Journal articles on the topic 'Lancelot propre'

(…) por ce est il droiz que li contes le vos die, car autrement seroit ce uns enlacemenz de paroles se il ne devisoit la vérité et il n'esclairoit ces choses porquoi eles furent ainsi establies.Au-delà d'un enchevêtrement de paroles trompeuses, illusoires car se bornant à effleurer la surface des choses, le récit se réclame d'une ambition plus haute : dire la vérité, faire la lumière sur tous les événements racontés, en circonscrire l'origine, en déterminer la cause. Toutefois, pour échapper à cette circularité déprimante, qu'il récuse, force lui est de recourir à d'autres paroles, d'ourdir d'autres toiles, si bien qu'il se trouve entraîné, pris au piège de sa propre logique, dans un engrenage sans fin. Les diverses Suites du Merlin s'inscrivent dans un tel processus. Ces textes, volontiers prolixes, qui visent à faciliter l'insertion du corps étranger que constitue le Merlin dans le cycle du Lancelot-Graal, ont vocation à explorer les antécédents de faits déjà connus qui seront exposés plus loin, compte tenu du décalage existant entre la chronologie interne du récit et celle de la composition.

Résumé La rumeur publique joue un rôle-clé dès les plus anciens textes français : elle motive les héros à la guerre et assure la renommée du saint auprès du bon peuple. Quand les auteurs vernaculaires délaissent les chansons de geste ou de saints (genres marqués par l’oralité) au profit d’une forme narrative bientôt appelée roman (genre défini d’abord par son rapport à l’écriture), la rumeur – qui fait et défait les héros – se voit concurrencée par l’écrit, auquel est attribuée une valeur de vérité supérieure. Le roman met ainsi en abyme sa propre quête de légitimité. Le statut ambigu de la narration médiévale, au carrefour de l’oralité et de l’écriture, se reflète dans la situation ambivalente de la rumeur, clairement associée au peuple et en position d’infériorité manifeste, mais demeurant néanmoins le véritable moteur de la narration. À ce titre, la rumeur, ou plus exactement la nouvelle « qui court et vole », devient un sujet autonome qui relance le récit, dans un apparent parallèle avec à la voix du narrateur. Au début du xiiie siècle, l’opposition entre roman et chanson se double d’une séparation entre vers et prose. Le roman en vers prend ses distances avec la rumeur en adoptant des accents parodiques, mais la prose est le lieu où la rumeur est mise en cause de la manière la plus systématique. Le roman en prose élabore ainsi un système complexe où la lettre et la voix se répondent. Par exemple, le grand cycle du Lancelot-Graal se clôt avec un roman, La Mort du roi Arthur, où la vérité vient de la lettre (missives révélatrices, inscriptions funéraires), alors même que la rumeur se révèle mortifère, depuis la rumeur de la fausse mort, qui a poussé Lancelot et Guenièvre au bord du suicide, jusqu’à celle qui condamne injustement la reine du meurtre de Gaheris de Karaheu. Le roman oppose ainsi à la voix de Merlin, le prophète à l’origine de ce royaume déchu, la permanence de la lettre, seule capable d’assurer la pérennité du royaume dans la mémoire et dans les lettres. La rumeur qui traverse les premières entreprises romanesques porte avec elle la question fondamentale du roman : celle de la vérité et du statut de la fiction, dans un monde où la langue vulgaire quitte la sphère de l’oralité et cherche à s’imposer comme langue d’écriture.

Este ensaio se propõe a pensar a construção histórica do corpo feminino ao longo dos séculos. Nosso recorte se inicia em 385 a.C e lança um olhar crítico até o século XIX, margeando também alguns momentos da contemporaneidade. Tecemos uma crítica com base numa abordagem qualitativa e de caráter bibliográfico revisando escritos de importantes teóricas feministas e filósofos/as. A conclusão é que as mulheres sempre estiveram na sombra da história, mas, mesmo nas sombras faziam reluzir as suas reinvindicações. Todavia, para compreender essas reivindicações é preciso que lancemos um olhar coexistente para a relação histórico entre mulheres e homens. Ambos percursos clarificam-se mutuamente.

The thorny issue of inappropriate authorship is a well recognized problem in research (Epstein, 1993). Recent editorials and articles in the British Medical Journal (BMJ), Lancet and Journal of American Medical Association (JAMA) have raised its profile amongst our medical colleagues. The current authors feel that clinical psychologists, nurses and other mental health professionals need to be more aware of the complexities of the area. Hence this paper intends to clarify the major concerns regarding proper accreditation and gives some recommendations and guidelines.

Este artigo propõe, por meio de um exame da personagem senex na peça O Mercador de Plauto, analisar as consequências do encontro com o deus Eros/Cupido sob a perspectiva da filosofia estoica, isto é, de uma doença (insânia), cujo tratamento era dado pela filosofia, e discutir, por meio das atitudes da personagem Demifão, os malefícios do descontrolo e da falta de moderação diante da paixão erótica. Tal investigação apoia-se principalmente em textos filosóficos de Platão (Fedro e O Banquete), Aristóteles (Retórica e Ética a Nicômaco) e Cícero (De Senectute e Diálogos em Túsculo) e em textos de autores contemporâneos, como Martha C. Nussbaum (Theory of Desire) e Aude Lancelin e Marie Lemonnier (Os Filósofos e o Amor).

Brain arteriovenous malformations (bAVMs) are vascular lesions that carry significant morbidity and mortality risk upon rupture. bAVM rupture causes either intracerebral or intraventricular hemorrhage, or both. In 2014, the first results of the ARUBA trial (A Randomized Trial of Unruptured Brain Arteriovenous Malformations) were published in The Lancet , causing a paradigm shift in clinical practice and suggesting the superiority of medical treatment in terms of mortality or stroke compared with any intervention designed to obliterate the AVM. In 2020, the final results of the ARUBA trial were published. In this Viewpoint, we critically review the clinical equipoise behind the trial, highlight issues regarding external validity, and place the results of the trial in the context of other results in scientific literature of bAVMs using Bayesian inference. ARUBA is a trial of decision-making, and only proper knowledge of the nuances of its interpretation within the broader context of bAVM research can lead to proper decision-making when confronted with patients with unruptured bAVMs.

Les bibliothèques ont le privilège d’offrir des catalogues qui indiquent d’une manière structurée aux usagers les titres possédés alors que sur Internet, lieu virtuel et infini de la recherche documentaire, règne l’anarchie. L’élaboration de catalogues sur le Net est laborieuse étant donné la quantité et la mouvance des ressources. Les bibliothécaires, qui appliquent de plus en plus leur expertise dans le monde de l’information électronique, se lancent dans un nouveau concept de bibliothèque sur Internet : la webthèque, un répertoire structuré de ressources électroniques accessibles. Contrairement à la majorité des outils de recherche sur Internet, la webthèque tend à la qualité plutôt qu’à l’exhaustivité. Elle est comme un filtre retenant les ressources pertinentes sur un sujet précis ou à l’attention d’un public particulier. Chaque ressource est sélectionnée, cataloguée et diffusée selon les principes de la bibliothéconomie, au même titre qu’un document traditionnel. Quelles sont les caractéristiques propres aux ressources électroniques en ligne ? Quels sont les avantages et les inconvénients reliés à leur catalogage ? Comment les traiter selon des normes ? Et enfin, quel est l’avenir du catalogage de ce genre de documents ?

quarentena causada pelo COVID-19 tem despertado o interesse da comunidade científica de diversas formas, desde relacionadas com abordagens de combate ao vírus para assegurar o retorno da normalidade a ações, que possam ser adotadas para reduzir os danos advindos do isolamento social, destacando-se a realização regular de exercícios físicos. Assim, propõe-se abordar as repercussões da prática regular de exercícios físicos durante a quarentena motivada pelo COVID-19 para a manutenção da saúde física e mental. Foi realizada uma Revisão Integrativa da Literatura, com buscas na Biblioteca Virtual de Saúde (BVS), Scientific Electronic Library Online, Google Acadêmico e na The Lancet Psychiatry. Inicialmente foram encontrados 53 artigos e após a utilização dos critérios de inclusão e exclusão, se limitaram em oito publicações. Verificou-se, a partir dos achados, que os artigos relataram, majoritariamente, tanto benefícios físicos como mentais (62,5%; n=5). Embora a quarentena seja a principal arma no combate ao COVID-19, há várias consequências para a população caso não mantenham ou adquiram um estilo de vida mais ativo mesmo em casa, devendo haver estímulo para esta prática.

The Lancet stated in its editorial on the 9th of May 2020 that the situation in Brazil was very problematic insofar as the COVID-19 pandemic was concerned. More than a year later, Brazil already registered more than half a million deaths from complications of COVID-19, which places it in second place in the world ranking of deaths despite having the seventh-largest population in the world. Despite this utterly tragic situation, in July 2021, almost 40% of the Brazilian population approved of the federal government's role in confronting the pandemic, and the Brazilian elites have defended openly the view that the economy was more important than individuals' lives. Given this context, in this article, we reflect on the issue of plutocracy, demonstrating its platonic authoritarian foundations, in order to understand the Brazilian elites' attitude toward the pandemic, which had no proper regard or care for the most vulnerable in society. Through this philosophical inquiry we indicate the importance of education, particularly of philosophy of education, in encouraging educationists and educational systems to reflect on problematic issues and self-reflect so as to identify possible educational deficiencies and shortcomings that created the conditions for individuals' attitudes of indifference to the victims of the pandemic and the vulnerable in society.

Attaining maternal and child health goals remains a challenge to the world. There is need to collect and manage reliable information on maternal and child health for resource generation and proper allocation. This is useful for assessing progress towards the Millennium Development Goals 4 and 5. This paper aims to assess the maternal and child health status in South East Asia Region.Literature search from PubMed, Medline, Lancet, WHO and Google web pages published from 2000 to 2012 was the method adopted for review. All the related references were cited and organized by using referencing software Endnote.Out of the South East Asian countries Thailand, South Korea, Sri-Lanka and Maldives have better maternal child health indicators. South Korea, Sri-Lanka and Maldives follow Thailand in almost indicators. Bangladesh, Bhutan, India, Indonesia, Myanmar, Nepal, and East Timor have poor indicators and are at the bottom of the group.In the South East Asia, there is wide divergence in socio-economic and health status among the countries. More than one-third of maternal and child deaths of global mortality occurs in this region. Many countries in this region are unlikely to achieve the Millennium Development Goals 4 and 5 even if maternal child health is made the priority agenda of all the countries. Nepal Journal of Obstetrics and Gynaecology / Vol 7 / No. 1 / Issue 13 / Jan- June, 2012 / 5-10 DOI: http://dx.doi.org/10.3126/njog.v7i1.8825

e14036 Background: Proper assessment of harms of cancer treatment is essential to make risk-benefit trade off decisions in oncology clinic. CONSORT guidelines require the authors of RCTs to provide exact data for adverse events (AEs) grade 3 or higher (severe AEs), serious AEs (SAEs) and fatal AEs (FAEs) and avoid using general terms (such as well-tolerated) that downplay the harms. We aimed to assess the incidence and risks of severe AEs, SAEs and FAEs in such RCTs of cancer drugs that downplayed the harms. Methods: We extracted all the phase 2 and 3 RCTs of cancer drugs from the five major journals (NEJM, Lancet, Lancet Oncology, JAMA, JCO) from 2016 January to 2016 December. The abstracts/full texts of the papers were studied to assess if the harms of the experimental arm were downplayed. Use of any of the following terms while describing toxicities or AEs or safety was assumed to downplay the harms: acceptable, feasible, tolerable (or well-tolerated) , favorable, safe, manageable. Data on severe AEs, SAEs and FAEs for both the experimental and control cohorts were extracted from these RCTs and pooled using random-effects model to determine the overall incidence and risk. Results: Of 122 phase 2/3 RCTs of cancer drugs identified, 53 (43.4%) reports used terms downplaying the toxicities of the experimental arm and were included in this analysis. The overall incidence of severe AEs, SAEs and FAEs with these cancer drugs were 50.6% (95% CI: 41.5%-59.7%), 21.9% (95% CI: 16.3%-28.7%) and 1.6% (95% CI: 1.2%-2.2%) respectively. Compared with control, the risk of severe AEs and SAEs were significantly increased with the use of these cancer drugs: severe AEs (RR 1.15, 95% CI: 1.04-1.27, p = 0.005) and SAEs ( RR 1.49, 95% CI: 1.26-1.77, p < 0.001) . However, the risk of FAEs was similar across the experimental and control arms ( RR 0.89, 95% CI: 0.72-1.11, p = 0.306) Conclusions: Our analysis shows that considerable proportions of patients suffer severe AEs, SAEs and FAEs and significantly increased risk of severe AEs and SAEs in the trials that downplay the toxicities of cancer drugs. Terms that falsely downplay the toxicities of cancer drugs should be avoided in the reporting of RCTs to encourage accurate risk-benefit assessment.

Background: The objective of this study was to assess disposal patterns for “sharps” among a cohort of patients with diabetes mellitus (DM) receiving insulin therapy. Method: A convenience sample of inpatients and outpatients was surveyed about how they disposed of sharps, how often they reused lancets and needles, and what education they had received about proper disposal. Safe disposal was defined as discarding sharps into a formal sharps or sealable container; otherwise, disposal was categorized as unsafe. Results: Of 150 respondents, 56% were men and 75% were white. The mean (SD) age was 56 (15) years; duration of DM, 20 (13) years; and hemoglobin A1c, 8.1% (2.0%). Half the respondents reused a lancet two or more times, and 21% reused an insulin needle two or more times. Thirty-eight percent of respondents discarded lancets unsafely, and 33% discarded insulin needles unsafely, typically by throwing these items into household trash. Most respondents (75%) discarded insulin pens, vials, cartridges, insulin pump supplies, and continuous glucose monitor sensors into household trash. Most (64%) indicated that they had not received education on safe sharps-disposal practices, and 84% had never visited their municipal website for information on medical waste disposal. Conclusion: Approximately one-third of patients unsafely disposed of sharps. Unsafe disposal could cause millions of sharps to appear in the municipal solid waste stream, thereby posing a substantial public health hazard. Point-of-care patient education is important, but a broader public health campaign may be required.

Using intravenous tissue plasminogen activator (IV tPA), improved functional outcomes are seen with earlier initiation of treatment. Recent studies have shown endovascular revascularization to be a revolutionary and effective treatment. There have been many initiatives focused on improving public education and awareness of stroke symptoms. The concept of a mobile stroke unit (MSU) was created as a way of bringing treatment to patients. Earlier CT scans, delivery of tPA, proper triage and on-scene goal-directed care were the primary goals with these units. It was thought that rapid implementation would shorten hospital stay and improve outcomes. The University of Saarland found a decrease of 41 minutes from stroke alarm to therapeutic decision when an MSU was used. A second trial found a decrease of 25 minutes in time to treatment, an increase in the rate of thrombolysis utilization, and no change in the rates of intracranial hemorrhage or 7-day mortality when an MSU was employed. In 2016, a Lancet article showed that 3 month modified Rankin Scale (mRS) and 3-month mortality were improved in MSU patients. Finally, starting thrombolytic therapy in the MSU was associated with higher probability of mRS of 0-3 but not an improved 3-month survival rate. Long-term results are thus far not available precluding an effective cost-benefit analysis. Many study results are not generalizable as they compare a single hospital system and specialized MSU team to conventional care delivered by a multiple healthcare systems. Future studies will target these limitations.

BackgroundNeedle phobia, clinically termed as Belonephobia strongly influences psychological behaviors. Physiological responses include palpitations, shortness of breath, nervousness and fainting. In Nepal, first year MBBS students prick their own finger for hematology practical. They use to suffer from Belonephobia and pain due to finger prick. The main objective of this study was to determine influential fear factors and assessment of pain during hematology practical.Material and Methods:One hundred and forty two first year medical students of basic sciences participated in the study. Standard pricking was performed by blood lancet in the middle and side of the middle finger during hematology practical for the assessment of pain in Young Baker scale and visually rating scale. They also responded to a questionnaire on factors associated with fear of needles and lancets, symptoms etc.Results:Out of 142 students, numbers of males were 76 and females were 66. Belonephobia persisted among 65.2% females and 42.1% males, p<0.01. Watching others during lancing or receiving injection was a significant fear factor. Lateral side pricking was preferred by students for less pain. Mild, moderate, “hurts little bit”, “little more”, “even more” were the maximum response for pain sensation.Conclusion:Positive approaches like separation of lancing area, systematic exposure, behavioral therapy, counseling and administration of anti-anxiety drugs for severely needle phobics, can alleviate fear and anxiety. Female students need more assistance. Development of proper strategies and necessary interventions are required, which will facilitate to overcome this phobia.DOI: http://dx.doi.org/10.3126/nje.v4i5.12024 Nepal Journal of Epidemiology 2014; 4(5):433-40

Global surgery is a rapidly developing multidisciplinary field, aiming to provide equitable and improved surgical care across international health systems often with a focus on underserved populations of low- and middle-income countries1. History is witness that Christian Missionaries, International Committee of the Red Cross, Aga Khan Foundation and Islamic Association of North America have been offering humanitarian health support, including Surgery, to the needy since long. These were joined by League of Nations Health Organization (since 1920; later became the World Health Organization in 1946) and Médecins Sans Frontières (since 1971)2. However, Surgery remained ‘The neglected stepchild of global health’3. Main reason for this was lack of data leading to knowledge gap about the magnitude of the problem. The much needed catalyst for development of Global Surgery was the launch of Lancet Commission on Global Surgery report in January 20144. This report provided the much needed data about unmet needs of Surgery which grabbed the World’s attention: 5 billion people not having access to safe, timely affordable surgery and anaesthesia; leading to 18.6 million preventable early deaths each year - more than the number of people who die from HIV/AIDS, malaria and tuberculosis combined; millions of patients facing catastrophic expenditures when faced with surgical costs and many low- and middle-income countries likely to lose up to 2% of GDP due to loss of proper surgical care leading to loss of productivity. They also predicted that to reach the necessary levels of access to surgery by 2030 would require an investment of $420 billion, which would save an estimated $12 trillion in lost GDP over the same period, making it a very sound investment. And global burden of surgical disease was estimated to be ~ 30%5.

For many years, concern about nutrition during pregnancy was closely linked to the well-being of the fetus, mother and prevention of perinatal mortality. In 2010, the number of newborn deaths up to 4 weeks of life was four million worldwide, with an unequal distribution among developed and developing countries (GLASSMAN ET AL. 2010). Mortality in the neonatal period, which comprises the period between birth and 28 days of life of the newborn, is one of the best markers of the quality of care for pregnant women in the neonatal period. Congenital malformations, prematurity, low birth weight, cancer and maternal complications related to childbirth appear in the neonatal mortality list. Although these causes are multifactorial in nature, all have in their genesis some potentially modifiable risk factor associated with maternal nutrition. More recently, the concern with nutrition in pregnancy has gained an added chapter, which is the prevention of chronic diseases in the future of children (MATS, 2011). Between 2008 and 2013, epidemiologists met to compile the Lancet Series. The goal was to study the 178 million malnourished children under 5 years of age. Early in the studies, epidemiologists identified that 32 million malnourished children were born with intrauterine growth restriction. The number, besides being significant, brought concern about what the future of these children would look like in terms of growth, neuropsychomotor development, chronic diseases and the impact on human capital. Throughout the studies, it has been proven that the impact of malnutrition during pregnancy has an intimate correlation not only adverse events in the peripartum period, but with chronic degenerative diseases such as diabetes mellitus, systemic arterial hypertension, obesity and even cancer ( The next stage of epidemiologists was to identify a possible intervention window, where risk factors could be identified and corrected, in order to reverse the chronic damage that malnutrition irreversibly establishes in the physical and cognitive health of the child (MARCINIAK, 2017) This intervention period, known as the golden period, was given the name 1000 days. The 1000 days, also known as the Golden Interval, is the period that runs from the first day of pregnancy to the two years of age. More recently, studies have spoken in 1100 days, extending this intervention window to 100 days before conception. The 1000 days not only include nutritional strategies, but these are certainly the ones with the greatest impact on long-term disease prevention. What the Lancet series advocate is that proper nutrition during pregnancy and during the first two years of life can not only impact the individual, but an entire society. GLASSMAN et al. (2010) published a projection that if nothing is done regarding the reduction of chronic degenerative diseases in Brazil, in 20 to 30 years public health spending will double. The Lancet series on malnutrition during pregnancy and childhood can prove that the improvement in the health of pregnant women and newborns brings social and economic benefits, which could change the course of society's rampant evolution to chronic degenerative disease. Therefore, it is a great opportunity for the individual and society and a great responsibility for health teams to establish adequate nutrition in the thousand days. Given the great importance that nutrition in pregnancy has in determining a healthy childhood and adult life, it is to be expected that this is a subject of fundamental importance in prenatal care. However, a study conducted in the state of Rio de Janeiro found failures in nutritional follow-up throughout prenatal care, reflecting the little importance given to nutrition during pregnancy. In this study, 90.7% of the pregnant women's portfolios had no record on the BMI graph per week of gestation. Pre-gestational weight and height measured were recorded in 65.9% and 57.7% of prenatal cards , respectively (NIQUINI, 2012). These are incompatible data with the objective of reversing causes of prenatal mortality as well as reversing chronic degenerative disease. It is of great importance to reverse the current situation in Brazil, which has an expressive number of maternal malnutrition, anemia, vitamin A and micronutrient deficiency, hypertensive syndromes and gestational diabetes. The first step to reverse the morbidity and mortality of mother and baby, as well as to decrease the illness of the population is to give adequate preconception care. This chapter aims to address these prenatal nutritional care, as well as each nutritional aspect associated with the prevention of chronic degenerative disease.

BACKGROUND & OBJECTIVE: The recent global health threat is the outbreak of a viral infectious disease caused by SARS-COV2 (Severe acute respiratory syndrome-corona virus). The origin of this outbreak is from the animal market in Wuhan, China. So, it is considered as zoonotic in origin as its mode of transmission is from animals to human. This outbreak is similar to previous outbreaks of coronavirus like SARS-COV (Severe Acute Respiratory syndrome) and MERS-COV (Middle East Respiratory Syndrome). Until now different pharmacological drugs have been used to mitigate the symptoms of the COVID-19 throughout the world. There is no specific medication prescribed as the treatment of this disease. However, pharmacological drugs and immune boosting dietary therapies have been proved effective in treatment strategies. METHODOLOGY: The latest epidemiological articles, research articles, review articles, WHO guidelines and news proceedings are selected in this review. Articles were searched under the keyword search of COVID-19, drugs for COVID-19, latest COVID-19 research, surveys for covid-19. PubMed, Lancet, Elsevier, BMJ and CDC were used to accumulate the latest findings. RESULTS: There is no vaccine or other proper treatment available for this infectious disease but the symptomatic treatment is usually given to the infected person as the use of certain pharmacological as well as traditional drugs are given to reduce the symptoms associated with this disease. Furthermore, COVID-19 serious patients on ventilator are treated with the plasma therapy as with the antibiotics from the plasma of recovered patients is also in use to reduce mortality rate. CONCLUSION: To prevent this infectious disease it is important to avoid the person-to-person transmission which is mainly via coughing, sneezing, droplets of the respiration, direct contact with the infected person. So, the social distancing and self-quarantine is preferred to avoid the spread of this infectious disease. The drugs which are commonly used to reduce or eliminate the symptoms of COVID-19 are Paracetamol, Aspirin/Loprin, Dabigatran, Azithromycin, Famotidine, Ipratopium bromide, Dexamethasone,Tocilizumab, and Moxifloxacin. These drugs have been practiced by the practitioners to treat the symptoms of covid-19. However no pertinent drug has been approved as a cure of covid-19.

Depuis leur apparition dans les années 1930, les comic books américains se présentent comme des œuvres collectives sur lesquelles travaillent à relais un nombre variable d’intervenants : le scénariste, le dessinateur, l’encreur, le coloriste, le lettreur et l’éditeur, principalement. Imposée par le rythme de publication (généralement mensuel) de ces imprimés fasciculaires, la création en équipe devient alors un gage de productivité. Ayant prouvé son efficacité, cette méthode de travail est aussi adoptée par la majorité des producteurs québécois qui se lancent dans l’édition de comic books à partir des années 1980. Or, dans ces cas, la collaboration dépasse parfois le partage du travail entre les créateurs à l’emploi d’une même maison d’édition. En effet, le péritexte des œuvres et la correspondance des éditeurs indiquent qu’un esprit de collégialité unit les producteurs rivaux, qui échangent idées et conseils au sujet de leurs séries respectives. Ce faisant, ils contribuent indirectement au contenu des comics publiés par leurs compétiteurs. Cela dit, on peut s’interroger quant aux motifs donnant lieu à cette entraide. De l’amitié entre collègues à l’opportunisme commercial, quels sont les enjeux propres au champ des comics québécois que révèle cette apparente fraternité ? Quelles sont les conditions favorisant les échanges de services entre éditeurs, scénaristes et illustrateurs ? Bref, comment s’explique la collaboration entre producteurs concurrents évoluant au sein d’un même marché? Cet article répondra à ces questions afin de mieux éclairer la dimension sociale liée à la production de comic books sériels au Québec et au Canada. Il révèlera que la collaboration entre agents évoluant dans le champ des comics québécois (et parfois dans les champs canadien-anglais et américain) vise à consolider la place occupée par les éditeurs indépendants dans le milieu restreint qu’ils tentent d’investir. La fraternité qui les réunit est bienvenue et nécessaire dans la mesure où elle encourage des relations d’ordre transactionnel plutôt que conflictuel, transformant des concurrents potentiels en instances publicitaires ou légitimantes, voire en partenaires créatifs. Une alliance se crée, de telle sorte que tous tirent profit d’une collégialité faisant office de défense contre la domination du marché par les géants de l’édition de comic books. Cela dit, on peut s’interroger quant aux motifs donnant lieu à cette entraide. De l’amitié entre collègues à l’opportunisme commercial, quels sont les enjeux propres au champ des comics québécois que révèle cette apparente fraternité? Quelles sont les conditions favorisant les échanges de services entre éditeurs, scénaristes et illustrateurs? Bref, comment s’explique la collaboration entre producteurs concurrents évoluant au sein d’un même marché? Cet article répondra à ces questions afin de mieux éclairer la dimension sociale liée à la production de comic books sériels au Québec et au Canada. Il révèlera que la collaboration entre agents évoluant dans le champ des comics québécois (et parfois dans les champs canadien-anglais et américain) vise à consolider la place occupée par les éditeurs indépendants dans le milieu restreint qu’ils tentent d’investir. La fraternité qui les réunit est bienvenue et nécessaire dans la mesure où elle encourage des relations d’ordre transactionnel, plutôt que conflictuel, transformant des concurrents potentiels en instances publicitaires ou légitimantes, voire en partenaires créatifs. Une alliance se crée, de telle sorte que tous tirent profit d’une collégialité faisant office de défense contre la domination du marché par les géants de l’édition de comic books.

7565 Background: Standard first-line chemotherapy for elderly NSCLC pts has been considered as a monotherapy with vinorelbine or gemcitabine globally. However, we have demonstrated the high efficacy of CP for elderly pts in our previous trial (Ann Oncol 2010). Meanwhile, D has been considered as an alternative option for this population in Japan according to the result of WJTOG9904 (JCO 2006). Thus we compared the two regimens to select the proper candidate for future phase III trial. Methods: Eligible pts were aged 70 years or older with newly diagnosed stage IIIB/IV NSCLC; ECOG performance status 0-1; adequate organ function; written informed consent. Pts were randomized to receive carboplatin (AUC 6) on day 1 and paclitaxel (70mg/m2 on day 1, 8, and 15) every 4 weeks or D (60mg/m2 on day 1) every 3 weeks. The primary endpoint was overall response rate (ORR), and secondary endpoints were progression-free survival (PFS), overall survival, and toxicity profile. Assuming that ORR of 40% would be potential usefulness while ORR of 20% would be the lower limit of interest, 40 pts in each arm were required if expect 10% loss to follow up. Results: Between July 2006 and September 2010, 84 pts were enrolled and 41 pts in CP arm and 42 pts in D arm were eligible (median age, 76 years; 75% male; 72% stage IV). Median treatment cycle was 4 in each arm (CP, range 1-6; D, range 1-8). ORRs were 51% (95%CI: 36-66%) and 26% (95%CI: 12-39%) in the CP and D arm, respectively. With a median follow-up of 18.4 months, median PFS were 6.5 and 3.9 months in the CP and D arm, respectively (Logrank, P=0.0027). Grade 3 or severer toxicities were as follows: neutropenia (CP, 56% and D, 79%), anemia (CP, 15% and D, 7%), thrombocytopenia (CP, 10% and D, 0%), infection (CP, 20% and D, 25%). One treatment-related death due to neutropenia, pneumonia, and lethal arrhythmia occurred in D arm but none in CP arm. Conclusions: The platinum doublet CP achieved higher activity with an acceptable toxicity profile for elderly pts with advanced NSCLC compared to monotherapy with D. The superiority of CP to the monotherapy in this trial is consistent with results of recent IFCT-0501 trial (Lancet 2011).

Abstract Thalassemia is a group of complex haemoglobin disorders common in the Mediterranean countries, the Middle East and South East Asia1. Thalassemia is common in the United Arab Emirates (UAE) affecting indigenous population and the expatriates. The exact prevalence of thalassemia is not known. The management of thalassemia has improved significantly due to improvement in transfusion support and the management it's complications. This has led to the improvement of the overall survival and most patients reaching their adulthood2. Despite this some die at young age mainly due to poor access to health care2, proper management and lack of compliance to chelation therapy which leads to the development of otherwise preventable complications2. Blood transfusion is the corner stone of the management of patient with thalassemia major and intermediate3. Blood transfusion improves the anemia and its symptoms but also suppress the resultant ineffective erythropoiesis. This is usually started once the patient has signs and symptoms of anemia and unable to compensate for the low haemoglobin3. The aim of blood transfusion is to maintain good quality of life and to prevent the skeletal abnormalities2. Although blood transfusion is essential in the management of patients with thalassemia, it will ultimately lead to iron overload. In addition there is excess of gastrointestinal iron absorption in these patients, secondary to the ineffective erythropoiesis4. To reduce the iron absorption the target is to maintain the pre-transfusion hemoglobin level between 9 and 10 g/dl. Iron overload is major cause of mortality and morbidity in patient's thalassemia major and intermedia5. In this retrospective analysis we reviewed the ferritin levels over 1 year in 25 patients with thalassemia major or intermedia attending the adult hematology department at Tawam hospital The patients received regular blood transfusion once every three weeks. Of the 25 patients 16 were males and 9 were females. The age range was 15 years to 47 years. Nineteen patients had their chelation therapy changed during the year from Exjade (Deferasirox tablets for oral suspension) to Jadenu (Deferasirox tablets) which improved our patient's compliance. The remaining 6 patients continued on Exjade. In addition to this 17 patients received additional Desferral infusion in connection with their blood transfusion. None of the patient was on subcutaneous desferral infusion. During our observation two patients were lost to follow up and one patient died. The medium ferritin level for our evaluable patients was at start of the review 2488 mcg/l, with a range between 609 mcg/l to 5147 mcg/l. The medium ferritin level at the end was 1691 mcg/l with a range between 470 mcg/l to 3731 mcg/l. Figure 1 one shows the ferritin value a start and end of the review for each patient. Our patients with the highest ferritin levels are despite repeated counselling not compliant with their medications. Despite significant improvement in the management of thalassemia patients, iron overload remain a challenge. The main problems to achieving full control over the iron overload are lack of compliance. Hopefully the newest oral formulation will increase the compliance and at least we have seen a decrease in the ferritin levels over the last year in most patients. References. 1 De Dreuzy E, Bhukhai K, Leboulch P, Payen E Current and future alternative therapies for Beta Thalassemia major. Biomedical Journal 39, 124-38 2 Modell, B., Khan, M., and Darlison, M. Survival in beta thalassaemia major in the UK: Data from the UK Thalassaemia Register. Lancet 355 [2000]: 2051-2052. 3 Rebulla P, Modell B. Transfusion requirements and effects in patients with thalassaemia major. Cooleycare Programme. Lancet 1991;337:277-80 4 Gardenghi S, Marongiu MF, Ramos P, et al. - Ineffective erythropoiesis in beta- thalassemia is characterized by increased iron absorption mediated by down- regulation of hepcidin and up-regulation of ferroportin. Blood 2007; 109:5027-35 5 Porter, J.B., and Davis, B.A. Monitoring chelation therapy to achieve optimal outcome in the treatment of thalassaemia. Best Practice & Research: Clinical Haematology 15 [2002]: 329-368 6 Ayidinok Y, Kattamis A, Cappellini MD, et al. Deferasirox- Deferoxamine combination therapy reduces cardiac iron with rapid liver iron removal after 24 months in patients with severe transfusional iron overload (abstract). Haematologica 2014;99:229. Disclosures No relevant conflicts of interest to declare.

Peu après l’accouchement de son cinquième enfant ma soeur a consulté son gynécologue. Elle sentait une masse dans son sein et était inquiète. Il l’a rassuré. Elle l’a cru. On était en Espagne, dans les années 80. Ma soeur était avocate et mère de famille. Une femme très occupée. Elle a fait confiance à son docteur. C’était un mauvais docteur. 15 ans plus tard elle mourrait de cachexie cancéreuse après d’innombrables radiothérapies, chimiothérapies, examens diagnostiques et complications en tout genre, entourée de ses enfants et dans la souffrance.Quand on est médecin praticien soi-même et qu’on travaille avec ce souvenir on est très sensibilisé et on cherche par tous les moyens d’éviter à ses propres patients de vivre un calvaire aussi affreux. J’étais très organisé dans ma pratique professionnelle. Nous apprenions aux femmes l’autopalpation, nous avions un échéancier pour les prévenir de faire leur mammographie de dépistage et nous étions satisfaits de trouver de temps en temps un cancer peu évolué, gardant l’impression d’avoir sauvé un patiente qui nous le rendait bien.La Belgique n’a pas de système de santé organisé et le dépistage se faisait et se fait encore de façon pittoresque et épisodique. L’état ou les hôpitaux ou quelques médecins de famille organisés lancent des campagnes qui sensibilisent toujours les mêmes femmes et en « sauvent » quelques-unes, fiers d’avoir mis en place un système de médecine dit préventive.Ce système ne prévient rien du tout et le taux de mortalité par cancer du sein n’a pas changé pendant toutes ses années. On recrute plus tôt, allongeant la période de conscience de la présence du mal. Les cancers fulgurants tuent toujours aussi vite et nous laissent démunis.Dans son article “Principios Éticos y Prevención Cuaternaria: ¿es posible no proteger el ejercicio del principio de autonomía?” le confrère Pizzanelli fait état d’un projet de dépistage systématique dont son pays, l’Uruguay, envisage de se doter, avec une contrainte d’obligation et de risque de perdre l’emploi pour les femmes qui le refuserait.Au moment où dans le monde entier, des voix s’élèvent contre le dépistage de masse, ou les médecins généralistes tentent de s’organiser pour identifier et accompagner les femmes porteuses de risque, des politiques, certainement emportés par leur désir de bien faire et probablement seulement de faire, proposent de mettre en place un système coercitif et obsolète. Cette attitude est politiquement risquée, éthiquement injustifiable et scientifiquement dépassée.Politiquement risquée parce qu’elle va engager des sommes importantes du budget de la santé dans une suffusion administrative (prévenir, en santé publique, c’est d’abord organiser) et dans des investissements majeurs pour du matériel couteux. En même temps s’installera un climat de contrôle et de suspicion qui ne peut que nuire à la convivialité d’une société.Ethiquement injustifiée parce que la maladie et la mort sont de l’ordre de l’intime et du symbolique et que la décision d’examiner un corps pour le savoir ou non malade n’appartient qu’à la personne elle-même et non à la société. Contrôler le corps est une main mise inacceptable sur le devenir humain et revient à assimiler la maladie à une tache ou une faute que le corps social s’autorise à châtier.Scientifiquement obsolète parce qu’on sait maintenant que le soi-disant dépistage ne met à jour que des cancers lents, qui n’auraient probablement pas tué la personne et qui rate les cancers rapides qui eux sont de toute façon mortels. Cette attitude repose sur une croyance d’après-guerre et son vocabulaire militaire. Combattre le cancer et croire qu’en arrivant plus tôt on pouvait le vaincre a été le leitmotiv de toutes les campagnes de masse depuis lors.On sait maintenant que les humains vivent avec le cancer, qu’ils arrivent parfois à s’en défendre et qu’ils ne meurent pas tous. On sait aussi que certaines femmes sont plus à risque que d’autres et qu’une écoute attentive et un relevé minutieux de leur histoire familiale permet de dégager des groupes à risque qu’il est bon de conseiller. Mais investir dans la communication n’a pas la même visibilité ni le même rendement qu’investir dans la technologie et il faudra beaucoup de courage aux politiques pour décider d’investir dans un système de première ligne performant et bien géré qui permettra de mettre la connaissance des grands nombres au sein des consultations individuelles des acteurs de soins primaires.Le Dr Pizzanelli est un collègue courageux. Il dit tout haut ce que beaucoup pensent tout bas et il doit être soutenu, pas ses pairs d’abord dans son pays, et par tous les collègues du monde qui pensent que la science c’est aussi cultiver le doute et se méfier de ses propres erreurs.

The COVID-19 pandemic has caused a lot of challenges to the globalized world. Globally, it has decimated over six million lives. Since 2019, it has shook the world in many respects, especially, it disrupted economies and societies and halted the majority of human endeavor. Commentaries and reports from the World Health Organization (WHO) and the media showed an alarming situation that could be damning in low and middle income countries. Economic pundits and global public health experts also anticipated doom and gloom for African countries. However, in terms of mortality, the Americas, Europe and Asia have suffered more losses. Irrespective of these loses in Europe, Africa’s case needs better appreciation within our contemporary historical discourse. The burgeoning challenge of the COVID disease and mortalities arising thereby, among other things, necessitated the introduction of policies based on the WHO’s historical understanding of how the world has dealt with pandemics in the past. Some of the strategies that were deployed to fight the pandemic included hand washing under running water with soap, the use of alcohol based hand sanitizers, the wearing of nose masks, social distancing, self-isolation as well as partial and complete lockdowns of states and communities. The major economic disruption really came about as a result of many lockdown policies that were implemented by several countries in Africa without proper reference to their own societal contexts. These issues notwithstanding, it is important to emphasize that the extent of the impact on different communities differed to a large extent, even though there were similar levels of the nature of the infection and the general economic outlook among the global community. This current contribution on the COVID-19 discourse used political economy and economic shock as bases to highlight the extent of the impact of the disease by highlighting examples from respective countries in Africa, namely, Ghana, Cameroon, Ethiopia, Algeria and South Africa. In particular, the impact of policies like lock-down on some of these African countries are highlighted for further discussions in future empirical research. The study relied on contemporary historical evidence from multidisciplinary sources on health, economics, policy, and other related studies on epidemiology, public health, health education and promotion, reports and sources from the World Health Organization (WHO). Specifically, the authors have used published research in Lancet, the International Journal of Infectious Diseases, BMJ Global Health, Frontiers in Public Health and the Pan African Medical Journal. The others were African Development Review, Transportation Research Interdisciplinary Perspectives, Africa Spectrum and International Journal of Financial Research including several other empirical researches. In attempting a social and economic interpretation based on contemporary historical sense, the findings of this present study suggest that African political actors or leaders should make persistent or steady efforts to strengthen the economies of their states to lessen economic shocks and social costs that come about as a result of pandemics such as the COVID-19. It also identified the fact that within the globalized space, application of policies from other countries including international organizations should not be devoid of context.

The estimated population of congestive heart failure (CHF) patients in Pakistan is 28 millions.1 Besides epidemics of type 2 diabetes mellitus and coronary heart disease, South Asian countries are also be at an increased risk of heart failure at earlier ages than other racial/ethnic groups.2 Heart failure sub classified into three categories: With preserved ejection fraction (LVEF>50%), Mid-range ejection fraction (LVEF41-49%), Reduced ejection fraction (LVEF<40%).3 According to studies in United States of American (USA) and United Kingdom (UK)4,5 heart failure with reduced ejection fraction (HFrEF) prevalence has increased due to ageing population, improved survival from myocardial infarction and high prevalence of co-morbid conditions like diabetes and obesity. With increasing number of young patients (<40 years) with acute myocardial infarction (AMI) 12%6 in our population, prevalence of heart failure with predisposing factors need to be explored. Other than diagnosing and work up of these patients, the most challenging part is the pharmacological treatment by therapeutic agents proven to reduce morbidity and mortality in HRrEF. Registries have shown under-usage of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitor (ARNI), Beta-blockers and mineralocorticoid receptor antagonists (MRA) in such patients.7 Reason of not acheving the outcomes were due to not attaining the target levels of drugs dosages.8 With recommendations from new guidelines new novel drug therapies i.e. sodium-glucose cotransporter-2 (SGLT2) inhibitors, most debatable questions from the physicians are keeping in view the hemodynamic status and kidney function. Questions coming to the Physicians minds include;9 Should all guideline directed medical therapies be started together or stage wise? Which drugs should be titrated first? How quick can one up-titrate B-blockers and ARNI? At what level of kidney impairment should one stop ACE/ARB/ARNI/SGLT2 inhibitors? When should one refer these patients for cardiac resynchronization therapy device (CRTD) or Heart Transplantation? When should one repeat transesophageal echocardiography (TEE)? Physicians need to have clear answers and stance on the above queries. HFrEF is a major public health concern in our population especially with early onset of ischemic heart disease (IHD). Awareness, education and up to date knowledge regarding early diagnosis, work up and adjustments of drugs in such patients with proper follow up is important to reduce the ever rising morbidity and mortality in our population. References Sheikh SA. Heart failure in Pakistan: A demographic survey. J Card Fail. 2006;12(8):S157. Martinez-Amezcua P, Haque W, Khera R, Kanaya AM, Sattar N, Lam CS, et al. The upcoming epidemic of heart failure in South Asia. Circ Heart Fail. 2020;13(10):e007218. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey Jr DE, Colvin MM, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Am Coll Cardiol. 2017;70(6):776-803. Virani SS, Alonso A, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, et al. Heart disease and stroke statistics—2020 update: a report from the American Heart Association. Circulation. 2020;141(9):e139-596. Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Heart disease and stroke statistics—2015 update: a report from the American Heart Association. Ccirculation. 2015;131(4):e29-322. Batra MK, Rizvi NH, Sial JA, Saghir T, Karim M. Angiographic Characteristics and in Hospital Outcome of Young Patients, Age Up to 40 Versus More Than 40 Years Undergoing Primary Percutaneous Coronary Intervention. J Pak Med Assoc. 2019;69(9):1308-12. Greene SJ, Butler J, Albert NM, DeVore AD, Sharma PP, Duffy CI, et al. Medical therapy for heart failure with reduced ejection fraction: the CHAMP-HF registry. J Am Coll Cardiol. 2018;72(4):351-66. Konstam MA, Neaton JD, Dickstein K, Drexler H, Komajda M, Martinez FA, et al. Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial. Lancet. 2009;374(9704):1840-8. Murphy SP, Ibrahim NE, Januzzi JL. Heart failure with reduced ejection fraction: a review. JAMA. 2020;324(5):488-504.

Cochlear implants are now the treatment of choice for patients with severe to profound hearing loss. Inclusion criteria for cochlear implantation have expanded, and a whole array of implantable hearing devices have been introduced over the years. To date, more than 250 cochlear implantations have now been performed in the Philippines (Figure 1). In 2006, the first auditory brainstem implantation, and first vibroplasty or middle ear implantation in the country were done at the Philippine General Hospital (PGH). In 2008, the first electroacoustic stimulation or partial deafness cochlear implantation surgery in the country was performed at the Capitol Medical Center by Professor Joachim Müeller of the University of Würzburg and the author. This concept, that cochlear implantation can be performed for patients with residual hearing or only partial deafness, is quite novel. There are patients whose low frequency hearing below 1.5 kHz is still be quite good while high frequency hearing loss above 1.5 kHz is in the severe to profound range (Figure 2). For such patients speech discrimination scores will typically fall below 60% at 65 dB sound pressure level (SPL) in the best aided condition. This technological advancement, often called electroacoustic stimulation (EAS), was developed in 1999 after Christoph Von Ilberg demonstrated preserved residual low frequency hearing in a patient who underwent cochlear implantation such that the patient wore a hearing aid in the implanted ear.1 Currently, EAS devices are available from two manufacturers. Contraindications to the use of EAS are shown in Table 1. Candidates for EAS devices should have stable low frequency hearing. There should be no progressive or autoimmune sensorineural hearing loss. Also there should be no history of meningitis, otosclerosis, or any other malformation that might cause an obstruction. The patient’s air-bone gap should be < 15 dB. Finally, there should not be any external auditory canal problems that can impede placement of the ear mould for the acoustic component. There are two main components of the EAS system (Figure 3). The external component is made up of a microphone that picks up sounds and a processor that separately encodes low and high frequency energy. After processing, low frequency energy is converted into an acoustic signal via the loudspeaker located in the ear hook and delivered into the external auditory canal. This acoustic signal will vibrate the tympanic membrane and ossicles so that cochlear fluids as well as the relatively intact structures of the cochlea in the apical region are stimulated. In contrast, high frequency energy is coded into radio-wave-like signals which are transmitted transcutaneously to the internal receiver. There, electric signals are delivered to the electrode array that has been surgically implanted into the cochlea. Thus the auditory nerve receives information using two different pathways from low and high frequency sounds, and the auditory nerve signals are then transmitted to the brain. Our Experience: Of the more than 100 implantations done under the Philippine National Ear Institute “CHIP” or Cochlear and Hearing Implants Programme only one was a case of EAS implantation. This particular case demonstrates key principles and concepts that every otolaryngologist should consider. Among these are audiological evaluation, temporal bone imaging, surgical technique for hearing preservation and some quality of life issues. Audiological Evaluation A 33 year old man had been seen at the clinic for over 7 years, with serial audiograms (Figure 4-6) illustrating the presence of good and stable low frequency hearing while high frequency hearing loss increased somewhat. The patient had been continually advised to get the best hearing aids available. However, a series of high-end hearing aids did not solve his problem of poor hearing in noisy places nor his difficulty understanding words when watching television and movies. Figure 7A shows the speech perception scores of this patient obtained with a Word Intelligibility by Picture Identification (WIPI) test, a “closed-set test” using isolated words while Figure 7B represents speech scores when “open-set” Bamford-Kowal-Bench (BKB) Sentence Lists were presented to the listener in both quiet and noise prior to the implantation. Temporal bone imaging A combination of high resolution computerized tomography (HRCT) of the temporal bone with both coronal and axial cochlear views, and T2-weighted normal anatomic Fast Spin Echo (T2 FSE) or 3D Constructive Interference in Steady State (3D CISS) MRI sequences of the inner ear should be done. Results from both studies should ascertain whether the cochlear duct is patent, ruling out any cochlear fibrosis or obstructive pathology. This patient’s HRCT and 3-D CISS MRI studies showed no such cochlear obliteration that would have posed intraoperative difficulties and constituted contraindications to EAS surgery (Figure 8). Surgical Technique for Hearing Preservation A variety of techniques have evolved over the years into what is now commonly called minimally invasive cochlear implantation. Using minimally invasive techniques, residual hearing can indeed be preserved in over 80%-90% of patients 3,4 Initially, a “Soft Cochleostomy” technique was introduced. This entailed careful low-speed drilling of the promontory with a Skeeter® drill (Medtronic Xomed, Jacksonville FL, USA) followed by the use of a mini-lancet to make an opening in the membranous labyrinth. This method avoids direct suctioning and prevents ingress of blood and bone dust into the intracochlear compartment. Also, for this method, the endosteum is left intact after drilling a cochleostomy antero-inferior to the round window. This allows proper placement of the electrode into the scala tympani with less chance of injury to the basilar membrane. Later, a round window approach was introduced, and it also proved to be a reliable way to preserve residual hearing during cochlear implantation. For this method, a more direct round window approach is performed after careful drilling of the round window niche. A limited incision is made just large enough to allow the electrode to be inserted. For both methods, after the endosteal or round window membrane incision is made with a micro lancet, a very flexible electrode of 20 mm length is slowly inserted. During the insertion process, the cochleostomy or round window is kept under direct vision so that insertion forces are minimized. Topical antibiotics and steroids are applied at this time to reduce any inflammatory or apoptotic reactions related to the trauma of opening the cochlea and introducing an electrode. Finally, a soft tissue plug is placed tightly around the electrode entry point into the membranous labyrinth to prevent perilymph leakage. New electrode designs that are thinner and more flexible are important contributors to the preservation of hearing. Postoperative Outcomes and Quality of Life After about 4-6 weeks from the time of surgery the EAS implant is switched on. Based on our experience and that of others,3 speech perception performance improves with prolonged experience with the implant. Roughly 1 ½ years post-surgery this patient has achieved dramatic improvement in hearing both in quiet and in noise using the EAS compared to using only the hearing aid component or the CI component alone. Figure 9 shows this dramatic improvement in free-field pure tone thresholds. Figure 10 demonstrates the speech perception following EAS implantation compared to pre-EAS implantation. Audiologic evaluation done at the PGH Ear Unit using 20 phonetically balanced Filipino words familiar to the patient in quiet and with 55 dB masking noise in the side of the implanted ear clearly showed an advantage with the EAS configuration compared to either hearing aid or CI component alone. Even with noise, this patient actually performed better presumably because he may have concentrated more with the introduction of masking noise. Another factor of course is that the words have now become familiar to the patient with the previous testing done in quiet. Notably, he reported great subjective improvement after only 10 months post-surgery.5 Interestingly the patient’s only complaint during his last follow-up was that he had not been offered bilateral EAS implantation. It is always important for the otolaryngologist to consider the quality of hearing and quality of life of patients with hearing loss. Intervention should not end with a referral note to a hearing aid center or dispenser. It is important to request proof of improvement not only of hearing thresholds but of speech perception outcomes in quiet and in noise. That is, one should document actual performance with the device in place, regardless of the type of device (hearing aid, an EAS device, or a Cochlear implant). Minimal disturbance of the remaining intact structures of the cochlea of patients with low frequency residual hearing can be achieved by employing a meticulous surgical technique, by using the advanced and flexible electrodes developed by some manufacturers, and instilling intraoperative antibiotics and steroids. Thus when one is faced with a ski-slope type audiogram it is likely the patient with this audiogram will not benefit from hearing aids. Such patients should be offered the option of EAS implantation which combines good acoustic stimulation with electric stimulation using a shorter (than conventional cochlear implantation) but very flexible electrode system. Counseling must also be done with a special emphasis on the risk of losing residual hearing, and noting that post-operative rehabilitation may take a long period of time. This patient now has a better quality of life than was obtainable from the most expensive and advanced hearing aids in the market, and has demonstrated a new implantable solution to partial deafness. Truly, EAS technology has opened a new era in prosthetic rehabilitation for hearing impaired adults and children.5 Acknowledgement Dr. Maria Rina Reyes-Quintos is gratefully acknowledged for performing all the excellent audiological testing following the surgery while Susan Javier and Angie Tongko of Manila Hearing Aid Center performed all the audiological testing prior to the surgery. Ms. Celina Ann Tobias, Professional Education Manager of Med-El is also credited with thanks for preparing the figures, reviewing the manuscript and interviewing the patient regarding his hearing performance following the surgery.

Abstract Background We previously demonstrated that the combination of Nilotinib (NIL) + Pegylated IFN-a2a (Peg-IFN) is able to induce high deep molecular response rates in chronic phase CML (CP CML) patients, as first-line therapy (Nicolini FE et al., Lancet Haematol. 2015). Aims Assessment of the molecular responses obtained with the same combination vs NIL alone prospectively, in newly diagnosed CP-CML. (EudraCT 2013-004974-82). Methods Patients (pts) ≤65 years with no history of arterial damage were randomized 1:1 to get NIL 300 mg BID alone (M0 to M48, arm A) vs Peg-IFN alone (± HU) for 30 days (M-1 to M0) 30 mg/wk as a priming, prior to a combination of NIL 300 mg BID + Peg-IFN 30 mg/wk 2 weeks, upgraded to 45 mg/wk thereafter if proper tolerance for up to 2 years (M0 to M24, arm B) followed by NIL alone for 2 more years. The primary endpoint was the rate of molecular response 4.5 (MR4.5) by 1 year. Molecular assessments were centralised, quantifications were expressed as BCR-ABL/ABL1 (IS) in % with ≥32,000 copies of ABL1 as control. Results Two hundred and one pts were randomized (100 in arm A, 101 in arm B), 65 males in both arms, 35 females in arm A, 36 in arm B. The median follow-up is 20.6 (9.1-34.7) months. Results are analysed in intention-to-treat. Sokal scores were high in 25%, intermediate in 36% and low in 39% of pts; Euro scores were high in 13%, intermediate in 44% and low in 43% of pts; Eutos LTS scores were high in 2%, intermediate in 17%, and 81% low; equally balanced in the 2 arms The median age was 46 (18-66) years, equally balanced. Eight (4%) pts had a cryptic Philadelphia chromosome, 12 (6%) a variant form, and 15 (7.5%) had ACAs, all pts had a "Major" BCR transcript. CHR was obtained in 9.6% of pts at M0 (arm B) and in 88% of pts in arm A and 90.4% of pts in arm B at M1. The rates of CCyR at M3 were 63% vs 65% in arms A and B, and BCR-ABL1≤1% at M6 were 83% in arm A vs 86% and arm B, on evaluable samples. The incidence of molecular responses are shown in Fig. 1. Of note, 90% of the pts had a BCR-ABL1 ≤10% at M3 in arm A vs 84% in arm B (p=ns). By M12, the rates of MMR were 69.9% vs 72.4% (p=0.079), MR4 were 34.65% vs 47.9% (p=0.094), MR4.5 were 17.9% vs 24.11% (p=0.272), MR5 12.1% vs 22.31% (p=0.075), in arm A and arm B respectively. Data from 11 pts in arm A and 16 in arm B at M12 are still pending. Definitive results at 1 year will be presented. One pt progressed toward accelerated phase in arm A with a Y253H mutation. Fifteen pts were withdrawn from study in arm A (toxicity 5, other cancer 2, failure 8) and 12 patients from arm B (toxicity 6, failure 6), no pt died. Interestingly, 5 mutated (ie. failure) pts were found in arm A (3 Y253H, 1 E225K, 1 F317L), vs only 1 pt (T315I) in arm B. The median dose of Peg-IFN delivered in arm B during the first month is 30 (0-30) mg/wk, 30 (0-45) mg/wk at M2, 45 (0-45) mg/wk at M3, 37.5 (0-45) mg/wk at M6, 30 (0-45) mg/wk at M9 and 12. The median doses of NIL delivered were 600 mg daily at M2, 3, 6, 9, 12 as initially planned in both arms. The rate of grade 4 hematologic toxicities overall was 15%, with no anemias, 1% and 4% thrombocytopenias, 3% and 4% neutropenias, 0% and 1% leucopenias, and 0 and 1% pancytopenias in arms A and B respectively. Grade ¾ non-hematologic toxicities consisted in 4% of cardiac disorders in arm A (1 coronaropathy, 2 thoracic pains and 1 atrial fibrillation) vs 1% in arm B (palpitation), 2% vascular disorders in arm A (1 pulmonary embolism, 1 transient ischemic attack) and 1% in arm B (PAOD). Three % of gastro-intestinal disorders in arm A (resolutive pancreatitis) vs 1% in arm B (anal fissure); 1% of skin disorders in arm A; 2% auto-immune disorders in arm B (1 recurrent pericarditis, 1 hemolytic anemia); 2 and 5 pregnancies (of the partner except 1) were observed in arm A and B respectively, despite recommended contraceptive methods. We observed 10% lipase elevations in arm A, 3 in arm B, 2% cholestatic episodes in arm A, 1% in arm B; 1% of transaminase elevations in each arm. There were 2% depressive episodes in arm B, 1% in arm A; infections were detected in 1% arm 1 and 3% in arm B. Finally 3 intercurrent cancers were detected in arm A (cervix, breast, thyroid). Conclusion The combination of NIL + Peg-IFN seems to provide slightly deeper molecular responses rates (especially MR5) by M12, but so far not significantly, in newly diagnosed CP CML pts without increasing the rate of more frequent early SAEs in such a setting. Definitive results at M12 will be updated for the meeting. Disclosures Nicolini: BMS: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; ARIAD: Honoraria, Speakers Bureau; Incyte Biosciences: Honoraria, Speakers Bureau. Etienne: Incyte: Speakers Bureau; BMS: Speakers Bureau; Novartis: Consultancy, Research Funding. Guerci-Bresler: BMS: Speakers Bureau; Incyte: Speakers Bureau; Novartis: Speakers Bureau; Pfizer: Speakers Bureau. Charbonnier: Incyte: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau. Legros: BMS: Speakers Bureau; Incyte: Speakers Bureau; Novartis: Speakers Bureau. Coiteux: Incyte: Speakers Bureau; BMS: Speakers Bureau. Cony-Makhoul: BMS: Speakers Bureau. Rousselot: Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sunesis: Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Pfizer: Research Funding. Guyotat: BMS: Speakers Bureau. Ianotto: Novartis: Other: Grant. Rea: BMS: Consultancy, Speakers Bureau; Incyte: Speakers Bureau; Novartis: Speakers Bureau; Pfizer: Speakers Bureau. Mahon: Pfizer: Speakers Bureau; Incyte: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau; Novartis: Research Funding, Speakers Bureau.

L’art contemporain nous a habitués à appréhender le corps de l’artiste performeur et agissant comme œuvre d’art. Ce corps artistique, par sa présence ou le déploiement d’actions ou de simples mouvements, ne s’inscrit pas seulement dans l’espace, mais il le décrit et le définit. Corps et espace s’interpellent. Comment l’artiste s’impose-t-il face à l’incommensurabilité de l’espace ? Et comment ce corps-œuvre d’art devient-il le lieu d’une expérience privilégiée de l’espace pour le spectateur ? Tenter de le mesurer à partir de l’échelle de son propre corps paraît être une solution, tantôt loufoque, tantôt sérieuse. Les quatre temps de cette démonstration (corps étalon, corps jeu, corps trace, corps universel) présentent des attitudes adoptées par une sélection d’artistes marquants, des années 70 à nos jours, qui se lancent le défi de Rendre le monde à sa mesure.

Le 7 janvier 2015 en fin de matinée à Paris, les frères Chérif et Saïd Kouachi lancent une attaque contre la rédaction de l’hebdomadaire satiriqueCharlie Hebdo. Cagoulés, vêtus de noir et armés de kalachnikovs, ils déciment la rédaction, faisant douze morts dont huit journalistes. Cet article examine comment Renald Luzier (« Luz »), dessinateur de presse àCharlie Hebdo, se réconcilie avec la mort, la réapprend par le truchement de la bande dessinéeCatharsis(2015).Autrement dit, comment la bande dessinée parvient-elle à donner du sens à une expérience traumatique ? Comment contribue-t-elle, par une expérience graphique, à nouer des liens entre un passé récent indicible, un présent douloureux et un possible futur ? Peut-elle être un moyen de (re)construction de soi ? Autant d’interrogations qui font la matière de ce texte où la bande dessinée n’est pas envisagée comme une illustration à un processus de deuil mais dans ses potentialités symboliques, imaginaires – anthropologiques - où un dessinateur, Luz, vit la mort des autres dans sa propre vie.

Background: Diabetes often requires the use of sharp objects (e.g. needles, lancets, etc) to maintain optimal glycemic control. Improper disposal of sharps poses substantial threats to the environment and public health. Objectives: To estimate the prevalence, and identify predictors, of improper sharps disposal among people with diabetes (PWD) in Saudi Arabia. Method: We surveyed PWD, visiting a diabetes center in Riyadh, Saudi Arabia in Sep- Oct, 2021. We asked questions about sociodemographics, type and duration of diabetes, methods of sharps disposal, and whether the study participants had received instructions on proper sharps disposal. We defined “proper sharps disposal” as: dispensing sharps into a designated sharps disposal container or home-made sealed container. Results: Of the 293 PWD surveyed, 60% were women, 54% were ≥35 years old, and 53% had type 1 diabetes. Majority (80% and 72%) reported improper disposal of needles and lancets, respectively. Approximately, 56% of needle users and 61% of lancet users reported that they had never received instructions on safe sharps disposal. Receiving education on safe sharps disposal was associated with a 66% reduction in the risk of improper sharps disposal practice[OR (95% CI) : 0.34 (0.16-0.68) ] after adjusting for age, gender, type and duration of diabetes, income, education, and nationality of the study participants. Among those who improperly dispose their needles, 67% thought their way of sharps disposal was appropriate and 47% did not know what type of infections can be transmitted via needlestick injuries. Conclusion: Our findings highlight the high prevalence of unsafe sharps disposal practices among PWD, and how providing education on safe sharps disposal can help address this environmental and public health threat. Policies to reduce diabetes-related waste, unify the approach to proper sharps disposal, and educate PWD on how to safely dispose sharps are needed to achieve a sustainable and safe waste management system. Disclosure G.Alsuwailem: None. M.Barakeh: None. G.A.Almarshoud: None. A.Zawawi: None. R.A.Bakader: None. M.Al-sofiani: None.

Background: The discovery of the vaccination technique has been revealed by Edward Jenner in 1796: undoubtedly, it represents the first scientific attempt to control an infectious disease by vaccines, followed by other important studies carried out by Pasteur and Koch, and Sabin, who developed the first technique to attenuate the virus. In recent decades, numerous scholars have begun to create dangerous theories against the effectiveness of vaccines through scientifically invalid or fraudulent studies. Aim: This critical review of the literature aims to analyse the main factors that have undermined the credibility of vaccines in the general population, to disprove false information and, on the other hand, emphasize the benefits of vaccines over the last 200 years. Discussions: Unfortunately, several studies have been carried out without the proper scientific rigour. The most impacting example is the study published by Andrew Wakefield in the Lancet journal that tried to correlate vaccines with the development of autism: this publication was withdrawn from the journal a few years after its publication, but the impact of incorrect scientific studies, fake news, and ambiguous healthcare policies has led to an adverse general opinion about the effectiveness of vaccines. Conclusion: The excess of uncontrolled information is a serious concerning in the Coronavirus pandemic. The modern science must tackle this problem with a better willingness to communicate even the clinical studies to those people not able to understand the medical information autonomously. Nevertheless, a reliable science must also limit the dissemination of studies that do not meet the basic criteria of a methodological rigor and certainty of results, in order not to feed confusion in the scientific community.

Introduction: Cardiovascular disease (CVD) risk scores are used to estimate an individual’s risk of developing a disease or death from a cardiovascular event. Recently, the American College of Cardiology/American Heart Association (ACC/AHA) introduced the Pooled Cohort risk equations (ACC/AHA model). It is important to know how comparable CVD risk predictions are in low-middle income countries (LMIC). Hypothesis: ACC/AHA model has a poor concordance with any other CVD risk score. Methods: We used secondary data from two Peruvian, age and sex-matched, population-based studies across five geographical sites. The ACC/AHA model was compared to five other CVD risk prediction tools: two versions of the Framingham Risk Score (FRS-Lipids and FRS-BMI), Reynolds Risk Score (RRS), four versions of the Systematic Coronary Risk Evaluation (SCORE 1-4), World Health Organization risk chart (WHO), and Lancet Chronic Disease risk chart (LCD). We calculated predicted risk as a continuous variable and used Lin’s concordance correlation coefficient (CCC). We also compared the high predicted risk prevalence between all the scores using the cut-off levels suggested by each score’s guidelines. Results: We included 2183 subjects in the risk scores age range of 45-65 years (mean age 54.3 (SD±5.6) years). CCC agreement values found in this study were generally poor. The highest concordance was observed between the ACC/AHA model and the risk scores derived from the Framingham Study (40% with FRS-BMI and 44% with FRS-Lipids). ACC/AHA model depicted the highest proportion of people with predicted high-risk of 10-year CVD, at 29.0% (95%CI 26.9-31.0%) and the same tendency was observed in all study sites. Conclusions: In Peruvian population-based samples, agreement between ACC/AHA model and five other CVD risk scores was generally poor. There is an urgent need to use an appropriate risk score for CVD in LMIC. In an ideal scenario, it would be significant to have a proper CVD risk score for LMIC.

IntroductionMitigating the spread of infectious disease is of great importancefor policy makers. Taking the recent outbreak of Ebola as an example,it was difficult for policy makers to identify the best course of actionbased on the cost-effectiveness of what was available.In effort to address the needs of policy makers to mitigate the spreadof infectious disease before an outbreak becomes uncontrollable, wehave devised a cost-benefit disease control model to simulate theeffect of various control methods on disease incidence and the costassociated with each of the scenarios. Here, we present a case studyof Ebola used to quantify the cost effectiveness of vaccination andisolation methods to minimize the spread of the disease. We evaluatethe impact of changing strategy levels on the incidence of the diseaseand address the benefits of choosing one strategy over the other withregards to cost of vaccine and isolation.MethodsDisease.We use a general SEIRJ model for disease transmission.Here, S-Susceptible, E- Exposed (latent), IA– Infected (asymptomatic),IM– Infected (mild symptoms), IS– Infected (severe symptoms),JM– Isolated (mild symptoms at home), JS– Isolated (severesymptoms in hospital), and R- Recovered individuals. In this model,we consider the dynamics of the system and the effect of the relativetransmissibility of isolated individuals (L) compared to other infectedindividuals1.Cost.Ebola vaccination and treatment are very expensive andnot widely available. Some preliminary data shows that it will take$73 million (M) to produce 27 M vaccines2plus the cost for vaccinedelivery and health care professionals (not included here). On theother hand, the treatment for Ebola in the U.S. would cost $25,000dollars a day per person3to ensure proper isolation and adequate care(treatment, health care professionals, facilities and special equipment).Although not included in this research, the proper isolation of Ebolapatients would also lead to a loss in hospital revenue of $148,000per day due to reduced patient capacity3. Here, we use $27,000 perindividual hospitalized per day and $2.70 per person vaccinated.Model.To evaluate the cost-effectiveness of control methods ondisease transmission, we assessed the affect of different levels ofvaccination coverage on the resulting number of infected individuals.Then, we calculated the overall estimated cost of vaccination andresulting hospitalization for each scenario to identify the lowest cost-benefit ratio.ResultsUsing a base population of 10 M individuals, we ran scenarios fordifferent levels of vaccination (μ= 0.01, 0.05, 0.1) while varying therelative transmissibility of isolated individuals (L = 0.5, 0.6, 0.65).For each combination, we calculated the incidence, vaccination andhospitalization cost per individual per day (Fig 1). We note that anincrease in the relative transmissibility of isolated individuals leads toa higher number of infected people and, therefore, a reduced numberof candidates for vaccination and an overall increase in cost. Since thecost of vaccination is 1 ten-thousandth of the cost of hospitalization,our results clearly show the cost-benefit of vaccinating over hospitaltreatment. In every scenario studied, we observed a measurablereduction in disease incidence when vaccinating a higher fraction ofthe population compared to isolating individuals post infection.ConclusionsGiven these preliminary results, we plan to extend the frameworkof our model to a dynamic control system where we consider the costof vaccination and isolation embedded in the system of differentialequations. This approach will allow us see the best availablecontrol implementation while minimizing the cost of treatment andvaccination.KeywordsControl; Epidemiological Modeling; Transmission Dynamics; Cost;EBOLAReferences1. Chowell D, Castillo-Chavez C, Krishna S, Qiu X, Anderson KS. 2015.Modeling the effect of early detection of Ebola.The Lancet InfectiousDiseases, 15(2), 148-149.2. http://www.forbes.com/sites/danmunro/2014/10/23/head-of-gsk-ebola-vaccine-research-can-we-even-consider-doing-a-trial/#3cbd929665db3. http://www.usatoday.com/story/news/nation/2014/11/25/ebola-costs-add-up/19346913/

Abstract INTRODUCTION Immune Checkpoint Inhibitors (ICIs) have become a revolutionary milestone in the immune-oncology field and have shown a significant improvement in survival rates and outcomes of advanced malignancies. ICIs including: Ipilimumab (1) - monoclonal antibody that inhibits Cytotoxic T Lymphocyte associated Antigen 4 (CTLA4) - Nivolumab (2) - monoclonal antibody that blocks Programmed Cell Death Ligand 1 (PDL1) - and others turn off the tumor mediated immune system inhibition and boost the immune response against tumor cells resulting in decreased tumor growth. However, targeted immunotherapy has a wide spectrum of immune related side effects (3) that can affect various body organs ranging from mild skin rash to a critical immunotherapy induced pneumonitis and severe colitis. We present a case report of Ipilimumab/Nivolumab induced fulminant DKA in a non-diabetic patient. CASE PRESENTATION We present a case of a 71 year old male with a history of hypertension, hyperlipidemia, hemorrhagic stroke and stage 4 renal cancer with metastasis to the lungs who presented to the Emergency Department with altered mental status for 1 day and respiratory depression. He was accompanied by his wife who provided most of the history and denied any head trauma, seizure, uncontrolled hypertension, recent infections, arrhythmias, endocrine diseases or alcohol/drug use. Initial blood glucose was 1052, pH 7.11, bicarbonate 6, potassium 6.7, CO2 20.1, anion gap of 29 and WBCs 19.3 without any source of infections. Diabetic ketoacidosis (DKA) protocol was started and patient was intubated for worsening respiratory depression. Patient’s wife denied any personal or family history of diabetes mellitus and stated that his Hemoglobin A1c (HbA1c) has always been below 6% during his follow ups. Upon further questioning about any new medications, she stated that 15 years ago he had renal cell carcinoma treated with left radical nephrectomy and was recently discovered to have pulmonary nodules that were biopsy positive for renal cell carcinoma, to which he recently started Ipilimumab and Nivolumab immunotherapy about 2 month and last received doses was 3 days prior to presentation. She also reported one-month history of lethargy, polyuria and polydipsia. HbA1c was found to be 8.0% and lipase enzyme &gt; 4000 u/L without any pancreatic changes or inflammation on Computed Tomography (CT) scan of the abdomen. Insulin autoantibodies, islet cells antibodies and serum C-peptide were undetectable. During the admission DKA and respiratory depression resolved but the patient continued to have hyperglycemia with blood glucose level of 300-400 and was treated with correctional insulin scale. Patient was discharged on long acting and regular insulin after appropriate education. DISCUSSION Ipilimumab and Nivolumab; the novel revolutionary targeted immunotherapy have been approved by the United States Food and Drug Administration in 2011 (4) and 2014 (5) respectively. They enhance the immune response against tumor cells through blocking the immune checkpoints CTLA4 and PDL1 which are activated by the tumor cells as an inhibitory mechanism to interrupt the T lymphocyte - tumor cell destruction pathway (6-7). Ipilimumab and Nivolumab are used in combination for inoperable or metastatic melanoma (8-9), advanced renal cell carcinoma (10), metastatic squamous non-small cell lung cancer (11) and currently in trials for recurrent small cell lung cancer treatment (12-13). They are also used for primary or metastatic urothelial carcinoma and prostate cancer (14). As ICIs enhance T lymphocytes immunity by disrupting the inhibitory signaling, they also decrease immune tolerance and, thereby; cause autoimmune toxicities. Yet, ICIs are usually not stopped since their beneficial outcomes seem to outweigh the adverse events. Immunotherapy related adverse events (irAEs) includes: systemic symptoms of fatigue, weakness, muscle and joint pain, dermatological: rash and itchy skin - reported in 10% of patients in trials for melanoma and lung cancer (15) - pneumonitis (16) (4%), gastrointestinal: decreased appetite, abdominal pain, nausea and vomiting, colitis (17) (10%), hepatic toxicity (18) (1-17%), and endocrinopathies: hypothyroidism and hyperthyroidism (19) (8.5% and 3.7% respectively). Severe neurologic disorders including acute demyelination polyneuropathy, ascending motor paralysis and myasthenia gravis have been reported (20). Although there are no guidelines for managing irEAs, most of them are managed with high-dose corticosteroids. Several cases of autoimmune diabetes mellitus have been reported (2% of cases) as endocrinologic irEAs, most of them were genetically susceptible to type 1 diabetes mellitus. Less than 1% of cases had diabetes mellitus of rapid onset and complete insulin insufficiency leading to fulminant DKA (19). However, the clinical course of their insulin secretion disruption was not well studied. To our knowledge, the case that we are presenting here is one of a few cases described in literature of fulminant diabetes/DKA caused by immunotherapy. In fulminant diabetes, patients present with severely elevated blood glucose or DKA; however, their HbA1c is unexpectedly low (7-8%) due to the abrupt onset of presentation. C-peptide and Islet cell autoantibodies levels are low or even undetectable which suggest that pancreatic B-cells are totally destroyed via a process that is not completely understood and not similar to the one causing classic autoimmune type 1 diabetes mellitus. In fulminant diabetes/DKA pancreatic islet cells are attacked by autoreactive T lymphocytes. Thiswas initially thought to be a cell-mediated phenomenon; however, some reported cases had 1 or more islet cell autoantibodies which suggests the implication of a humoral immune response component as well. Diagnosis of such an endocrinopathy should be proper and prompt due to the increased risk of death within the first 24 hours. CONCLUSION Identification of rare but serious irAEs like DKA, is very important. This requires a multi-dimensional approach involving effective education about the symptoms of DKA and hyperglycemia in patients receiving immunotherapy along with close monitoring of these patients. More research is needed in this area to clarify the frequency of this entity and its mechanism. DISCLAIMER This research was supported (in whole or in part) by HCA Healthcare and/or HCA Healthcare affiliated entity. The views expressed in this publication represent those of author(s) and do not necessarily the official views if HCA Healthcare or any of its affiliated entities. REFRENCES 1-Tarhini A., Lo E., Minor D.R. Releasing the brake on the immune system: Ipilimumab in melanoma and other tumors. Cancer Biother. Radiopharm. 2010;25:601-613. doi: 10.1089/cbr.2010.0865. 2-Guo L, Zhang H, Chen B. Nivolumab as programmed death-1 (PD-1) inhibitor for targeted immunotherapy in tumor. J Cancer. 2017;8(3):410-416. doi: 10.7150/jca.17144. 3-Kadono T. Immune-related adverse events by immune checkpoint inhibitors. Nihon Rinsho Meneki Gakkai Kaishi. (2017) 40:83-9. 10.2177/jsci.40.83 4-Lacroix, Marc (2014). Targeted Therapies in Cancer. Hauppauge, NY: Nova Sciences Publishers. ISBN 978-1-63321-687-7. 5-“Nivolumab Monograph for Professionals”. Drugs.com. Retrieved 14 November 2019. 6-Rotte, A. Combination of CTLA-4 and PD-1 blockers for treatment of cancer. J Exp Clin Cancer Res 38, 255 (2019) doi:10.1186/s13046-019-1259-z 7-Seidel JA, Otsuka A, Kabashima K. Anti-PD-1 and anti-CTLA-4 therapies in cancer: mechanisms of action, efficacy, and limitations. Front Oncol. (2018) 8:86. 10.3389/fonc.2018.00086 8-Johnson DB, Peng C, Sosman JA (March 2015). “Nivolumab in melanoma: latest evidence and clinical potential”. Therapeutic Advances in Medical Oncology. 7 (2): 97-106 9-Syn, Nicholas L; Teng, Michele W L; Mok, Tony S K; Soo, Ross A (December 2017). “De-novo and acquired resistance to immune checkpoint targeting”. The Lancet Oncology. 18 (12): e731-e741. 10-Motzer RJ, Rini BI, McDermott DF, et al. Nivolumab plus ipilimumab vs. sunitinib in first-line treatment for advanced renal cell carcinoma: Extended followup of efficacy and safety results from a randomized, controlled, phase 3 trial. Lancet Oncol. 2019 Aug 16; 11-Sundar R, Cho BC, Brahmer JR, Soo RA (March 2015). “Nivolumab in NSCLC: latest evidence and clinical potential”. Therapeutic Advances in Medical Oncology. 7 (2): 85-96 12-S.J. Antonia, J.A. Lopez-Martin, J. Bendell, P.A. Ott, M. Taylor, J.P. Eder, et al.Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial, Lancet Oncol., 17 (2016), pp. 883-895 13-Clinical trial number NCT00527735 at ClinicalTrials.gov Phase II Study for Previously Untreated Subjects With Non Small Cell Lung Cancer (NSCLC) or Small Cell Lung Cancer (SCLC) 14-“Impact of gemcitabine + cisplatin + ipilimumab on circulating immune cells in patients (pts) with metastatic urothelial cancer (mUC). - 2015 ASCO Annual Meeting - Abstracts - Meeting Library” 15-Nivolumab Label. Last updated November 2015. 16-Tay, Rebecca Y. et al., Checkpoint Inhibitor Pneumonitis — Real-World Incidence and Risk, Journal of Thoracic Oncology, Volume 13, Issue 12, 1812 - 1814 17-Som A, Mandaliya R, Alsaadi D, Farshidpour M, Charabaty A, Malhotra N, Mattar MC. Immune checkpoint inhibitor-induced colitis: a comprehensive review. World J Clin Cases. 2019;7(4):405-418. doi: 10.12998/wjcc.v7.i4.405. 18-Larkin J, Chiarion-Sileni V, Gonzalez R et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med 2015;373: 23-34. 19-de Filette J, Andreescu CE, Cools F, Bravenboer B, Velkeniers B (March 2019). “A Systematic Review and Meta-Analysis of Endocrine-Related Adverse Events Associated with Immune Checkpoint Inhibitors”. Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Metabolisme. 51(3): 145-156. doi:10.1055/a-0843-3366. PMID 30861560 20-“Two Cases of Myasthenia Gravis Seen With Ipilimumab”. 2014-04-29. 21-Godwin, J.L., Jaggi, S., Sirisena, I. et al. Nivolumab-induced autoimmune diabetes mellitus presenting as diabetic ketoacidosis in a patient with metastatic lung cancer. j. immunotherapy cancer 5, 40 (2017) doi:10.1186/s40425-017-0245-2 22-Gaudy C., Clévy C., Monestier S., et al. Anti-PD1 pembrolizumab can induce exceptional fulminant type 1 diabetes. Diabetes Care. 2015;38(11):e182-e183. doi: 10.2337/dc15-1331.

Photo by Mufid Majnun on Unsplash INTRODUCTION In 2007, the Nuffield Council of Bioethics introduced the “Intervention ladder” as a guiding framework[1] to evaluate the impact on individual liberty of various public health measures. One criticism of the ladder is that it reflects a narrow view of liberty, yet other researchers adapted the intervention ladder to incorporate a more autonomy-based view. Recently, academics and public health officials have used intervention ladders as guides in framing policies, particularly COVID-19 pandemic policies.[2] Analyzing the Indian COVID-19 vaccination drive under these two ladders can illuminate the concepts of liberty underlying those ladders and help determine the best framework on a philosophical basis. ANALYSIS l. Case Study: The Indian COVID-19 Vaccination Drive On January 16, 2021, India attempted a public vaccination drive.[3] The drug regulatory body Central Drugs Standards Control Organization (CDSCO) approved two vaccines, Covishield and Covaxin, for emergency use.[4] The approval was granted despite a clear lack of phase 3 clinical trial data for both of these vaccines.[5] Covishield, produced by the Serum Institute of India, is the Indian variant of the Astra-Zeneca vaccine that has shown an average efficiency of 70.4 percent after trials in the UK.[6] Covaxin, manufactured by Bharat Biotech in collaboration with the Indian Council of Medical Research (ICMR) National Institute of Virology, was developed and manufactured in India. [7] Covishield relied on the safety and efficacy data from large trials conducted in Brazil, South Africa, and the UK with 24,000 participants and a small cohort for the Indian study. Covaxin was given approval based only on phase-1 trial data. [8] An article published in The Lancet called for further efficacy data from the Covaxin study.[9] The officials associated with Bharat Biotech, as well as the Indian Council of Medical Research, maintained that fast production of the vaccine does not indicate a compromise in safety, even though they had little data to produce.[10] However, transparency is key to vaccination policy, which requires public participation. The media reported that the Covaxin clinical trials compromised research integrity by providing a monetary incentive of around 7 euros, to research subjects. People’s University, a private medical college, and hospital, recruited survivors of the Bhopal Gas tragedy for the Covaxin study. The participants were told that they were being provided a vaccine against COVID-19 without clarifying that data was being collected for their clinical study. There was no record of informed consent from these participants for the Covaxin study.[11] The media reported the death of a 42-year-old individual who received his first dose on December 23, 2020. [12] Although it was reported that the cause of death was not linked to the vaccine, the death added to vaccine hesitancy. The vaccines were provided for free to the frontline healthcare workers with no choice on which vaccine the recipients would receive.[13] Similarly, in the US, some people do not have a choice between Pfizer or Moderna. In the UK and the US, data from phase 3 trials are known with a periodic follow-up after the administration of the second dose.[14] The WHO developed a tracking system for COVID-19 vaccine recipients which was updated on March 19, 2021, to reflect the results of Covaxin phase 3 trials.[15] India eliminated choice although the two vaccines approved for emergency use did not have the depth of research that those used elsewhere had. The intervention ladder, discussed below, which uses proportionality and the harm principle to justify the lack of choice between the vaccines in the UK and the US, should not be applied to India’s vaccination policy. ll. The Nuffield Intervention Ladder The foundational principle underlying the Nuffield Intervention Ladder is Mill’s conception of individual liberty from the prominent work, On Liberty.[16] However, the Council recognizes that the intervention ladder is conceived on a broader interpretation of Mill’s liberty, using the principle of proportionality as a tool for justification i.e., the desired effect from the intervention is proportional to the loss incurred in liberty.[17] As shown in Table 1, an ideal intervention that is least infringing would then be no intervention at all. An intervention that would be more difficult to justify would be one that significantly restricts individual liberty. Intuitively, eliminating occupies the topmost rung on the ladder. The metaphor of the ladder suggests that as one climbs up the rungs of the ladder, stronger justifications would be required. Table 1: Examples of interventions at each level of the intervention ladder adapted and improvised from the Nuffield Council of Bioethics Report, 2007. A voluntary vaccination policy is one public health intervention that is acceptable and justifiable in terms of the principle of proportionality as well as Mill’s Harm Principle, with emphasis on diminishing individual liberties when actions might result in harm to others.[18] Although a vaccination policy in the context of a global pandemic seems justifiable through the lens of the intervention ladder, the Indian modus operandi is unique because of inherent problems with the original conception of the intervention ladder. By pausing to elaborate and reflect on the Indian context as a case study, we can demonstrate that individual liberty should not be the sole variable in framing justifiability. lll. Critiquing the Nuffield Intervention Ladder & Adding a Precautionary Approach In his paper, ‘Snakes and Ladders: State Interventions and the Place of Liberty in Public Health Policy’, Angus Dawson criticizes the intervention ladder’s focus on individual liberty,.[19] and its inability to account for the different treatment of incentives and disincentives and the role of information. Public health institutions require public participation to restrict the infectious spread of COVID-19. The lack of transparency and minimal information surrounding the vaccines have been a major hurdle in increasing public participation. It is contradictory to think that the public does not require information about interventions and have the ability of self-determination to guide them, when in fact self-determination presupposes possession of relevant information. A voluntary vaccination policy can be seen as sitting on either the lowest rung (providing information) or the rung of enabling choice, as a vaccination campaign does both. However, in India, the precautionary principle should also be applied as providing the choice should not permit ‘harm’. The precautionary principle holds that anything that poses a risk to human health or the environment should be avoided or accompanied by precautionary measures. In India, because the clinical trials were smaller and there is less proof of safety and efficacy, a vaccination requirement, or a public health campaign to encourage vaccination violates the principle. The proportionality principle governing the intervention ladder only requires that the benefits of the intervention justify the restrictions on liberty. The intervention ladder should prevent requiring healthcare worker vaccination without a choice of vaccine because a free choice requires transparency and more information than is available from the small early-stage clinical trials. Actions surrounding the vaccines in India do not reflect proper precaution or a proportionate and thus acceptable restriction on liberty. If there is no ability to choose between the two possible vaccines, then they should not be mandatory for healthcare workers. The Indian government and its officials have urged healthcare worker compliance by invoking the seriousness of the pandemic and the alarming rates of mortality rather than providing transparent data pursuant to the regulatory mechanisms of the vaccine clinical trial. For a healthcare worker, the duty to provide service and a stronger obligation to do so in the time of a pandemic already imposes certain restrictions on their liberty. The lack of choice in opting for a preferred vaccine puts it on a higher rung on the intervention ladder and thus requires stronger justifications. This case study reveals how the same public health intervention falls on different rungs of the intervention ladder depending on the target group in consideration. Or to put this simply, choice is contextual. Table 2: The ethical values at stake when it comes to “choice” lV. An Autonomy-Based Intervention Ladder Liberty and autonomy differ slightly: liberty revolves around the constraints on the ability to act, whereas autonomy stresses on the independence and the authenticity of the willingness to act.[20] It is thus possible for an individual to be autonomous but unfree, as can be seen from the inability to opt for a preferred vaccine.[21] Figure 1 shows an adapted schematic of an autonomy-based intervention ladder as proposed by Griffiths et al. Figure 1: An adapted schematic of the autonomy-based intervention ladder proposed by Griffiths, P.E and West, C. In comparing the original intervention ladder with their proposal, we see that the autonomy-based model allows for a negative scale in terms of its effects on autonomy. Thus, on this ladder, actions can be autonomy-enhancing or autonomy-diminishing. Such a model challenges the one-directional view of the ladder and rearranges interventions on a scale that ranges from negative to positive. A few interventions that were shown to have restrictive effects on liberty now have reinforcing effects when viewed through the lens of autonomy. Thus, providing information and educating can be seen as positive reinforcements for autonomous choice rather than infringing on individual liberty. The autonomy-based intervention ladder requires the State to implement interventions and design policies in a manner that reinforces autonomy. Information and education allow individuals to be free and equal participants in public health discourses. As seen in the original intervention ladder restricting choice, as well as eliminating it, still fall in the negative, autonomy-infringing side of the ladder. Thus, requiring stronger justifications for their implementation. The only difference between the two is the manner in which the new model ensures the availability of a choice when the precautionary, as well as the proportionality principle, have not been met to a sufficient extent. Ensuring choice and exercising it becomes much more relevant in making people autonomous. The frontline worker thus can opt for a vaccine they prefer. Thereby, helping them navigate the moral conundrum of opting to get vaccinated, easing their moral burden. It also places strict vigilance over regulatory mechanisms that are involved in clinical trials since the burden of proof now involves providing information as a clear operational motive. This ameliorates public tendencies of hesitancy can be alleviated in this respect. An autonomy-based intervention ladder is not in conflict with Mill’s conception of liberty since Mill himself does not automatically assume a cost to liberty when the State seems to employ public education campaigns to inform the public.[22] CONCLUSION The original intervention ladder was conceived to remedy the hurdles that a traditional liberal landscape brings in implementing a public health intervention and to protect individual liberties. The intervention ladder assumes an inverse relationship between public health and freedom. Rethinking the intervention ladder from a different perspective allows a proper role of the dissemination of information, recognizing that consent relies on information. An autonomy ladder acts as a starting point for rethinking public health and how it can foster autonomy as well as impede it. By focusing on autonomy, the benefits that can be gained from educational and informational campaigns are viewed as reinforcing autonomy. Autonomy is vital to liberty. COVID-19 has brought a unique set of ethical issues that have questioned conventionally accepted frameworks and calls for a substantive, alternative approach to public health ethics. [1] Nuffield Council on Bioethics, “Public Health: Ethical Issues.” Nuffieldbioethics.org, Nov 13, 2007. www.nuffieldbioethics.org/publications/public-health. Accessed 9 May 2021. [2] Giubilini A, The Ethics of Vaccination [Internet]. Cham (CH): Palgrave Pivot; 2019. Chapter 3, “Vaccination Policies and the Principle of Least Restrictive Alternative: An Intervention Ladder.” 2018 Dec 29, 2018. www.ncbi.nlm.nih.gov/books/NBK538385/. [3] Dash, Sachinta. “India Begins Its COVID-19 Vaccination Drive — Here’s a Look at How the World’s Largest Vaccine Rollout Is Set to Take Place.” Business Insider India, January 16, 2021, www.businessinsider.in/india/news/india-will-begin-its-covid-19-vaccination-drive-tomorrow-heres-everything-you-need-to-know/articleshow/80281740.cms. Accessed 9 May 2021. ‌ [4] Special Correspondent, “Coronavirus | India Approves COVID-19 Vaccines Covishield and Covaxin for Emergency Use,” The Hindu, January 3, 2021, www.thehindu.com/news/national/drug-controller-general-approves-covishield-and-covaxin-in-india-for-emergency-use/article33485539.ece. Accessed 9 May 2021. ‌ [5] Thiagarajan, Kamala, “Covid-19: India Is at Centre of Global Vaccine Manufacturing, but Opacity Threatens Public Trust.” BMJ, January 28, 2021. www.bmj.com/content/372/bmj.n196, 10.1136/bmj.n196. [6] Thiagarajan, Kamala. [7] Bharat Biotech, “COVAXIN - India’s First Indigenous Covid-19 Vaccine | Bharat Biotech.” www.bharatbiotech.com/covaxin.html. [8] Prasad, R. “Coronavirus | Vaccine Dilemma — to Take or Not to Take Covaxin.” The Hindu, January 15, 2021, www.thehindu.com/sci-tech/health/vaccine-dilemma-to-take-or-not-to-take-covaxin/article33577223.ece. [9] Ella, Raches, et al. “Safety and Immunogenicity of an Inactivated SARS-CoV-2 Vaccine, BBV152: A Double-Blind, Randomised, Phase 1 Trial.” The Lancet Infectious Diseases, vol. 21, no. 5, January 21, 2021, pp. 637–646, www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30942-7/fulltext, 10.1016/S1473-3099(20)30942-7. [10] Thiagarajan, Kamala. [11] Thiagarajan, Kamala. ‌ [12] Nichenametla, Prasad. “Bhopal Volunteer’s Death Unrelated to Covaxin, Says Bharat Biotech.” Deccan Herald, 9 Jan. 2021, www.deccanherald.com/national/bhopal-volunteers-death-unrelated-to-covaxin-says-bharat-biotech-937199.html. [13] Thiagarajan, Kamala. ‌ [14] Thiagarajan, Kamala. ‌ [15] World Health Organization, “Draft Landscape of COVID-19 Candidate Vaccines.” www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines. Accessed 9 May 2021. ‌ [16] John Stuart Mill. On Liberty. 1859. S.L., Arcturus Publishing Ltd, 1859. [17] Nuffield. “Public Health: Ethical Issues.” [18] John Stuart Mill. On Liberty. p 13. [19] Dawson, Angus J. “Snakes and Ladders: State Interventions and the Place of Liberty in Public Health Policy.” Journal of Medical Ethics, vol. 42, no. 8, May 23, 2016, pp. 510–513, 10.1136/medethics-2016-103502. [20] Griffiths, P.E., and C. West. “A Balanced Intervention Ladder: Promoting Autonomy through Public Health Action.” Public Health, vol. 129, no. 8, August 2015, pp. 1092–1098, pubmed.ncbi.nlm.nih.gov/26330372/, 10.1016/j.puhe.2015.08.007 [21] Thaler, Richard H, and Cass R Sunstein. Nudge: Improving Decisions about Health, Wealth, and Happiness. London, Penguin Books, 2008. ‌ [22] Griffiths, P.E., and C. West.

It was on January 30, 2020 when the World Health Organization (WHO) declared the coronavirus disease 2019 (COVID-19) outbreak a public health emergency of international concern. By March 11, 2020, it was declared a pandemic.1 This was just several weeks after Dr. Li Wenliang, an ophthalmologist from Wuhan, first recognized a possible outbreak of an illness that resembled severe acute respiratory syndrome.2 Over the next three years, we saw the world race against timeto understand the nature of the disease to save those infected and control further transmission across the continents. To date, almost 800 million people, that is, one out of 10 people have been infected, resulting in 7 million deaths worldwide.3,4 In an effort to control the spread of COVID-19, governments imposed lockdown measures. However, this resulted in the de-prioritization of non-communicable diseases including eye diseases as health facilities focused on treating infected patients or implementing vaccination programs. In a report by the WHO, at least 30% of countries had disrupted services for noncommunicable diseases.5 The crisis also resulted in changes in people’s health-seeking behavior, as the fear of COVID-19 outweighed the need for eye care. In the United States, a 60% drop in patient visits for eye care services was reported.6 In fact, the fear of exposure to COVID-19 was found to be associated with a four-fold increased risk of defaulting follow-up.7 Similarly, a study in India and Singapore also reported the fear of COVID-19 infection as a cause of the decline in patient consults.8In response to this crisis, eye care professionals struggled to strike a balance between delivering quality eye care services while mitigating the risk of infection. Various international and local ophthalmologic professional organizations including the American Academy of Ophthalmology,9,10 Philippine Academy of Ophthalmology,11 and the Philippine Society of Cataract and Refractive Surgery12 have issued guidelines on the practice of ophthalmology during the COVID-19 pandemic.These recommendations have become the basis for new standards in eye care. The use of personal protective equipment has become essential at the workplace. Physical barriers such as large slit lamp breath shields and clinic dividers, temperature scanners, alcohol dispensers, and air purifiers with high efficiency particulate air filters have now become common fixtures in most if not all clinics. Changes in clinic processes and protocols have also been adopted to ensure the safety not just of the health care team but also the patients and their families. These include the use of telemedicine where applicable, meticulous patient scheduling, symptom screening prior to clinic visits, enforcement of proper social distancing, disinfection of ophthalmologic equipment, clinic furniture and fixtures, and sterilization of instruments. Even contactless, cashless payment options have now become standard in many facilities. COVID-19 precautions have also become part of ophthalmologic laser and surgical procedure protocols. The pandemic is far from over and it seems that we will have to live with COVID-19 for a very long time. There are many opportunities to improve eye care services by applying the lessons we learned during the pandemic.1. There is no room for complacency. Infection control protocols must remain in place if we are to reassure patients that clinic visits are safe.2. Telemedicine will continue to be an alternative to face-to-face consultations. However, a survey of ophthalmologists reported confidence in using telemedicine for diagnosing gross conditions of the eye but not posterior pole conditions or orbital fractures.13 Improving confidence in telemedicine consults may be accomplished with the use of home monitoring devices such as tonometers and digital applications for various tests including visual acuity, color vision, and visual fields.14 Innovations in home-based ophthalmic imaging will revolutionize tele-ophthalmology, such as the home-optical coherence tomography that may be particularly useful for patients with age-related maculardegeneration and diabetic retinopathy.15Enhancing physician confidence in telemedicine must be paralleled by building patient confidence as well. Technology can disenfranchise certain patient populations like the elderly and those without internet access, and we must continuously strive to reach them and encourage them to try remote consultations when needed. Telemedicine applications should also ensure data privacy and security. 3. Patient education remains crucial in affecting health-seeking behavior. It is important to maximize the utilization of various social media platforms for patient education. As we live in an age of disinformation, we must also remain vigilant against the peddling of wrong or harmful health-related information. In eye care, this may range from cureall eye drops to miracle spectacles to supplements which have no sound scientific basis. Community-based patient education programs and information campaigns may be useful for those without access to digital technologies. 4. It is time to reprioritize ophthalmologic care for patients with non-communicable conditions such as diabetes, hypertension, cancer, and autoimmune diseases. We should also renew collaborative ties with other members of the healthcare team. Many of our patients have suffered worsening of their eye conditions in the past three years, whether by neglect or due to the pandemic-related barriers that prevented their access to timely intervention. Vision is a precious sense that translates very heavily into one’s quality of life. Some of our patients who experienced a decline in their vision during the pandemic – from errors of refraction, cataract, and the like – may be fortunate to have their sight restored in the future. However, our patients suffering from conditions such as glaucoma or proliferative diabetic retinopathy, are in a race against time to control or prevent irreversible visual loss. We move forward with more urgency for their sake, taking our lessons from the pandemic and adapting to this new normal with a renewed commitment to deliver eye care. Kristine Margaret Bacsal-Flores, MD, MBAHClinical Associate ProfessorDepartment of Ophthalmology and Visual SciencesCollege of Medicine and Philippine General HospitalUniversity of the Philippines Manila Felice Katrina T. Ranche, MDAssociate ProfessorDepartment of Ophthalmology and Visual SciencesCollege of Medicine and Philippine General HospitalUniversity of the Philippines Manila REFERENCES 1. World Health Organization [Internet]. WHO Director-General’sopening remarks at the media briefing on COVID-19 - 11 March 2020.2020 Mar 11. [cited 2023 Jan 27]. Available from: https://www.who.int/director-general/speeches/detail/who-director-general-s-openingremarks-at-the-media-briefing-on-covid-19---11-march-2020.2. Green A. Obituary - Li Wenliang. The Lancet. 2020 Feb; 395(10225):682. doi: 10.1016/S0140-6736(20)30382-2.3. World Health Organization [Internet]. WHO Coronavirus(COVID-19) Dashboard. [cited 2023 Jan 27]. Available from:https://covid19.who.int/.4. Worldometers.info [Internet]. Current World Population. [cited2023 Jan 27]. Available from https://www.worldometers.info/worldpopulation/.5. World Health Organization [Internet]. Rapid assessment of servicedelivery for NCDs during the COVID-19 pandemic. 2020 May 29. [cited 2023 Jan 20]. Available from: https://www.who.int/publications/m/item/rapid-assessment-of-service-delivery-forncds-during-the-covid-19-pandemic.6. Mehrotra A, Chernew ME, Linetsky D, Hatch H, Cutler DM.The Impact of the COVID-19 Pandemic on Outpatient Visits: ARebound Emerges. 2020 May 19. [cited 2023 Jan 20]. Availablefrom: https://www.commonwealthfund.org/publications/2020/apr/impact-covid-19-outpatient-visits7. Lindeke-Myers A, Zhao PYC, Meyer BI, Liu EA, Levine DA, Bennett OM, et al. Patient perceptions of SARS-CoV-2 exposure risk andassociation with continuity of ophthalmic care. JAMA Ophthalmol.2021 May; 139(5): 508-15. doi: 10.1001/jamaophthalmol.2021.0114.8. Low R, Lee JM, Lai SS, Rousselot A, Agarwal M, Agrawal R.Eye care during the COVID-19 pandemic: a report on patients’perceptions and experiences, an Asian perspective. Ophthalmol Ther.2022 Feb; 11(1):403-19. doi: 10.1007/s40123-021-00444-0.9. American Academy of Ophthalmology [Internet]. ImportantCoronavirus Updates for Ophthalmologists. 2020 Mar 23. [cited2023 Jan 20]. Available from: https://www.aao.org/headline/alertimportant-coronavirus-context.10. American Academy of Ophthalmology [Internet]. SpecialConsiderations for Ophthalmic Surgery during the COVID-19Pandemic. 2020 May 27. Updated 2021 Mar 22. [cited 2023 Jan 20].Available from: https://www.aao.org/headline/special-considerationsophthalmic-surgery-during-c11. King JH, Aquino JM, Anzures RG, de Leon JMS, Rondaris MVA,Santiago MDD, et al. for the PAO Committee on Standards 2020.COVID-19 guidance on the resumption of eye surgery. PhilippJ Ophthalmol [Internet]. 2021 Jan-Jun [cited 2023 Jan 20];46(1):2-14. Available from: https://paojournal.com/article/covid-19-guidance-on-the-resumption-of-eye-surgery/.12. Naval CG, Cabrera BG for the Philippine Society of Cataract andRefractive Surgery. PSCRS guide to ophthalmic practice in the timesof COVID-19. Philipp J Ophthalmol [Internet]. 2021 Jan-Jun [cited2023 Jan 20];46(1):20-34.. Available from: https://paojournal.com/article/pscrs-guide-to-ophthalmic-practice-in-the-times-of-covid-19/.13. Azarcon CP, Ranche FKT, Santiago DE. Tele-ophthalmologypractices and attitudes in the Philippines in light of the COVID-19pandemic: a survey. Clin Ophthalmol. 2021 Mar; 15:1239-47. doi:10.2147/OPTH.S291790.14. Aruljyothi L, Janakiraman A, Malligarjun B, Babu BM. Smartphoneapplications in ophthalmology: a quantitative analysis. Indian JOphthalmol. 2021 March;69(3):548-53. doi: 10.4103/ijo.IJO_1480_20.15. Miller J, Zeng R. The Future of Home-Based OCT for RetinaPatients. Retina Today [Internet]. 2019 Nov/ Dec; 35-37. [cited2023 Jan 20]. Available from: https://retinatoday.com/articles/2019-nov-dec/the-future-of-home-based-oct-for-retina-patients.

Photo by Robina Weermeijer on Unsplash INTRODUCTION Geographic inequities in access to donor lungs have persisted since the first successful lung transplant in 1983.[1] With unanswered questions regarding organ preservation and transport in the early days of transplantation, the United Network of Organ Sharing (UNOS) understandably incorporated geography in the allocation algorithm. Today, geography is still the most influential criterion in the lung allocation algorithm.[2] As a result, patients in urban centers often receive transplants before patients in less-resourced rural areas. Ex vivo machine perfusion can significantly improve lung procurement and transport, offering longer preservation times before, after, or during transportation. Out-of-hospital perfusion centers, a recent addition to the healthcare field, may increase both the number of lungs available and potentially the distance they can travel. Before the adoption of machine perfusion becomes commonplace, UNOS should direct how to integrate machine perfusion into procurement networks best and shed the antiquated geographical confines that govern allocation today and compromise the ethical standards on which the field was founded. ANALYSIS l. The Past: A History of Geographic Disparities in Lung Transplantation Since the founding of UNOS in 1986, patient geography has been the first filter for all lung procurements. In the early days of the field, implementing these so-called donor service areas, while arbitrarily formed, made sense given the unknowns pertaining to lung preservation and transportation. For almost two decades, donor service areas and time on the waitlist governed lung allocation. In 1998, after physician protest and advocacy, the U.S. Department of Health and Human Services (HHS) delivered the Final Rule on Organ Transplantation to create a more equitable organ allocation system. Even then, it was not until 2005 that UNOS developed the lung allocation score, a quantitative metric that considered predicted waitlist survival and transplant benefit. The implementation of the lung allocation score in the U.S. and abroad by Eurotransplant was a success by multiple standards, most importantly reducing waitlist mortality to record lows.[3] However, a glaring problem remained: the donor service area criterion remained, and arbitrary geographical boundaries continued to govern the distribution of all procured lungs. Despite the improvements in waitlist mortality, regions with low rates of lung donation, primarily rural areas, have suffered disproportionately. Areas in the lowest quartile of lung availability had an 84 percent increased risk of waitlist death and a 57 percent lower transplantation rate than the top quartile.[4] In fact, simply moving to an adjacent donor service area a few miles away might double a patient’s chances of receiving a lung transplant, significantly more than that patient being bumped into a higher lung allocation score bracket.[5] That is, driving across an arbitrary border might increase one’s chances of receiving a new set of lungs. Unsurprisingly, analysis of data over the last decade shows that donor service areas are independently associated with disparities in access to lung transplants significantly more than any other factor, including gender, ethnicity, diagnosis group, or age. ll. The Future: Machine Perfusion and Equity in Organ Allocation Farther allocation distances are associated with sharper drops in waitlist mortality. A model from Stanford University demonstrates that expanding the existing 250-mile threshold to a 500-mile threshold would decrease waitlist mortality by 21.3 percent; an expansion of 1000 miles would lower it by 31.8 percent.[6] Since lungs are already more delicate than other solid organs,[7] an expansion would require better and longer preservation. The answer is already here: machine perfusion. Ex vivo machine perfusion of organs prior to transplantation has grown remarkably over the past two decades, with recent clinical trial results demonstrating the ability of machine perfusion to resuscitate and assess “marginal” organs prior to transplantation.[8] Many centers around the U.S. already apply machine perfusion to expand the donor pool, and the adoption of machine perfusion as common practice is burgeoning. While the availability of more organs will decrease waiting list mortality, it alone will not address the longstanding geographical disparities. In fact, unless there is deliberate preparation by UNOS, this new biotechnology could very easily exacerbate geographic disparities. It is currently an expensive technology that is exclusive to urban centers with an already high organ availability. Proper foresight before widespread adoption is critical. As machine perfusion will extend the preservation of all solid organs, discussions must start taking place now regarding larger allocation boundaries or even a boundless system altogether. One concern is that organs resuscitated in this manner will have lower efficacy than organs preserved on ice and rapidly transplanted. Yet, a recent retrospective study from the Toronto group showed that longer perfusion times over 12 hours do not impact patient outcomes,[9] and some groups have had success with preservation times over 20 hours.[10] In addition to longer preservation times, machine perfusion can easily be made portable. Data from a recent international pivotal trial using the Organ Care System (OCS) from the Massachusetts-based company TransMedics showed the promising ability of portable machine perfusion to preserve and resuscitate marginal lungs. Indeed, while much of the attention around machine perfusion has been about its capability to resuscitate marginal organs, its secondary ability, allowing farther transport of lungs, could end geographic disparities in organ allocation. Before it is universally adopted into clinical practice, it is imperative that UNOS acts now to direct hospitals on how to integrate machine perfusion into procurement networks. There also must be preemptive policies regarding out-of-hospital perfusion centers. The first and only example thus far is the private corporation Lung Bioengineering, located in Silver Spring, Maryland. This standalone center aims to resuscitate and analyze declined lungs via machine perfusion, shipping viable ones to nearby U.S. transplant centers. The company is currently finishing a phase 2 clinical trial assessing the safety of extending lung preservation times with it. Unless decisive action is taken now, these centers will continue to open exclusively in urban areas surrounded by high-volume centers. To engage in the UNOS organ allocation system, private corporations should be required to distribute to rural and previously under-resourced areas. This could be accomplished by setting up satellite campuses or investing in the necessary infrastructure to preserve and deliver organs far distances portably. CONCLUSION We finally have the tools to extinguish the perennial problem of geographic disparities in organ allocation. Within the next five to ten years, there will be widespread adoption of machine perfusion, both in hospitals and in out-of-hospital perfusion centers. In an already convoluted organ allocation system, it will further complicate organ allocation and will potentially worsen disparities if action is not taken upfront. Establishing regulations to ensure machine perfusion is leveraged in a way that is equitable to all who need solid organ transplants, not only those who live within 250 miles of transplant centers, is crucial. It is necessary for UNOS to be ahead of the curve, mitigate these potential consequences, and reprioritize the ethical principles on which the field was founded. This example should serve as a model for how biotechnology can ameliorate disparities – geographic or otherwise – in scarce resource allocation in healthcare. [1] Lynch, R. J., and R. E. Patzer. 2019. "Geographic inequity in transplant access." Curr Opin Organ Transplant 24 (3): 337-342. https://doi.org/10.1097/MOT.0000000000000643. [2] Goff, R. R., E. D. Lease, S. Sweet, A. Robinson, and D. Stewart. 2020. “Measuring and Monitoring Equity in Access to Deceased Donor Lung Transplants among Waitlisted Candidates.” J Hear Lung Transplant 39 (4): S216. https://doi.org/10.1016/j.healun.2020.01.847. [3] Egan, T. M. 2018. "From 6 years to 5 days for organ allocation policy change." J Heart Lung Transplant 37 (5): 675-677. https://doi.org/10.1016/j.healun.2017.12.010. [4] Benvenuto, L. J., D. R. Anderson, H. P. Kim, J. L. Hook, L. Shah, H. Y. Robbins, F. D'Ovidio, M. Bacchetta, J. R. Sonett, S. M. Arcasoy, and Program From the Columbia University Lung Transplant. 2018. "Geographic disparities in donor lung supply and lung transplant waitlist outcomes: A cohort study." Am J Transplant 18 (6): 1471-1480. https://doi.org/10.1111/ajt.14630. [5] Kosztowski, M., S. Zhou, E. Bush, R. S. Higgins, D. L. Segev, and S. E. Gentry. 2019. "Geographic disparities in lung transplant rates." Am J Transplant 19 (5): 1491-1497. https://doi.org/10.1111/ajt.15182. [6] Mooney, J. J., J. Bhattacharya, and G. S. Dhillon. 2019. "Effect of broader geographic sharing of donor lungs on lung transplant waitlist outcomes." J Heart Lung Transplant 38 (2): 136-144. https://doi.org/10.1016/j.healun.2018.09.007. [7] Possoz, J., A. Neyrinck, and D. Van Raemdonck. 2019. "Ex vivo lung perfusion prior to transplantation: an overview of current clinical practice worldwide." J Thorac Dis 11 (4): 1635-1650. https://doi.org/10.21037/jtd.2019.04.33. [8] Noah, C. V., P. Tratnig-frankl, S. Raigani, C. Cetrulo, K. Uygun, and H. Yeh. 2020. “Moving the Margins: Updates on the Renaissance in Machine Perfusion for Organ Transplantation.” Curr Transplant Reports 7 (2): 1-10. https://doi.org/10.1007/s40472-020-00277-z. [9] Yeung, J. C., T. Krueger, K. Yasufuku, M. de Perrot, A. F. Pierre, T. K. Waddell, L. G. Singer, S. Keshavjee, and M. Cypel. 2017. "Outcomes after transplantation of lungs preserved for more than 12 h: a retrospective study." Lancet Respir Med 5 (2): 119-124. https://doi.org/10.1016/S2213-2600(16)30323-X. [10] Cypel, M., A. Neyrinck, and T. N. Machuca. 2019. "Ex vivo perfusion techniques: state of the art and potential applications." Intensive Care Med 45 (3): 354-356. https://doi.org/10.1007/s00134-019-05568-3.

Photo by Ishan @seefromthesky on Unsplash ABSTRACT A strike to highlight the plight facing contract doctors which has been proposed has received mixed reactions from those within the profession and the public. This unprecedented nationwide proposal has the potential to cause real-world effects, posing an ethical dilemma. Although strikes are common, especially in high-income countries, these industrial actions by doctors in Malaysia are almost unheard of. Reviewing available evidence from various perspectives is therefore imperative to update the profession and the complexity of invoking this important human right. INTRODUCTION Contract doctors in Malaysia held a strike on July 26, 2021. COVID-19 cases are increasing in Malaysia. In June, daily cases ranged between 4,000 to 8,000 despite various public health measures. The R naught, which indicates the infectiousness of COVID-19, remains unchanged. During the pandemic, health care workers (HCWs) have been widely celebrated, resulting in a renewed appreciation of the risks that they face.[1] The pandemic has exposed flawed governance in the public healthcare system, particularly surrounding the employment of contract doctors. Contract doctors in Malaysia are doctors who have completed their medical training, as well as two years of internship, and have subsequently been appointed as medical officers for another two years. Contract doctors are not permanently appointed, and the system did not allow extensions after the two years nor does it offer any opportunity to specialize.[2] Last week, Parliament did decide to offer a two-year extension but that did not hold off the impending strike.[3] In 2016, the Ministry of Health introduced a contract system to place medical graduates in internship positions at government healthcare facilities across the country rather than placing them in permanent posts in the Public Service Department. Social media chronicles the issues that doctors in Malaysia faced. However, tensions culminated when and contract doctors called for a strike which ended up taking place in late July 2021. BACKGROUND Over the past decade, HCW strikes have arisen mostly over wages, work hours, and administrative and financial factors.[4] In 2012, the British Medical Association organized a single “day of action” by boycotting non-urgent care as a response to government pension reforms.[5] In Ireland, doctors went on strike for a day in 2013 to protest the austerity measures implemented by the EU in response to the global economic crisis. It involved a dispute over long working hours (100 hours per week) which violated EU employment laws and more importantly put patients’ lives at risk.[6] The strike resulted in the cancellation of 15,000 hospital appointments, but emergencies services were continued. Other major strikes have been organized in the UK to negotiate better pay for HCWs in general and junior doctors’ contracts specifically.[7] During the COVID-19 pandemic, various strikes have also been organized in Hong Kong, the US, and Bolivia due to various pitfalls in managing the pandemic.[8] A recent strike in August 2020 by South Korean junior doctors and medical students was organized to protest a proposed medical reform plan which did not address wage stagnation and unfair labor practices.[9] These demands are somewhat similar to the proposed strike by contract doctors in Malaysia. As each national health system operates within a different setting, these strikes should be examined in detail to understand the degree of self-interest involved versus concerns for patient’s welfare. l. The Malaysia Strike An anonymous group planned the current strike in Malaysia. The group used social media, garnering the attention of various key stakeholders including doctors, patients, government, and medical councils.[10] The organizers of the strike referred to their planned actions as a hartal. (Although historically a hartal involved a total shutdown of workplaces, offices, shops, and other establishments as a form of civil disobedience, the Malaysian contract doctors pledged no disturbance to healthcare working hours or services and intend a walk-out that is symbolic and reflective of a strike.)[11] The call to action mainly involved showing support for the contract doctors with pictures and placards. The doctors also planned the walk-out.[12] Despite earlier employment, contract medical doctors face many inequalities as opposed to their permanent colleagues. These include differences in basic salary, provisions of leave, and government loans despite doing the same job. The system disadvantages contract doctors offering little to no job security and limited career progression. Furthermore, reports in 2020 showed that close to 4,000 doctors’ contracts were expected to expire by May 2022, leaving their futures uncertain.[13] Some will likely be offered an additional two years as the government faces pressure from the workers. Between December 2016 and May 2021, a total of 23,077 contract doctors were reportedly appointed as medical officers, with only 789 receiving permanent positions.[14] It has been suggested that they are appointed into permanent positions based on merit but the criteria for the appointments remain unclear. Those who fail to acquire a permanent position inevitably seek employment elsewhere. During the COVID-19 pandemic, there have been numerous calls for the government to absorb contract doctors into the public service as permanent staff with normal benefits. This is important considering a Malaysian study that revealed that during the pandemic over 50 percent of medical personnel feel burned out while on duty.[15] This effort might be side-lined as the government prioritizes curbing the pandemic. As these issues remain neglected, the call for a strike should be viewed as a cry for help to reignite the discussions about these issues. ll. Right to strike The right to strike is recognized as a fundamental human right by the UN and the EU.[16] Most European countries also protect the right to strike in their national constitutions.[17] In the US, the Taft-Hartley Act in 1947 prohibited healthcare workers of non-profit hospitals to form unions and engage in collective bargaining. But this exclusion was repealed in 1947 and replaced with the requirement of a 10-day advanced written notice prior to any strike action.[18] Similarly, Malaysia also recognizes the right to dispute over labor matters, either on an individual or collective basis. The Industrial Relations Act (IRA) of 1967[19] describes a strike as: “the cessation of work by a body of workers acting in combination, or a concerted refusal or a refusal under a common understanding of a number of workers to continue to work or to accept employment, and includes any act or omission by a body of workers acting in combination or under a common understanding, which is intended to or does result in any limitation, restriction, reduction or cessation of or dilatoriness in the performance or execution of the whole or any part of the duties connected with their employment” According to the same act, only members of a registered trade union may legally participate in a strike with prior registration from the Director-General of Trade Unions.[20] Under Section 43 of the IRA, any strike by essential services (including healthcare) requires prior notice of 42 days to their employer.[21] Upon receiving the notice, the employer is responsible for reporting the particulars to the Director-General of Industrial Relations to allow a “cooling-off” period and appropriate action. Employees are also protected from termination if permitted by the Director-General and strike is legalized. The Malaysian contract healthcare workers’ strike was announced and transparent. Unfortunately, even after legalization, there is fear that the government may charge those participating in the legalized strike.[22] The police have announced they will pursue participants in the strike.[23] Even the Ministry of Health has issued a warning stating that those participating in the strike may face disciplinary actions from the ministry. However, applying these laws while ignoring the underlying issues may not bode well for the COVID-19 healthcare crisis. lll. Effects of a Strike on Health Care There is often an assumption that doctors’ strikes would unavoidably cause significant harm to patients. However, a systematic review examining several strikes involving physicians reported that patient mortality remained the same or fell during the industrial action.[24] A study after the 2012 British Medical Association strike has even shown that there were fewer in-hospital deaths on the day, both among elective and emergency populations, although neither difference was significant.[25] Similarly, a recent study in Kenya showed declines in facility-based mortality during strike months.[26] Other studies have shown no obvious changes in overall mortality during strikes by HCWs.[27] There is only one report of increased mortality associated with a strike in South Africa[28] in which all the doctors in the Limpopo province stopped providing any treatment to their patients for 20 consecutive days. During this time, only one hospital continued providing services to a population of 5.5 million people. Even though their data is incomplete, authors from this study found that the number of emergency room visits decreased during the strike, but the risks of mortality in the hospital for these patients increased by 67 percent.[29] However, the study compared the strike period to a randomly selected 20-day period in May rather than comparing an average of data taken from similar dates over previous years. This could greatly influence variations between expected annual hospital mortality possibly due to extremes in weather that may exacerbate pre-existing conditions such as heart failure during warmer months or selecting months with a higher incidence of viral illness such as influenza. Importantly, all strikes ensured that emergency services were continued, at least to the degree that is generally offered on weekends. Furthermore, many doctors still provide usual services to patients despite a proclaimed strike. For example, during the 2012 BMA strike, less than one-tenth of doctors were estimated to be participating in the strike.[30] Emergency care may even improve during strikes, especially those involving junior doctors who are replaced by more senior doctors.[31] The cancellation of elective surgeries may also increase the number of doctors available to treat emergency patients. Furthermore, the cancellation of elective surgery is likely to be responsible for transient decreases in mortality. Doctors also may get more rest during strike periods. Although doctor strikes do not seem to increase patient mortality, they can disrupt delivery of healthcare.[32] Disruptions in delivery of service from prolonged strikes can result in decline of in-patient admissions and outpatient service utilization, as suggested during strikes in the UK in 2016.[33] When emergency services were affected during the last strike in April, regular service was also significantly affected. Additionally, people might need to seek alternative sources of care from the private sector and face increased costs of care. HCWs themselves may feel guilty and demotivated because of the strikes. The public health system may also lose trust as a result of service disruption caused by high recurrence of strikes. During the COVID-19 pandemic, as the healthcare system remains stretched, the potential adverse effects resulting from doctor strikes remain uncertain and potentially disruptive. In the UK, it is an offence to “willfully and maliciously…endanger human life or cause serious bodily injury.”[34] Likewise, the General Medical Council (GMC) also requires doctors to ensure that patients are not harmed or put at risk by industrial action. In the US, the American Medical Association code of ethics prohibits strikes by physicians as a bargaining tactic, while allowing some other forms of collective bargaining.[35] However, the American College of Physicians prohibits all forms of work stoppages, even when undertaken for necessary changes to the healthcare system. Similarly, the Delhi Medical Council in India issued a statement that “under no circumstances doctors should resort to strike as the same puts patient care in serious jeopardy.”[36] On the other hand, the positions taken by the Malaysian Medical Council (MMC) and Malaysian Medical Association (MMA) on doctors’ strikes are less clear when compared to their Western counterparts. The MMC, in their recently updated Code of Professional Conduct 2019, states that “the public reputation of the medical profession requires that every member should observe proper standards of personal behavior, not only in his professional activities but at all times.” Strikes may lead to imprisonment and disciplinary actions by MMC for those involved. Similarly, the MMA Code of Medical Ethics published in 2002 states that doctors must “make sure that your personal beliefs do not prejudice your patients' care.”[37] The MMA which is traditionally meant to represent the voices of doctors in Malaysia, may hold a more moderate position on strikes. Although HCW strikes are not explicitly mentioned in either professional body’s code of conduct and ethics, the consensus is that doctors should not do anything that will harm patients and they must maintain the proper standard of behaviors. These statements seem too general and do not represent the complexity of why and how a strike could take place. Therefore, it has been suggested that doctors and medical organizations should develop a new consensus on issues pertaining to medical professional’s social contract with society while considering the need to uphold the integrity of the profession. Experts in law, ethics, and medicine have long debated whether and when HCW strikes can be justified. If a strike is not expected to result in patient harm it is perhaps acceptable.[38] Although these debates have centered on the potential risks that strikes carry for patients, these actions also pose risks for HCWs as they may damage morale and reputation.[39] Most fundamentally, strikes raise questions about what healthcare workers owe society and what society owes them. For strikes to be morally permissible and ethical, it is suggested that they must fulfil these three criteria:[40] a. Strikes should be proportionate, e., they ‘should not inflict disproportionate harm on patients’, and hospitals should as a minimum ‘continue to provide at least such critical services as emergency care.’ b. Strikes should have a reasonable hope of success, at least not totally futile however tough the political rhetoric is. c. Strikes should be treated as a last resort: ‘all less disruptive alternatives to a strike action must have been tried and failed’, including where appropriate ‘advocacy, dissent and even disobedience’. The current strike does not fulfil the criteria mentioned. As Malaysia is still burdened with a high number of COVID-19 cases, a considerable absence of doctors from work will disrupt health services across the country. Second, since the strike organizer is not unionized, it would be difficult to negotiate better terms of contract and career paths. Third, there are ongoing talks with MMA representing the fraternity and the current government, but the time is running out for the government to establish a proper long-term solution for these contract doctors. One may argue that since the doctors’ contracts will end in a few months with no proper pathways for specialization, now is the time to strike. However, the HCW right to strike should be invoked only legally and appropriately after all other options have failed. CONCLUSION The strike in Malaysia has begun since the drafting of this paper. Doctors involved assure that there will not be any risk to patients, arguing that the strike is “symbolic”.[41] Although an organized strike remains a legal form of industrial action, a strike by HCWs in Malaysia poses various unprecedented challenges and ethical dilemmas, especially during the pandemic. The anonymous and uncoordinated strike without support from the appropriate labor unions may only spark futile discussions without affirmative actions. It should not have taken a pandemic or a strike to force the government to confront the issues at hand. It is imperative that active measures be taken to urgently address the underlying issues relating to contract physicians. As COVID-19 continues to affect thousands of people, a prompt reassessment is warranted regarding the treatment of HCWs, and the value placed on health care. [1] Ministry of Health (MOH) Malaysia, “Current situation of COVID-19 in Malaysia.” http://covid-19.moh.gov.my/terkini (accessed Jul. 01, 2021). [2] “Future of 4,000 young doctors who are contract medical officers uncertain,” New Straits Times - November 26, 2020. https://www.nst.com.my/news/nation/2020/11/644563/future-4000-young-doctors-who-are-contract-medical-officers-uncertain [3] “Malaysia doctors strike, parliament meets as COVID strain shows,” Al Jazeera, July 26, 2021. https://www.aljazeera.com/news/2021/7/26/malaysia-doctors-strike-parliament-meets-as-covid-strains-grow [4] R. Essex and S. M. Weldon, “Health Care Worker Strikes and the Covid Pandemic,” N. Engl. J. Med., vol. 384, no. 24, p. e93, Jun. 2021, doi: 10.1056/NEJMp2103327; G. Russo et al., “Health workers’ strikes in low-income countries: the available evidence,” Bull. World Health Organ., vol. 97, no. 7, pp. 460-467H, Jul. 2019, doi: 10.2471/BLT.18.225755. [5] M. Ruiz, A. Bottle, and P. Aylin, “A retrospective study of the impact of the doctors’ strike in England on 21 June 2012,” J. R. Soc. Med., vol. 106, no. 9, pp. 362–369, 2013, doi: 10.1177/0141076813490685. [6] E. Quinn, “Irish Doctors Strike to Protest Work Hours Amid Austerity,” The Wall Street Journal, 2013. https://www.wsj.com/articles/no-headline-available-1381217911?tesla=y (accessed Jun. 29, 2021). [7] “NHS workers back strike action in pay row by 2-to-1 margin,” The Guardian, 2014. https://www.theguardian.com/society/2014/sep/18/nhs-workers-strike-pay-unison-england (accessed Jun. 29, 2021); M. Limb, “Thousands of junior doctors march against new contract,” BMJ, p. h5572, Oct. 2015, doi: 10.1136/bmj.h5572. [8] J. Parry, “China coronavirus: Hong Kong health staff strike to demand border closure as city records first death,” BMJ, vol. 368, no. February, p. m454, Feb. 2020, doi: 10.1136/bmj.m454; “MultiCare healthcare workers strike, urging need for more PPEs, staff support,” Q13 FOX, 2020. https://www.q13fox.com/news/health-care-workers-strike-urging-need-for-ppes-risks-on-patient-safety (accessed Jun. 29, 2021); “Bolivia healthcare workers launch strike in COVID-hit region,” Al Jazeera, 2021. https://www.aljazeera.com/news/2021/2/9/bolivia-healthcare-workers-strike-covid-hit-region (accessed Jun. 29, 2021). [9] K. Arin, “Why are Korean doctors striking?” The Korea Herald, 2020. http://www.koreaherald.com/view.php?ud=20200811000941 (accessed Jun. 29, 2021). [10] “Hartal Doktor Kontrak,” Facebook. https://www.facebook.com/hartaldoktorkontrak. [11] “Hartal,” Oxford Advanced Learner’s Dictionary. https://www.oxfordlearnersdictionaries.com/definition/english/hartal (accessed Jun. 29, 2021). [12] “Hartal Doktor Kontrak,” Facebook. https://www.facebook.com/hartaldoktorkontrak. [13] R. Anand, “Underpaid and overworked, Malaysia’s contract doctors’ revolt amid Covid-19 surge,” The Straits Times, 2021. [14] Anand. [15] N. S. Roslan, M. S. B. Yusoff, A. R. Asrenee, and K. Morgan, “Burnout prevalence and its associated factors among Malaysian healthcare workers during covid-19 pandemic: An embedded mixed-method study,” Healthc., vol. 9, no. 1, 2021, doi: 10.3390/healthcare9010090. [16] Maina Kiai, “Report by the Special Rapporteur on the Right to Freedom of Peaceful Assembly and Association,” 2016. [Online]. Available: http://freeassembly.net/wp-content/uploads/2016/10/A.71.385_E.pdf. [17] ETUI contributors, Strike rules in the EU27 and beyond. The European Trade Union Institute. ETUI, 2007. [18] National Labor Relations Board, National Labor Relations Act. 1935, pp. 151–169. [19] Ministry of Human Resources, Industrial Relations Act 1967 (Act 177), no. October. 2015, pp. 1–76. [20] Article 10 of the Federal Constitution states that all citizens have the right to form associations including registered trade or labor unions. A secret ballot with two-third majority will suffice to call for a strike required for submission to the DGTU within 7 days as stated in Section 25(A) of the Trade Union Act 1959. [21] Ministry of Human Resources Malaysia, Guidelines on Strikes, Pickets and Lockouts in Malaysia. Putrajaya, 2011. [22] Ordinance Emergency which was declared in Malaysia since 12 January 2021. Under the Ordinance Emergency, the king or authorized personnel may, as deemed necessary, demand any resources. [23] “Malaysia doctors strike, parliament meets as COVID strain shows,” Al Jazeera, July 26, 2021. https://www.aljazeera.com/news/2021/7/26/malaysia-doctors-strike-parliament-meets-as-covid-strains-grow [24] S. A. Cunningham, K. Mitchell, K. M. Venkat Narayan, and S. Yusuf, “Doctors’ strikes and mortality: A review,” Soc. Sci. Med., vol. 67, no. 11, pp. 1784–1788, Dec. 2008, doi: 10.1016/j.socscimed.2008.09.044. [25] M. Ruiz, A. Bottle, and P. Aylin, “A retrospective study of the impact of the doctors’ strike in England on 21 June 2012,” J. R. Soc. Med., vol. 106, no. 9, pp. 362–369, 2013, doi: 10.1177/0141076813490685. [26] G. K. Kaguthi, V. Nduba, and M. B. Adam, “The impact of the nurses’, doctors’ and clinical officer strikes on mortality in four health facilities in Kenya,” BMC Health Serv. Res., vol. 20, no. 1, p. 469, Dec. 2020, doi: 10.1186/s12913-020-05337-9. [27] G. Ong’ayo et al., “Effect of strikes by health workers on mortality between 2010 and 2016 in Kilifi, Kenya: a population-based cohort analysis,” Lancet Glob. Heal., vol. 7, no. 7, pp. e961–e967, Jul. 2019, doi: 10.1016/S2214-109X (19)30188-3. [28] M. M. Z. U. Bhuiyan and A. Machowski, “Impact of 20-day strike in Polokwane Hospital (18 August - 6 September 2010),” South African Med. J., vol. 102, no. 9, p. 755, Aug. 2012, doi: 10.7196/SAMJ.6045. [29] M. M. Z. U. Bhuiyan and A. Machowski, “Impact of 20-day strike in Polokwane Hospital (18 August - 6 September 2010),” South African Med. J., vol. 102, no. 9, p. 755, Aug. 2012, doi: 10.7196/SAMJ.6045. [30] M. Ruiz, A. Bottle, and P. Aylin, “A retrospective study of the impact of the doctors’ strike in England on 21 June 2012,” J. R. Soc. Med., vol. 106, no. 9, pp. 362–369, 2013, doi: 10.1177/0141076813490685. [31] D. Metcalfe, R. Chowdhury, and A. Salim, “What are the consequences when doctors strike?” BMJ, vol. 351, no. November, pp. 1–4, 2015, doi: 10.1136/bmj.h6231. [32] D. Waithaka et al., “Prolonged health worker strikes in Kenya- perspectives and experiences of frontline health managers and local communities in Kilifi County,” Int. J. Equity Health, vol. 19, no. 1, pp. 1–15, 2020, doi: 10.1186/s12939-020-1131-y. [33] The study has shown that there were 9.1% reduction in admissions and around 6% fewer emergency cases and outpatient appointments than expected. An additional 52% increase in expected outpatient appointments cancelations were made by hospitals during that period. D. Furnivall, A. Bottle, and P. Aylin, “Retrospective analysis of the national impact of industrial action by English junior doctors in 2016,” BMJ Open, vol. 8, no. 1, p. e019319, Jan. 2018, doi: 10.1136/bmjopen-2017-019319. [34] D. Metcalfe, R. Chowdhury, and A. Salim, “What are the consequences when doctors strike?” BMJ, vol. 351, no. November, pp. 1–4, 2015, doi: 10.1136/bmj.h6231. [35] R. Essex and S. M. Weldon, “Health Care Worker Strikes and the Covid Pandemic,” N. Engl. J. Med., vol. 384, no. 24, p. e93, Jun. 2021, doi: 10.1056/NEJMp2103327. [36] M. Selemogo, “Criteria for a just strike action by medical doctors,” Indian J. Med. Ethics, vol. 346, no. 21, pp. 1609–1615, Jan. 2014, doi: 10.20529/IJME.2014.010. [37] Malaysian Medical Association, “Malaysian Medical Association Official Website.” https://mma.org.my (accessed Jun. 29, 2021). [38] M. Toynbee, A. A. J. Al-Diwani, J. Clacey, and M. R. Broome, “Should junior doctors strike?” J. Med. Ethics, vol. 42, no. 3, pp. 167–170, Mar. 2016, doi: 10.1136/medethics-2015-103310. [39] R. Essex and S. M. Weldon, “Health Care Worker Strikes and the Covid Pandemic,” N. Engl. J. Med., vol. 384, no. 24, p. e93, Jun. 2021, doi: 10.1056/NEJMp2103327. [40] M. Selemogo, “Criteria for a just strike action by medical doctors,” Indian J. Med. Ethics, vol. 346, no. 21, pp. 1609–1615, Jan. 2014, doi: 10.20529/IJME.2014.010; A. J. Roberts, “A framework for assessing the ethics of doctors’ strikes,” J. Med. Ethics, vol. 42, no. 11, pp. 698–700, Nov. 2016, doi: 10.1136/medethics-2016-103395. [41] “Malaysia doctors strike, parliament meets as COVID strain shows,” Al Jazeera, July 26, 2021. https://www.aljazeera.com/news/2021/7/26/malaysia-doctors-strike-parliament-meets-as-covid-strains-grow

Photo by Sébastien Goldberg on Unsplash ABSTRACT Rohingya women face challenges that ought to be acknowledged and addressed to ensure that when they seek health care, they can act autonomously and decide freely among available options. Self-determination theory offers valuable insight into supporting these women within their unique situations. INTRODUCTION In August of 2017, military and paramilitary forces in Myanmar began purging the Rohingya Muslim population from the country, motivated by anti-Muslim prejudice of the Buddhist political and social majority. Mass murder, property destruction, kidnapping, torture, and sexual violence still affect Rohingya communities. As a result, more than a million individuals have fled Myanmar.[1] As of February 2021, approximately 880,000 Rohingya Muslims have taken refuge in Cox’s Bazar, Bangladesh, the site of the largest refugee camps in the world.[2] The public health focus in these camps is on treatment of physical ailments and infectious diseases.[3] While women of reproductive age and adolescent girls experience the highest level of violence among Rohingya communities in both Myanmar and Bangladesh, they have consistently lacked access to sufficient sexual and reproductive care. In 1994, the Women’s Commission for Refugee Women and Children exposed issues surrounding the sexual and reproductive health of displaced populations and propelled the recognition of SRH as a human right.[4] Human rights interventionists and public health officials have made progress in the integration of sexual and reproductive health education, facilities, and resources into refugee camps in Cox’s Bazar. This includes the introduction of menstrual cleanliness facilities and educational conversations. However, Rohingya women and male cultural leaders, or gatekeepers, remain reluctant to accept these resources and education.[5] The prevalence of gender-based violence against women and restrictive policies enforced by the Bangladesh government heighten the barriers to the effective introduction of sexual and reproductive health resources and services.[6] A wealth of literature has pushed for the extension of clinical duties of beneficence and non-maleficence in the diagnosis and treatment of refugee and asylum-seeking communities.[7] Additionally, extensive research on Rohingya refugee communities has searched for ways to work around the complex social history and to accommodate power structures by integrating gatekeepers into SRH discussions.[8] However, as interventions have sought to overcome cultural and religious barriers, they have largely overlooked the protection of autonomy of sexual and reproductive health patients in Cox’s Bazar. This paper argues two points. First, attempts at improving outcomes in Cox’s Bazar ought to lead to Rohingya women’s autonomy and self-determination, both in mitigating control of male leaders over sexual and reproductive decisions and in ensuring the understanding and informed consent between patients and providers. Second, policy decisions ought to ensure post-treatment comprehensive care to shield Rohingya women from retribution by male community members. Self-determination theory offers guidance for state leaders and healthcare providers in pursuing these goals. l. Barriers to Sexual and Reproductive Health Services for Rohingya Women As part of its anti-Muslim narrative, the Buddhist majority has painted Rohingya women as hyper-reproductive. False narratives “of a Rohingya plan to spread Islam by driving demographic shifts” and accusations against Rohingya women for having “unusually large families” have motivated violent behavior and discriminatory regulations against Rohingya communities.[9] In reality, demographic data shows that “the Rohingya population has remained stable at 4% since 1980.”[10] In 2013, the government of Myanmar imposed regulations on Rohingya families in the Rakhine state, the region with the highest population of Rohingya Muslims, enforcing a two-child limit and requiring that Rohingya women obtain government authorization to marry and take a pregnancy test before receiving such permission. The majority has also subjected Rohingya females to acts of sexual violence to ostracize them and “dilute” Rohingya identity.[11] As a result, Rohingya women in Cox’s Bazar experience unique illnesses and vulnerabilities requiring imminent treatment. Due to national policies in Bangladesh, “Rohingya [women] cannot receive HIV/AIDS testing and treatment in camps; birth control implants delivered by midwives; and comprehensive abortion care.”[12] Additionally, in accordance with patriarchal Rohingya community structure, male gatekeepers hold high authority over sexual and reproductive decisions of women, evidenced by the persistence of gender-based violence within refugee camps and traditional practices such as the marriage of minor girls to older Rohingya men.[13] Surveys of community members reveal that cultural and religious stigma against sexual and reproductive health care exists among these male gatekeepers as well as Rohingya women.[14] Due to their cultural and political position, Rohingya women are subject to unique power relations. This paper analyzes the ethical dilemmas that arise from two of those power relations: Rohingya women’s relationships with male gatekeepers and their relationships with interventionist healthcare providers. ll. Ethics of Including Male Community Members in Decisions Affecting Women’s Healthcare Autonomy A November 2019 survey of Rohingya women in Cox’s Bazar that had married or given birth within the past two years found that “around one half of the female Rohingya refugees do not use contraceptives, mainly because of their husbands’ disapproval and their religious beliefs.”[15] There are widespread misconceptions such as the belief that Islam does not permit the use of contraceptives.[16] The existence of such misconceptions and the power husbands and male leaders hold over the delivery of treatment creates dilemmas for healthcare practitioners in conforming to ethical principles of care. lll. Beneficence in Providing Care to Refugees While public health scholars and government officials hold divided opinions on the level of treatment required to fulfill refugees’ right to sexual and reproductive health care, most support enough care to ensure physical and psychological well-being.[17] Beneficence requires that healthcare providers and states “protect the rights of others[,] prevent harm from occurring to others[, and] remove conditions that will cause harm to others.”[18] Under the principle of beneficence, there is a duty to provide sexual and reproductive treatment to Rohingya women in Cox’s Bazar that is comparable to that received by citizens of the host state. In addition, the ethical principle of nonmaleficence may call for the creation of specialized care facilities for refugee communities, because a lack of response to refugees’ vulnerability and psychological trauma has the potential to generate additional harm.[19] In response to gendered power relations among the Rohingya community, husbands and male leaders are included in decisions surrounding maternal health and sexual and reproductive care for women. For example, healthcare professionals “have been found to impose conditions on SRH [sexual reproductive health] care that are not stated in the national… [menstrual regulation] guidelines, such as having a husband’s permission.”[20] The refugee healthcare community could do more to mitigate the potential of retribution taken by male community members against women that accept care by dispelling common misconceptions and precluding male community members from influencing female reproductive choices.[21] However, some current practices allow the infiltration of male community leaders and husbands into the diagnosis, decision-making, and treatment spaces. Deferring decisions to male leaders for the sake of expediency risks conditioning women’s access to care on male buy-in and diminishes Rohingya women’s autonomy over their sexual and reproductive health. lV. Male Influence and Female Autonomy Ensuring patients control their own treatment decisions is an essential component of the ethical obligation of healthcare professionals to respect patients’ autonomy. While patients can exercise their autonomy to accept the direction of the community, their autonomy is undermined when “external sources or internal states… rob [such persons]… of self-directedness.”[22] Sexual and reproductive health research on Rohingya women revealed that the presence of male family members during conversations “made female respondents uncomfortable to speak openly about their SRH [sexual and reproductive health]related experiences.”[23] The same study found that when male family members were absent, Rohingya women were more transparent and willing to discuss such topics.[24] These findings indicate that the mere presence of male family members exerts control over Rohingya women in conversations with practitioners. Male involvement also stalls conversations between providers and Rohingya women which may harm the achievement of understanding and informed consent in diagnosis and treatment spaces.[25] Women do have the option of bringing their male community leaders and family members into sexual health discussions. Yet healthcare providers ought to monitor patients individually and avoid programmatic decision making regarding male involvement in the treatment space. While it is the ethical imperative of health interventionists and the state of Bangladesh to fulfill the duties of care required by the principles of beneficence and non-maleficence, the sole prioritization of expanding sexual and reproductive health care in Cox’s Bazar risks ignoring autonomy. V. Ethics of Paternalism in Provide-Patient Relations Rohingya women’s negative beliefs about contraceptives, such as the belief that they cause irreversible sterilization, are the second largest factor inhibiting their use.[26] To an extent, the Rohingya are justified in their skepticism. Prior to the 1990’s, Bangladesh used nonconsensual sterilization as a mechanism of population control to attain access to international aid. Though the international conversation surrounding reproduction shifted its focus towards reproductive rights following the 1994 UN International Conference on Population and Development, delivery of reproductive care in the global South is frequently characterized by lack of transparency and insufficient patient understanding of the risks and consequences of treatment. Additionally, women’s lack of control impacts follow-up care and long-term contraception. For example, when women seek the removal of implantable contraceptives, healthcare professionals often refuse to perform the requisite operation.[27] Patients must understand the risks of treatment in their own culture and circumstances where societal views, misconceptions, or fears may influence healthcare practices. Healthcare providers need to recognize the coercive potential they hold in their relations with patients and guard against breaches of patient autonomy in the delivery of treatment. In accordance with the principle of beneficence, healthcare providers treating refugees or individuals seeking asylum ought to abide by the same fiduciary responsibilities they hold toward citizens of the host state.[28] When patients show hesitancy or refusal toward treatment, healthcare providers ought to avoid achieving treatment by paternalistic practice such as “deception, lying, manipulation of information, nondisclosure of information, or coercion.”[29] Although well-intentioned, this practice undermines the providers’ obligation to respect patients’ autonomy.[30] The hesitancy of Rohingya women to accept some sexual or reproductive health care does not justify intentional lack of transparency, even when that treatment furthers their best health interests. However, paternalistic actions may be permissible and justified during medical emergencies.[31] Vl. Informed Consent Respecting Rohingya women’s autonomy also places affirmative duties on healthcare providers to satisfy understanding and informed consent. However, language barriers and healthcare providers’ misconceptions about Rohingya religion and culture impede the achievement of these core conditions of autonomy for Rohingya women.[32] In an interview, a paramedic in Cox’s Bazar described the types of conversations healthcare providers have with Rohingya women in convincing them to accept menstrual regulation treatment, a method to ensure that someone is not pregnant after a missed period: “We tell them [menstrual regulation] is not a sin… If you have another baby now, you will get bad impact on your health. You cannot give your children enough care. So, take MR [menstrual regulation] and care for your family.”[33] This message, like others conveyed to Rohingya women in counseling settings, carries unvalidated assumptions regarding the beliefs, needs, and desires of clients without making a proper attempt to confirm the truth of those assumptions. Healthcare providers’ lack of cultural competence and limited understanding of Bangladesh’s national reproductive health policy complicates communication with Rohingya women. Additionally, the use of simple language, though recommended by the WHO’s guideline on Bangladesh’s policy, is inadequate to sufficiently convey the risks and benefits of menstrual regulation and other treatments to Rohingya women.[34] For informed consent to be achieved, “the patient must have the capacity to be able to understand and assess the information given, communicate their choices and understand the consequences of their decision.”[35] Healthcare providers must convey sufficient information regarding the risks, benefits, and alternatives of treatment as well as the risks and benefits of forgoing treatment.[36] Sexual and reproductive health policies and practices must aim to simultaneously mitigate paternalism, promote voluntary and informed choice among Rohingya women, and foster cultural and political competency among healthcare providers. Vll. Self-Determination Theory Self-determination theory is a psychological model that focuses on types of natural motivation and argues for the fulfillment of three conditions shown to enhance self-motivation and well-being: autonomy, competence, and relatedness.[37] According to the theory, autonomy is “the perception of being the origin of one’s own behavior and experiencing volition in action;” competence is “the feeling of being effective in producing desired outcomes and exercising one’s capacities;” and, relatedness is “the feeling of being respected, understood, and cared for by others.”[38] Bioethicists have applied self-determination theory to health care to align the promotion of patient autonomy with traditional goals of enhancing patient well-being. Studies on the satisfaction of these conditions in healthcare contexts indicate that their fulfillment promotes better health outcomes in patients.[39] Like principlism, self-determination theory in Cox’s Bazar could allow for increased autonomy while maximizing the well-being of Rohingya women and behaving with beneficence Fostering self-determination requires that healthcare professionals provide patients with the opportunity and means of voicing their goals and concerns, convey all relevant information regarding treatment, and mitigate external sources of control where possible.[40] In Cox’s Bazar, health care organizations in the region and the international community can act to ensure women seeking health care are respected and able to act independently. A patient-centered care model would provide guidelines for the refugee setting.[41] Providers can maximize autonomy by utilizing language services to give SRH patients the opportunity and means to voice their goals and concerns, disclose sufficient information about risks, benefits, and alternatives to each procedure, and give rationales for each potential decision rather than prescribe a decision. They can promote the feeling of competence among patients by expressly notifying them of the level of reversibility of each treatment, introducing measures for health improvement, and outlining patients’ progress in their SRH health. Finally, they can promote relatedness by providing active listening cues and adopting an empathetic, rather than condescending, stance.[42] Healthcare organizations ought to provide training to promote cultural competency and ensure that practitioners are well-versed on national regulations regarding sexual reproductive health care in Bangladesh to avoid the presumption of patients’ desires and the addition of unnecessary barriers to care. Increased treatment options would make autonomy more valuable as women would have more care choices. Given the historical deference to international organizations like the UN and World Bank, multilateral and organizational intervention would likely bolster the expansion of treatment options. International organizations and donors ought to work with the government of Bangladesh to offer post-treatment comprehensive care and protection of women who choose treatment against the wishes of male community members to avoid continued backlash and foster relatedness.[43] CONCLUSION Rohingya women in Cox’s Bazar, Bangladesh face unique power relations that ought to be acknowledged and addressed to ensure that when they seek health care, they are able to act autonomously and decide freely among available options. While providers have duties under the principles of beneficence and non-maleficence, patient well-being is hindered when these duties are used to trump the obligation to respect patient autonomy. Current approaches to achieving sexual and reproductive health risk the imposition of provider and communal control. Self-determination theory offers avenues for global organizations, Bangladesh, donors, and healthcare providers to protect Rohingya women’s autonomous choices, while maximizing their well-being and minimizing harm. DISCLAIMER: As a male educated and brought up in a Western setting, I acknowledge my limitations in judgement about Rohingya women’s reproductive care. Their vulnerability and health risks can never be completely understood. To some extent, those limitations informed my theoretical approach and evaluation of Rohingya women's SRH care. Self-determination theory places the patients’ experiences and judgement at the center of decision-making. 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