strong focus on the biological aspect social of the disease however, there is a push to implement psycho-social into its Model of curriculum. Medicine

Medical education follows the bio-psycho-social model and is discussed throughout the curriculum.

Heavy incorporation of Traditional Chinese Medicine in the medical curriculum reflecting the demographic of patients in Guangzhou.

No incorporation of alternative medicine into the curriculum.

Alternative Treatment

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Health care is very dependent on geographical location in terms of facilities, staffing and accessibility. Rural patients have poorer health outcomes in both countries.

Divorce Figure 2. Canton Tower and Guangzhou’s skyline

Family dynamics

A publicly funded universal health care system, Medicare, provides for all citizens, Permanent Residents, and migrants with a valid visa and a first degree relative with Permanent Residency. There is no funding disparity between rural and urban patients.

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Patient population First Affiliated Hospital, Sun Yat-sen University, is one of the major tertiary hospitals in China and receives complex cases from the surrounding regions. As such, we were fortunate to witness the clinical aspects of rare conditions including dermatomyositis, amyloidosis, and amyotrophic lateral sclerosis. The major disease burden in China is related to non-communicable diseases (NCDs) and the leading causes of mortality are cerebrovascular disease, cardiovascular disease, and respiratory illness [1]. This differs slightly to Australia, where coronary heart disease, dementia and Alzheimer’s disease, and cerebrovascular disease are the top three causes of mortality [2]. China’s large population translates into a high patient-to-doctor ratio. We experienced this in the Sun Yat-sen emergency department (ED) where there were huge crowds of patients in each treatment room with one doctor and one nurse looking after more than ten patients simultaneously. The other hospital departments that we visited were also significantly larger than those we have experienced in Australia, often spreading across multiple floors in the building, in order to look after huge numbers of presenting patients. The volume of patients in Chinese hospitals is also significantly higher than in Australia. The staff at Sun Yat-sen report that each day over 20,000 patients pass through their ED. Despite our initial scepticism, this became quickly believable when we observed the swarming ED during our visit. The rooms were packed with patients and their families, and beds had to be placed in the hallways to accommodate the large numbers. There were no curtains or partitions separating the patient beds, and physical examinations and investigations such as ultrasounds were conducted openly. This way of practice appeared to be the norm, however, despite being in a busy and time-pressured environment, we observed several instances where doctors devoted considerable time to patients requiring further assessment. This method of assessment of patients differed to our experiences in Australia, where patient information is discussed behind curtains or partitions at the bedside. It may be that inadequate infrastructure for the number of patient presentations plays a role in this process of more open patient assessment in China [3].

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Healthcare system The healthcare system in China is different from its Australian counterpart in many ways. For instance, in mainland China there is no concept of General Practice. The patients in urban areas rely on outpatient clinics in the hospital or immediate treatment through the emergency department, from where they can be transferred either vertically or horizontally, within the hospital. Vertical integration being the ability to transfer between generalists and specialists, while horizontal integrations is the collaboration or transfer between different specialists. On the other hand, rural regions have ‘medical care centres’, that act as the first point of contact, from where patients can then be transferred, if required [4]. China, and more specifically Chinese healthcare, varies greatly between regions. One of the most significant differences between rural and urban areas is the medical insurance policy. Unlike Australia, where there is a publicly funded universal health care system for all citizens and permanent residents, China provides variable public health insurance according to one’s place of residence and employment status. China has three major health insurance schemes - the rural New Cooperative Medical Scheme, the Urban Employee-Based Medical Insurance and the Urban Residence-Based Medical Insurance. Overall, Urban Employee-Based Medical Insurance provides more comprehensive packages and benefits than the other two schemes, especially in terms of outpatient services. Furthermore, migrants from rural regions who are living or employed in urban regions are not eligible for the urban insurance schemes, and most provinces do not accept New Cooperative Medical Scheme reimbursements. This has led to a huge disparity between populations that are originally from the city and those who have moved there from rural areas. This is further exacerbated by the large influx of people into cities due to urbanisation [5]. This effect is compounded by the Hokou System, which mandates that changes to place of residence require legal permission [6]. As such, migrant populations often feel especially discontent with the quality and extent of health services they receive in urban settings, leading to a reduced engagement of this population subset with the urban healthcare systems in China [7].

We experienced the lack of available healthcare in the Guangdong province when we were introduced to a 51-year-old man from a rural area who had presented with a three-month history of cough. He had been diagnosed with lung cancer, for which he was recommended treatment with monoclonal antibodies. Due to the insurance system in China, there was no public funding available for his treatment in Guangzhou, which forced the patient to opt for palliative care. We were told that this was just one of the thousands of similar cases of rural-born patients living in urban China. In Australia, the Medicare system provides for all citizens, permanent residents, and migrants with a valid visa and a first-degree relative with permanent residency. As such there is no funding disparity between rural and urban patients, with respect to public health insurance. But, there is a disparity in Australia between accessibility of health care in rural and remote communities compared to the urban population. Geographic locations, as well as distinct cultural and linguistic differences in the Aboriginal and Torres Strait Islander populations, play a major role in the lack of delivery of adequate medical attention in rural and remote Australia [8]. In China, healthcare services, hospitals and pharmacies are also less accessible to the rural population, and this leads to further healthcare discrepancies between the rural and urban populations [6]. Family dynamics During our stay in China, we observed that patient care and medical practice both revolve strongly around traditional beliefs and customs and family ties. There is a strong focus on family. Statistics show a low divorce rate of 1.4 per thousand marriages, and that only 1.5% of those over 65 live in an elderly care home [3]. Comparative Australian rates are two divorces per thousand marriages and 6% nursing home dwellers [9,10]. In the hospital setting we typically observed at least one family member with the patient at all times, and a young female patient with an unknown cerebellar pathology had up to five family members with her at any one time. A strong sense of duty was observed in the older people and thus a hierarchy of sorts was apparent [3]. This hierarchy appeared to take precedence over confidentiality, with family members present in all medical consultations.

An instance where this hierarchy was experienced occurred when one of our colleagues acted as a volunteer to demonstrate the Enhanced External Counterpulsation. This is a non-invasive therapy for people with angina or heart failure which helps increase blood flow to the heart with the use of strong pulsating cuffs around the calves and thighs. Upon completion, the student’s blood pressure was measured and was found to be unexpectedly high. Upon discovering this, the examining doctor proceeded to discuss this with our coordinator, without first indicating to our colleague that there was an anomaly. Doctor-patient relationship A study has found that in China the doctor-patient relationships are poor due to the brief nature of consultations and the lack of trust in doctors [11]. The combination of traditional Chinese values, low medical literacy rates, and high patient numbers mean that the majority of consultations we observed were short and, on occasion, appeared rushed. Despite this, we witnessed doctors with a fluid and systematic approach to consulting and assessment who demonstrated an excellent approach to both verbal and non-verbal communication. Differences in doctor-patient interactions are inevitable due to the rigid biomedical model of education seen in Chinese hospitals [12]. There was a strong focus on the biological aspect of the disease in China, as opposed to the bio-psycho-social model used in Australian medical schools. The Western curriculum aims to accommodate the changing role of a doctor as, not just a scientist, but a humanist, secondary to a belief that this creates compassionate and empathic doctors [13]. Chinese culture is based around family, and such family dynamics and beliefs may not support patients’ autonomy in making healthcare decisions. This may explain the differences in teaching and learning we experienced whilst visiting China compared to that experienced at our Australian medical school.

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Doctors in China must consider the country’s diverse culture that possesses the many contrasting philosophies founded in Confucianism [11]. We observed many patients hold on to superstitious or religious beliefs, and think that these could help “cure” their illnesses. An example is the belief that the drinking of water from the temple could cure their disease. The lack in patients’ knowledge, coupled with the brief nature of the consultation, led to most patient-care decisions being made by the physicians. This paternalistic model of medicine in China which could be due to the lack in patients’ medical knowledge, especially in the rural areas where most people have less education. Education We were fortunate enough to be able to attend lectures as well as a demonstration of how Problem Based Learning (PBL) is run in China. Although the PBL system was almost identical to that with which we were familiar, with students working collaboratively through a case, the content differed slightly, with respect to national policies and cultural backgrounds to be studied. Another significant difference between medical education in Western countries and China is the incorporation of alternative medicine into the medical curriculum [14]. Alternative medicine in China mentioned and taught included acupuncture, moxibustion, cupping, guasha, massage, and oral herbal medication. Chinese herbal medication and traditional remedies were very important in Chinese everyday health and lifestyle. Chinese medicine is often used in conjunction with pharmaceutical drugs, thus making it critical for a health professional to have a sound understanding of its effects, contraindications, and interactions. Doctors were observed routinely asking their patients specifically about their Chinese traditional medications, and they possessed extensive knowledge of them, allowing safe clinical decisions to be made. There was an entire floor for the Department of Traditional Medicine at the hospital, highlighting the importance of this branch of alternative medicine. The department’s role in patient care involved incorporating traditional Chinese medicine into their Western style evidence-based medication regime.

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Education continues to evolve worldwide, and current literature suggests that China is adapting its medical school curricula to keep pace with the Western World [13]. In almost all Chinese medical schools, humanities is a compulsory course. Sun Yat-sen University has implemented behavioural science, humanities and social sciences, and medical ethics into the official medical curriculum. Sun Yat-sen University has also facilitated an exchange program with Curtin University Medical School with the aim of observing how psychosocial aspects of our course are incorporated into our learning. Our challenges faced One of our biggest early challenges was the language barrier. Very few of the hospital staff spoke English and we did not speak Cantonese, the local language. Fortunately, our facilitating clinicians and the supervisor from our medical school were bilingual, and served as our translators. It was an interesting experience to be taking histories, or asking for consent before a physical exam, through a translator. Our non-verbal skills such as eye contact, gestures, facial expressions, and reading expressions and cues, were useful in connecting with the patient, and our lack of direct verbal communication sharpened these skills. Australia is a diverse and multicultural country and it is not unusual for health professionals and patients to encounter a linguistic divide. The use of interpreters and non-verbal cues for communication in China allowed us to improve our patient communication and highlighted the similarities in communication irrespective of location.

Conclusion Our visit to the First Affiliated Hospital, Sun Yatsen University, was an invaluable experience made extremely memorable by the warm welcome we received from our host. During the threeweek exchange, we gained significant insight into healthcare delivery at a tertiary hospital in a metropolitan city of China. As pre-clinical medical students with limited patient exposure, it was an incredible opportunity that was both exciting and challenging. To be in a clinical setting with patients, and to observe clinical signs of common, as well as rare, medical conditions was a rewarding experience. Despite our initial concerns regarding the language barrier, it did not cause difficulties because of the incredible support of our professor, Dr Daniel Xu, as well as the clinicians and administrative staff at Sun Yatsen University. We learnt a great deal during our placement, furthering both our medical knowledge as well as the cultural and social norms that guide medical practice in China. We hope to grow the partnership between the two universities and maintain the relations we built during our visit, and would love to return, given the opportunity. It was an experience that we will remember and cherish for the rest of our lives (Figure 3).

Conflict of Interest None Acknowledgement Prof Daniel Xu – supervisor for the exchange program and proofreading. Funding None required Author Contribution Shivangi and Lachlan: First authors designing, initially drafting and reviewing the manuscript Gillian Cowen: Editing and critically reviewing the manuscript Editor-in-Chief Mabel Leow Proofreaders Rosalind O’Neill Emily Feng-Gu

Figure 3. Front office of The First Affiliated Hospital, Sun Yat-sen University

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AIHW. Australian Burden of Disease Study: impact and causes of illness and death in Australia 2011 [Internet]. Australian Government; 2016. Available from: https:// www.aihw.gov.au/reports/burden-of-disease/abdsimpact-and-causes-of-illness-death-2011/contents/ summary]

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Ling R. A British Medical Student’s perspective on the Chinese healthcare system. Australasian Medical Journal. 2010;:370-371.

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Hougaard J, Østerdal L, Yu Y. The Chinese Healthcare System. Applied Health Economics and Health Policy. 2011;9(1):1-13.

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Meng Q, Fang H, Liu X, Yuan B, Xu J. Consolidating the social health insurance schemes in China: towards an equitable and efficient health system. The Lancet. 2015;386(10002):1484-1492.

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Li Y. Understanding Health Constraints Among Rural-toUrban Migrants in China. Qualitative Health Research.

Musculoskeletal Disorders in Surgeons Date of submission: 13 September 2019 Date of acceptance: 5 May 2020 Date of online publication: 15 May 2020 Xiang Rong Sim 4th Year Medical Student, Monash University Biography: Xiang Rong is a final year medical student with a special interest in surgery. He undertook a placement in minimally invasive surgery in 2019, where he developed an appreciation for the physical strains that surgery can place on members of the surgical team and approaches to assist in the management of this. Alex Ades MBBS MD PhD FRANZCOG Consultant Advanced Gynaecological Laparoscopic and Robotic Surgeon, Epworth Hospital Consultant Advanced Gynaecological Laparoscopic Surgeon, Royal Womens’ Hospital Consultant Advanced Gynaecological Laparoscopic Surgeon, Frances Perry House Clinical Associate Professor, University of Melbourne Shane Nanayakkara MBBS FRACP PhD Cardiologist, Alfred Hospital Clinical Research Fellow, Baker IDI Pavitra Nanayakkara MBBS BMedSc (Hons) DRANZCOG Minimally Invasive Gynaecological Surgery Fellow, Epworth Hospital

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Abstract Background Musculoskeletal disorders (MSDs) are an occupational hazard amongst surgeons, causing detrimental effects in up to 20% of surgeons in their lifetime. However, there is a paucity of data examining solutions for the problem. There is also a lack of research comparing MSDs in surgeons who perform open surgery compared with those who perform newer methods of surgery such as laparoscopic and robotic surgery. Aims We aim to explore existing literature about the various risk factors and the consequences of MSDs. We believe that by raising awareness of such risk factors to medical students from early on in their medical careers, they can develop an appreciation of the potential long-term impacts and take an early approach to prevention. We discuss preventative strategies in the categories of individual, occupational, institutional, and intra-operative techniques. Materials and Methods Ovid Medline, Cochrane Library, and PubMed databases were used to identify articles. Studies reporting on work-related MSDs in surgeons were included. Articles relevant to medical fields with a high level of surgical involvement, such as gynaecology, were also included. This information was used to construct a narrative review of the literature (see Appendix 1 for full methodology).

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Within each database search, only a few articles relevant to this review were generated. Therefore, the citations were also screened to find additional articles that fit within the scope of this review. Results Multiple factors were found to contribute to the development of MSDs, including individual and occupational factors. MSDs have resulted in a high percentage of surgeons performing fewer surgeries or taking more time off work. Similar risk factors applied to laparoscopic and robotic surgery. Few studies examined strategies to combat MSDs, but techniques such as intraoperative exercise and ergonomic training have shown to be promising. Conclusion There is a need for ongoing research into strategies to prevent MSDs in surgeons. Currently there are no evidence-based guidelines for management of work-related MSDs. Medical students should be aware that this occupational hazard has deleterious effects on the body and should be encouraged to employ some of the currently available strategies to prevent MSDs. The authors of this review advocate for ergonomics education to be integrated into surgical training programs via collaboration between ergonomists and surgical program directors.

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Key learning points 1. MSDs in surgeons are under-researched but are still an important occupational hazard that can be potentially debilitating. 2. There are no guidelines to manage MSDs – current best strategies involve having a well-balanced lifestyle, seeking help early, and being ergonomically aware of mechanisms of injury. 3. Greater awareness of ergonomics among surgeons could possibly reduce the incidence of MSDs among high risk groups. Introduction Work performed by healthcare professionals, especially surgeons, carries an inherent risk for physical wellbeing. One of the most common examples are musculoskeletal disorders (MSDs), which is an umbrella term that includes pain and injuries to various muscles and bones of the body [1]. Examples of MSDs include carpal tunnel syndrome and rotator cuff tendonitis. MSDs commonly arise from factors such as the overuse of certain muscle groups, poor posture, and sustained positions that strain the body. If not addressed early, MSDs can reduce work productivity and result in prolonged disability [1]. Doctors are at high risk of developing workrelated MSDs, due to risk factors such as long hours of standing, extended working hours, and lack of periods of rest [2]. This is even more so in surgeons, who tend to experience greater severity and incidences of MSDs due to the physical nature of their work [3]. Yet, less attention has been given to work-related MSDs than other occupational hazards such as burnouts [4]. In Australasia, the incidence of MSDs among surgeons is about 27% [1]. In the United States, the rates are even higher at around 40% [1]. This can impact on the surgeons’ daily performances, as well as cause long-term disabilities. The only strategies available currently revolve around recuperating or seeking physiotherapy help, and are not preventative. In this review, we will focus on the specific hazards that surgeons face, the consequences of the hazards, and some of the novel solutions created to manage and prevent these injuries. Ultimately, we hope to facilitate awareness of such injuries amongst medical students and aspiring surgeons and discuss current strategies to combat MSDs.

Methods Literature review of articles from MEDLINE (Ovid), PubMed (National Library of Medicine), and Cochrane Library was performed. Included articles reported information on the prevalence, consequences, prevention, and proposed solutions of work-related MSDs. MeSH terms used were “musculoskeletal disorders” and “surgeons” and combined with the prefix ‘AND’. UpToDate articles regarding the mechanism for musculoskeletal injury were consulted as they described the pathophysiology of MSDs comprehensively. There were no language restrictions in any of the searches (refer to Appendix 1 for complete methodology). Studies on the prevalence of work-related MSDs amongst surgeons There is currently a paucity of quality data about the prevalence of MSDs in the healthcare profession. A systematic review by Epstein et al. included studies on the prevalence of MSDs among doctors. Sixteen studies qualified under the inclusion criteria, and most of them were cross-sectional or survey studies with considerable heterogeneity [1]. From the systematic review, the overall lifetime prevalence of degenerative musculoskeletal disease amongst surgeons was reported to be 19% [1], with the highest prevalence of MSDs reported at 87%, by gynaecological oncologists [5].The same systematic review also showed that different specialties have higher incidences of certain types of MSDs (Table 1) [5-11], though in general, the neck, back, upper limb, and shoulders are the most common locations for MSDs. A study by Davis et al. reports that less than 40% of recordable injuries were reported to their respective institutions [11]. One possible reason could be lack of knowledge on accessing institutional support, however studies identifying these reasons are lacking [11]. Surgeons frequently experience physical discomfort while performing surgery [5-11]; over 85% [5] report this, however poor ergonomic working conditions within the operating theatre are usually tolerated, and likely under-reported.

Figure 1 – The multifactorial development of MSDs in surgeons

During non-neutral postural positions, frequently used during surgery, extended periods of isometric action put pressure on the cartilage. Pro-inflammatory cytokines eventually erode the articular cartilage, causing degenerative osteoarthritis. Simultaneous reactive growth of bony spurs [osteophytes] either impinge nerve roots or affect the spinal canal, both of which can lead to chronic pain [12]. Inflammation and repeated stress can also cause disc herniation to occur and cause radiculopathy, with similar negative effects on surrounding muscles and tendons. Repeated and extended periods of action and stress can tire out muscles and put excess tensile loading on the tendons, which in turn causes more impingement and pain [13].

Individual factors, such as age, comorbidities, and past trauma directly affect the integrity of the joint and tendon anatomy. Aging tendons, for instance, are more prone to microtears and calcifications, which can predispose the surgeon to a higher likelihood of MSDs when coupled with repetitive overuse [13]. Occupational factors, such as posture and positioning during surgery and work schedule, affect the loading of the joint or tendon. During surgery, surgeons often adopt awkward positions for extended periods, placing unnatural pressures on joints, tendons, and muscles. Work scheduling and work periods without break affect the duration of action on the affected structure, which then cause progressive degeneration [14]. Poor sitting postures in review clinics are also contributory to MSDs. Finally, workplace factors such as work culture affect surgeons’ tolerance and response to pain [1]. Short leaves for work-related MSDs, confusion over what constitutes a reportable injury, and acceptance of pain as part of the surgeon’s role all delay help-seeking behaviours and reporting of symptoms [11]. Consequences of work-related MSDs on surgeons The consequences of MSDs can be divided into short-term and long-term categories (Figure 2). The short-term impacts influence the surgeons’ daily performance, while long-term consequences may influence surgeons’ well-being and futures based on the degree of debilitation.

Specific risk factors The development of MSDs is multifactorial and influenced by individual, occupational, and situational factors (Figure 1).

Figure 2 – The impact of MSDs on surgeons can be significant both in the short and long-term

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The presence of pain and discomfort from a musculoskeletal disorder can impact on surgeons’ posture, mobility, level of concentration, and physical stamina [15]. Most surgeons do not usually operate every day [15], which allows rest time for injuries; for some, symptoms persist even during the recovery days. 41% of surgeons report that pain affected their relations with other people, while 51% reported that it affected their sleep [15]. In the United States, 22% of work-related MSD injuries resulted in missed work and 35% of work-related MSD injuries resulted in surgeons performing fewer surgeries [11]. Approximately 5% of respondents took at least two weeks off work to recuperate from injuries [11], with economic and logistical implications [11]. In the UK, 23% of work-related MSD injuries sustained by otolaryngologists resulted in taking time off work [16]. In more severe cases, MSDs can cause surgeons to restrict the number of surgeries performed per day, undergo surgery themselves, or even retire prematurely. There have been no studies done on the long-term implications of MSD on aging surgeons, however, Epstein et al. approximated that 12% of surgeons required leave of absence, practice restriction, or even early retirement due to MSDs [1]. Minimally invasive surgery (MIS), whilst offering several benefits to the patient, including smaller incisions, less postoperative pain and infection risk, and quicker postoperative recovery, has the potential to cause greater strain on the surgeon [10].

Compared to conventional surgery, MIS is associated with an increased risk of disc herniation [17] and a tendency to require longer periods of static posture, especially of the neck [18], which predisposes to MSDs. Due to the unique motions of laparoscopic instruments, laparoscopic surgeons can develop a unique MSD known as the laparoscopist’s thumb [19]. Conversely, open surgery provides a greater range of motion [18]. There have been no systematic reviews comparing MSDs between MIS and open surgery so far. It is clear, however, that an awareness of the increased musculoskeletal strain, particularly associated with poor ergonomics, is imperative for the surgeon to employ measures to mitigate these risks. General strategies for the prevention and treatment of MSDs At present, there are no evidence-based recommendations for management of work-related MSDs. Based on current practices, the following framework for the prevention and management of MSDs was formulated (Figure 3). Individual level Personal health reduces the number of comorbidities and negative factors that can predispose to MSDs. Workers in all occupations are encouraged to stay healthy by adhering to a balanced diet of fruits and vegetables with less intake of free sugars and saturated fats, and a moderate aerobic exercise regime of 30 minutes on most days [20].

Figure 3 – There are institutional, occupational, and individual strategies in addressing MSDs

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This is because healthy eating and exercise is associated with a better quality of life and lower risk of musculoskeletal pain, especially in the long-term [21]. Therefore, surgeons are advised and encouraged to keep active and eat healthy to meet the demands of the job. Unfortunately, due to the poorer work-life balance and long hours, only about a third of surgeons engage in regular exercise and this can predispose them to MSDs [22]. Traditionally, surgeons would turn to therapy and/or pharmacological analgesia after surgery to numb musculoskeletal pain. One study briefly looked at alternative therapies employed by surgeons who had sustained an MSD. Of those who had MSDs, 44% sought assistance from a physiotherapist or an occupational therapist, 23% managed on simple analgesia alone and 13% tried alternative therapy, such as acupuncture and Ayurvedic medicine [23]. There is minimal data on the effectiveness of such strategies. On the whole, the effectiveness of these therapies depended on the individual surgeon’s MSD and the skill of the therapist. General occupational level Occupationally, surgeons would benefit from basic awareness regarding proper posturing and exercises, as well as additional support when performing surgery. In a survey of surgeons on methods to reduce the incidence of work-related stress injuries [11], responses included “early education as to what position can lead to injury”, “a formal curriculum for residents in training about how to reduce the likelihood of injury”, and “lifting assistance during manual handling of patients” [11]. Ongoing research is looking into strategies to improve surgeon posture and surgical ergonomics [24], which are two of the key risk factors associated with the development of MSDs. One randomised clinical crossover trial examining a group of surgeons who participated in an interventional program based on ergonomic principles reported significant reduction in lower back pain and analgesic consumption compared to pre-trial [24]. The Alexander technique (AT), is a method of psychophysical re-education of the body, teaching users to have greater awareness of postural strains in their body. It has been previously used for musculoskeletal conditions [25] and this was tried as a strategy to improve posture during surgery [26]. In a study, seven subjects were taught the Alexander technique by a professional AT coach face-to-face over two group sessions, six individual lessons and exercises in their own time, and then assessed twice for laparoscopic skills before and after the intervention.

All reported significant improvements to their posture and ergonomics, which would then decrease the risk of MSD [26]. For surgeons already with MSD, Kinesio Tape, a type of kinetic tape which is normally used for injuries in athletes, was used to help such surgeons achieve better functional performances during surgery [22]. In this study, the tapes were applied to the trapezius or the sacrospinal muscles for relief of shoulder and back pain over several days. Kinesio Tape showed a significant improvement in scores of both the Neck Disability Index (3.84 to 2.52) and the Owestry Low Back Disability Index (4.38 to 2.77) in surgeons [22] and significantly improved the cervical range of motion from 0.35 to 0.59 [22]. Intraoperative strategies When faced with pain in the middle of an operation, surgeons use varying techniques to reduce symptoms while operating; 25% of surgeons slowed down the pace of the surgery, 63% changed positions, and 38% adjusted their equipment to suit their needs, be it to allow for a different posture or to rest [15]. These strategies however are often limited by constraints of the sterile field and the instruments, and consequently physical symptoms persist. In prolonged surgeries, surgeons are prone to fatigue, decreased strength, and technical accuracy. Some studies have investigated the use of microbreaks during surgery in order to reduce MSDs [15,27,28]. One crossover experimental study demonstrated that micropauses of less than 20 seconds every 20 minutes was shown to significantly improve strength and reduced the number of technical errors by sevenfold during evaluation. Surgeons were given 20 seconds of time for stretching and rest every 20 minutes for long surgeries, and physical discomfort was evaluated using a visual analogy scale, with follow-up fatigue and accuracy testing by holding a weight and using a pair of Metzenbaum scissors to cut out a star-shaped track after the surgery respectively. No impairment of surgical performance was reported [27].

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Besides using micropauses, there is also some evidence that specific stretching exercises during surgery have the potential to reduce MSDs and enhance performance. Two multi-centre cohort studies were done on the use of intraoperative microbreaks with stretching exercises to combat physical fatigue and discomfort during surgery [15,28]. Surgeons were asked to perform standardised exercises that worked the neck, shoulders, hands, and back that lasted 90 seconds at appropriate 20 to 40-minute intervals throughout the surgery. Both studies showed significant reduction in pain symptoms as well as improvement in physical performance [15,28]. There was marked improvement of pain in the shoulders [15,28] as well as improvement of pain in the back and neck [28]. Already, there has been development of an exercise set that addresses the increased strain on select muscle groups during surgery [29]. Future research could be done to explore the long-term consequences of microbreaks and standardised exercises during surgery. Organisation level Institutional reporting allows surgeons to access institutional support and receive adequate compensation for their injuries [30]. However, due to fears of medicolegal matters, institutions may instead recommend measures on reporting surgeons that are unsatisfactory, such as forced leaves. In a study done in Tennessee, United States, up to 30% of surgeons surveyed did not know how to report occupational injuries, which was defined as “any wound or damage to the body resulting from an event in the work environment”, to their institution [11]. Medical institutions should be reminded of their legal obligation to protect their employees’ health and thus should promote general education about the reporting process, enabling surgeons to seek medical help earlier. The reporting process should also be done in an anonymous manner so as to avoid reputational harm for either the surgeon or the medical institution. Ergonomics: A novel solution? While doing a literature search of solutions to control MSDs among surgeons, the field of ergonomics was at the forefront of the list. Ergonomics is described as the science of improving the efficiency of human performance within their working environment [31,32].

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A number of studies have been done on analysing surgical work from an ergonomic point of view. Ergonomic assessment of the surgical theatre has shown that surgeons work in conditions similar to or even harsher than those of industrial workers [33-37]. Furthermore, surgeons have shown to be severely lacking in ergonomic awareness and knowledge. Only 25.4% of surgeons have undergone any type of ergonomics education, which in part explains the acceptance of poor ergonomics in their working environment [1,33,34]. With such a great need for workplace reforms in surgery, ergonomics can play a vital part in the surgical world, by understanding the interaction between surgeon’s posture, surgical procedure, and work environment, in order to devise ways to reduce the risk of injury and the burden of MSDs [1]. However, implementation of an ergonomic intervention is not without its difficulties. It appears that a key challenge has been the standardisation and measurement of ergonomics in surgery. A computerised observational tool, ErgoPART, was developed to quantify postural demands of surgery [38]. It is a software designed to record, track, and measure the frequencies and duration of surgeons’ postures during surgery in real time [38]. As surgeons maintain positions for long periods of time during surgery, ErgoPART was able to code these positions. Using broad categories to classify different body postures, ErgoPART successfully managed to help quantify the frequency and duration of non-neutral body postures [38]. In addition, ErgoPART has also been used to look at pain outcomes based on the postural differences between sitting and standing and the postural differences between primary surgeons and assistant surgeons during vaginal surgery [39,40]. Collection of more data is necessary to make recommendations to reducing work-related MSDs. Future research could develop new quantitative measurements of musculoskeletal stress. Combined with some basic ergonomics training, this should adequately equip surgeons with techniques to reduce incidence of MSDs in the long-term. Specific to MIS, ergonomic assessment revealed that laparoscopic surgery was even more taxing on the surgeon [41]. One possible reason for this is that laparoscopic instruments come in standard sizes and lengths which may not fit the hands of all surgeons. Given that MIS is quickly becoming the mainstay mode of surgery in view of the patient benefits, it is pertinent to optimize ergonomics for the MIS work environment.

Implications of the article Further research is warranted to examine solutions to reduce MSDs among surgeons in a systematic approach, either in terms of ergonomic changes to the work environment, or in terms of education so that surgeons can avoid such injuries pre-emptively. This article remains very relevant for all medical students. Aspiring surgeons should be aware of such occupational hazards and pay attention to their own physical health, as well as that of their peers and superiors. Since there is a shortage of high-quality studies on the topic of MSDs in surgeons, research-inclined medical students can endeavour to conduct studies in this area or contribute to such studies if already ongoing. Furthermore, while searching the literature, we found evidence that the problems of MSDs are also prevalent in physicians, albeit at a lower rate. This means that all medical students should be aware that their future occupation will also predispose them to MSDs and develop adaptive habits of self-care. Limitations of the article The authors of this narrative review acknowledge that. unfortunately, most of the data on this subject is observational, and there are no systematic reviews on strategies for preventing MSDs among surgeons. However, it is precisely the shortage of longitudinal and interventional studies that motivates the writing of this review article, so that awareness on this issue is increased and can hopefully spur more interest in this area of self-care for doctors. While searching the literature, results for ergonomic interventions of microsurgery, laparoscopic, and robotic surgery were generated. While MSDs for newer forms of surgery are beyond the scope of this article, it would be an interesting area to research in the future.

Conclusion Surgeons are at high risk of developing MSDs because of personal, occupational, and workplace-based factors, with deleterious effects for both the patient and surgeon. While current data is predominantly observational, it is well demonstrated that MSDs are an increasing issue amongst the surgical profession. Yet, there are no formal recommendations on how surgeons can avoid or manage MSDs. At present, a well-balanced lifestyle, with improved clinician education regarding ergonomic principles on reducing musculoskeletal strain during surgery are the only general advice for preventing MSDs. In the future, there will likely be more evidence to support incorporating ergonomics into surgical training programs. Through this article, medical students should have a greater awareness of MSDs and learn to practise greater self-care. Acknowledgement None Conflict of interest The authors declare no conflict of interest with any organization or entity with financial interest, or non-financial interest in the writing of this article. Funding The authors declare no funding in the manuscript writing and editing process. Authors Contribution XS performed the literature review, drafted the first version of the article and made revisions as per supervisor and editor suggestions, AA proofread the article and approved final submission, SN performed literature review, edited the article and approved final submission, PN proposed the outline of the article, created diagrams, oversaw the literature review and edited the manuscript. Editor Sharon Del Vecchio Senior Editor Mabel Leow Senior Proofreader Emily Feng-Gu

Australian Medical Student Journal 45

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46 Australian Medical Student Journal

Australian Medical Student Journal

48 Australian Medical Student Journal Auerbach J, Weidner Z, Milby A, Diab M, Lonner B.

Dianat I, Bazazan A, Souraki Azad M, Salimi S

Work-related physical, psychosocial and individual factors associated with musculoskeletal symptoms among surgeons: Implications for ergonomic interventions [14]

Davis W, Fletcher S, Guillamondegui O.

Musculoskeletal occupational injury among surgeons: effects for patients, providers, and institutions [11]

Musculoskeletal Disorders Among Spine Surgeons [7]

Park A, Lee G, Seagull F, Meenaghan N, Dexter D.

Patients Benefit While Surgeons Suffer: An Impending Epidemic [10]

Study aims

Healy K, Pak R, Cleary R, Colon-Herdman A, Bagley D.

Hand Problems Among Endourologists [8]

Author

Auerbach J, Weidner Z, Milby A, Diab M, Lonner B.

Musculoskeletal Disorders Among Spine Surgeons [7]

Mal R, Costello C.

Epstein S, Tran B, Capone A, Ruan Q, Lee B, Singhal D.

Work-Related Musculoskeletal Disorders among Plastic Surgeons: A Systematic Review [6]

Title

Kim-Fine S, Weaver A, Woolley SM, Gebhart J.

Musculoskeletal disorders among vaginal surgeons [5]

Is shoulder impingement syndrome a problem in otolaryngologists? [9]

To assess prevalence of hand problems among endourologists and generate possible causes

Rambabu T, Suneetha K.

Prevalence of work related musculoskeletal disorders among physicians, surgeons and dentists: A comparative study [3]

To analyse the effects of each physical, psychosocial, and individual factor on the presence of MSDs among surgeons in Iran.

To assess whether spine surgeons are at an increased risk of MSDs as compared to the general population

To assess the likelihood of work-related musculoskeletal injury in a surgeon’s career and subsequent effects on their patients, providers, and institutions.

“To investigate the association of demographics, ergonomics, and environment and equipment with physical symptoms reported by laparoscopic surgeons.” [10]

To find out the incidence of shoulder disease in otolaryngologists compared to a control group of endocrinologists.

To assess whether spine surgeons are at an increased risk of MSDs as compared to the general population

To synthesize the available literature regarding prevalence of MSDs, and potential solutions to treat MSDs amongst plastic surgeons

“To estimate the prevalence of MSDs in vaginal surgeons and identify work-related characteristics in order to guide further research” [5]

To evaluate and compare work-related MSDs across three groups: physicians, surgeons and dentists

“To estimate the prevalence of work-related MSDs among at-risk physicians and to evaluate the scope of preventive efforts.” [1]

Epstein S, Sparer E, Tran B, et al

Prevalence of Work-Related Musculoskeletal Disorders Among Surgeons and Interventionalists [1]

Study aims

Author

Title

Outcomes of study

20.3% of endourologists and 12.8% of psychiatrists responded, giving a total sample size of 196. Hand and wrist problems were reported by 39 (32%) endourologists compared with 14 (19%) psychiatrists.

62% of members responded. Mean age was 54 years old. 62% of respondents complained of neck pain, 49% complained of shoulder pain.

16 articles were included in this systematic review. The evidence was of poor quality, but points at a high prevalence of career-related musculoskeletal injury amongst plastic surgeons.

18% of members responded. Among respondents, 86.7 % reported ever having work-related MSDs.

Musculoskeletal pain was most prevalent among dentists at 61%, followed by surgeons at 37%, and physicians at 20%.

21 articles were included in this systematic review, all of which had considerable heterogeneity.

Outcomes of study

Study findings

Hand and wrist problems are prevalent among endourologists. Interestingly, surgeons who preferred a different method of surgery (counterintuitive ureteroscope deflection) were more likely to have problems.

The authors’ hypothesis was correct. Heavier caseload was correlated with higher rates of MSDs, especially in the cervical region.

High prevalence of MSDs amongst plastic surgeons are worrying and need to be researched further. Half of the articles looked at altering ergonomics of surgery.

A large proportion of vaginal surgeon respondents reported work-related MSDs, majority of these involving the neck and back. These surgeons were also more likely to be female, younger, and be in surgical teaching.

There is a higher prevalence of MSDs experienced by dentists than both surgeons and physicians.

Primary finding of this study showed that musculoskeletal disorders amongst surgeons have a 19% overall lifetime prevalence which cannot be ignored. Other interesting findings include a gross lack of awareness of ergonomics in surgery which can potentially mitigate musculoskeletal disorders.

Study findings

62% of members responded. Mean age was 54 years old. 62% of respondents complained of neck pain, 49% complained of shoulder pain.

33% of members responded. 40% of surgeons sustained ≥ 1 injuries in the workplace. 50% of injured surgeons received medical care for their most recent injuries yet 20% of these injuries were reported to their institution. 53% of injured surgeons reported that pain from their injury had a minimal or moderate effect on their performance in the operating room.

There was a response rate of 14.4%. 86.9% of respondents reported physical symptoms or discomfort. High case volume was most associated with symptoms. 58.7% reported being slightly or not aware of surgical ergonomics and its recommendations.

The authors’ hypothesis was correct. Heavier caseload was correlated with higher rates of MSDs, especially in the cervical region.

Surgeons have moderate-to-high risk for sustaining MSDs, but there appears to be a low rate of institutional reporting which must be addressed. Open responses highlighted a need for some ergonomic-based guidelines to reduce MSDs.

The high prevalence of MSDs amongst laparoscopic surgeons is very serious and needs further research beyond survey methodologies. Future guidelines on surgical ergonomics should be widely taught to surgeons.

All surgeons from 3 major Iranian 62.4% of surveyors responded. Improved working conditions The following factors were can improve quality of life cities who have at least 1 year of associated with MSDs: Time and enhance patient care working experience were invited spent on surgeries each week, overall. This study also highto participate, giving a sample number of hours working in lights the correlation between size of 500. A pre-existing standing position per day, psychosocial stressors such survey, the standardised Nordic moderate to high levels of as family conflict, and the Musculoskeletal Questionnaire work, family conflict, duration presence of MSDs. was utilised and translated of each surgery, number of into Persian language. Details years worked as a surgeon included demographics, a body (>10 years), and surgical map of musculoskeletal injuries, specialty, particularly cardiowork-family conflict scale and thoracic and obstetric and details about surgery work. Data gynaecologic surgeries. was analysed using Odds Ratio.

Authors modified an official Physical Discomfort Survey and surveyed members of the Scoliosis Research Society via mail and email.

Authors used pre-existing surveys that assessed occupational injury and emailed to members of the Tennessee chapter of the American College of Surgeons. Descriptive statistics were used to analyse survey data and qualitative analysis was performed on open response questions.

An online survey was sent to members of the Society of American Gastrointestinal and Endoscopic Surgeons and results were analysed using chi-square and logistic regression.

A brief questionnaire survey There was a 65.1% response Otolaryngologists are more was posted to a list of members rate overall. 24.0% of the affected by shoulder impingein the British Association otolaryngologists had suffered ment than endocrinologists, of Otolaryngologists. from impingement syndrome suggesting an association Endocrinologists were used compared with 10.9% of between profession and as the control group and were the endocrinologists. For injury. given the same questionnaire. those without impingement Questionnaire was brief and syndrome, 19.7% of otolarynasked for impingement syndrome gologists compared to 7.3% of without grading of symptoms. endocrinologists gave history of injury or overuse.

Methods

Computer survey given to the two different groups: members of the Endourological Society and psychiatrists in academic and community settings. Parameters queried included symptoms of hand pain, neuropathy, and/or discomfort.

Authors modified an official Physical Discomfort Survey and surveyed members of the Scoliosis Research Society via mail and email.

Literature search conducted using Medline, Embase, Web of Science, and PubMed until 2016 for all articles reporting on prevalence of work-related musculoskeletal injuries or ergonomic challenges amongst plastic surgeons

De novo surveys were distributed to members of the International Urogynecological Association and American Urogynecological Society. Exclusion criteria included inability to read English, no computer access, invalid or unavailable e-mail address, and missing >50% of responses.

Self-reporting questionnaires on MSDs were distributed, including information on the location of MSD symptoms in the past 12 months and the pain experienced, to a small sample size of 300.

“Systematic search in MEDLINE (Ovid), Embase (Elsevier), Web of Science, PubMed, and 2 clinical trial registries, for studies reporting on the prevalence and prevention of work-related MSDs among at-risk physicians published until December 2016.” [1]

Methods Table 1: List of studies

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50 Australian Medical Student Journal Auerbach J, Weidner Z, Milby A, Diab M, Lonner B.

Karatas N, Bicici S, Baltaci G, Caner H.

Vijendren A, Yung M, Sanchez J, Duffield K.

Musculoskeletal Disorders Among Spine Surgeons [7]

The effect of kinesiotape application on functional performance in surgeons who have musculo-skeletal pain after performing surgery [22]

Occupational musculoskeletal pain amongst ENT surgeons – are we looking at the tip of an iceberg? [23]

Dorion D, Darveau S.

Do Micropauses Prevent Surgeon’s Fatigue and Loss of Accuracy Associated With Prolonged Surgery? An Experimental Prospective Study [27]

Park A, Zahiri H, Hallbeck M, Augenstein V, Sutton E, Yu D et al.

Reddy P, Reddy T, RoigFrancoli J, Cone L, Sivan B, DeFoor W et al.

The Impact of the Alexander Technique on Improving Posture and Surgical Ergonomics During Minimally Invasive Surgery: Pilot Study [26]

Intraoperative “Micro Breaks” With Targeted Stretching Enhance Surgeon Physical Function and Mental Focus [28]

Giagio S, Volpe G, Pillastrini P, Gasparre G, Frizziero A, Squizzato F.

A Preventive Program for Work-related Musculoskeletal Disorders Among Surgeons [24]

Author

Vijendren A, Yung M.

An overview of occupational hazards amongst UK Otolaryngologists [16]

Title

Author Hallbeck M, Lowndes B, Bingener J, Abdelrahman A, Yu D, Bartley A et al.

Title The impact of intraoperative microbreaks with exercises on surgeons: A multi-center cohort study [15]

Study aims

To assess the effect of 5TSMBs on pain, fatigue, physical functions, and mental focus of surgeons during surgery.

To evaluate the effectiveness of 4MPs in preventing muscular fatigue on surgeons during long surgeries.

To evaluate if adoption of 3AT by laparoscopic surgeons during work will improve posture and surgical ergonomics.

To elicit risk factors for various work-related MSDs and to assess effectiveness of intervention in MSDs reduction for 6 months

Study aims

To investigate prevalence of work-related musculoskeletal disorders amongst UK ENT surgeons and comparisons with existing literature.

To evaluate the effectiveness of using Kinesiotape on pain and surgical performance in surgeons with pre-existing MSDs

To assess whether spine surgeons are at an increased risk of MSDs as compared to the general population

To investigate the prevalence of various 1OH amongst ENT doctors in the UK.

Does the introducing of intraoperative microbreaks with exercises during long surgeries reduce fatigue in surgeons?

Methods

Outcomes of study

KT is very helpful in mitigating musculoskeletal injury in surgeons already presenting with MSDs.

The authors’ hypothesis was correct. Heavier caseload was correlated with higher rates of MSDs, especially in the cervical region.

Both this study and online literature suggests that OHs are prevalent within the UK ENT community. However, studies of higher quality are required to thoroughly investigate the causes and risk factors.

Outcomes of study

Having MPs prevented the muscular fatigue that would have arisen in surgeons who just underwent long procedures, and reduced the number of errors when doing an accuracy test. Finally MPs had significantly resulted in reduction in physical discomfort in various body parts in surgeons.

Subjects showed both objective (ergonomically) and subjective improvements to their posture and an improved ability to complete assessments.

MPs have the potential to improve muscle fatigue for surgeons during long operations.

AT education has the potential to improve surgical ergonomics. Further studies of AT are warranted to validate the benefits for surgeons.

Implementation of an education program based on surgical ergonomics and specific physical exercises is effective in reducing MSDs and improves quality of life.

Study findings

TSMB improved surgeon Intraoperative TSMB is a 66 participants were recruited, novel method of reducing including surgeons and assisting post-procedural pain scores in staff from four medical centres. various regions throughout the surgeon musculoskeletal pain body. Surgeons self-reported and increasing mental focus. They were assessed using standardised questionnaires regard- improvements in physical performance and mental focus ing musculoskeletal pain and and respondents planned to performance over two days, one as a control without intervention, continue TSMB. Traditionally, surgeons either changed the other including TSMB at 20 positions or took breaks to to 40-minute intervals throughmitigate MSDs. out each surgical case

16 surgeons participated. Surgeons were tested three times: once in a control situation before surgery and twice after a prolonged, reproducible operation, one of these with formal MP the other without. Muscular fatigue was tested by holding a 2.5-kg weight as long as possible with a stretched arm. Accuracy was evaluated measuring the mistakes made when following a predetermined path on a board., any discomfort was measured by visual analogue scale.

Small sample size of 7 surgeons. Each subject served as their own control. Before intervention, subjects underwent assessment of their posture and laparoscopic skills. They were then given the intervention of education about AT and underwent post- intervention assessment of posture and laparoscopic skills.

Study findings Microbreaks improved self-reported physical performance and mental focus during surgery, yet did not significantly increase surgery duration.

24% response rate giving samDespite the scarcity of ple size of 323. Work-related studies, work-related MSDs had been experienced musculoskeletal disorders by 47.4 % of respondents, of are common amongst ENT which 44% had to undergo surgeons in the UK, which physiotherapy. The literature highlights the need for greater search identified five related research beyond survey studies, which showed that methodologies. MSDs are common amongst ENT surgeons.

KT has resulted in significant reduction in neck and back pains, and range of motions have increased.

62% of members responded. Mean age was 54 years old. 62% of respondents complained of neck pain, 49% complained of shoulder pain.

24% of members responded, giving sample size of 323. 70.6 % had reported a form of OH throughout their career. The literature search also revealed 16 articles pertaining to OH amongst ENT doctors.

141 surgeons participated. After Both groups had similar cluster randomisation by surgical demographics and anthrodivision, surgeons were allocated pometrics at the start of the to 2 groups: The control group, study. The intervention group and the intervention group. The had showed a statistically intervention group had education significant reduction of lower about ergonomic principles and back pain and analgesic applied these in the operating consumption at 6 months. room, supervised by a physThey also self-reported an iotherapist. The groups were improvement in their quality of followed up at 3 and 6 months life at 3 and 6 months.

Methods

A de novo survey covering questions on work-related MSDs was distributed to the entire membership of ENT-UK electronically. A literature search on the subject was then performed using PubMed, Embase, Medline and Google scholar databses.

32 surgeons from a university hospital participated. Pain assessments were logged using a Visual Analog Scale. Owestry Low Back and Neck Disability Indexes were used to assess pain effects on activities of daily living. Control day is a day without application of 2KT. KT is applied on the shoulders and lower back when there is a day of similar surgical load, and the tape remains for a few days.

Authors modified an official Physical Discomfort Survey and surveyed members of the Scoliosis Research Society via mail and email.

Survey was created combining two validated questionnaires for general health, and also gathered demographics and work data. With the assistance of ENT-UK, the survey was sent out to its members. A literature search was also conducted to search for articles within English literature.

Preliminary questionnaire that 80% of the surgeons self-recovered body part discomfort ported that they had ongoing and after-effects was completed pain at the start of the day, before intervention. The intervenwith 41% reporting that the tion involved standardized 2-minpain interfered with interute guided microbreak exercises personal relationships and performed intraoperatively within 51% reporting that the pain the sterile field at 20–40 min interfered with sleep. intervals throughout each case After the intervention, 34% over a surgical day. Other days self-reported improvement in where microbreaks were not per- physical pain scores, and only formed were the control group. 12% reported a decrement, At the end of all surgical days while 57% reported physical another questionnaire was filled performance improvement out to cover current self-reported with none reporting a decrephysical pain. Sample size was ment in physical performance. small at 56.

Table 1 (Cont): List of studies

Australian Medical Student Journal

52 Australian Medical Student Journal To develop and evaluate the effectiveness of an ergonomics analysis tool in tracking real-time postural data of surgeons.

ErgoPART: A Computerized Zhu X, Yurteri-Kaplan L, Observational Tool to Cavuoto L, Sokol A, Iglesia Quantify Postural Loading in C, Gutman R et al. Real-Time During Surgery. [38]

OH – Occupational-related Hazard KT – Kinesiotape 3 AT – Alexander Technique 4 MP – Micropause 5 TSMB – Targeted Stretching Microbreak 6 MIS – Minimally Invasive Surgery 7 ET – Ergonomic Training 8 REBA – Rapid Entire Body Assessment 9 SEE – Surgical Ergonomics Education 1

To gather data of surgical ergonomics education in the United States.

Epstein S, Tran B, Capone A, Ruan Q, Fukudome E, Ricci J et al.

The Current State of Surgical Ergonomics Education in U.S. Surgical Training. [37]

To elucidate potential areas for ergonomic improvement in the operating theatre.

Study aims

To confirm the presence of MSDs experience using a validated score system, and to evaluate ergonomic knowledge of otolaryngologist surgeons

Author

Vaisbuch Y, Aaron K, Moore J, Vaughan J, Ma Y, Gupta R et al

Ergonomic hazards in otolaryngology. [35

To evaluate if the application of an evidence-based 7ET program into surgeon’s training is both feasible and accepted.

Matern U, Koneczny S

Franasiak J, Craven R, Mosaly P, Gehrig P.

Feasibility and Acceptance of a Robotic Surgery Ergonomic Training Program. [34]

To identify aspects of an operating theatre environment and describe common ergonomic errors in surgeon posture during laparoscopic and robotic surgery

Title

Rosenblatt P, McKinney J, Adams S.

Ergonomics in the Operating Room: Protecting the Surgeon [33]

Study aims To create an exercise set of microbreak activities for 6MIS surgeons to perform intraoperative in order to reduce work-related MSDs.

Safety, hazards and ergonomics in the operating room. [36]

Author Coleman Wood K, Lowndes B, Buus R, Hallbeck M.

Title Evidence-based intraoperative microbreak activities for reducing musculoskeletal injuries in the operating room [29]

Methods

Outcomes of study

Sample size of 42 surgeons. 45% experienced MSD from performing robotic surgery and 26.3% reported persistent strain. All surgeons who participated in the personal ET found it helpful and felt formal ET should be standard. 88% changed their practice as a result of the training, and 74% of those reporting strain noticed a decrease in strain after their ET.

Aspects identified in the theatre that can be modified include the display monitor height, table height, use of arm boards, and foot pedal placement. Literature has identified lack ergonomic awareness among surgeons, and the study identified errors in forward head posture, shoulder elevation and weight bearing asymmetry as common problems faced by surgeons

Specific problems highlighted to overcome were: 1) posture correction; 2) normalisation of tissue tension and soft tissue mobility/gliding; and 3) relaxation/stress reduction. The study gave examples of how problems in a body area can be addressed by the solutions ranked the highest. On average, these activities only take one minute to perform.

Study findings

Evidence-based ET was easily implemented, and well accepted by the robotic surgeons. A larger intervention study is needed to analyse effectiveness of this new training program.

Proper theatre setups, posture positioning, awareness and readjustments are necessary components for reducing long-term MSDs.

By incorporating clinical and ergonomic expertise, it is possible to create an exercise of intraoperative microbreaks.

Software and interface development were completed by the collaboration of surgeons and ergonomics researchers. A preliminary assessment was conducted during one vaginal surgery involving four observers with varying degrees of ergonomics experience logging non-neutral postural data.

A de novo questionnaire was distributed to program directors from 14 surgical and interventional medical specialties, gathering data about the use of formal or informal 9SEE in their programmes.

A 5-part survey was given to surgeons working in German hospitals, gathering data on 1) demographics, 2) Spatial conditions in theatre, 3) Theatre equipment, 4) Working posture and 5) Individual preferences when working in the operating theatre.

Methods

Study findings The results showed many potential areas for ergonomic improvement and calls for future collaboration between healthcare and engineering to develop more ergonomic theatre rooms.

Inter-observer quantitative information gathered for the entire surgery was fairly homogenous, and is available immediately after completion of surgery.

ErgoPART is a promising software in assessing body postures during surgeries ergonomically, and can record various individual, environmental and work factors that can predispose to greater musculoskeletal strain.

130 questionnaires were SEE is hardly present in completed. 1.5% of directors medical training programs. provided formal SEE and Even though SEE is viewed as 25.4% provided informal SEE an essential tool for reducing in their specialty program. Two work-related MSDs, lack of programs discontinued SEE evidence-based clinical data due to lack of evidence-based makes SEE implementation guidelines. However, trainees unfeasible. felt that learning surgical ergonomics skills was a worthwhile time investment in 100% and 76.7% of current formal and informal SEE, respectively.

425 questionnaires were generated. Many surgeons had concerns with the foot stand, patient positioning, and various equipment handling and admitted to a degree of musculoskeletal discomfort. 97% of the surveyed surgeons see ergonomic improvement in the operating room as necessary.

Outcomes of study

70 surgeons participated. Musculoskeletal pain Using the 8REBA score system to 72.9% of surgeons suffered induced by poor ergonomics identify ergonomic hazards, the are common among otolarauthor conducted intraoperative from back pain, cervical being the most common location, yngologists and surgeons observations of the surgeons. which corresponded to the lack ergonomic knowledge to Surgeons had given a separate REBA score. Only 24% of sur- change their workplace setup. survey regarding current MSDs and prior ergonomic knowledge. geons had any prior ergonomic training or education

A two-part survey was conducted. The first survey assessed musculoskeletal strain using the standardised Nordic Musculoskeletal Questionnaire. Participants were then given the option to participate in ET session. ET was developed from Occupational Safety and Health Administration guidelines and by an engineer experienced with health care ergonomics. After ET, a follow-up survey were completed.

A video article was created based on clinical experience and a review of the literature.

Authors used principles of guideline development to identify areas of concerns highlighted by practitioners and the literature, ranked them in terms of severity, compared potential solutions to them and created an exercise set incorporating these solutions.

Table 1 (Cont): List of studies

Australian Medical Student Journal 53

Welcome to the wards: Pilot study on microbial contamination of medical students during initial clinical rotations Date of submission: 14 October 2019 Date of acceptance: 25 February 2020 Date of online publication: 14 May 2020 Yanning Elisabeth Xu MBBS Monash University, Melbourne Despina Kotsanas BSc(Hons) (Monash) MClinEpi (Monash) FASM Monash Infectious Diseases, Monash Medical Centre

Ellie is a final year medical student commencing internship in Singapore next year. She is interested in both becoming a good doctor and physician training with a special interest in infection control and global health. Despina is a senior scientist at Monash Medical Centre and secretary of the Australian Society for Antimicrobials. She has extensive research experience in adult and paediatric infectious diseases.

A/Prof. Rhonda L Stuart MBBS, FRACP, PhD. Monash Infectious Diseases, Monash Medical Centre School of Clinical Sciences, Monash University

Rhonda is an Infectious Diseases Physician and Medical Director of Infection Prevention & Epidemiology at Monash Health. She is a global expert in infection control in long-term care facilities.

A/Prof. Ian Woolley MBBS FRACP DTMH MD Monash Infectious Diseases, Monash Medical Centre School of Clinical Sciences, Monash University

Ian is an Infectious Diseases physician and Director of HIV Medicine in Monash Health. He is also a clinical tutor to medical students and mentors young researchers.

Abstract Background Pathogenic bacteria can colonise the hands, medical equipment, and personal belongings of healthcare workers (HCW) exposed to clinical environments. Healthcare-associated infections (HAI) arising from the transmission of these pathogens to patients causes morbidity, mortality, and an economic burden. Despite widespread healthcare worker education and policy change, the incidence of HAI remains high in Australia. Aim To identify potentially pathogenic bacterial contamination of clinically unexposed medical students’ hands and items upon entry into the clinical environment and subsequent design of a definitive study. Materials and methods A pilot prospective cohort study was performed at a large tertiary hospital in Melbourne, Victoria. Eight medical students had two- to six-week samples taken from their dominant hand, mobile phones, and stethoscopes in the first six months of entering the clinical environment.

54 Australian Medical Student Journal

Results Pathogenic bacteria were detected throughout the six-month testing period on five of the eight students’ hands, mobile phones, or stethoscopes. Pathogenic bacteria grown included methicillin-sensitive Staphylococcus aureus, Enterococcus faecalis, and Gram-negative pathogens, such as Serratia marcescens, Pseudomonas spp. and Acinetobacter baumanii. No multi-resistant organisms were detected. Low decontamination rates of items, universal use of phones while on the toilet, and recent hand hygiene credentialing were reported by participants. Conclusion Colonisation by nosocomial pathogens on medical students’ hands, mobile phones, and stethoscopes was identified during the first six months of clinical study. Further research to characterise bacterial contamination of new HCW, risk factors, and strategies to improve infection control practices has the potential to reduce HAI.

Key learning points 1. Upon entering the clinical environment, medical students can be quickly colonised by pathogenic bacteria which poses a risk of transmission to patients. 2. Mobile phones were frequently found to be contaminated but infrequently cleaned, which raises questions on adequacy of education regarding mobile phone decontamination. 3. Hand hygiene is a personal duty and a priority of patient care which requires the support of healthcare institutions and community awareness to encourage compliance. Introduction Ever since Antonie van Leeuwenhoek first observed bacteria through his microscope in the 1670s [1], healthcare workers (HCWs) have studied the colonisation of our bodies and equipment with microorganisms and subsequent transmission to others [2]. In fact, roughly 20-40% of all hospital acquired infections (HAI) have been attributed to cross-infection from the hands or equipment of HCWs [3]. Currently, one in ten acute adult hospitalised patients in Australia has a HAI [4] despite widespread understanding that correct hand hygiene practices reduce the transmission of HAI by a third. As medical students transition to a clinical hospital environment, their microbiota changes [5]. However, there are insufficient data regarding the time required for HCWs to become colonised by hospital pathogens. Existing cross-sectional studies involve participants who have had years of exposure to the clinical environment [2, 3, 6, 7]. Junior medical students comprise a population of HCWs with minimal exposure to the clinical environment and new medical equipment. In this pilot prospective cohort study, a group of eight medical students were followed through their induction into the clinical environment with regular microbiological monitoring. The primary aim was to identify potentially pathogenic bacterial contamination of clinically unexposed medical students’ hands and items as well as the acquisition of multi-resistant organisms (MRO), guiding subsequent design of a definitive study.

Methods Study design This pilot prospective cohort study took place from February 2019 to July 2019 at a single tertiary hospital in Melbourne, Australia. Study participants consisted of eight third-year medical students, beginning their first year of clinical medicine. Participants in clinical contact with researchers were sampled opportunistically. Students subsequently rotated through various medical and surgical departments during the study period. The study was approved as a quality assurance project by the Monash Health Human Research Ethics Committee (HERC –RES-19-0000-085Q). Microbiological methods Samples were self-collected from hands, mobile phones, and stethoscopes of each student at two- to six-week intervals from February to July 2019 as follows: At each collection, direct fingerprints from each finger of the dominant hand were sampled without hand decontamination. Hand hygiene was performed using 3M Avagard 9250-P (chlorhexidine gluconate 0.5% w/v in 70% v/v ethanol) hand rub before collection of the mobile phone and stethoscope samples. Cotton swabs moistened in sterile normal saline (0.9% w/v sodium chloride) were used to sample the front and back of students’ personal mobile phones and their stethoscope diaphragms. Hand samples were directly imprinted onto a whole horse blood agar (HBA) plate. Split horse blood/MacConkey (HBA/MAC) agar were used to culture samples from phones and stethoscopes. Participants performed their sample collection in the middle of their shift at the beginning of the working week. Bacterial identification and antibiotic susceptibility testing All plates were incubated at 35oC for 48 hours aerobically. Suspect colonies of Staphylococcus (S.) aureus, Enterococcus spp., and Gram-negative bacilli (GNB) were assessed for anti-microbial resistance. as per standard microbiological methods which included identification by MALDITOF (Matrix Assisted Laser Desorption IonizationTime of Flight (Bruker). Antibiotic susceptibility testing specifically tested for methicillinresistant S. aureus (MRSA), vancomycin-resistant Enterococcus (VRE), and carbapenemaseproducing Enterobacteriaceae (CRE).

Australian Medical Student Journal 55

Antibiotic susceptibility testing was performed by an experienced trained microbiologist as per laboratory methodology using VITEK® 2 (bioMérieux) microbial identification system using EUCAST (European Committee on Antimicrobial Susceptibility Testing) interpretations. MRO were defined as having acquired non-susceptibility to at least one agent in three or more anti-microbial categories [8]. Medical student demographics and risk factors for exposure Student data were collected from de-identified questionnaires and included gender, hand hygiene certification by online training, frequency of decontamination of hands and stethoscopes, personal illness during the six months, use of mobile phone in the lavatory, and schedule of clinical rotations.

Results Demographics Eight medical students in their first clinical year at a tertiary hospital in Melbourne agreed to have their hands and belongings sampled for the study period. Table 1 summarises the student demographics and clinical rotations units during this period. All students received hand hygiene accreditation in the same year but also used their phones while in the lavatory. None of them reported other potential sources of pathogenic bacterial acquisition such as working or volunteering in other healthcare settings before starting their clinical placement. Three students suffered mild viral respiratory illnesses and gastroenteritis during the study, increasing the possibility of contamination of hands and personal items with respiratory and faecal bacteria.

Microorganisms recovered Table 2 summarises the potential pathogenic microorganisms that were recovered from student finger imprints, phones and stethoscopes over the six-month period. No student samples grew any MRSA, VRE, or CRE during the study period and none of the isolates were multi-drug resistant. Hand samples from Student 1 grew methicillin-sensitive S. aureus (MSSA) on all four occasions, and from all sample sites on one occasion. Figure 1 shows large cream MSSA colonies grown from each finger imprint on HBA and the same cream colonies growing from this student’s mobile phone on HBA/MAC from collection 3. Of the other participants, only Student 8 yielded MSSA from their phone on one occasion.

Discussion There is a rich body of evidence that, beginning from medical school, HCWs have their mobile devices and medical equipment contaminated by pathogenic organisms [6, 7, 9, 10]. Despite the widespread implementation of hospital infection control strategies, HCWs are still colonised by pathogenic bacteria and MROs [5, 7]. In this prospective pilot study, we observed that medical students and their equipment can be contaminated by pathogenic bacteria soon after entering the clinical environment.

Table 1: Medical student demographics and risk factors for exposure

Medical student no. Gender Clinical rotation

Respiratory Cardiology GM Anaesthetics Oncology Gastro

Colonisation by Serratia marcescens was seen on Student 3’s hands and mobile phone in week 1, without persistent colonisation. Subsequently, Pseudomonas spp. was cultured from the same student’s phone on collection six. There was a notable acquisition of environmental and nosocomial pathogens on phones, hands, and stethoscope from later collections. Gramnegative bacteria (GNB), including Pseudomonas spp., Aeromonas spp., Acinetobacter spp., and Enterobacter asburiae, were recovered in heavy growth from Student 8. Most organisms may have been acquired from the hospital environment or possibly from external aquatic and plant sources [8, 11]. There were transient colonisations of fingers and phones but less frequently stethoscopes with GNB and Enterococcus faecalis.

Figure 1: Horse blood agar (HBA; left) plate and HBA/ MacConkey agar biplate with large cream colonies of methicillin sensitive Staphylococcus aureus cultured from all dominant hand finger imprints (left) and mobile phone (right) from Student 1 at Collection 3.

ID Haematology Renal Neurology

Personal illness Use of mobile phone in toilet Frequency of phone decontamination Frequency of stethoscope decontamination

Table 2: Potential pathogenic bacteria recovered from student samples Feb-July 2019

Collection interval Medical Student 1

MSSA F,P MSSA F,P,S MSSA F,P,S MSSA F,P

Never

Smar F, P

Pspp P

Occasionally

Aspp F Pdis S

Pspp P

Never Occasionally

= Yes; F = female, M = male, GM = General Medicine; Gastro = Gastroenterology; ID = Infectious Diseases; URTI = Upper respiratory tract infection;

Anos F

Abau Pspp P MSSA P

F,P

× = did not attend F = Finger imprints from dominant hand; P = Mobile phone; S = Stethoscope Abau = Acinetobacter baumanii; Ajun = Acinetobacter junni; Ahyd = Aeromonas hydrophila; Anos = Acinetobacter nosocomialis; Easb = Enterobacter asburiae; Efae = Enterococcus faecalis; MSSA = Methicillin sensitive Staphylococcus aureus; Pdis = Pantoea dispersa; Pspp = Pseudomonas species; Smar = Serratia marcescens

56 Australian Medical Student Journal

Australian Medical Student Journal

Previous cross-sectional studies have documented that mobile phones and the nasal and rectal mucosae of clinical year medical students can be colonised by pathogenic bacteria, such as MSSA, viridans group streptococci, Pantoea spp., and resistant bacteria, such as extended spectrum β-lactamase producing Enterobacteriaceae [5, 9]. In this study, HAI-associated pathogenic bacteria were isolated from five of the eight participants’ hands, mobile phones, and stethoscopes during a six-month testing period. Organisms grown included MSSA, Enterococcus faecalis and GNB., such as Aeromonas hydrophila, Pseudomonas spp. and Acinetobacter baumannii. No MRO were detected. Serratia marcescens, an opportunistic nosocomial pathogen associated with outbreaks of HAI [12] was detected on Student 3’s fingers and mobile phone one month into their first rotation (Table 2). This bacterium belongs to a group of GNB called ESHCAPPM, which are characterised by inducible β-lactamases that render them resistant to cephalosporins. Bacteria in this group include Enterobacter spp., Serratia spp., Hafnia spp., Citrobacter freundii complex, Aeromonas spp., Providencia spp., Proteus spp. (excluding P. mirabilis), and Morganella spp. Treatment of infections caused by these bacteria with cephalosporins induced resistance to the antibiotics, risking treatment failure [11]. AmpC β-lactamase producing organisms were also acquired including Acinetobacter baumannii, Acinetobacter junii, and Enterobacter asburiae [13]. The plasmid-mediated AmpC β-lactamase is a cephalosporinase that hydrolyses extended-spectrum cephalosporins and is poorly inhibited by clavulanic acid. Infection often requires the use of broad-spectrum antibiotics. Of the three surfaces sampled, the most frequently colonised surface was the hands. Intermittent, but significant, pathogens were grown from fingerprint imprints of Students 1, 6, and 8. Contaminated inanimate surfaces and direct patient shedding provides a constant source of microbial contamination for students’ hands and items, which require regular decontamination [14]. Our findings suggest a degradation of clinical adherence to hand hygiene amongst the participants despite receiving prior credentialing in the same year. A re-evaluation of hand hygiene education and reinforcement methods to address the key factors may instil better practice early in students’ careers.

58 Australian Medical Student Journal

A recent Cochrane review confirmed our concerns regarding the hand hygiene compliance and suggested that further research on this topic is urgently needed [17]. The World Health Organization (WHO) has global guidelines on hand hygiene for patient safety which promote a multi-modal approach of implementation, including system change, education, evaluation, and a climate of institutional safety [15]. Community behaviour, attitudes, and peer student behaviours have been identified as the most significant factors influencing hand hygiene compliance [16]. It would be worthwhile for institutions to create an environment and culture amongst students that encourages them to consider hand hygiene as a personal duty and a priority of patient care. Acquisition of bacteria from personal illnesses and external sources reinforce the need for strict hand decontamination strategies. Colonisation of student 1 with MSSA most likely represented colonisation from the nose or groin microbiome to their hands [8]. Some of the bacteria identified, such as Acinetobacter junii and Pantoea dispersa, are more commonly acquired from sources external to the hospital [8]. We observed that MSSA and pathogenic GNB, such as Serratia marcescens and Pseudomonas spp., were grown from mobile phone surfaces, sometimes in the absence of hand colonisation. The literature suggests that there is heavy cross contamination between these devices and the environment [14]. Contaminated mobile phones are a potential reservoir for the re-inoculation of hands, as they provide an optimum warm environment for bacterial proliferation and are in contact with HCWs’ hands in between hand hygiene, thus increasing the risk of HAI [18]. Decontamination of mobile phones and medical equipment was low amongst participants, with four out of eight participants never cleaning their mobile phones at all despite all of them having used their mobile phones while on the toilet. General awareness regarding mobile phone hygiene is lacking amongst medical students [19] and HCWs in general, with mobile phone cleaning rates as low as 10.5% in some healthcare settings [20].

As limiting the use of these items is impractical, the priority should be to identify effective decontamination strategies to improve infection control. Regular cleaning with either 70% isopropyl alcohol [21], microfibre cloths, [22] or UV disinfection devices has been found to reduce bacterial load on mobile phones [19]. There is a mounting need for the promotion of effective mobile phone cleaning in infection control guidelines. Limitations of our study include our small sample size and short follow-up period that precluded analysis for statistical significance. There were also insufficient data correlating clinical rotations and personal illness with time of culture. Also, no baseline microbiological data were collected prior to the students’ commencing their clinical year, thus limiting our ability to comment on acquisition at the first collection. Lastly, due to human resource shortages, samples were self-collected which could introduce significant variability of microbiological data. A definitive study would have an increased sample size and stricter sampling protocols. The aim would be to demonstrate a statistically significant increase in student colonisation with resistant organisms over time. Potentially, a control group of students of another discipline, not exposed to the hospital could be added. Conclusion This study revealed that the colonisation of medical students’ fingers, stethoscopes, and mobile phones with pathogenic bacteria occurs within the first six months of entering the hospital environment. A definitive study would allow us to better characterise the timing and pattern of bacterial contamination of new HCWs and their equipment. An analysis of infection control strategies and modifiable risk factors of transmission could have public health policy implications and be an invaluable education tool. As medical students, we should be aware of the role we have in the acquisition and transmission of pathogens to the patients we interact with, to reduce the risk of HAI.

Acknowledgement We would like to thank the medical student volunteers for their kind participation in the study, as well as the Microbiology Laboratory of Monash Medical Center for their technical assistance. Conflict of interest The authors declare that they have no competing interests. Funding No external sources of funding was used in this research study. Authors contribution IW conceived the review and DK helped in the study design. YX performed the initial literature search, coordination of the study and data collection. YX, DK and IW drafted the manuscript with review and editions from RS. All authors read and approved the final manuscript. Ethics board approval name, number, and date The study was approved as a quality assurance project by the Southern Health Human Research Ethics Committee (HERC –RES-19-0000-085Q) in March 2019. Acknowledgements We would like to thank the study participants and staff of the Monash Infectious Disease laboratory and medical department for their kind assistance, without which this research would not have been possible. Senior Editor Subhashaan Sreedharan Mabel Leow Proofreader Eleazar Leong Senior Proofreader Emily Feng-Gu

Australian Medical Student Journal 59

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60 Australian Medical Student Journal

Do medical students practice what they preach? A review of their dietary patterns over the last decade. Date of submission: 8 October 2019 Date of acceptance: 16 August 2020 Date of online publication: 20 August 2020 Sara Hussain Emergency Department, Rashid Hospital, Dubai Health Authority, Dubai, United Arab Emirates Zaynab Gerashi Intern, Dubai Health Authority, Dubai, United Arab Emirates Kosar Hussain General Medicine, Goulburn Valley Health, Shepparton, Victoria, Australia Sahar Hussain Dubai Pharmacy College, Dubai, United Arab Emirates

Khan A, Rao A, Reyes-Sacin C, Hayakawa K, Szpunar S, Riederer

Infection Control. 2019;8(1):114. doi: 10.1186/s13756-019-0570-y Abdallah W. Single-institution experience of medical students’

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Smit P, Heniger J. Antoni van Leeuwenhoek (1632-1723) and the

Abstract Background While many studies have been performed to evaluate different indicators of psychological distress among medical students, the amount of published data evaluating their dietary habits is limited. Therefore, the purpose of this scoping review was to provide an overview of medical students’ dietary behavior. This is the first review paper to summarise the information available about dietary practices among medical students. Materials and Methods A scoping review was performed in 2018 using the PRISMA-ScR framework and the MEDLINE database was searched by combining the terms ‘eat’, ‘diet’, ‘meals’, ‘nutrition’ with the word ‘medical student’ by using the ‘AND’ function. Some additional papers were also selected from the citations of relevant publications. Data was independently extracted by two authors using pretested forms. Results A total of 739 articles were found by using the search terms. Thirty-three articles fulfilled the eligibility criteria and four further articles were found from the citations of relevant publications. Medical students showed an increasing tendency to exhibit conventionally unhealthy eating patterns, both as a whole and within different dietary categories. In particular, decreased fruit and vegetable intake, overindulgence of fast food, and a tendency to skip meals. Gender discrepancies were also noted in some categories.

Conclusion Medical students, while for the most part displaying a full understanding of the nutritional science behind dietary recommendations, did not always meet the advised levels for most of the categories explored. Lapses in personal dietary choices may affect patient counselling, in addition to the many direct consequences of improper nutrition on the health and wellbeing of the student themselves.

Key learning points 1. Eating patterns in medical students are subject to many influences from external environments; stress and time constraints being one of the most commonly cited reasons for unhealthy dietary habits. 2. Unhealthy eating choices among medical students can lead to an increased risk of heart disease, obesity, fatigue, among other health risks. 3. Meal patterns are also subject to discussion as many students were found to skip meals on a regular basis, particularly breakfast.

Australian Medical Student Journal

Introduction Medical students spend countless hours learning about the human body, but in the midst of all the stress clouding the student’s life, how well do they take care of their own? Poor dietary habits are a generalized concern among students transitioning to higher education, including medical students [1-3]. Stress and time constraints were cited as some reasons for unhealthy diet [1-3], which have been found to lead to the development of many unhealthy habits and activities [4]. Over time, the poor diet becomes an ingrained habit, which becomes harder for the physician to break or overcome. The diet may affect the physician’s physical and mental health in the long term, and it may eventually overflow onto the professional aspect of a physician’s life during patient counselling [5,6]. Medical students who were more compliant with nutritional recommendations themselves are more likely to have a positive attitude when counselling patients regarding weight loss [7]. When discussing the practice of diet monitoring and healthy eating among doctors, it becomes pertinent to address the possible lapse of nutritional knowledge among some trained medical professionals. International papers advocating for nutrition-centered education of physicians have been published over the years [8,9]. Unfortunately, there appears to be a decreasing level of interest regarding the clinical aspects of nutrition among physicians and medical students in recent times [10.11]. Many Colombian fifth year medical students were unhappy about the support system in their university for advocating healthy eating habits in two different studies [17,12], and while over two thirds acknowledged the importance of physician role models for patients and the importance of preventive counseling, less than 10% believed that prevention is more important than treatment in the medical practice [12].

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A study assessing the dietary patterns of new Polish students reported that 78% considered their lifestyle to be nutritionally adequate [13]. However, a Russian study comparing many disciplines found the highest prevalence of behavioral risk factors to be among medical students. The medical group had the lowest rate of three categories: non-obese individuals, normal physical activity, and normal nutrition when compared to the other professions. They also had the highest hip/ waist ratio and Body Mass Index (BMI) values [14]. Another study found that just 15.3% of 629 students had a conventionally healthy diet, and this was statistically more likely to be among women (p=0.001) [15]. Comparing students of the medical specialty to control groups displayed no superiority of better dietary choices in the former category. Coincidentally, medical students were statistically more likely to consume fast food than their non-medical peers [2,16]. Therefore, while numerous research articles have been published that highlight the importance of nutrition-based education among medical students, this will be the first paper to address this as a possibly global concern. Educational seminars have been proposed as a strategy to improve nutritional knowledge amongst medical students and physicians, with varying results [17]. In this paper we reviewed and summarized the data available regarding the dietary practices among medical students, globally, and within the last decade. To the best of our knowledge, this will be the first review article to address this concern. Because of the inconsistency of the type of data collected, we decided a scoping review approach would be most appropriate to highlight the more important information from the relevant literature.

Material and Methods The PRISMA-ScR (PRISMA extension for Scoping Reviews) was used as a checklist for designing the review paper. A comprehensive Medline literature review was conducted in July 2018 using the appropriate search terms. In this manner, the terms “eat”, “diet”, “meals” and “nutrition” were searched to be in conjunction with the word “medical student” by using the ‘AND’ function. The found search results were then filtered according to relevance, date of publication and language. Appropriate exclusion and inclusion criteria were applied as necessary, and the remaining papers were then reviewed in detail (Figure 1).

Following a pilot test, the data was then collected and charted by two separate individuals working independently to reduce bias, after which it was cross checked to ensure reliability. The common information between papers were then grouped together for further review and discussion. For the interest of comparing nutritional factors from the collected research papers to a single recommendation, we have quoted the recommended daily allowances from the United States Department of Agriculture (USDA) guidelines [20]. Henceforth, all calculated findings will be compared to these recommendations unless otherwise specified. Results

Figure 1: Flowchart highlighting the paper selection process

The inclusion and exclusion criteria applied were as follows: all original research articles that were published between 2008 to 2018, and were related to the dietary habits of medical students were considered for inclusion in the current review. Studies were excluded if they 1) were not published in English; 2) only mentioned diet as an insufficiently explored consequence of another primary disease; or 3) where diet was inadequately analyzed for comparative purposes. We also excluded publications regarding eating disorders among medical students, as these have been explored in depth in recent review articles [18]. Studies that were only investigating the use and levels of micronutrients such as vitamins and minerals in the diet were also excluded as they were outside the scope of this review. All authors participated in the initial literature review and the short-listed papers were entered into a virtual spreadsheet [19], where it was screened twice by two different individuals to ensure reliability of the collected data.

3.1. Selection and description of included studies: While an initial 46 studies were collected from Medline through title and abstract screening, nine papers were then excluded after reading the full text publication with regards to the above-mentioned exclusion criteria. Finally, a total of 37 papers were selected for further review and comparison, of which 33 were found directly from Medline, and a further four were gathered from the references section of the relevant publications found (Figure 1). Almost all reviewed articles were conducted through anonymized questionnaires that were distributed among medical students. Due to the nature of the study question, very few papers used control groups, and even fewer were blinded, thus a high risk of bias was present (Table 1). Most publications that were assessed within the appointed inclusion criteria took limited dietary factors into account. Fruit and vegetable intake were noted to be the commonest components in the studies, followed by unhealthy snacks and fast food. Relatively fewer papers assessed other various macronutrient intake; including dietary carbohydrate, protein, fat, and fiber consumption. Each component is discussed independently below.

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64 Australian Medical Student Journal Tanaka et al. [40] 2008, Japan Rustagi et al. [41] 2011, India Nola et al. [42] 2010, Croatia

29 30 31

Brehm et al. [49] 2016, United States of America

Allam et al. [39] 2012, Saudi Arabia

Fredriksson et al. [38] 2016, Sweden

Krishnamohan et al. [48] 2017, India

Nisar et al. [37] 2009, Pakistan

Purohit et al. [36] 2015, India

Vargas et al. [47] 2018, United States of America

Ekpanyaskul et al. [35] 2013, Thailand

Cecil et al. [34] 2014, United Kingdom

Baydemir et al. [46] 2018, Turkey

Kanikowska et al. [33] 2017, Poland

Chourdakis et al. [32] 2010, Greece

Boo et al. [45] 2018, Singapore

Al-Qahtani. [31] 2016, Saudi Arabia

Fiore et al. [30] 2015, Italy

Rye et al. [43] 2012, Canada

Rehman et al. [29] 2013, Pakistan

Al-Alimi et al. [28]

Health status and lifestyle habits of us medical students: A longitudinal study.

Efficacy of Health Education using Facebook to Promote Healthy Lifestyle among Medical Students in Puducherry, India: A NonRandomized Controlled Trial.

Integrating nutrition education into the cardiovascular curriculum changes eating habits of second-year medical students

Evaluation of adherence to Mediterranean diet in medical students at Kocaeli University,

The prevalence of obesity among clinical students in a Malaysian medical school.

Comparing health behaviours of internal medicine residents and medical students: An observational study.

Differences in eating and lifestyle habits between first- and sixthyear medical students from Zagreb.

Cardiovascular risk behavior among students of a Medical College in Delhi.

Relationships between dietary habits and the prevalence of fatigue in medical students.

Nutritional and health status of medical students at a university in Northwestern Saudi Arabia

Dietary intake in Swedish medical students during 2007–2012.

Dietary habits and life style among the students of a private medical university Karachi

Prevalence of Obesity in Medical students and its correlation with cardiovascular risk factors: Emergency Alarm for Today?

Overweight/Obesity and Related Factors Among Thai Medical Students.

Behaviour and burnout in medical students.

Do medical students adhere to advice regarding a healthy lifestyle? A pilot study of BMI and some aspects of lifestyle in medical students in Poland.

Eating habits, health attitudes and obesity indices among medical students in northern Greece.

Dietary Habits of Saudi Medical Students at University of Dammam

Medical school fails to improve Mediterranean diet adherence among medical students.

Health and spirituality ‘walk along’ in wellness journey of medical students.

Prevalence of Iron Deficiency Anemia among University Students in Hodeida Province, Yemen

Risk factors of coronary heart disease among medical students in King Abdulaziz University, Jeddah, Saudi Arabia.

Hazardous Health Behaviour among Medical Students: a Study from Turkey.

Modifiable Risk Factors for Major Non-communicable Diseases Among Medical Students in Nepal.

Ibrahim et al. [27] 2014, Saudi Arabia

Eating breakfast, fruit and vegetable intake and their relation with happiness in college students.

zImpact of learning nutrition on medical students: their eating habits, knowledge and confidence in addressing dietary issues of patients.

Nacar et al. [26] 2015, Turkey

Lesani [21] 2016, Iran

Impact of an undergraduate course on medical students’ self-perceived nutrition intake and self-efficacy to improve their health behaviours and counselling practices.

Shaikh [20] 2011, India

Healthy lifestyle habits among Greek university students: differences by sex and faculty of study.

Mishra et al. [25] 2015, Nepal

Crowley [17] 2014, New Zealand

Medical students’ health behaviour and self-reported mental health status by their country of origin: a cross-sectional study.

Tirodimos [16] 2009, Greece

Dietary habits and physical activity in students from the Medical University of Silesia in Poland.

Terebessy [15] 2016, Hungary

Attitude toward preventive counseling and healthy practices among medical students at a Colombian university.

Gender Differences and Clustering of Modifiable Risk Factors of Non-communicable Diseases Among Medical Students: A Cross Sectional Study in Nepal.

Likus [13] 2013, Poland

The association between Colombian medical students’ healthy personal habits and a positive attitude toward preventive counseling: cross-sectional analyses.

Validation of a brief diet survey instrument among medical students.

Alba [12] 2015, Colombia

An Analysis of California Pharmacy and Medical Students’ Dietary and Lifestyle Practices.

Spencer et al. [22] 2005, USA

Duperly [7] 2009, Colombia

Knowledge and practice of healthy lifestyle and dietary habits in medical and non-medical students of Karachi, Pakistan.

Shakya et al. [24] 2015, Nepal

Bergeron [3] 2017, California

Title Social and psychological factors affecting eating habits among university students in a Malaysian medical school: a cross-sectional study.

Sajwani [2] 2009, Pakistan

Author Ganasegeran [1] 2012, Malaysia

Design

Longitudinal

Longitudunal, Non-randomized controlled trial

Longitudinal

Cross sectional

Longitudinal

Cross sectional

Longitudinal

Cross sectional

Longitudinal

Cross sectional

125

354

240

117

441

433

127

194

698

384

138

5441

356

270

300

562

1038

736

500

214

339

191

541

218

300

629

239

149

661

200

350

Questionaire, anthropometric measurements, blood tests

Questionaire

Questionaire, vital signs, anthropometric measurements, blood tests

Questionaire, anthropometric measurements

Questionaire, 3 day food diary, vital signs, anthropometric measurements, blood tests, number of steps walked

Questionaire

24 hour recalls

Questionaire

3 day food diary

Questionaire

Questionaire, vital signs, anthropometric measurements

Questionaire

Questionaire, blood tests

Questionaire, vital signs, anthropometric measurements, blood tests

Questionaire

24 hour recalls

Questionaire

Method Questionaire

N 132

Table 1: Summary of papers that were selected for review, respective to the inclusion and exclusion criteria

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During our literature review, many studies revealed some rather concerning statistics regarding dietary patterns among medical students, elements of which are explained in more detail below. However, some reported a healthier correlation between the two factors. For instance, most medical students from a region in India reported healthy eating habits, despite a large number not feeling confident enough to be able to counsel patients regarding the same [21]. This is reassuring to observe, as healthy eating habits in students have been linked to higher happiness levels in addition to the many other benefits elucidated above [22]. 3.2. Food intake: 3.2.1. Fruits and vegetables: Fifteen papers were found to evaluate the intake of fruits or vegetables among the student population on a regular basis [1,3,13,24-35]. According to recent recommendations, students are advised to consume five servings of fruits and vegetables in a day [23]. However, studies assessing medical students from Nepal reported inadequate intake of fruits and vegetables [24,25]. Turkish students fared slightly worse, with a third admitting to not consuming any cooked vegetables in their food, and a quarter did not include fruits or salads as part of their regular meals [26]. A large percent of Saudi medical students were found to consume either fruits or vegetables once a week or lesser (82.2% and 40.6% respectively) [27]. Medical students from Yemen had a somewhat similar result, where the majority would either infrequently or never include plants in their diet [28]. On the other hand, Malaysian medical students had a larger general consumption of produce, and seemingly preferred the intake of vegetables over fruits. According to the research, 80% of the students surveyed consumed vegetables over three times a week while around 50% ate fruits less than three times a week [1]. While looking for gender discrepancies, we found that females tend to consume fruits more regularly than their male counterparts [3,13,26,29,33], similar results were found for vegetable intake [3, 13, 26, 30-34]. For instance, female Italian medical students were more likely to have additional servings of vegetables, and this result was found to be statistically significant [30], while male Turkish students were at least twice as likely to rarely, if ever, include produce in their average meal when compared to the women [26]. A highly significant number of male Polish students admitted to never consuming fruits in between their regular meals (p<0.001) [13].

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Similarly, in a study published in 2010 in Greece, the evaluators found that the dietary practices of male medical students leaned more towards convenience and fast food, while the women were more likely to eat fruits and vegetables. The BMI calculations they performed on the same population showed a higher percentage of obese and overweight men (5.9%, 32.1%), compared to women (1.5%, 8.4%) [32]. Interestingly, a paper based in Thailand found that male students who consumed more than 400g of vegetables daily were statistically more likely to be overweight, after adjustment for confounding factors were made [35]. Contradictorily, men were found to include more plant-based food in their diet than women in one Nepalese study [24]. 3.2.2. Fast food and unhealthy snacks: Due to the time constraints in a medical student’s life, they might find prepackaged or convenience food more appealing [36]. This might explain the reported overindulgence on fast food and unhealthy snacks [3,13,26,27,29,31-33,36,37]. In fact, medical students were more likely to consume fast food than other university students [2]. On the other hand, the majority of medical students studying in Malaysia did not like eating fast food, and preferred spending meal times with family [1]. Some gender discrepancies can be found here as well, where male Italian medical students were found to have a significantly greater amount of unhealthy food than the corresponding female population [30]. Similar results were found for other studies [3,13,29,31-33,37], while contradicting findings were discovered in others [26]. Perhaps somewhat reassuringly, students were not completely disregarding the opportunities to learn more about what they eat on a regular basis. One study reported that more than two thirds of medical students used nutritional food labels when deciding what to eat [3]. While the majority of undergraduates were equally aware of the detrimental effects of unhealthy food in a second study, female students were significantly more likely to seek nutritional information of what they consume [32]. This may explain some of the abovementioned variations in dietary preferences seen between the gender groups.

3.2.3. Macronutrients: When appraising the dietary intake of macronutrients, the following studies reported normal mean values for carbohydrates [38], total fat [3,38] and protein [3,38] intake in the diet. Fiber consumption levels were under the recommended values in one or both gender subgroups in the papers [3,38,39]. For example, in a Swedish study, while the mean intake of fiber was normal among women, and significantly higher among men, neither group reached the recommended daily intake (RDI) for their gender [38]. When evaluating for more gender discrepancies in the given data, men were noticed to favor more protein [3,13,26,38,39], and women consumed more carbohydrates [3,38] than their counterparts. For example, around 10% of Turkish students either rarely or never consumed any major sources of protein, and the majority were women [26]. On the other hand, while a majority of Malaysian students preferred a balanced diet, the percentage of students relying more heavily on protein was higher than other categories [1]. Students who did not consume most animal sources of protein in their diet were statistically highly likely to be anemic (p <0.001) [28]. When assessing the consumption of carbohydrates, a large number of students in a Swedish study admitted to having a lower than recommended carbohydrate consumption in their diet, which was instead substituted for by a higher intake of alcohol and fat in that population [38]. Saudi students ingested an average of over 380 grams of carbohydrates daily [39]. The difference between genders is significant, with males ingesting a higher average amount, and both values being far higher than the 130 grams/day recommendations. Fat intake in the same population was also noted to be above recommended levels, particularly animal fat, and cholesterol [39]. Ekpanyaskul et al. reported that an imbalance of macronutrients in the diet can lead to increased BMI in both male and female medical students, particularly high fat foods among men [35]. Fried food was a popular choice among students [1,32]. In particular, more than two thirds of Saudi students consumed high fat food on a daily basis [27]. On the other hand, male Polish undergraduates were statistically more likely to not fry their food at all when compared to females (p<0.001). Both genders were also found to prefer butter for spreading, which is high in saturated fat [13].

3.3. Alcohol and Beverages: 3.3.1. Alcohol: There may be a relationship between alcohol intake and fatigue among medical students [40]. Among 239 Polish students, frequent alcohol consumption (between 5-6 times a week) was recorded to be 4%, while 13.8% abstained from its use, and the remaining falling in between [13]. A study found that among the students that admitted to drinking alcohol, the average student drank a maximum of about 6 units in one occasion during the last month and the mean number of binge drinking episodes occurred between 1 to 3 times in the given period [25]. However, on a more general basis, the average amount of alcohol consumed among Polish students was around 34 and 66 grams per week among females and males respectively [33]. On this note, males that consumed alcohol on a more regular basis had a statistically significant possibility of being overweight [33,35]. A study investigating overconsumption of alcohol amongst Scandinavian medical students found that the given population were more likely to overindulge in drinks (p= 0.006, OR 3.11, CI 1.39–6.93). Age was another factor that was plotted against the possibility of alcohol over consumption; younger students were also more likely to drink excessively than their older classmates (p=0.005, OR 0.82, CI 0.71–0.94) [15]. We found a total of eight papers that reported at least half of their studied population rarely, if ever, consumed alcohol [1,16,24,26,32,41-43]. 3.3.2. Other Drinks: When attempting to chart the types of fluids consumed among the different studied populations, we found a total of ten papers, with a particular emphasis on carbonated and sweetened drinks [2, 3,13,27-29,31,33,37,42]. A fifth of a Saudi medical student population consumed soft drinks on a daily basis, while half of them admitted to drinking it at least once a week [27]. Polish male students were significantly more likely to consume energy drinks (42.5%, p<0.01) and carbonated beverages (40%, p<0.01) daily than the women (20.6%, 19.6%) [13]. While similar findings were appreciated in some studies [33,37], contradicting results were found in others [29, 31]. In an American study based in California, the total daily energy intake from the sugar in sweetened beverages was found to be 2%, with no significant difference between the two genders [3]. Many students also reported a regular intake of caffeinated drinks [2,28,42].

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3.4. Patterns of Meal Intake: There have been several studies discussing the harmful long-term effects of unhealthy breakfast practices. The habit has been linked to developing an increased risk of adverse cardiovascular events, obesity, fatigue and other undesirable aftereffects [35,40,42,44,45]. When collecting the relevant data published assessing the regularity of meals among medical students, skipping meals happened to be a frequent finding, particularly breakfast [1,2,13,26,28,30,32,33,42,5]. Over 80% of Turkish first and third year students regularly skipped having breakfast [45]. Categorically, Turkish males were almost three times more likely to not eat regularly, and twice as likely to skip breakfast when compared to the females [26]. Males were more likely to skip meals in several other papers as well [30, 33]. Students who had an irregular pattern of breakfast intake were statistically more likely to have anemia (p <0.001) [28]. 3.5. Change in dietary habits of medical students over time: Longitudinal studies are of interest when attempting to uncover some patterns of decision making among medical students. Six papers were found to have been designed as a longitudinal study [12,17 22,47-49]. A Columbian longitudinal study found that while 74.1% of first-year medical students consumed four or more servings of fruits and vegetables a day, the fifth-year students never had more than two servings. This result was found to be highly significant (p=<0.001). The main reason cited across both groups was a general dislike of fresh produce [12]. A study evaluating the healthy eating habits of first year medical students both before and after a nutrition course found an overall significant improvement in the total score at the end of the sessions. In particular, a greater than 10% change was seen in the fruits and vegetable intake, as well as table spreads and frozen desserts. Other categories that underwent a relatively lower increase included the intake of some kinds of animal protein, and the frequency of consumption of several unhealthy snacks [47].

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Similarly, a study performed in India to assess the efficacy of social media on health education among medical students found a significant decrease in junk food intake after the course in the social media group, compared to the control group. The other results among fruit and vegetables intake generally showed improvement, but these results were non-significant [48]. A second study based in the United States found that while the HDL cholesterol intake increased significantly between the start and end of medical school, the other fat parameters did not change. When assessing the participants’ total dietary sources of energy in the same study, it was found that while the total energy consumption remained unchanged over the years, students were more heavily relying on fat in their diet rather than carbohydrate. Intake of alcohol as an energy source was also increased, however the average number of units consumed remained low [49]. While cross-sectional studies may have certain limitations when compared to the longitudinally designed ones, some points of interest were noted in several papers that correlated students in their early years with their more academically senior counterparts. For example, a greater number of older students were found to favor having lunch and supper rather than breakfast [42]. A large cross-sectional study among Thai medical schools found that male students were statistically more likely to gain a significant amount of weight during the course of their education [35]. Similar results were found in other papers [26], including a study assessing the differences between medical students and a group of residents [43]. This latter study also found other various points of interest between the two groups. Residents had a higher ratio of total cholesterol to high density lipoprotein, as well as a cumulatively lesser average intake of fruits and vegetables, grains, dietary protein, and fat containing food items [43]. Discussion While discussing the published evidence about the dietary habits among medical students, it’s prudent to address the possible implications to the medical society. As mentioned earlier, improper dietary habits can have long-standing consequences, both for the students themselves and their patients [5,6].

The findings of this review suggest that the majority of medical students consume less than the recommended portion of fruits and vegetables as part of their regular diet. We also found that students tend to rely more on convenience food and skipped meals on a regular basis. However, their alcohol and beverage consumption was much more variable. As stated earlier, these findings can in part be explained by the perceived stressors that can cloud the student’s judgement. Food of convenience may thus unfortunately not always be convenient in other regards. While more research is certainly needed to be able to draw upon a recommended approach to reinstate the importance of a well-balanced lifestyle, the current data suggests that time may be a strong motivating factor for encouraging unhealthy dietary practices [1-3]. We also found it interesting to note that gender discrepancies were apparent, with females in many papers generally displaying a lower prevalence of unhealthy eating choices [3,13,26,29-34,37], while males were found to make healthier selections in other papers [24,26]. Upon looking for variabilities across the years among medical undergraduates, while an increasing intake of fresh fruits and vegetables was seen in some papers [30,34], contrary results were found in others [7,41,45,48]. Similarly, when assessing trends for fast food or unhealthy snacks and drinks consumption, an increasing [34,41,45] and decreasing [30,42,48] pattern was observed. Regular consumption of alcohol was also another factor that became more [41] and less [12,7,42] popular over the years. However, not all the found results were statistically significant. In addition to a decrease in some sources of dietary protein intake [17,26,30,42,45], a general decrease in major carbohydrates was also observed [30, 38, 45]. Coincidentally, a relatively increased consumption of fat rich food was seen in other studies [38]. The use of caffeinated beverages was on the rise [42], along with an increased tendency to skip meals [30]. Limitations This paper was limited by the resources used, as the primary source of collecting information was Medline. The phrases that were used as search terms can be considered a limitation, if other papers have been published that did not use the words “eat”, “diet”, “meals”, “nutrition” or “medical student”. Other dietary factors were not included due to paper length limitations, for example micronutrients and water. The reviewed papers, in turn were mostly limited due to their use of questionnaires and the ensuing possibility of reporting bias.

Conclusion While unhealthy eating habits among medical students cannot be considered a universal phenomenon, it certainly does raise some concern over the health of the future generation of healthcare workers. Lifestyle changes now can affect a lifetime of patient counselling and guidance in the future. The authors recommend a more comprehensive study into the dietary choices of medical students and doctors alike. It would be interesting to see more papers that highlight the effects that diet may have towards patient counselling and how these habits evolve after graduation from medical school. Conflict of interest None to declare Funding None to declare Acknowledgement None Authors contribution Sara Hussain has drafted the content, with an extensive literature review and took the lead in writing the manuscript. Zaynab Gerashi oversaw the creation of the report, provided critical feedback, and assisted in the literature review. Sahar Hussain, Kosar Hussain oversaw the creation, as well as assisted in the production and critical revision of the report. Associate editor Domenico Nastasi Senior editor Shahzma Merani Mabel Leow Proofreader Margaret Hezkial Senior proofreader Emily Feng-Gu

Australian Medical Student Journal 69

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Australian Medical Student Journal

Experimental pharmacotherapy approaches to prevention of alcohol dependency Date of submission: 16 April 2019 Date of acceptance: 2 February 2020 Date of online publication: 10 February 2020 Chelsea Linda Smith 4th Year Medicine (of 6) James Cook University Student Chelsea is a fourth-year medical student at James Cook University who aspires to be a Medical Officer in the Australian Army. She has developed an interest in public health conditions following her experiences as an emergency department volunteer for The Townsville Hospital Foundation and from her placements at Lavarack Health Centre. Abstract Background Alcohol dependency is a major public health concern in Australia. One aspect of the medical management of alcohol dependence is the use of medication to reduce craving for alcohol, alcohol consumption, and/or relapse drinking. However, there exists no single pharmacotherapy that is universally effective amongst patients suffering from alcohol dependency. Thus, personalised approaches to medication and the development of new medication or new uses of established medication may all be necessary to develop effective treatments. Objective: To review the literature for any potentially effective experimental pharmacotherapy approaches to the prevention of alcohol dependency. Methods: Using ‘MeSH’ terms for ‘alcoholism’ and ‘drug therapy’, a literature search on Medline Ovid and PubMed was conducted for preclinical or clinical studies of the effectiveness of any medication in the reduction of alcohol craving, alcohol consumption, and/or relapse drinking. Relevant preclinical and clinical studies since 2013 were retained. Current approved medications such as disulfiram, acamprosate, and naltrexone were excluded from the review.

72 Australian Medical Student Journal

Results: 14 studies were included for review. Review of the studies identified four drugs as potential pharmacotherapies for the prevention of relapse in alcohol dependence: baclofen, nalmefene, oxytocin, and CERC-501. Findings showed that the efficacy of baclofen in maintaining abstinence from alcohol has not been demonstrated, although there is some evidence for its effectiveness in reducing cravings for alcohol. Nevertheless, clinically significant evidence was found in support of nalmefene and oxytocin’s abilities to reduce alcohol consumption in heavy drinkers. Preliminary studies on CERC-501 have found a decrease in stress-induced relapse drinking in people with alcohol dependency who were previously in remission. Conclusion: This review found evidence of the efficacy of baclofen, nalmefene, oxytocin, and CERC-501 in the prevention of alcohol dependency, targeting the reduction of alcohol craving, consumption, and relapse drinking. Further investigations using preclinical and clinical trials, including randomised controlled trials, are warranted.

Introduction Alcohol dependence (AD), also called alcohol use disorder, is a chronic relapsing disorder that is defined by the DSM-5 as the compulsive use of alcohol despite its adverse effects. It may manifest physiologically and/or behaviourally with characteristic symptoms of tolerance, withdrawal, and craving [1-5]. One in five Australians drink at levels that exceed the lifetime risk guidelines, which is more than two standard drinks per day, in turn placing them at risk of AD [6]. AD is a serious problem as excessive drinking can result in serious consequences such as alcoholic cirrhosis, chronic pancreatitis, and WernickeKorsakoff syndrome. The neurobiological mechanism associated with AD is believed to be the chemical stimulation of the mesolimbic dopamine pathway in the reward centre of the brain, the nucleus accumbens. Thus, the mesolimbic dopamine pathway is a major therapeutic target for drugs involved in the treatment of AD [2,5,7]. The medical management of AD serves as a form of tertiary prevention which aims to reduce the severity, discomfort, and disability of the disorder [8,9]. Current approved treatments in Australia, as outlined in the Therapeutic Guidelines (eTG), include disulfiram, acamprosate, and naltrexone. However, these drugs have their own adverse effects [10]. Disulfiram irreversibly inhibits aldehyde dehydrogenase which in turn blocks acetaldehyde breakdown. As a result, a person will experience unpleasant symptoms, such as flushing, sweating, nausea, and vomiting, if alcohol is consumed. These unpleasant symptoms can potentially cause serious adverse effects including dyspnoea, seizures, and arrhythmias [10,11]. Acamprosate derives its therapeutic nature from its ability to decrease the neuronal hyperexcitability experienced with alcohol use and, in turn, prolonging abstinence. This is achieved by modulating the glutamate system. Its major adverse effects include rashes, diarrhoea, and changes in libido [10,12,13]. Naltrexone reduces the pleasurable effects of alcohol by blocking endogenous opioid release. Headache, dizziness, and fatigue are common adverse effects of naltrexone administration. It is contraindicated in patients suffering from acute hepatitis and liver failure as it is metabolised by the liver [10,13,14].

Despite the efficacy of the existing pharmacotherapies, the influence of genetic and environmental factors on a patient’s phenotype renders it unlikely that a single treatment intervention will be effective for all individuals who suffer from AD. Hence, experimental pharmacotherapy approaches for the prevention of AD has become of interest in recent literature [5,15]. The focus of the review is on experimental pharmacological approaches that have made recent developmental advancements since 2013 both preclinically and clinically. Pre-existing treatments, such as disulfiram, acamprosate or naltrexone, were not deemed ‘experimental’ and, thus, were excluded from the review [10]. The aim was to assess the efficacy of experimental medications in reducing relapse drinking, craving for alcohol, and/or alcohol consumption, in turn determining their capability as a tertiary prevention strategy to improve the quality of life of patients with AD. Methods A broad literature search strategy on Medline Ovid and PubMed for studies published since 2013 was developed based on focused ‘MeSH’ terms for ‘alcoholism’ and ‘drug therapy’. The year 2013 was identified as the beginning of the preclinical and clinical studies for the most recent experimental pharmacotherapies for AD. Experimental pharmacotherapies for AD were identified and the literature pertaining to these drugs was considered for possible inclusion in the review. A narrative review approach was chosen because of the diversity of study designs existing in the literature. For the current review, the most salient findings limited to post-2013 studies were extracted.

Australian Medical Student Journal 73

74 Australian Medical Student Journal Prospective cohort study Phase II RCT

Phase II RCT

Imbert et al. (2015) Muller et al. (2015)

Ponizovsky et al. (2015) Reynaud et al. (2017)

Phase IV single-arm, open-label study Phase IV open-label, primary care study Phase III RCT

Phase III RCT

Barrio et al. (2017) Castera et al. (2018) Gual et al. (2013)

Mann et al. (2013)

Van den Brink et al. (2014)

Australian Medical Student Journal

Domi et al. (2018)

Experimental study

Peters et al. (2017)

CERC-501

Clinical pilot study

Hansson et al. (2018)

Oxytocin

Phase III RCT

Aubin et al. (2015)

CERC-501 in AD rats

OXT infusion in AD rats

AD post-mortem brains OXT infusion in AD rats

As-needed nalmefene and placebo

As-needed nalmefene and normal practice

Nalmefene only

As-needed nalmefene and placebo

High-dose baclofen (180mg/day) and placebo

Baclofen or placebo in combination with psychosocial treatment

Low-dose baclofen (30mg/day), high-dose baclofen (270mg/day) and placebo

Baclofen exposure and variation of craving

Low-dose baclofen (30mg/day), high-dose baclofen (150mg/day) and placebo

Comparing

675

604

718

378

110

667

320

192

Sample size

Neuroscience

Neurobiology

Institute of mental health

Outpatient treatment centre

Inpatient and outpatient treatment centres

Primary care

Outpatient treatment centres

Adults with AD

Specialised hospital centres

Outpatient treatment centre

Outpatient psychiatry

Outpatient addictology

Inpatient and outpatient treatment centres

Sample or healthcare focus

Sweden

Australia, Germany

Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Russia, Slovakia, Ukraine, United Kingdom

Austria, Finland, Germany, Sweden

Belgium, Czech Republic, France, Italy, Poland, Portugal, Spain

France, Germany, Spain, United Kingdom

Spain

France

Israel

Germany

France

Netherlands

Country

CERC-501 is effective in blocking stress-induced relapse drinking

OXT-induced blockade of ethanol-induced dopamine release within the nucleus accumbens is responsible for the reduction of alcohol self-administration

Upregulation of OXT receptors was found in brain tissues of alcohol-dependent rats and deceased patients with alcoholism in response to reduced OXT expression in hypothalamic nuclei

Nalmefene was more effective than placebo in reducing HDD

Nalmefene was more effective than normal practice in reducing HDD

Nalmefene was effective in reducing HDD

Nalmefene was more effective than placebo in reducing HDD

No significant difference between groups found for the maintenance of abstinence

High-dose baclofen group maintained total abstinence longer than placebo

Relationship between baclofen exposure and craving defined

No significant difference between groups found for the maintenance of abstinence

Results

Nausea, dizziness

Dizziness, nausea, fatigue

Nausea, dizziness, insomnia

Nausea, dizziness

Drowsiness, dizziness

Drowsiness, headache

Fatigue, vertigo/ dizziness

Fatigue, drowsiness, dry mouth

Adverse effects

Table 1. Characteristics of included studies.

Nalmefene

Phase II RCT

Baclofen

Figure 1. PRISMA flow diagram.

Beraha et al. (2016)

Study design

Results The following drugs were identified as being the most recent experimental pharmacotherapy approaches to prevention of AD and, hence, were given priority in the review: 1. Baclofen 2. Nalmefene 3. Oxytocin 4. CERC-501 From 3598 citations, 174 citations of potential relevance were retained and subjected to secondary searches to identify evidence relevant to the topic reviewed. After the screening of abstracts and full-text assessment for eligibility, 14 articles remained for inclusion in the review. Of the 14 articles, eight randomised controlled trials (RCT), three prospective cohort studies, two experimental studies and one clinical pilot study were found. Figure 1 presents the PRISMA flow diagram. We present the results of the four drugs. A summary of the included studies in Table 1. Table 1. Characteristics of included studies.

Baclofen Baclofen is a GABA B receptor agonist [16-18]. Since GABA B receptors are located in the same areas as the mesolimbic dopamine neurons involved in alcohol addiction, baclofen has become an attractive potential drug for the prevention of AD [16-19]. Nevertheless, the efficacy of baclofen remains controversial in the current literature with inconsistent results between studies [16,17,19,20]. Moreover, the eTG does not currently recommend baclofen for the management of AD. The eTG has requested further research prior to any reconsideration of its role [10]. Of the five studies that were reviewed, four of which were phase II RCT, the varied dosages, low number of patients and durations of treatment and follow-up between studies may explain the inconsistent findings [16-20]. In a 12-week randomised, double-blind, placebo-controlled study of 56 patients, Muller et al. [16] demonstrated promising results with more patients treated with baclofen (270 mg/ day) maintaining alcohol abstinence in contrast to those receiving placebo (15/22, 68.2 % vs. 5/21, 23.8 %; p=0.014) [16]. However, Ponizovsky et al. [20] and Reynaud et al. [17] found no evidence for the superiority of baclofen over placebo in maintaining abstinence from alcohol [17,20]. Reynaud et al. conducted an RCT on 320 patients over 20 weeks. The percentage of patients who maintained abstinence in Reynaud et al.’s study was low (baclofen (180 mg/day): 11.9 %; placebo: 10.5 %) and not statistically significant between the two groups (OR 1.20; [95 % CI: 0.58 to 2.50]; p=0.618) [18]. There exist a number of important differences between Muller et al, Ponizovsky et al and Reynaud et al.’s studies. Muller et al. administered a much higher dosage of baclofen (270 mg/ day) [16] compared to Reynaud et al. (up to 180 mg/day). Reynaud et al. elected to administer baclofen at a lower dose for safety reasons as high dose baclofen may result in severe exacerbations of its adverse effects (fatigue, drowsiness, and dizziness) leading to the inability for patients to tolerate treatment [17]. The large study group size in Reynaud et al.’s RCT compared to Muller et al.’s strengthens the reliability of Reynaud et al.’s statistically insignificant finding (p=0.618) of the effectiveness of baclofen in maintaining abstinence compared to placebo [16,17].

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Although Muller et al. achieved significant results with a higher dose of baclofen, Beraha et al. [19] found no significant difference between low-dose baclofen (30mg/day), high-dose baclofen (270mg/ day), and placebo in maintaining abstinence [19]. These divergent results may be explained by the absence of extensive psychosocial treatment in Muller et al.’s study which resulted in higher relapse rates in the placebo group (70 %) [16] compared to Beraha et al. (25 %) [19]. All patients in Beraha et al’s study received psychosocial interventions that consisted of support counselling based on cognitive behaviour therapy principles that aimed to address problems contributing to or resulting from AD [19]. This finding is supported by the high placebo response observed in Ponizovsky et al.’s study which also incorporated similar psychosocial interventions to all test groups [20]. Psychosocial intervention might help to reduce AD, thus reducing the effectiveness of baclofen in treatment of AD. Although psychosocial interventions could be effective in reducing AD, patients who lack access or the motivation for intensive psychotherapy might benefit most with baclofen management [19]. Baclofen may play a pivotal role in the prevention of AD as anti-craving drug therapy. Ponizovsky et al. and Reynaud et al. found a significant decrease in alcohol craving associated with baclofen use in the secondary outcomes [17,20]. This was similarly made evident in the prospective cohort study conducted by Imbert et al. [18]. The exact mechanism of baclofen’s effect on anti-craving is not fully understood and why baclofen’s anti-craving characteristic does not contribute to the maintenance of alcohol abstinence remains in question. The trials were conducted in various countries and in different settings. Reynaud et al.’s RCT was conducted in specialised hospital centres in France [17]. Muller et al.’s study was carried out in an outpatient unit in Berlin [16]. Ponizovsky et al.’s trial similarly took place in an outpatient unit in Israel [20].

Nalmefene Nalmefene is the first drug approved in Europe for reduction of alcohol consumption, as opposed to the maintenance of abstinence [21,22]. It is yet to be available in the United States [23] and is not recommended by the eTG in Australia [10]. For many patients suffering from AD, complete abstinence from alcohol is not deemed an achievable aim of tertiary prevention. Thus, nalmefene has the potential to revolutionise current AD management strategies [21,22]. Nalmefene is structurally similar to the widely used naltrexone in that it is an opioid receptor antagonist. Nalmefene, however, has a longer duration of action, higher bioavailability, and no dose-dependent hepatotoxicity [21-23]. Six studies had been conducted to evaluate the effectiveness of nalmefene which included four RCTs and two prospective studies. The first phase III RCT conducted by Mann et al. [24] in 2013 demonstrated a significant benefit of using nalmefene in reducing the number of heavy drinking days (HDD) (-2.3 days/month [95 % CI: -3.8 to -0.8]; p=0.0021) [24]. Subsequent studies by Gual et al. [25], van den Brink et al. [26] and Aubin et al. [21] found similar results [21,25,26]. Additionally, van den Brink et al. and Aubin et al. observed reduced γ-glutamyltransferase, alanine aminotransferase, and aspartate aminotransferase elevations with nalmefene administration, thus supporting the hypothesis that nalmefene is less hepatotoxic than naltrexone and is not contraindicated in patients with acute hepatitis or liver disease [21,26]. Following the positive outcomes of phase III clinical trials, research has since progressed to phase IV open-label studies. Phase IV trials aim to evaluate the effectiveness of nalmefene in a primary care setting. Primary care services play a pivotal role in the management of AD and contrast with the specialist settings where prior phase III trials were conducted. Castera et al. [22] and Barrio et al. [27] found nalmefene to be efficacious in decreasing HDD and a highly achievable management option in the primary care setting [22,27]. Castera studied 43 primary care sites across four countries (n=378). They found that patients in all countries showed a significant decrease in the number of HDD; the adjusted mean change in the number of HDDs at week 12 compared to the screening visit was -13.1 days/ month; [95 % CI: -14.4 to -11.9]; p<0.0001 [22].

The present studies raise the possibility that nalmefene could be used as a form of secondary prevention – to reduce alcohol consumption in people with heavy drinking prior to slipping into dependence. It should be noted that, because nalmefene is the only drug available for the reduction of heavy drinking in the treatment of AD, comparisons were made by necessity with drugs indicated for abstinence maintenance in the included studies [21,22,24-27]. Oxytocin There is growing interest in the use of oxytocin (OXT) as a novel therapeutic target for the prevention of AD following positive results in cocaine, heroin, and methamphetamine addiction [28,29]. OXT is a nanopeptide that, along with its role in prosocial and sexual behaviours, is associated with addiction. It exerts its effects through the dopamine mesolimbic pathway. An emerging body of preclinical and clinical data has suggested that OXT may have a role in reducing alcohol consumption, with the possibility of becoming an alternative to nalmefene intervention. However, the underlying mechanisms remain unknown [29]. One clinical pilot study [28] and one experimental study [29] were found. After studying male Wistar rats under the influence of ethanol, Peters et al. [29] concluded that the OXT-induced blockade of ethanol-induced dopamine release within the nucleus accumbens is responsible for the reduction of alcohol self-administration [29]. Hansson et al. [28] develops on Peters et al.’s findings from their analysis of the OXT system in alcohol-dependent rats as well as post-mortem brains of humans who suffered from AD and controls. A pronounced upregulation of OXT receptors was discovered in brain tissues of alcohol-dependent rats and deceased patients with AD in response to reduced OXT expression in hypothalamic nuclei. An impaired OXT system, therefore, may explain the effectiveness of OXT administration in attenuating voluntary alcohol consumption [28].

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Of particular note in Peters et al.’s experiment is OXT’s ability to antagonise dopamine release in both ethanol naïve and chronically ethanol-treated rats. As a result, OXT may not be limited to the management and treatment of alcoholism. Similar to nalmefene, OXT has the potential to be utilised as a secondary prevention strategy whereby patients reduce their alcohol intake and thus avoid AD [28]. CERC-501 A new drug therapy for AD that has completed its first preclinical trial in 2018 is CERC-501 (previously LY2456302). CERC-501 is an orally available kappa opioid receptor (KOR) antagonist. Accumulating evidence has revealed the crucial role KOR’s play in the stress reactivity and negative emotionality associated with alcoholism rendering CERC-501 a potential clinical candidate. The experimental study on male Wistar rat models by Domi et al. [30] concluded that CERC-501 is effective in blocking stress-induced, however not cue-induced, relapse drinking. This proves to be the opposite of the widely used mu opioid receptor antagonist naltrexone. Naltrexone selectively inhibits cue-induced alcohol relapse. Therefore, CERC-501 may be more beneficial in patients with stress-driven alcohol use making it a potentially positive addition to the existing AD drug therapies [30]. Discussion There exists no single treatment intervention that is universally effective amongst all patients suffering from AD. Thus, personalised approaches to medication, and the development of new medication or new uses of established medication, is necessary to develop effective treatments [5,15]. The present review aimed to review and summarise the current literature on the efficacy of baclofen, nalmefene, OXT, and CERC-501 as novel pharmacotherapies for the prevention of AD. The review found some evidence-based results that support the further research and inclusion of experimental pharmacotherapies for AD. Firstly, the five studies examining the effect of baclofen over placebo on the maintenance of abstinence had mixed results, with one study showing a trend that favoured baclofen [16] and four studies showing no difference [17-20].

However, three of the five studies found evidence to support the use of baclofen as an anti-craving therapy [17,18,20]. Additionally, hypotheses exist surrounding the use of baclofen as a replacement for psychosocial intervention in patients who lack the access or motivation [19]. Baclofen’s efficacy as a mainstream pharmacotherapy for AD is yet to be proven. Further phase II clinical trials evaluating baclofen’s role as an alternative to psychotherapy management in AD and as anti-craving pharmacotherapy is recommended prior to advancement to phase III trials. Evidence from six studies suggest that nalmefene is an efficacious treatment for the reduction of HDD in patients suffering from AD. These findings are strengthened by the several RCTs that were conducted, the large sample sizes included in the RCTs, and the wide range of countries where the studies took place [21,22, 24-27]. The results support the approval of nalmefene as a treatment for AD in Australia. OXT may also reduce the number of HDD following the discovery that an impaired OXT system drives alcohol self-administration., although, the number of studies is small (two) and limited to experimental trials on animals [28-29]. Several questions remain unanswered at present. Investigations into the therapeutic dose of OXT in AD, the adverse effects of OXT, and OXT’s sex-specific responses (due to the gender differences that exist in the OXT system) are necessary. The review found weak evidence to support CERC-501’s effectiveness in reducing stress-induced relapse drinking due to the existence of only one experimental study in animals [30]. Further research is required to establish CERC501’s required dose and its adverse event profile in a human population. The main observed adverse effects of baclofen and nalmefene remained comparable with the currently approved pharmacotherapies for AD, namely naltrexone. The adverse effects of baclofen include fatigue, drowsiness and dizziness [16,17,19] and those of naltrexone include nausea, dizziness and fatigue [24-26]. However, it is worthwhile noting that Beraha et al. observed the highest frequency of adverse effects in the high-dose baclofen group. Whilst it is hypothesised that high-dose baclofen is more therapeutic, particularly in the absence of psychosocial intervention, the increased safety risk associated with high-doses reinforces the prematurity of large-scale prescription of baclofen [19].

The main confound of the review is the addition of psychosocial treatment which most studies do not describe in detail and is capable of affecting medication efficacy. Another major difficulty in comparing studies is the lack of uniformity of drinking outcome measures. In addition, definitions for outcomes such as ‘HDD’ or ‘relapse’ vary between studies. Conclusion Alcohol dependency is a chronic relapsing disorder that is an important public health concern in Australia. As patients with AD express varying phenotypes, rendering no single intervention universally effective, experimental pharmacotherapy approaches are indicated for secondary and tertiary prevention strategies. Baclofen has not consistently been shown to be effective for the maintenance of alcohol abstinence, however, it may be effective as an anti-craving therapy. Research on nalmefene and OXT has found them to have efficacy in reducing heavy drinking, suggesting promise as new treatment strategies. Despite being early in the research pipeline, CERC-501 has also demonstrated promise as an effective drug for the prevention of stress-induced relapse drinking. The conclusions of this narrative review are limited by the substantial heterogeneity of study designs in the literature. Further research using experimental studies and RCTs is warranted. Acknowledgements The author wishes to acknowledge Dr Julie Mudd, Public Health Physician at Queensland Health and Senior Lecturer in Medicine at James Cook University, for information on alcohol dependency. Conflicts of Interest There are no conflicts of interest to declare.

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Funding No funding was required. Authors Contribution The narrative literature review was prepared and written entirely by the author.

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Editor Nikhil Dwivedi Senior Editor Subhashaan Sreedharan Mabel Leow

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Proofreader Tessa Lim Senior Proofreader Emily Feng-Gu 78 Australian Medical Student Journal

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The impact of COVID-19 on the mental health of medical students in Australia Date of submission: 22 May 2020 Date of acceptance: 29 May 2020 Date of online publication: 5 June 2020 Madeleine J. Cox B. Med.Sci., B. Sci(Hons), M.D. 6th year of a 7 year degree University of New South Wales Medical student and casual academic Madeleine is a final phase UNSW medical student passionate about reproductive endocrinology with publications and prizes in the field of PCOS. She is a founding member of ACUR, peer-reviewed for a number of international journals and is a current UNSW casual academic. The coronavirus disease 2019 (COVID-19) is a highly infectious disease placing a large burden on hospitals worldwide, with an overwhelming number of patients requiring hospital admissions [1]. This has placed tension on some of the most well-resourced healthcare systems such as those of the United States [2] and the United Kingdom [3]. The presence of medical students in Australia on clinical placement during this pandemic has been discussed at all levels of government, university, and hospital management. Although conversations have been started, are current recommendations and rulings being passed onto medical students effectively? In my own personal experience, miscommunication between different managerial bodies left me in periods of confusion, dejection, and ultimately fatigue. It is important that all forms of management recognise the impact ambiguity has had on medical students in Australia, in order to restore students’ mental health wellbeing and for future disease outbreaks. It is understandable that the presence of medical students in Australia on clinical placement during the pandemic has been unwelcome, since students increase the risk of hospital-outbreaks due to their frequent rotations between departments, use already low stocks of personal protective equipment (PPE), and carry associated liability issues if students were to contract the virus [4,5]. Nevertheless, the current health crisis of COVID-19 provides a phenomenal learning opportunity for students. This includes acquiring proficiencies in recognising, investigating, and managing infectious diseases in preparation for an inevitable outbreak in the future [5,6]. Personally, the most challenging part about the

pandemic, as a medical student, were the mixed messages communicated from an array of management bodies. These messages included where we were and were not permitted to be, expectations of online learning and attendance, and additional roles available for medical students. From my own experience, streams of information were sent from all levels of government, medical boards, university heads, university departments, local hospital networks, and clinical school administration. Additionally, the constant feed was beamed from all available technological sources making it increasingly more difficult to remain informed about the COVID-19 crisis. Even upon attending regulated clinical placements, last minute cancellations were not uncommon. Weeks-upon-weeks of these convoluted recommendations and regulations left me in a confused state. Prior to the COVID-19 crisis, it was wellestablished that medical students are at an increased risk of developing mental health issues due to the pressure placed on them during their degree. Mental health issues include depression, anxiety, and burning out which notably increase the risk of suicide [7,8]. To date, small studies suggest that there is an increased risk of mental health issues globally and in healthcare workers residing in China during COVID-19 [9,10]. It would be interesting to see the effect this pandemic has had specifically on medical students in Australia.

Australian Medical Student Journal

Moreover, even when clinical placement went ahead, the environment provided for the medical students was hostile and combative. Medical students are no strangers to an unwelcoming atmosphere, however, with the current situation it has been intensified. Equally disheartening, many other student healthcare placements continued ahead as we were left to the confines of self-directed online learning. This left me in periods of despair, dejection, and disappointment [11]. The chronic state of confusion and dejection, in combination with the unknowns ahead, left me exhausted. The situation I experienced was unfortunately, not unique. The COVID-19 pandemic has placed a lot of stress upon the current medical students in Australia undertaking clinical placement. Miscommunication between all levels of healthcare and administration have created unclear messages, placing a great deal of confusion, despair, and fatigue upon medical students. It is imperative that we do not ignore this issue. Now is the time to act and provide medical students with accessible mental health resources so that they can care and support the Australian community in the future.

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COVID-19: US healthcare system, one of the best in the world, under deep stress. The Economic Times [Internet]. 2020 March 30. Available from: https://economictimes.indiatimes. com/news/international/world-news/covid-19-us-healthcaresystem-one-of-the-best-in-world-under-deep-stress/articleshow/74887314.cms?from=mdr

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Cheng M. Europe’s hospitals among the best but can’t handle COVID-19 pandemic. Chattanooga Time Free Press [Internet]. 2020 April 1. Available from: https://www.timesfreepress. com/news/national/international/story/2020/apr/01/ europes-hospitals-among-best-cant-handle-pandemic/519600/

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1281. doi:10.7326/M20-1281. Ahmed H, Allah M, Elghazaly H. COVID-19 and medical education. Lancet Infect Dis. 2020. doi: 10.1016/ s1473-3099(20)30226-7. [6]

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Kemp S, Hu W, Bishop J, Forrest K, Hudson JN, Wilson I, et al. Medical student wellbeing – a consensus statement from Australia and New Zealand. BMC Med Educ. 2019;19:69.

Acknowledgements I would like to thank Dr. Mark Norden and the UNSW Rural Clinical School Albury campus for their ongoing support.

[8]

Conflict of interest Statement and Funding The Author has no funding, financial relationships or conflicts of interests to disclose.

[9]

Authors contributions Conceptualisation: MJC. Writing – Original Draft: MJC. Writing – Review & Editing: MJC

doi:10.1186/s12909-019-1505-2. Hu KS, Chibnall JT, Slavin SJ. Maladaptive perfectionism, impostorism, and cognitive distortions: threats to the mental health of pre-clinical medical students. Acad Psychiatry. 2020;43:381–5. doi:10.1007/s40596-019-01031-z. Lai J, Ma S, Wang Y, Cai Z, Hu J, Wei Ning, et al. Factors associated with mental health outcomes among health care workers exposed to coronavirus disease 2019. JAMA Netw Open. 2020;3(3):e203976. doi:10.1001/jamanetworkopen.2020.3976. [10]

Torales J, O’Higgins M, Castaldelli-Maia JM, Ventrigiol A. The outbreak of COVID-19 coronavirus and its impact on global mental health. Int J Soc Psychiatry. 2020.

Senior editor Mabel Leow Shahzma Merani Senior Proofreader Emily Feng-Gu

82 Australian Medical Student Journal

doi:10.1177/0020764020915212. [11]

Date of submission: 30 May 2020 Date of acceptance: 31 May 2020 Date of online publication: 5 June 2020 Pabasha Savindi Nanayakkara Bachelor of Medical Studies/Doctor of Medicine 1st year of a 6 year degree University of New South Wales Medical student I am a part of the Australian Medical Students Association (AMSA) Journal of Global Health and Medical Students’ Aid Project, a global health group at UNSW. I also volunteer for Phil’ at UNSW, where we aim to raise funds for the Child Life and Music Therapy Program at Sydney Children’s Hospital. Previously, I have worked as a freelance writer for Teen Inc. of Ceylon Today, an English newspaper in Sri Lanka. My interests include advocating for equity in medicine, raising awareness about issues relating to global health and writing.

Miller DG, Pierson L, Doernberg S. The role of medical students during the COVID-19 pandemic. Ann Intern Med. 2020;M20-

[5]

How COVID-19 has changed my medical experience

Komer L. COVID-19 amongst the Pandemic of Medical Student Mental Health. IJMS. 2020;8(1):56-7.

February 2020: Although I had heard of the “novel coronavirus” and the devastation it was blazing in Wuhan, thoughts of a global pandemic were far from my mind as I slowly got accustomed to life as a first-year medical student in sunny Sydney. It soon became clear, however, that my firstyear university experience would not at all be what I expected. As February progressed, the “novel coronavirus” had become “COVID-19” and was spreading rapidly around the world [1]. Shortly after the World Health Organization declared COVID-19 a global pandemic, the virus infiltrated New South Wales with the docking of the infected Ruby Princess cruise ship in Sydney [2]. By late March, my university had announced that all lectures, practical classes, and examinations would be moving online to contain the spread of the virus, with no clear dates in place for a return to campus. As an international student, this left me free to fly back home to Sri Lanka and continue online learning. However, Sri Lanka’s tough approach to tackling COVID-19 included the imposition of curfews and a nationwide lockdown starting March 20 [3]. Additionally, the Sri Lankan army had built 45 quarantine centres in the country by March 23 and all citizens arriving from abroad were to be detained in these centres for a period of 14 days [4]. Therefore, I eventually decided to remain in Sydney, unwilling to rely on the limited internet facilities likely to be available in these quarantine camps to complete my endof-term exam coming up in early April.

In Australia, COVID-19’s contagious nature meant major changes to my newly established lifestyle. I rejected the archetype of a messy university student and spent hours disinfecting every fruit, vegetable, and juice carton I bought from the supermarket before placing them in the fridge. I no longer had any physical contact with the new friends I had just started to get to know and had to opt instead to join their Zoom parties. To do my part in flattening the curve, I chose not to eat out anymore and followed Zumba tutorials online in lieu of exercising at the gym. Like my personal life, my academic life had changed tremendously. All our lectures and group classes were, by now, being delivered online either live or via recordings. The biggest change I had to get used to, however, was the switch from on-campus practical sessions to our new online practical classes. These newly designed practical classes involved watching videos of faculty professors carrying out experiments in the lab or pointing out important anatomical features on a cadaver prior to the class, followed by a live online ‘Q&A’ to clarify any questions arising from these video recordings. A major impediment of these classes is that we do not have the opportunity to practice experiments first-hand or use laboratory equipment. This makes a lot of the practical content understandably confusing for a first-year medical student like me and renders the idea of an end-of-year practical exam incredibly daunting. Even worse still is the fact that all first-year hospital placements were cancelled, although we continue to have ‘Clinical Skills Sessions’ online where we elicit histories from a tutor who takes on the persona of a patient.

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Validating my concerns, research has suggested that COVID-19 could have a detrimental impact on a medical student’s exam performance and competency as a junior doctor due to the fact that several medical schools, like mine, have cancelled or delayed hospital rotations to quash the risk of students becoming vectors for COVID-19 [5]. In spite of my worries about falling behind, it is undeniable that COVID-19 has presented us medical students with a unique learning experience. Having had the opportunity to meet with simulated patients online as part of my university’s online clinical sessions, I have gained glimpses into telemedicine. Telemedicine is referred to as a “21st century approach to medicine” as it allows patients to communicate with physicians 24/7 and provide detailed descriptions of their travel histories [6]. A key advantage of advanced telemedicine systems is their use of automated screening algorithms and local epidemiological information that are applied to standardise screening and practice techniques across healthcare providers [6]. Learning how to conduct consultations online has armed me with a modern set of skills that I am confident will be an asset in the future. By pushing medical schools to employ new and innovative teaching strategies, COVID-19 has unwittingly given me the opportunity to experience a fresh facet of medical education. Acknowledgements None Conflict of interest None Funding None Authors contributions Written by Pabasha Nanayakkara Senior editor Mabel Leow Senior Proofreader Emily Feng-Gu

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References [1]

Coronavirus Disease (COVID-19) - events as they happen [Internet]. World Health Organization. World Health Organization; 2020 [cited 2020 May 31]. Available from: https://www. who.int/emergencies/diseases/novel-coronavirus-2019/ events-as-they-happen

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Where in the world is the COVID-19 vaccine? Date of submission: 8 June 2020 Date of acceptance: 17 July 2020 Date of online publication: 1 August 2020 Clara Dahlenburg Clara is a fourth-year medical student at Bond University located on the Gold Coast, Australia. She grew up in Canberra and completed the French Baccalaureate at the Lycee Franco-Australian de Canberra despite coming from an entirely English-speaking background. Clara has a special interest in Emergency Medicine and aspires to use her bilingualism to practice overseas.

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Ahmed H, Allaf M, Elghazaly H. COVID-19 and medical education.

Key learning points 1. Vaccine development is a rigorous process spanning over many years in order to ensure maximum safety, tolerability, and efficacy. 2. The need for a vaccine to protect against SARS-CoV-2 has sparked ground-breaking research worldwide with over 100 candidate vaccines currently in progress. 3. The acceleration of the Phase I, II, and III clinical trials raises concerns for the safety of the new vaccine.

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Introduction In December 2019, an outbreak of severe viral pneumonia of unknown origin was reported in the city of Wuhan, China. A novel coronavirus Severe Acute Respiratory Syndrome–Coronavirus 2 (SARS-CoV-2) was isolated on January 7th and subsequently sequenced on January 11th 2020 [1]. By the end of January, cases were appearing outside China and it was evident that local transmission had occurred in 18 countries, sparking travel bans, whole city lockdowns, and social distancing restrictions [1]. On March 11th, the World Health Organisation (WHO) declared the coronavirus disease of 2019 (COVID-19) outbreak as a pandemic [1]. As of May 20, over 5 million cases in 187 countries have been reported with more than 325,000 deaths [2]. Development of a vaccine is crucial to provide adequate herd immunity to mitigate the spread of SARS-CoV-2, especially as there is no current effective treatment. Almost overnight, researchers were faced with the near-impossible task of developing a vaccine to protect against a poorly understood virus in the midst of a pandemic. The following article explores COVID-19, vaccine development, the global race to find a solution, and the many challenges faced by researchers during this unprecedented time.

The virus responsible for COVID-19 COVID-19 refers to the disease caused by infection from the virus SARS-CoV-2. SARS-CoV-2 is a member of the Coronaviridae family meaning “crown-like” due to the appearance of the S spike surface proteins that surrounds the single-stranded RNA virus [1]. Coronaviruses are commonly found in animals but have been previously identified in humans, and four circulating human coronaviruses are known to cause the common cold [1]. Past epidemics, SARS (caused by SARS-CoV-1) and Middle East respiratory syndrome (caused by MERS-CoV), were caused by coronavirus infections [3]. The virus, transmitted through droplet, direct, or fomite contact spread, primarily affects the respiratory system. An individual infected by SARS-CoV-2 can be asymptomatic or may experience mild symptoms including fever, sore throat, dry cough, fatigue, loss of smell, and myalgia. In severe cases, the individual may require mechanical ventilation [4]. The mortality rate has been shown to increase with age and co-morbidities. That said, cases of the disease have been reported in all age groups, further pushing the need for a vaccine that is distributable on an immense global scale [4].

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A guide to vaccine development Vaccine is derived from the Latin word vacca meaning “cow” after Edward Jenner discovered in the late 18th century that cowpox protected against smallpox. A vaccine contains antigens that stimulate the immune system against a pathogen in order to prevent the development of an infectious disease thus developing active acquired immunity by exposing the body to components or attenuated forms of infectious agent [5]. Most vaccines are combined with adjuvants in order to increase the immune response and ensure longer lasting immunity [6]. A vaccine takes on average 10 to 15 years of research and testing before it becomes readily available to the public [7]. To add to this immense investment, only 6% of vaccine candidates progress from pre-clinical studies to licensure [8]. The candidate must successfully pass through all stages of development: exploratory, pre-clinical, clinical development, regulatory review and approval, manufacturing, and quality control [9]. Initial research establishes the biological feasibility of the trial vaccine. Pre-clinical testing confirms efficacy, toxicity, and pharmacokinetic properties in animal and in vitro studies. Once the vaccine candidate has shown to be safe in animals, it progresses to clinical studies on human volunteers, in three sequential phases. The first phase (Phase I) assesses the safety of the vaccine within a small cohort of less than 100 healthy volunteers. Phase II expands testing to a larger population and once deemed safe, Phase III trials is implemented to test the vaccine candidate to thousands of subjects, of varying health status, to confirm safety and determine efficacy. The current cost of developing a new vaccine from concept to market costs between 200 and 500 million US dollars [8]. As of May 15th 2020, eight candidate vaccines against SARS-CoV2 entered into clinical evaluation and another 110 are in preclinical evaluation. Amongst the global efforts there could be just a handful that will be ultimately successful.

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The global race for a vaccine COVID-19 vaccine developers worldwide are currently attempting an unprecedented feat: the conception, production, and worldwide distribution of a vaccine against a novel virus in a matter of months. International organisations such as the WHO, the Coalition for Epidemic Preparedness Innovations (CEPI), the Gates Foundation, and the Global Alliance for Vaccines and Immunization (GAVI) are funding the most promising of the candidate vaccines [10]. As of May 15th 2020, there are eight vaccines in clinical evaluation [11]. These eight candidates cover an array of vaccine platforms: two non-replicating viral vector by CanSinoBio (Tiajin, China) and The University of Oxford (Oxford, England), three inactivated virus by Sinopharm (Shanghai, China) and Sinovac (Beijing, China), two RNA by Moderna (Massachusetts, United States) and BioNTech (Mainz, Germany), and one DNA vaccine by Inovio Pharmaceuticals (Pennsylvania, United States). Gene based vaccines using nucleic acids constitute a relatively new approach in the realm of vaccinology. This format is conveniently fast to produce, easy to modify, and safe to administer. The disadvantages however are that they are less efficient [2] and currently there are no licensed nucleic acid vaccines anywhere in the world [9]. Moderna in the United States have shown promising results with a lipid nanoparticle-encapsulated mRNA vaccine, mRNA-1273 [12]. mRNA-1273 carries the genetic code for producing a portion of the SARS-CoV-2 spike protein. When injected, the vaccine is incorporated into the host cells to produce the viral protein antigen. The host immune system recognises the antigen to be foreign and develops an immune response against it. The vaccine candidate has entered into Phase II trials and, if effective, is hoping to be licensed as soon as 2021. German company BioNTEch/Pfizer has entered Phase I/II trials with a mRNA-based vaccine similar to Moderna. The trial involves 7,600 subjects who will be given the mRNA vaccine BNT162b1 in 4 dosing regimens [12]. The US company Inovio Pharmaceuticals are currently working on the only DNA based vaccine to reach clinical trials. INO-4800 is a DNA plasmid vaccine delivered by electroporation [13]. It is more difficult for DNA to enter into cells, so subjects are given a small electrical impulse to open the cell membrane pores [14]. In April, Inovio entered into phase I and has plans to enter into phases II/ III in June [13].

Viral vector vaccines have been highly efficacious in the past few decades. Vectors use harmless genetically modified viruses to mimic SARS-CoV-2 to trigger an immune response. This method has seen recent success in the development of Ervebo, an Ebola Zaire vaccine licensed in 2019 [15]. The disadvantage of this method is that pre-existing immunity to the vector (eg. Adenovirus or Vesticular stomatitis virus) can diminish the immune response. The University of Oxford Jenner Institute were initially at the forefront of the race with their vaccine candidate ChAdOx1, a non-replicating vectored vaccine using a weakened version of a common chimpanzee adenovirus. The results from animal trials have revealed that ChAdOx1 decreased disease severity but was unable to prevent infection in six rhesus macaque monkeys [16]. The risk with delivering this vaccine would be that immunised individuals, whilst protected from the disease, are still capable of transmitting the virus to others. The vaccine candidate still progressed into Phase I trials in April which confirmed the safety and tolerability of the candidate and Phase II is currently underway [17]. CanSino Biologics in China have developed another adenovirus vector vaccine Ad5-nCoV, similar to ChAdOx1, which entered Phase II in Wuhan in April [13]. This was the first vaccine to enter the second phase of clinical trials. Inactivated virus vaccines have become increasingly popular. There is pre-existing commercial experience with this method and capacity for large scale production. Chinese company Sinovac Biotech have recently published positive results with their inactivated virus vaccine PiCoVacc in eight rhesus macaque monkeys which were protected from SARS-CoV-2 infection with no known side effects [18]. It is still uncertain if monkeys are the best animal model and if the number involved in this study was too small to produce statistically significant results. Sinovac have progressed to Phase I/II with a favourable safety and tolerability profile as well as a simple manufacturing process making this candidate the most promising in China. They have already begun manufacturing thousands of vaccines to give high risk individuals if human trials are successful [18]. Similarly, Wuhan Institute of Biological Products/ Sinopharm have been approved for Phase II trials with another chemically inactivated virus formerly known as COVID-19 vaccine. China is expected to have five candidate vaccines in clinical studies by the end of May [10].

The challenges of developing a vaccine against SARS-CoV-2 With 20,000 new cases daily and a rising death toll, the need to develop a vaccine against SARSCoV-2 has never been greater. In addition to the prevention of infection, other factors that need consideration include the safety and durability of immunity, as well as the speed, scale, and cost of manufacture of the vaccine [19]. In order to accelerate the development of the vaccine, clinical trials are no longer following a step-by-step approach but rather occurring simultaneously. Accelerating a decade-long process does not come without substantial costs and safety concerns. A major concern with the accelerated trial periods is that the vaccine could lead to a dangerous phenomenon known as antibody dependant enhancement (ADE). ADE is poorly understood but refers to a condition where antibody levels are low and unable to neutralise the virus subsequently leading to increased infectivity and virulence if infected. The vaccine in this circumstance could worsen the disease severity [20]. At present there is a lack of strong evidence supporting the role of ADE in humans, however, animal studies on cats vaccinated against feline coronavirus showed significantly poorer outcomes in those vaccinated compared to the unvaccinated cats implicating the involvement of ADE [16]. Smaller trials cohorts can omit rare complications. During a swine flu outbreak in USA in 1976 an emergency vaccine was administered to 45 million people in a 10-week period. They later discovered a rare association with the nervous system disorder, Guillain-Barre Syndrome [21]. This unfortunate event raises the importance of Phase IV studies and post-marketing surveillance which will be more important than ever if a COVID-19 vaccine is fast-tracked and widely distributed.

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A suggested strategy to accelerate the testing process of candidate vaccines is with controlled human challenge trials. This involves administering the experimental vaccine to a small number of healthy subjects then exposing them to the SARS-CoV-2 virus. Replacing Phase III testing with this trial could significantly accelerate the development process as usually scientists must wait for patients to naturally encounter the virus to check the efficacy of the vaccine [22]. This type of trial has been performed in the past for malaria, typhoid, and influenza [22]. These infectious diseases, however, have had treatments readily available if necessary whereas COVID-19 does not, thus raising a number of ethical issues if challenge trials were to proceed. Current data has found only minor genetic drift during the current SARS-CoV-2 pandemic which shows promise that a vaccine based on the current strain will still be effective on strains in 12 months [23]. There is speculation that SARSCoV-2 may not be eradicated completely in which case it could develop into a seasonal circulating virus similar to influenza [24]. Even when a vaccine is shown to be effective, a major challenge lies in meeting global production and equitable distribution. With nearly eight billion people in the world at risk of COVID-19, the necessary facilities capable of meeting the production demand do not exist. It is important to take into account that existing manufacturers cannot cease the production of other fundamental vaccines, such as measles, in order to produce the SARS-CoV-2 vaccine. Many researchers are calling for larger investment into the development and distribution of vaccines moving forward [25]. This pandemic has revealed the worldwide need for more facilities capable of developing and producing vaccines, as well as more advanced technology for health surveillance. The popular phrase “health is wealth” alludes to the inherent relationship between public health and the economy. It is estimated that this pandemic may cost the global economy up to four trillion dollars [26]. Investing in vaccine development is costly and requires global political will and vision but could ultimately prevent the devastating economic impact in the long term [27].

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Conclusion Promising research into vaccine development is being conducted worldwide. Nonetheless, the future of the COVID-19 vaccine remains filled with uncertainty. With novel platforms and international cooperation, researchers are confident that within two years, there may be a vaccine developed which can be administered to high risk individuals, such as the elderly and health care workers. Until then, we continue to rely on surge hospital capacity and public mitigation strategies. Conflict of interest None. Funding None. Acknowledgement With thanks to the team at AMSJ for their assistance in the editing of this article. Author’s contribution This article was written by Clara Dahlenburg.

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Medicine in the age of COVID-19: Considerations for the ongoing use and development of telehealth Date of submission: 16 June 2020 Date of acceptance: 16 July 2020 Date of online publication: 20 July 2020 Jaidyn Muhandiramge Bachelor of Medical Science and Doctor of Medicine Medical Student (Bachelor of Medical Science (Honours)), Monash University Jaidyn Muhandiramge is a Bachelor of Medical Science/Doctor of Medicine student at Monash University. He completed his 4th year of medical school in 2019 and is currently undertaking an Honours year in oncology at the School of Public Health and Preventive Medicine, Monash University. Hannah Matthiesson Bachelor of Medical Science and Doctor of Medicine Medical Student (Bachelor of Medical Science (Honours)), Monash University Hannah Matthiesson is a Bachelor of Medical Science/Doctor of Medicine student at Monash University. She completed her 4th year of medical school in 2019 and is currently undertaking an Honours year in obstetrics at the School of Public Health and Preventive Medicine, Monash University. Coronavirus disease 2019 (COVID-19) has been the source of mass disruptions to healthcare systems globally. The virus, however, has prompted a time of unprecedented medical innovation. Telehealth, a means of delivering healthcare via telecommunication technologies, is one medical technology that has undergone expeditious development in recent months. Of note, telehealth is not a new technology – Australia has previously utilised telehealth during national emergencies, including severe droughts and bushfires, albeit with limited uptake and therefore, limited impact [1]. Social distancing laws during the coronavirus pandemic however, have necessitated the rapid adoption of telehealth as a pragmatic solution to maintaining public health during COVID-19. Telehealth services have been crucial during the COVID-19 pandemic, enabling screening and treatment of both infected individuals and non-infected vulnerable populations. China, the initial epicentre of the virus, led the way with telehealth development. Several large telecommunication providers rapidly adapted to enable remote health consultations while health insurance providers modified policies to enable reimbursement of telehealth consultations [2,3]. In response to China’s success, many other countries have followed suit. Over 50 health systems in the United States have designed programs that enable virtual screening of high-risk patients [4].

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Scotland has similarly promoted the development of telehealth, with a £9.24 million investment to support the implementation of video consultations for general practitioners [5]. Australia has also rapidly updated its telehealth services; video consultations that were previously only accessible to individuals in remote settings are now commonplace in many outpatient clinics [3,5]. Notably, telehealth has shown promise as an effective method of healthcare delivery in prisons [6,7], during war [8], in low-income countries [9], and during pandemics [10]. There is evidence of benefits for Australian rural communities in particular, including reduced costs, improved access to healthcare for rural patients, and improved access to professional development for rural clinicians [11].There is also some evidence to suggest that telehealth may be an effective method of healthcare delivery for patients with chronic diseases including chronic obstructive pulmonary disease (COPD) [12], chronic heart failure [13] and lower back pain [14]. This may be attributed to the fact that the frequent reviews which play a core role in long-term chronic disease management can easily be substituted by videoconference consultations, particularly for patients with stable disease. There is additional evidence for efficacy in patients with mental illness, specifically in improving medication adherence and reducing symptom severity [15].

In spite of this, there is a lack of high-quality evidence surrounding the cost-effectiveness of telehealth. Trials assessing telehealth are often poor quality and typically lack solid economic analysis [12-15]. High quality trials that do provide economic analyses tend to report poor cost-effectiveness. Dixon et al. reports that whilst telehealth provided a small positive benefit for patients with depression, the cost of the intervention was high relative to the small gain in quality-adjusted life years [16]. Conversely, Clarke et al. demonstrates cost-effectiveness of an intervention targeting patients with COPD but reports that the variability of savings between intervention groups was too great to produce statistical significance [17]. The study highlights perhaps the single greatest difficulty in determining cost-effectiveness of telehealth is the fact that measured outcomes are overly reliant on variables other than telehealth technology itself. Several logistical barriers to telehealth also exist. For example, 14% of Australians lack internet access, with rural and elderly populations being disproportionately affected [18]. Concerningly, these two demographics stand to benefit the most from ongoing telehealth services. A lack of internet technology skills, particularly in older patients and clinicians, adds difficulty to navigating telehealth services [19]. Both patients and physicians have raised additional concerns regarding establishing a provider-patient relationship and the incompleteness of physical examinations [20,21]. Finally, privacy concerns are widespread, particularly in the context of the rapid adoption of systems that may not have been adequately tested [22,23]. The undeniably challenging environment of COVID-19 has called for the rapid development of telehealth. There is a paucity of high-quality evidence supporting telehealth however, with existing research rarely providing conclusive data, further large-scale clinical trials with robust economic data is necessary. Accessibility must be addressed, particularly for rural and elderly patients. Education for both medical students and clinicians is similarly vital to ensure proficiency in telehealth use amongst healthcare workers. There must also be rigorous testing of telehealth infrastructure, not only to address security concerns, but also to ensure usability of the service. Telehealth undoubtedly shows promise as an effective healthcare delivery system but will require evolution from its current form before it can establish itself in the modern medical landscape.

Conflict of interest The authors declare that they have no competing interests Funding No funding was received for the preparation and submission of this manuscript. Acknowledgement None. Author’s contribution JM and HM contributed to the conception and design of the manuscript, prepared the manuscript and contributed to manuscript editing and review. JM and HM both approved the final manuscript. Editor Onur Tanglay Senior Editor Subhashaan Sreedharan Mabel Leow Proofreader Eleazar Leong Senior Proofreader Emily Feng-Gu

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Dixon P, Hollinghurst S, Edwards L, Thomas C, Foster A,

2020;395(10231):1180-1. doi:10.1016/S0140-6736(20)30818-7

NEJMp2003539 [5]

Lawes-Wickwar S, McBain H, Mulligan K. Application and

amid the coronavirus pandemic: HealthAffairs; 2020 hblog20200315.319008/full/.] [3]

Dario AB, Moreti Cabral A, Almeida L, Ferreira ML, Refshauge K,

Smith AC, Thomas E, Snoswell CL, Haydon H, Mehrotra A,

The AMSJ accepts submissions from all medical students in Australia. What makes the AMSJ unique is that it provides the opportunity to show-case your work within the academic rigours of a peer-reviewed biomedical journal whilst sharing your ideas with thousands of students and professionals across the country. Whether your passions lie in advocacy, education or research, you can submit to the AMSJ today.

Submissions open now!

cost and cost-effectiveness of telehealth for patients suffering from chronic obstructive pulmonary disease. J Telemed Telecare. 2014;20(4):212-20. doi:10.1177/1357633X14533896 [13]

Grustam AS, Severens JL, van Nijnatten J, Koymans R, Vrijhoef HJ. Cost-effectiveness of telehealth interventions for chronic heart failure patients: a literature review. Int J Technol Assess Health Care. 2014;30(1):59-68. doi:10.1017/S0266462313000779

92 Australian Medical Student Journal

AMSJ.ORG

Staff List 2020-2021 Editorial team

Internal team

We are grateful to the following reviewers for this issue:

Editor-in-Chief Mabel Qi He Leow

Internal Director Sara Kim

Senior Editors Justin Smith (Surgery) Subhashaan Sreedharan (Psychosocial) Shahzma Merani (Preventive Medicine) Daniel Wong (Medicine)

Deputy Internal Director Sean Mangion

Associate Editors Sharon Del Vecchio Naomi Cohen Onur Tanglay David Chen Cameron Wright Victor Lai Aloysius Ng Dhruv Jhunjhnuwala Domenico Nastasi Marisse Sonido Esther Johns Mark Ranasinghe Nikhil Dwivedi Dion Paul Ross Andrew Robertson Elizabeth Kaganov Simran Dahiya

Expert Liaison Officer Sophia Jin

Dr Kate Simpson Dr Esther Johns Dr Sally Rosengren Dr Joshua Hawson Michael Cardamone Prof Theresa Jacques Dr Shian Chao Tay Dr Sarah Anderson Prof Roy Robins-Browne Dr Stefan Oehlers A/Prof Nancy Sturman Dr Lana Mitchell Lars Ellegård

Senior Proofreaders Emily Feng-Gu Rosalind O’Neill

Print and Graphic Design Officer Isabel Lee

Proofreaders Ivy Jiang Margaret Hezkial Nadiah Shariff Ke Sun Eleazar Leong Tessa Lim Annora Kumar Pabasha Nanayakkara Alistair Lau Abhishekh Srinivas Trung Tran

94 Australian Medical Student Journal

Secretary Alex Savage

Creative Officer Emanuel Cabral

Griffith University University of Wollongong Royal Prince Alfred Hospital Royal Melbourne Hospital Sydney Children’s Hospital ICU, St George Hospital Singapore General Hospital La Trobe University University of Melbourne University of Sydney University of Queensland Griffith University University of Gothemburg

External team External Director Zak Doherty (Ending October) Teresa To (From October onwards) Deputy External Director Teresa To (Ending October) Sinali Seneviratne (From October onwards) Publicity Officer Kaela Armitage

Online Publications Officer Ashly Liu Sponsorship Officer Sinali Seneviratne Social Media Officer Sarah Loria Finance Officer Cathy King

Australian Medical Student Journal 95

Australian Medical Schools 1. Australian National University 2. Bond University 3. Deakin University 4. Flinders University 5. Griffith University 6. James Cook University 7. Monash University

8. University of Adelaide 9. University of Melbourne 10. University of Newcastle 11. Unversity of New England 12. University of New South Wales 13. University of Notre Dame (Fremantle) 14. University of Notre Dame (Sydney)

15. University of Queensland 16. University of Sydney 17. University of Tasmania 18 University of Western Australia 19. University of Western Sydney 20. University of Wollongong