tag:theconversation.com,2011:/id/topics/the-lancet-27511/articlesThe Lancet – The Conversation2023-11-28T16:52:50Ztag:theconversation.com,2011:article/2171952023-11-28T16:52:50Z2023-11-28T16:52:50ZNazi doctors weren’t just ‘a few bad apples’, shows report – and simplistic stories won’t help guard against future medical abuses<figure><img src="https://images.theconversation.com/files/561553/original/file-20231124-19-9jisak.jpeg?ixlib=rb-1.1.0&rect=0%2C3%2C2380%2C1705&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Jewish children kept alive in Auschwitz for use in Mengele's medical experiments.</span> <span class="attribution"><a class="source" href="https://collections.ushmm.org/search/catalog/pa14532">Alexander Voronzow/Wikimedia Commons</a></span></figcaption></figure><p>Extraordinary evil involves a total moral collapse across society caused by failure of individual humanity and ethical judgment. This was the conclusion of the philosopher <a href="https://www.newyorker.com/magazine/1963/02/16/eichmann-in-jerusalem-i">Hannah Arendt</a> after witnessing the trial of Adolf Eichmann – the chief architect of the Holocaust – in Jerusalem.</p>
<p>Medicine, which is supposed to alleviate human suffering, became a <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)02501-1/fulltext">willing accomplice</a> in Nazi mass murder. Although medical professionals had been involved in <a href="https://www.theguardian.com/education/2022/aug/11/london-medical-school-benefited-from-colonial-exploitation-report-finds">abusive practices</a> on human subjects and populations before, under Nazi rule the scale of their professional lapse was extreme in every respect. </p>
<p>Even before they launched the “final solution” against the Jews, Nazi authorities had already engaged in a covert, murderous project directed at people with disabilities in Germany. The <a href="https://www.sciencespo.fr/mass-violence-war-massacre-resistance/en/document/extermination-mentally-ill-and-handicapped-people-under-national-socialist-rule.html#footnote28_24kqndc">T-4 “euthanasia” programme</a> marked a terrifying climax of trends in medicine that was long in the making – and not unique to Germany. </p>
<p>These and other related failings of medical practice in the Third Reich were the subject of the Lancet Commission on medicine, Nazism, and the Holocaust. The conclusions were recently published in a <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01845-7/fulltext">comprehensive report</a>. The report was accepted for publication before October 7 – the date of the Hamas attack on Israel.</p>
<p>The report highlights the urgent need to expand our understanding of the history of medicine in Nazi Germany in order to “emphasise the unique opportunities and responsibilities of health professionals” to eliminate antisemitism and racism, and to protect “vulnerable populations against stigmatisation and discrimination”. </p>
<p>Learning about this dark episode in the recent past is not only crucial for fostering a “history-informed professional identity” but serves as a poignant cautionary tale of the fragility of core values of healthcare. </p>
<h2>Uncomfortable truths</h2>
<p>The report highlights uncomfortable truths, not only for Germany at the time but for humanity as a whole, then and now. </p>
<p>Once the second world war had ended and the full horror of the crimes perpetrated by the Nazi regime started to come to light, it was tempting to attribute all these excesses to the small clique of fanatical Nazis and staunch ideological followers, <a href="https://encyclopedia.ushmm.org/content/en/article/the-biological-state-nazi-racial-hygiene-1933-1939">motivated by extreme racial hatred</a>. This was the logic behind the <a href="https://www.roberthjackson.org/speech-and-writing/the-influence-of-the-nuremberg-trial-on-international-criminal-law/">post-war international trials</a> set up to bring to justice political, military and <a href="https://encyclopedia.ushmm.org/content/en/article/the-doctors-trial-the-medical-case-of-the-subsequent-nuremberg-proceedings">medical elites</a> of the Nazi regime. </p>
<p>Yet the Nazis did not invent modern racism – medical or otherwise. <a href="https://amp.theguardian.com/science/2022/jun/19/where-science-meets-fiction-the-dark-history-of-eugenics">Eugenics</a>, the belief in the ability of science to achieve human and social perfection through invasive interventions in genetics, was the product of 19th-century western modernity. So was the development of a modern global pseudoscience of “racial hygiene” that combined empirical research with long-standing prejudices and colonial mindsets. </p>
<p>Germany was already part of this broader trend. It was <a href="https://www.washingtonpost.com/archive/opinions/1994/02/20/aryan-nation-germanys-cruel-african-heritage/fe183603-d8c6-481b-bfe3-0ab31a637842/">on the cutting edge</a> but <a href="https://www.theguardian.com/news/2017/nov/10/how-colonial-violence-came-home-the-ugly-truth-of-the-first-world-war">not a lone pioneer</a>, let alone an outlier, in the 1930s. There were mainstream figures and doctors around the world who <a href="https://time.com/5414055/american-nazi-sympathy-book/">applauded the supposed boldness of Hitler’s regime</a> when it embarked on early experiments with forced sterilisations. </p>
<p>Inspiration for many Nazi racialist policies came from elsewhere, not least the <a href="https://muse.jhu.edu/article/3681/summary">western world</a>.</p>
<h2>Uncomfortable myths</h2>
<p>Still, under the Nazi regime medicine became “<a href="https://encyclopedia.ushmm.org/content/en/oral-history/benno-mueller-hill-discusses-genetics-and-eugenics">murderous science</a>” on an unprecedented scale. </p>
<p><a href="https://www.sciencedirect.com/science/article/pii/S0160252712000854?via%3Dihub">More than half of German doctors</a> had joined the Nazi party. This proportion was significantly higher compared with most other professional groups. </p>
<p>When the T-4 programme went into full murderous gear in 1940-41, it was overseen by distinguished research scientists in world-class establishments and <a href="https://www.gedenkstaette-hadamar.de/en/history/the-t4-programme-and-the-hadamar-killing-centre-1941/">medical staff across several institutions in Germany</a>, who translated <a href="https://encyclopedia.ushmm.org/content/en/article/euthanasia-program">Hitler’s order</a> into medical practice.</p>
<p>Doctors, nurses and care staff, as well as managers and “<a href="https://www.spiegel.de/international/germany/the-desk-murderer-exhibition-marks-50-year-anniversary-of-eichmann-trial-a-756261.html">desk murderers</a>” formed a chain of complicity that made all these murders possible and the system so brutally efficient.</p>
<p>Such a catastrophic failure of medical education, codes of practice, and individual moral judgment cannot be comprehended as the result of ideological fanaticism of the few and coercion of the many. Far from being a case of “a few bad apples”, the complicity of medical practitioners to Nazi evil was extensive, sustained and very often willing.</p>
<p>From the <a href="https://academic.oup.com/book/40410/chapter-abstract/347295636?redirectedFrom=fulltext">early forced sterilisation programmes</a> to the <a href="https://www.claimscon.org/about/history/closed-programs/medical-experiments/personal-statements-from-victims/">horrific medical experiments</a> conducted within the camps and the <a href="https://www.theguardian.com/commentisfree/cifamerica/2010/oct/21/secondworldwar-russia">mass starvation of enemy prisoners of war</a>, long-standing prejudices fed the Nazi machine, ensuring high levels of willing complicity or passive acceptance across all stages of implementation. </p>
<h2>Cautionary message</h2>
<p>All this matters for appreciating how eugenics and biological racism were allowed to run amok under the Nazi rule. It also carries a cautionary message that is relevant for the contemporary world. </p>
<p>Today, scientific progress, cultural sensibilities and ethics often find themselves on a collision course. <a href="https://www.who.int/news/item/16-05-2023-who-calls-for-safe-and-ethical-ai-for-health">Recent advances</a> in medical science and technology confront us with unprecedented possibilities but also complex dilemmas about patient safety and the value of human life. </p>
<p>The Lancet report highlights how learning about the history of health practice can prepare medical practitioners for confronting these and other challenges about the role of their profession in the 21st century. </p>
<p>More broadly, history-informed identities can also help undermine the deeper cultural and social biases that often weaken the moral resolve of whole societies, medical professionals included, and make the most radical form of evil possible, <a href="https://www.cabinetmagazine.org/issues/5/baer.php">in small, unspectacular steps</a>.</p><img src="https://counter.theconversation.com/content/217195/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Aristotle Kallis does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>It’s a fallacy that the medical atrocities carried out by the Nazis involved just a handful of radicalised doctors.Aristotle Kallis, Professor of Modern and Contemporary History, Keele UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1940492022-11-08T19:40:36Z2022-11-08T19:40:36ZFrom deficits to a spectrum, thinking around autism has changed. Now there are calls for a ‘profound autism’ diagnosis<figure><img src="https://images.theconversation.com/files/493985/original/file-20221107-14-gmzv1x.jpg?ixlib=rb-1.1.0&rect=24%2C40%2C5439%2C3596&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-photo/hanleystokeontrent-staffordshireunited-kingdom-july-14-600w-2178385225.jpg">Shutterstock</a></span></figcaption></figure><p>A heated debate about autism was reignited after the recent publication of an <a href="https://www.spectrumnews.org/opinion/viewpoint/its-time-to-embrace-profound-autism/?utm_source=Spectrum+Newsletters&utm_campaign=410c2aae31-DAILY_20221027_THURSDAY_PROFOUND+AUTISM+VP&utm_medium=email&utm_term=0_529db1161f-410c2aae31-168616145">article</a> advocating for use of the term “profound autism”.</p>
<p>This term is not an official part of the autism diagnosis. But the 2021 <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01541-5/fulltext">Lancet Commission on autism</a> – part the journal’s program to gather expertise on pressing global health and science issues – argued the term should refer to people with a diagnosis of autism who have very high support needs, such as 24-hour care for basic needs and safety. The Lancet Commission estimated that around 20% of autistic people meet criteria for “profound autism”.</p>
<p>Now debate centres on whether this term is an appropriate way to highlight the high support needs of a subgroup of autistic people – or whether the term may be a <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01541-5/fulltext">step backwards</a> for <a href="https://www.thenation.com/article/society/autism-division/">community understanding and acceptance</a>.</p>
<h2>The autism spectrum</h2>
<p>Our understanding of autism has changed dramatically over the past 30 years.</p>
<p>The term “autism” was <a href="https://link.springer.com/article/10.1007/s10803-021-04904-1">first introduced</a> into the diagnostic manual in 1980. To receive this diagnosis, children demonstrated significant development difficulties, such as “gross deficits in language development” and “a pervasive lack of responsiveness to other people”.</p>
<p>These difficulties meant people with a diagnosis of autism in the 1980s and 1990s tended to have high support needs – likely 24-hour care.</p>
<p>The 2000s and 2010s saw a major reconceptualisation of autism. Autistic behaviours became understood as present in people who do not have intellectual or significant language difficulties. </p>
<p>This new understanding of autism led to people with a much more diverse range of abilities receiving a diagnosis of autism. The “<a href="https://link.springer.com/chapter/10.1007/978-3-030-27275-3_7">autism spectrum</a>” was born.</p>
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<h2>Advocacy and representation</h2>
<p>The rethinking of autism to a “spectrum” emerged out of a large body of high-quality research.</p>
<p>Another important catalyst was the extraordinary work of autistic people themselves, who through important <a href="https://www.frontiersin.org/articles/10.3389/fpsyg.2021.635690/full">advocacy</a>, championed the rights and needs of all autistic people. This advocacy reshaped community views about autism, in particular, that not all autistic people have intellectual disability.</p>
<p>Media <a href="https://www.spectrumnews.org/opinion/viewpoint/portrayals-autism-television-dont-showcase-full-spectrum/">portrayals</a> of autism accelerated the shift in community views about autism. TV shows focused on stereotypes of men (it was almost always men) who were intellectually gifted, but had social difficulties. Shaun Murphy in The Good Doctor and Sheldon Cooper from The Big Bang Theory are two examples.</p>
<p>The greater community visibility of autism has been overwhelmingly positive. It has fostered greater acceptance of difference and increased support for a broader range of people. However, like all important societal changes, there have been challenges too.</p>
<p>A key source of debate has been whether broadening the diagnosis of autism has made the diagnostic label no longer entirely fit-for-purpose.</p>
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Read more:
<a href="https://theconversation.com/autism-is-still-underdiagnosed-in-girls-and-women-that-can-compound-the-challenges-they-face-176036">Autism is still underdiagnosed in girls and women. That can compound the challenges they face</a>
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<h2>Diagnosis and ‘profound autism’</h2>
<p>The purpose of a diagnosis is to help define and identify a health condition or disability. Diagnoses provide understanding about what a condition is, and what it may mean for the person diagnosed. In many cases, a diagnosis can also provide information about the most appropriate clinical management.</p>
<p>A current criticism of the autism diagnosis (officially, “<a href="https://www.cdc.gov/ncbddd/autism/hcp-dsm.html">autism spectrum disorder</a>”) is that it is too broadly defined. How can a single diagnostic label that incorporates television’s Dr Cooper as well as people who require around-the-clock care, serve all autistic people?</p>
<p>This was part of the argument the Lancet Commission made when proposing the term “profound autism”. The experts involved claimed that, because people with very high support needs are unable to advocate for themselves, they “are <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01541-5/fulltext">at risk of being marginalised</a> by a focus on more able individuals”.</p>
<p>The term “profound autism”, they <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01541-5/fulltext">argued</a>, would </p>
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<p>spur both the clinical and research global communities to prioritise the needs of this vulnerable and underserved group of autistic people.</p>
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<p>Strong counter points have been made against the use of the term “profound autism”. These include advocating for alternative ways to describe the different needs of autistic people. For example, using brief descriptions such as “autistic person with intellectual disability”.</p>
<p>A <a href="https://www.thenation.com/article/society/autism-division/">key criticism</a> is that, after the significant gains of the past few decades in recognising the broad spectrum of autistic people, dividing autistic people into two groups using relatively arbitrary criteria would represent a retrograde step.</p>
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Read more:
<a href="https://theconversation.com/should-adhd-be-in-the-ndis-yes-but-eligibility-for-disability-supports-should-depend-on-the-person-not-their-diagnosis-191576">Should ADHD be in the NDIS? Yes, but eligibility for disability supports should depend on the person not their diagnosis</a>
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<h2>A discussion of great significance</h2>
<p>It is clear there is a large group of people who do not feel well served by the broad nature of the current autism diagnosis. There is a clinical and moral responsibility to acknowledge and value this perspective, and explore it further.</p>
<p>To do so would be entirely consistent with the history of our changing understanding of autism over time.</p>
<p>Whether or not “profound autism” is eventually seen as an appropriate diagnostic term, it is important to acknowledge that this debate touches on deeply personal issues of identity and understanding.</p>
<p>The voice of autistic people must be central in this discussion. The voices of families who care for autistic people must also be valued.</p>
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Read more:
<a href="https://theconversation.com/an-autism-minister-may-boost-support-and-coordination-but-governments-that-follow-south-australias-lead-should-be-cautious-188885">An autism minister may boost support and coordination. But governments that follow South Australia's lead should be cautious</a>
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<p class="fine-print"><em><span>Andrew Whitehouse receives funding from the NHMRC, the ARC, the Autism CRC, and the Angela Wright Bennett Foundation. </span></em></p>A reignited debate centres around whether broadening the diagnosis of autism has made the diagnostic label no longer entirely fit-for-purpose.Andrew Whitehouse, Bennett Chair of Autism, Telethon Kids Institute, The University of Western AustraliaLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1906582022-09-15T02:28:33Z2022-09-15T02:28:33ZWe were on a global panel looking at the staggering costs of COVID – 17.7m deaths and counting. Here are 11 ways to stop history repeating itself<p>A global report released <a href="https://www.thelancet.com/commissions/covid19">today</a> highlights massive global failures in the response to COVID-19.</p>
<p>The report, which was convened by The Lancet journal and to which we contributed, highlights widespread global failures of prevention and basic public health.</p>
<p>This resulted in an estimated 17.7 million excess deaths due to COVID-19 (including those not reported) to September 15.</p>
<p>The report also highlights that the pandemic has reversed progress made towards the United Nations <a href="https://sdgs.un.org/goals">Sustainable Development Goals</a> in many countries further impacting on health and wellbeing.</p>
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<p>The report, from <a href="https://covid19commission.org">The Lancet COVID-19 Commission</a>, found most governments were ill-prepared, too slow to act, paid too little attention to the most vulnerable in their societies, and were hampered by low public trust and an epidemic of misinformation.</p>
<p>However, countries of the Western Pacific – including East Asia, Australia and New Zealand – adopted <a href="https://theconversation.com/australias-response-to-covid-in-the-first-2-years-was-one-of-the-best-in-the-world-why-do-we-rank-so-poorly-now-187606">more successful</a> control strategies than most.</p>
<p>This had resulted in an estimated 300 deaths per million in the region
(around <a href="https://ourworldindata.org/grapher/total-covid-cases-deaths-per-million?country=%7EAUS">558 per million</a> in Australia and <a href="https://ourworldindata.org/grapher/total-covid-cases-deaths-per-million?country=%7ENZL">382 per million</a> in New Zealand to September 12). This is compared with more than 3,000 per million in the <a href="https://ourworldindata.org/grapher/total-covid-cases-deaths-per-million?country=%7EUSA">United States</a> and the <a href="https://ourworldindata.org/grapher/total-covid-cases-deaths-per-million?country=%7EGBR">United Kingdom</a>. </p>
<p>The report also sets out 11 key recommendations for ending the pandemic and preparing for the next one.</p>
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Read more:
<a href="https://theconversation.com/imagining-covid-is-like-the-flu-is-cutting-thousands-of-lives-short-its-time-to-wake-up-190545">Imagining COVID is 'like the flu' is cutting thousands of lives short. It's time to wake up</a>
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<h2>Co-operation lacking</h2>
<p>The report is the result of two years’ work from global experts in public policy, health, economics, social sciences and finance. We contributed to the public health component.</p>
<p>One of the report’s major criticisms is the failure of global cooperation for the financing and distribution of vaccines, medicines and personal protective equipment for low-income countries. </p>
<p>This is not only <a href="https://theconversation.com/wealthy-nations-starved-the-developing-world-of-vaccines-omicron-shows-the-cost-of-this-greed-172763">inequitable</a> but has raised the risk of <a href="https://theconversation.com/new-covid-variants-have-changed-the-game-and-vaccines-will-not-be-enough-we-need-global-maximum-suppression-157870">more dangerous variants</a>.</p>
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<p>The report highlighted the critical role of strong and equitable public health systems. These need to have: strong relationships with local communities; investment in behavioural and social science research to develop more effective interventions and health communication strategies; and continuously updated evidence.</p>
<h2>11 recommendations</h2>
<p>The report made 11 recommendations to end the pandemic and prepare for future ones.</p>
<p><strong>1. Vaccines plus other measures</strong> – establishing global and national “vaccination plus” strategies. This would combine mass immunisation in all countries, ensure availability of testing and treatment for new infections and long COVID, coupled with public health measures such as face masks, promotion of safe workplaces, and social and financial support for self-isolation.</p>
<p><strong>2. Viral origins</strong> – an unbiased, independent and rigorous investigation is needed to investigate the origins of SARS-CoV-2, the virus that causes COVID-19, including from a natural spillover from animals or a possible laboratory-related spillover. This is needed to prevent future pandemics and strengthen public trust in science and public authorities.</p>
<p><strong>3. Bolster the World Health Organization</strong> and maintain it as the lead organisation for <a href="https://theconversation.com/too-late-already-bolted-how-a-faster-who-response-could-have-slowed-covid-19s-spread-160860">responding to emerging infectious diseases</a>. Give WHO new regulatory authority, more backing by national political leaders, more contact with the global scientific community and a larger core budget.</p>
<p><strong>4. Establish a global pandemic agreement</strong> and strengthen <a href="https://theconversation.com/at-what-point-is-a-disease-deemed-to-be-a-global-threat-heres-the-answer-185547">international health regulations</a>. New pandemic arrangements should include bolstering WHO’s authority, creating a global surveillance and monitoring system for infectious disease outbreaks. It would also include regulations for processing international travellers and freight under global pandemic conditions, and the publication of an annual WHO report on global pandemic preparedness and response.</p>
<p><strong>5. Create a new WHO Global Health Board</strong> to support WHO decision-making especially on controversial matters. This would be composed of heads of government representing each of the six WHO regions and elected by the member states of those regions.</p>
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<p><strong>6. New regulations to prevent pandemics</strong> from natural spillovers and research-related activities and for investigating their origins. Prevention of <a href="https://theconversation.com/5-virus-families-that-could-cause-the-next-pandemic-according-to-the-experts-189622">natural spillovers</a> would require better regulation of domestic and wild-animal trade and enhancement of surveillance systems for pathogens (disease-causing micro-organisms) in domestic animals and humans. The <a href="https://globalhealth.org/programs/world-health-assembly/">World Health Assembly</a> should also adopt new global regulations on biosafety to regulate international research programs dealing with dangerous pathogens.</p>
<p><strong>7. A ten-year global strategy</strong> by <a href="https://www.dfat.gov.au/trade/organisations/g20">G20 (Group of Twenty)</a> nations, with accompanying finance, to ensure all WHO regions, including the world’s poorer regions, can produce, distribute, research and develop vaccines, treatments and other critical pandemic control tools. </p>
<p><strong>8. Strengthen national health systems</strong> based on the foundations of public health and universal health coverage and grounded in human rights and gender equality.</p>
<p><strong>9. Adopt national pandemic preparedness plans</strong>, which include scaling up community-based public health systems, investment in a skilled workforce, investment in public health and scientific literacy to “immunise” the public against dis-information, investment in behavioural and social sciences research to develop more effective interventions, protection of vulnerable groups, establishment of safe schools and workplaces, and actions to improve coordinated surveillance and monitoring for new variants.</p>
<p><strong>10. Establishment of a new Global Health Fund</strong> where – with the support of WHO – there is increased and effective investment for both pandemic preparedness and health systems in developing countries, with a focus on primary care. </p>
<p><strong>11. Sustainable development and green recovery plans</strong>. The pandemic has been a setback for sustainable development so bolstering funding to meet sustainability goals is needed.</p>
<h2>Unlock a new approach</h2>
<p>To improve the world’s ability to respond to pandemics we need to unlock a new approach. The key component to any meaningful transformation is to collaborate and work towards a new era of multilateral cooperation. </p>
<p>Governments in Australia, Aotearoa New Zealand and elsewhere have talked about “building back better”. We need to take the lessons learnt from the failures of the past few years and build a stronger framework. This will not only help reduce the dangers of COVID-19 but also forestall the next pandemic and any future global crisis. </p>
<p>By reassessing and strengthening global institutions and co-operation, we can build and define a more resilient future.</p>
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<p><em>Chris Bullen, Professor of Public Health, University of Auckland, co-authored this article and The Lancet COVID-19 Commission report on which it was based.</em></p><img src="https://counter.theconversation.com/content/190658/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>John Thwaites is Chair of Monash Sustainable Development Institute and ClimateWorks Australia which receive funding for research, education and action projects from the Australian and state governments as well as from philanthropy and industry. He is former Deputy Premier of Victoria and a member of the Australian Labor Party.</span></em></p><p class="fine-print"><em><span>Liam Smith receives funding from a number of government schemes, government bodies and private sector funders. </span></em></p><p class="fine-print"><em><span>Margaret Hellard receives funding from a number of government funding schemes and government bodies and philanthropic organisations for work on COVID-19.
Margaret Hellard also receives funding from Gilead Sciences and Abbvie for research unrelated to COVID-19.</span></em></p>We found most governments were ill-prepared, too slow to act, paid too little attention to the most vulnerable, and were hampered by low public trust and an epidemic of misinformation.John Thwaites, Chair, Monash Sustainable Development Institute & ClimateWorks Australia, Monash UniversityLiam Smith, Director, BehaviourWorks, Monash Sustainable Development Institute, Monash UniversityMargaret Hellard, Adjunct Professor, Monash University; Associate Director and Head, Centre for Population Health, Burnet InstituteLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1605752021-05-19T15:59:30Z2021-05-19T15:59:30ZCOVID vaccines: the danger of journals being seen as substitute regulators<p>A superficial reading of the history of vaccination might lead you to believe that it is simple. Dried smallpox pustules had been used for 1,000 years to inoculate people against smallpox before the first successful vaccine trial, conducted by Edward Jenner in 1796 on a single eight-year-old boy.</p>
<p>A more detailed reading, however, reveals two significant risks both extremely relevant in the current pandemic.</p>
<p>The first is that bad vaccines don’t just fail to protect, they can cause direct harm to patients. Some make subsequent infection with the disease they are intended to protect against more serious.</p>
<p>The second risk is that trust in vaccines is easily damaged and slow to recover. People feel anxious about interventions given to the well – the <a href="https://www.bbc.co.uk/news/uk-england-leicestershire-50713991">first anti-vaccination movement</a> appeared just a few years after Jenner’s successful trial.</p>
<figure class="align-center ">
<img alt="An anti-vaccination caricature by James Gillray, The Cow-Pock – or – The Wonderful Effects of the New Inoculation!" src="https://images.theconversation.com/files/400737/original/file-20210514-21-1w97g4e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/400737/original/file-20210514-21-1w97g4e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=429&fit=crop&dpr=1 600w, https://images.theconversation.com/files/400737/original/file-20210514-21-1w97g4e.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=429&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/400737/original/file-20210514-21-1w97g4e.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=429&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/400737/original/file-20210514-21-1w97g4e.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=539&fit=crop&dpr=1 754w, https://images.theconversation.com/files/400737/original/file-20210514-21-1w97g4e.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=539&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/400737/original/file-20210514-21-1w97g4e.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=539&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">An anti-vaccination caricature by James Gillray, The Cow-Pock – or – The Wonderful Effects of the New Inoculation!</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/w/index.php?curid=2289666">Library of Congress/Wikimedia Commons</a></span>
</figcaption>
</figure>
<p>The Russian government appeared to be taking both these risks when in August 2020, the president, Vladimir Putin, announced the registration of a new COVID-19 vaccine: Sputnik V. While Putin said that it had gone through “all the necessary trials”, the registration certificate said that it had been trialled on just 38 participants. The international responses ranged from concern to outrage and, since that announcement, everything about Sputnik has seemed worthy of detailed scrutiny, as I argued in a <a href="https://www.bmj.com/content/373/bmj.n1108">recent essay in The BMJ</a>.</p>
<p>In September, the first peer-reviewed Sputnik V data was published in <a href="https://www.thelancet.com/article/S0140-6736(20)31866-3/fulltext">the prestigious medical journal The Lancet</a>: two studies each of 38 people who all seemed to develop a robust immune response with no serious problems.</p>
<p>Very quickly inconsistencies were found in the paper by an Italian scientist, Enrico Bucci. He runs a research integrity company and posted an <a href="https://cattiviscienziati.com/2020/09/07/note-of-concern/">open letter</a> noting that the results on several graphs seemed identical between participants - more than might be expected by chance. Bucci and several others (including myself) wrote to The Lancet requesting access to the data from which the figures were generated to resolve the issue.</p>
<p>We expected to have the backing of The Lancet with this request since they are enthusiastic about data transparency. Their website declares: “The Lancet journals will continue to hold authors and editors accountable for the data published in our pages, and we encourage our readers to do the same.” The Sputnik team <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31970-X/fulltext">responded</a> that the patterns in the data were “coincidences” but confirmed that they would make individual participant data available on request.</p>
<p>Despite these assurances and several requests, neither The Lancet nor the Sputnik team have provided any further data.</p>
<p>We might expect The Lancet to be cautious when it comes to papers on COVID-19 or vaccines. In the summer of 2020, they published – and then retracted – a major COVID-19 study based on a <a href="https://www.theguardian.com/world/2020/jun/12/covid-19-studies-based-on-flawed-surgisphere-data-force-medical-journals-to-review-processes">flawed dataset</a>. They made a similar mistake on a 1998 paper <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(97)11096-0/fulltext">fraudulently linking the MMR vaccine to autism</a>, which contributed to huge increases in measles rates around the world.</p>
<p>Despite this history and the errors in the previous paper, in February 2021 <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00234-8/fulltext">The Lancet</a> published an interim report on a much larger study of thousands of people. This was accompanied by favourable <a href="https://www.thelancet.com/journals/lanepe/article/PIIS2666-7762(21)00054-5/fulltext">editorials</a>. <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00191-4/fulltext">One</a> announced that: “Sputnik V COVID-19 vaccine candidate appears safe and effective” and added that “another vaccine can now join the fight”.</p>
<p>Once again, Bucci and other internationally regarded scientists identified many minor errors – surprising in a study of this importance. Data tables that didn’t add up and more anomalous graphs. Not evidence of fraud but a concerning lack of rigour on the part of both the Sputnik team and The Lancet.</p>
<p>These errors and the uncritically glowing editorials are particularly concerning given that Sputnik was developed at an institution in a country with no significant track record of vaccine development and at the time of publication of the phase 3 trial, Sputnik had not been submitted to a major regulator. The European Medicines Agency (EMA) didn’t begin reviewing the Sputnik team’s application until a month after The Lancet publication.</p>
<p>Meanwhile, the publications in The Lancet have been used very effectively by the Sputnik V marketing team online, in every <a href="https://sputnikvaccine.com/newsroom/pressreleases/">press release</a>, and in <a href="https://sputnikvaccine.com/newsroom/pressreleases/a-vaccine-for-all-mankind-sputnik-v-s-efficacy-in-fighting-covid-19-is-validated-by-internationally-/">several interviews</a>. While 16 countries had authorised Sputnik V before the phase 3 trial publication, <a href="https://sputnikvaccine.com/newsroom/pressreleases/">more than 40</a> have authorised it since, mainly low and middle-income countries without effective regulators. Understandably, they may have had to rely on The Lancet’s vetting of the science. But the peer-review process is not adequate to evaluate a new vaccine in the way that a regulator can.</p>
<h2>Peer review is nothing like a regulator’s scrutiny</h2>
<p>At most journals, following inspection by the editorial team and a statistician, peer review is undertaken over a few hours, by a few anonymous, unpaid experts, without publicly declared interests and without access to underlying data.</p>
<p>By contrast, the major regulators (such as the EU’s EMA, the FDA in the US, and the UK’s MHRA) typically use named teams of in-house and external experts, all with declared interests. They work full time for many months with unlimited access to all the non-clinical, clinical and manufacturing data. They frequently inspect research and manufacturing sites. If they choose to exercise it, they have the power to look at individual patient notes to confirm data. A journal has no such power, which is why using the words “safe and effective” in the title of an editorial about an unauthorised drug is so unusual.</p>
<p>Finally, the regulatory output is far more transparent than peer review. The EMA has published thousands of pages of data and analysis from the vaccines submitted to them.</p>
<p>The EMA may declare Sputnik to have a favourable risk-benefit balance despite the errors in the published papers. If so, this will be a boost to global health. But this episode will still raise questions about The Lancet’s commitment to open data and to the wider claims they make about “applying scientific knowledge to improve health and advance human progress”.</p>
<p>If it is not authorised, then we will need to ask more serious questions about how many people have been harmed by a misguided faith in peer review, and how much damage has been caused to public confidence in the vaccines that are actually safe and effective.</p>
<hr>
<p><em>Prior to publication, The BMJ provided The Lancet with a list of allegations contained in Dr Chris van Tulleken’s <a href="https://www.bmj.com/content/373/bmj.n1108">essay</a> – which are the same allegations contained in this article. The BMJ received the following response from Emily Head, media relations manager:</em></p>
<p><em>“This research was independently peer reviewed by international experts on covid-19 and vaccines, including a statistical reviewer. At the Lancet journals, our editors treat communication with authors as confidential, and details of peer review including dates and peer review comments are not shared publicly.</em></p>
<p><em>"All publicly available information for Lancet articles is published with the article, in the Supplementary Materials or Linked Articles sections on the article webpage. In addition, explanations of any errors that have been corrected within an article are provided in the Department of Error notice.</em></p>
<p><em>"Our policies on peer review, data access, and corrections are available here: https://www.thelancet.com/publishing-excellence.”</em></p><img src="https://counter.theconversation.com/content/160575/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Christoffer van Tulleken does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Sixteen countries authorised the use of Russia’s Sputnik V vaccine before phase 3 clinical trial results were published.Christoffer van Tulleken, Honorary Associate Professor, UCLLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1582272021-04-22T22:40:53Z2021-04-22T22:40:53ZStandard IVF is fine for most people. So why are so many offered an expensive sperm injection they don’t need?<figure><img src="https://images.theconversation.com/files/394939/original/file-20210414-13-10bvrbn.jpg?ixlib=rb-1.1.0&rect=0%2C4%2C1000%2C727&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/intracytoplasmic-sperm-injection-icsi-part-ivf-1394225165">from www.shutterstock.com</a></span></figcaption></figure><p>An expensive IVF technique, routinely offered in fertility clinics around the world, offers no extra benefits to standard IVF in the vast majority of cases, our new research shows.</p>
<p>The technique, known as intracytoplasmic sperm injection or ICSI, was developed to help couples where the man has a low sperm count. But it is now the main fertilisation method clinics use in Australia and New Zealand, even when sperm counts are normal. </p>
<p>In an article published today in <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00535-3/fulltext">The Lancet</a> we show that when there’s a normal sperm count, ICSI does not improve the chance of a baby when compared with standard IVF. So why do clinics routinely offer it?</p>
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Read more:
<a href="https://theconversation.com/considering-using-ivf-to-have-a-baby-heres-what-you-need-to-know-108910">Considering using IVF to have a baby? Here's what you need to know</a>
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<h2>What is ICSI?</h2>
<p>In IVF, several thousand sperm compete to be the one to fertilise an egg. However, for the small percentage of couples with what doctors call severe male-factor infertility — for instance, where there is a very low sperm count or the sperm doesn’t look or move normally — IVF is not an option. </p>
<p>In 1992, ICSI <a href="https://pubmed.ncbi.nlm.nih.gov/1351601/">was introduced</a>, where a single sperm was injected into the egg using a glass needle. This allowed the expansion of IVF to people where low sperm counts or poor sperm quality was an issue.</p>
<p>Its introduction across the world has helped thousands of couples have biologically related children, who otherwise would have needed donor sperm or remained childless.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/396213/original/file-20210421-19-1aj9ka7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="IVF versus ICSI" src="https://images.theconversation.com/files/396213/original/file-20210421-19-1aj9ka7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/396213/original/file-20210421-19-1aj9ka7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=376&fit=crop&dpr=1 600w, https://images.theconversation.com/files/396213/original/file-20210421-19-1aj9ka7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=376&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/396213/original/file-20210421-19-1aj9ka7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=376&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/396213/original/file-20210421-19-1aj9ka7.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=472&fit=crop&dpr=1 754w, https://images.theconversation.com/files/396213/original/file-20210421-19-1aj9ka7.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=472&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/396213/original/file-20210421-19-1aj9ka7.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=472&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">With IVF, thousands of sperm compete to fertilise an egg. But with ICSI, a single sperm is injected into the egg.</span>
<span class="attribution"><a class="source" href="https://www.shutterstock.com/image-illustration/types-artificial-fertilization-egg-spermotozoydami-plant-1437755195">from www.shutterstock.com</a></span>
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<h2>How common is it?</h2>
<p>ICSI was expected to be used only where male infertility was an issue, but over time it has become the most used method of fertilisation even when it isn’t.</p>
<p>In the United States, between 1996 and 2012, ICSI use <a href="https://jamanetwork.com/journals/jama/fullarticle/2091303">increased</a> from 15% to 67% of couples where the male has a normal sperm count; in Europe about <a href="https://pubmed.ncbi.nlm.nih.gov/30032255/">70% of cycles</a> use ICSI.</p>
<p>In <a href="https://npesu.unsw.edu.au/sites/default/files/npesu/data_collection/Assisted%20Reproductive%20Technology%20in%20Australia%20and%20New%20Zealand%202018_0.pdf">Australia</a> around 60% of cycles used ICSI in 2018. This is even though <a href="https://www.auanet.org/guidelines/azoospermic-male-best-practice-statement">only</a> 30% of infertile couples have male infertility and 15% severe male infertility.</p>
<p>Clinics in Australia use ICSI to different extents. For instance, in Victoria in 2019-20, ICSI was used between <a href="https://www.varta.org.au/sites/default/files/2021-01/varta-annual-report-2020.pdf.pdf">34% and 89%</a> of the time, depending on the clinic.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/sperm-why-these-secretive-swimmers-are-the-key-to-the-future-of-fertility-and-contraception-81773">Sperm: why these secretive swimmers are the key to the future of fertility – and contraception</a>
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<hr>
<h2>What we did and what we found</h2>
<p>Today we report, with our collaborators in Vietnam, the results of a large study in which more than 1,000 infertile couples with a normal sperm count were randomly allocated to ICSI or IVF. We found couples in either group were just as likely to have a baby.</p>
<p>This adds to evidence from other <a href="https://pubmed.ncbi.nlm.nih.gov/29897449/#:%7E:text=What%20is%20known%20already%3A%20The,with%20non%2Dmale%20factor%20infertility">large observational studies</a> in as many as 15,000 women that the widespread use of the more expensive and technically demanding ICSI does not offer any benefit to couples where the man has a normal sperm count. </p>
<p><a href="https://pubmed.ncbi.nlm.nih.gov/32896391/">Excellent clinics</a> internationally and in Australia perform ICSI in fewer than 35% of their treatments, while achieving success rates equal to or better than clinics using ICSI more commonly.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/fertility-miracle-or-fake-news-understanding-which-ivf-add-ons-really-work-118585">Fertility miracle or fake news? Understanding which IVF 'add-ons' really work</a>
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<h2>How did ICSI become so popular?</h2>
<p>There are a <a href="https://www.hfea.gov.uk/treatments/treatment-add-ons/">growing number</a> of fertility treatments that <a href="https://www.fertstert.org/article/S0015-0282(19)32454-9/fulltext">aren’t backed by reasonable evidence</a>. </p>
<p>Some are relatively cheap, such as vitamins and antioxidants. Others are invasive or expensive. These include <a href="https://www.hfea.gov.uk/treatments/treatment-add-ons/endometrial-scratching/">endometrial scratching</a> (where the lining of the uterus is scraped with a thin tube, which is said to improve the chance of an embryo implanting), video microscopy of embryos, and <a href="https://www.acog.org/clinical/clinical-guidance/committee-opinion/articles/2020/03/preimplantation-genetic-testing">pre-implantation genetic diagnosis</a> for potential chromosome abnormalities (where an embryo is tested for genetic disease before being implanted).</p>
<p>In fact, ICSI is about A$500 more expensive than standard IVF, although costs vary between clinics, and some costs can be claimed on <a href="http://www9.health.gov.au/mbs/fullDisplay.cfm?type=item&q=13218&qt=item">Medicare</a> under specific circumstances.</p>
<p>So why are these so-called “add-ons” or “adjuvants” so common?</p>
<p>Fertility treatment, especially IVF and ICSI, is overwhelmingly practised in the private sector in Australia and New Zealand. It is strongly marketed to the public and promoted in social media by individual doctors, clinics and corporations. Doctors and clinics also compete for patients, often offering <a href="https://theconversation.com/fertility-miracle-or-fake-news-understanding-which-ivf-add-ons-really-work-118585">unproven therapies</a>.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/the-business-of-ivf-how-human-eggs-went-from-simple-cells-to-a-valuable-commodity-119168">The business of IVF: how human eggs went from simple cells to a valuable commodity</a>
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<p>Couples may overlook a doctor seeking to practise fertility medicine based solely on evidence, and instead find a nearby clinic or doctor <a href="https://obgyn.onlinelibrary.wiley.com/doi/abs/10.1111/ajo.13321">prepared to offer</a> add-ons they believe will improve their chance of a baby.</p>
<p>In the case of ICSI, doctors may recommend it for fear of patients’ reactions if the eggs don’t fertilise, even if ICSI doesn’t improve the ultimate chance of a baby for those with a normal sperm count.</p>
<p><div data-react-class="Tweet" data-react-props="{"tweetId":"1191669372747538439"}"></div></p>
<h2>What can we do about it?</h2>
<p>Infertility is distressing and, in most cases, can be easily treated with good advice, simple drugs and, if needed, quality assisted reproductive procedures such as IVF.</p>
<p>However, unrestrained, unnecessary use of ICSI is a salutary example of why we need to act on widely accepted evidence.</p>
<p>Until now, the fertility industry has promoted <a href="https://www.abc.net.au/radio/programs/pm/ivf-specialists-hit-back-at-four-corners-story-on/7464870">self-regulation</a> over being made to follow government-imposed, evidence-based guidelines of which fertility treatments are needed. And there’s a <a href="https://www.fertstert.org/article/S0015-0282(19)32454-9/fulltext">growing concern</a> the industry is not doing enough to combat unproven and expensive treatments.</p>
<p>Couples with infertility belong to a <a href="https://pubmed.ncbi.nlm.nih.gov/18025030/">very vulnerable group</a> who will do almost anything to achieve a pregnancy. They deserve our dedicated care and evidence-based treatment.</p><img src="https://counter.theconversation.com/content/158227/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Robert Norman is not involved financially in any IVF or fertility clinic </span></em></p><p class="fine-print"><em><span>Ben W. Mol receives funding from NHMRC (Investigatorgrant GNT1176437) Guerbet, and Ferring.
</span></em></p>Our new study shows a widely used fertility treatment, known as ICSI, is no better than standard IVF for most people. Yet, it’s being routinely offered around the world.Robert Norman, Professor of Reproductive and Periconceptual Medicine, The Robinson Institute, University of AdelaideBen W. Mol, Professor of Obstetrics and Gynaecology, Monash UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1517552020-12-10T05:43:25Z2020-12-10T05:43:25ZThe Oxford/AstraZeneca vaccine is the first to publish peer-reviewed efficacy results. Here’s what they tell us — and what they don’t<figure><img src="https://images.theconversation.com/files/374091/original/file-20201210-15-4xe9k9.jpg?ixlib=rb-1.1.0&rect=8%2C8%2C5982%2C3979&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>The Oxford/AstraZeneca vaccine this week became the first major COVID vaccine candidate to have efficacy results from phase 3 trials <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext">published</a> in a peer-reviewed journal.</p>
<p>The vaccine, AZD1222, is a viral vector vaccine. Researchers took an <a href="https://www.nature.com/articles/s41586-020-2608-y">adenovirus from chimpanzees</a> and modified it with the aim of training the immune system to mount a strong response against SARS-CoV-2 (the virus that causes COVID-19).</p>
<p>The <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext">Lancet</a> paper confirms interim analysis <a href="https://www.astrazeneca.com/content/dam/az/media-centre-docs/press-releases/2020/AZD1222-HLR-RNS.pdf">AstraZeneca released</a> last month showing the vaccine is safe and has an overall efficacy of 70% in protecting against symptomatic COVID-19.</p>
<p>Let’s take a look at these latest results — and why they’re important.</p>
<h2>Safety first</h2>
<p>The <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext">published article</a> consolidated safety data across four human trials with 23,848 volunteers from Brazil, South Africa and the United Kingdom. </p>
<p>Only three people experienced serious adverse events (which were possibly related to the vaccine, but we don’t know for sure) over more than three months of follow-up. Each of these cases is recovering or has recovered.</p>
<p>While safety monitoring will be ongoing, this analysis gives us confidence the Oxford/AstraZeneca vaccine is safe.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/oxford-covid-19-vaccine-newly-published-results-show-it-is-safe-but-questions-remain-over-its-efficacy-151774">Oxford COVID-19 vaccine: newly published results show it is safe – but questions remain over its efficacy</a>
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<h2>Efficacy</h2>
<p>The authors also analysed efficacy data for two of the above trials with a total of 11,636 participants. The follow-up period of the remaining two trials hasn’t yet been long enough to get a good sense of the vaccine’s efficacy — but this data will be coming.</p>
<p>Among the participants, there were 131 cases of symptomatic COVID-19. This included 30/5,807 (0.5%) in the vaccine group, and 101/5,829 (1.7%) in the control group. Based on <a href="https://theconversation.com/how-to-read-results-from-covid-vaccine-trials-like-a-pro-149916">the formulae</a> researchers use to calculate how well vaccines work in clinical trials, this equates to an efficacy of 70%.</p>
<p>Of ten COVID-related hospital admissions, none were among the AZD1222 vaccine recipients — they were all people who received the placebo. </p>
<p>Although these numbers are small and will need confirmation with further data, this indicates the vaccine has strong potential to prevent severe COVID-19 disease. </p>
<figure class="align-center ">
<img alt="An older man wearing a mask has his sleeve rolled up in preparation for a vaccination." src="https://images.theconversation.com/files/374093/original/file-20201210-20-1svtx5j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/374093/original/file-20201210-20-1svtx5j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/374093/original/file-20201210-20-1svtx5j.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/374093/original/file-20201210-20-1svtx5j.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/374093/original/file-20201210-20-1svtx5j.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/374093/original/file-20201210-20-1svtx5j.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/374093/original/file-20201210-20-1svtx5j.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The study looked at the vaccine’s safety and efficacy at preventing symptomatic COVID-19.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<h2>The dosing debacle</h2>
<p>While 70% is the overall efficacy figure, we learnt in <a href="https://www.astrazeneca.com/content/dam/az/media-centre-docs/press-releases/2020/AZD1222-HLR-RNS.pdf">AstraZeneca’s interim analysis</a> that there were actually two separate dosing regimens. Variation in dose measurement methods — widely reported to have been <a href="https://www.bbc.com/news/health-55086927">an error</a> — meant some participants received half of the expected dose for their first of the two shots.</p>
<p>The latest analysis confirmed that for people who received the low dose initially, followed by the standard dose, the vaccine displayed 90% efficacy, compared to 62.1% in participants who received the full dose at both time points.</p>
<p>While this error appears to have had a positive outcome, it’s concerning that we don’t really understand why the regimen with the half dose worked better. </p>
<p>The full, higher first dose may have induced more antibodies that recognise the vaccine’s chimpanzee adenovirus components than the half first dose did, and it’s possible these “anti-vaccine vehicle” antibodies could have interfered with the efficacy of the booster dose. This is a recognised concern when using <a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0040385#pone.0040385-Sheehy1">adenoviruses as vaccine components</a>.</p>
<p>Alternatively, the Lancet authors speculate the low dose may have induced a different type of immune response that we are yet to know about. If this were the case, it could raise questions for other vaccine developers too about the way the immune system behaves.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/how-to-read-results-from-covid-vaccine-trials-like-a-pro-149916">How to read results from COVID vaccine trials like a pro</a>
</strong>
</em>
</p>
<hr>
<h2>A unique candidate</h2>
<p>It’s exciting the Oxford/AstraZeneca vaccine could potentially work comparably well to the other front-runners from <a href="https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-conclude-phase-3-study-covid-19-vaccine">Pfizer/BioNTech</a> and <a href="https://investors.modernatx.com/news-releases/news-release-details/modernas-covid-19-vaccine-candidate-meets-its-primary-efficacy">Moderna</a>, because this vaccine is one of the most practical vaccines to produce, store and distribute.</p>
<p>It only needs to be stored at <a href="https://www.astrazeneca.com/content/astraz/media-centre/press-releases/2020/azd1222-oxford-phase-iii-trials-interim-analysis-results-published-in-the-lancet.html">2-8°C</a> — so in a normal fridge — compared to the mRNA-based vaccines, which need to be stored <a href="https://www.pfizer.com/news/hot-topics/covid_19_vaccine_u_s_distribution_fact_sheet">around -70°C</a>.</p>
<p>It’s also the cheapest so far, at about <a href="https://www.cnbc.com/2020/12/09/coronavirs-oxford-astrazeneca-vaccine-to-immunize-the-planet-more-effectively-lancet-editor-says.html">US$4 a dose</a> (roughly A$5), making it highly attractive for global deployment. Oxford/AstraZeneca has an agreement with the <a href="https://www.gavi.org/covax-facility">COVAX facility</a> which will enable equitable access for countries who may not be able to afford the more expensive mRNA vaccines from Pfizer and Moderna.</p>
<figure class="align-center ">
<img alt="A health worker dressed in full PPE holds a syringe and a vial." src="https://images.theconversation.com/files/374094/original/file-20201210-21-1e7zior.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/374094/original/file-20201210-21-1e7zior.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/374094/original/file-20201210-21-1e7zior.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/374094/original/file-20201210-21-1e7zior.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/374094/original/file-20201210-21-1e7zior.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/374094/original/file-20201210-21-1e7zior.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/374094/original/file-20201210-21-1e7zior.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">The Oxford/AstraZeneca vaccine would be easier than some of the other candidates to store and distribute.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<p>Australia has signed a deal to receive <a href="https://www.health.gov.au/australias-vaccine-agreements#university-of-oxfordastrazeneca">3.8 million doses</a> of the Oxford/AstraZeneca vaccine should it be approved for use. Meanwhile, biotechnology company CSL has been upscaling its manufacturing capacity for this vaccine, which will enable it to produce a further 30 million doses in Australia next year.</p>
<p>If a lower initial dose is recommended, this would also mean the available supply could be distributed to more people.</p>
<h2>Some questions remain</h2>
<p>One factor we still need to consider is the efficacy in older people (70 and above), as this age group is <a href="https://theconversation.com/why-we-should-prioritise-older-people-when-we-get-a-covid-vaccine-148432">most susceptible</a> to severe disease. </p>
<p>The current published efficacy results are mostly based on 18 to 55-year-olds. Although these trials do have older participants, they were recruited later, so collection of efficacy data for this group is ongoing.</p>
<p>A recent paper which looked at <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32466-1/fulltext">immune responses</a> to the vaccine showed similar levels of antibodies across age groups (18-55, 56-69, and >70), which is encouraging. So it will be interesting to see efficacy results in older people as they become available. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/why-the-oxford-astrazeneca-vaccine-is-now-a-global-gamechanger-150660">Why the Oxford AstraZeneca vaccine is now a global gamechanger</a>
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</em>
</p>
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<p>Publication in a peer-reviewed journal means the data has been evaluated by expert independent reviewers whose job is to find any holes or problems. With this, the Oxford/AstraZeneca data now becomes more credible to the scientific community. </p>
<p>The data will likely encourage developers to move rapidly to request regulatory approvals for this vaccine, while awaiting further analysis on efficacy — and, importantly, how dosage affects this vaccine’s efficacy.</p><img src="https://counter.theconversation.com/content/151755/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The authors do not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and have disclosed no relevant affiliations beyond their academic appointment.</span></em></p>The reason the vaccine appears to have worked better in participants who initially received only half a dose is still somewhat of a mystery.Kirsty Wilson, Postdoctoral Research Fellow, RMIT UniversityMagdalena Plebanski, Professor of Immunology, RMIT UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1510272020-12-03T05:08:50Z2020-12-03T05:08:50ZClimate change is resulting in profound, immediate and worsening health impacts, over 120 researchers say<figure><img src="https://images.theconversation.com/files/372711/original/file-20201203-21-p86u64.jpg?ixlib=rb-1.1.0&rect=24%2C16%2C5439%2C3604&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p>Climate change is resulting in profound, immediate and worsening health impacts, and no country is immune, <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32290-X/fulltext">a major new report</a> from more than 120 researchers has declared. </p>
<p>This year’s annual report of The Lancet Countdown on Health and Climate Change, released today, presents the latest data on health impacts from a changing climate. </p>
<p>Among its results, the report found there were 296,000 heat-related premature deaths in people over 65 years in 2018 (a 54% increase in the last two decades), and that global yield potential for major crops declined by 1.8–5.6% between 1981 and 2019. </p>
<p>We are part of the Lancet Countdown sub-working group focusing on <a href="https://theconversation.com/how-many-people-will-migrate-due-to-rising-sea-levels-our-best-guesses-arent-good-enough-145776">human migration in a warming world</a>. We estimate that, based on current population data, 145 million people face potential inundation with global mean sea-level rise of one metre. This jumps to 565 million people with a five metre sea-level rise. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/coronavirus-is-a-wake-up-call-our-war-with-the-environment-is-leading-to-pandemics-135023">Coronavirus is a wake-up call: our war with the environment is leading to pandemics</a>
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<p>Unless urgent action is taken, the health consequences of climate change will worsen. A globally coordinated effort tackling COVID-19 and climate change in unison is vital, and will mean a triple win: better public health, a more sustainable economy and environmental protection. </p>
<h2>Drought, fires and excessive heat</h2>
<p>The 2020 report brings together research from a range of fields, including climate science, geography, economics and public health. It focuses on 43 global indicators, such as altered geographic spread of infectious disease, health benefits of low-carbon diets, net carbon pricing, climate migration and heat-related deaths.</p>
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<iframe width="440" height="260" src="https://www.youtube.com/embed/Bp6avcskCcg?wmode=transparent&start=0" frameborder="0" allowfullscreen=""></iframe>
<figcaption><span class="caption">The Lancet Countdown on Health and Climate Change: 2020 report.</span></figcaption>
</figure>
<p>The five hottest years on record have occurred since 2015, and 2020 is on track to be the <a href="https://www.carbonbrief.org/state-of-the-climate-2020-set-to-be-first-or-second-warmest-year-on-record">first or second hottest year on record</a>. </p>
<p>The 2020 Lancet Countdown report found extreme heat continues to rise in every region in the world and particularly affects the elderly, especially those in Japan, northern India, eastern China and central Europe. It is also a big problem for those with pre-existing health conditions and outdoor workers in the agricultural and construction sectors. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/the-world-endured-2-extra-heatwave-days-per-decade-since-1950-but-the-worst-is-yet-to-come-141983">The world endured 2 extra heatwave days per decade since 1950 – but the worst is yet to come</a>
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<p>While attributing heat-related deaths to climate change isn’t straightforward, rising temperatures and humidity will mean we can expect heat-related deaths to increase further. </p>
<p>Climate change is also an important contributing factor to drought. The report found that in 2019 <a href="https://theconversation.com/the-science-of-drought-is-complex-but-the-message-on-climate-change-is-clear-125941">excess drought</a> affected over twice the global land surface area, compared with the 1950-2005 baseline. </p>
<p>Drought and health are intertwined. Drought can cause dwindling drinking water supplies, reduced livestock and crop productivity, and an increased risk of bushfire. </p>
<p>Mental health is also at risk, as Australian <a href="https://www.sciencedirect.com/science/article/abs/pii/S0921800919302368">research</a> from earlier this year confirmed. This looked at the declining mental health of drought-affected farmers in the Murray-Darling Basin over 14 years.</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/372712/original/file-20201203-15-z691yo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="Smoke and fire in the understory of a eucalyptus forest" src="https://images.theconversation.com/files/372712/original/file-20201203-15-z691yo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/372712/original/file-20201203-15-z691yo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=399&fit=crop&dpr=1 600w, https://images.theconversation.com/files/372712/original/file-20201203-15-z691yo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=399&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/372712/original/file-20201203-15-z691yo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=399&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/372712/original/file-20201203-15-z691yo.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=502&fit=crop&dpr=1 754w, https://images.theconversation.com/files/372712/original/file-20201203-15-z691yo.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=502&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/372712/original/file-20201203-15-z691yo.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=502&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">More than 445 deaths were attributed to the smoke from the Black Summer bushfires.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<p>Further, the Lancet Countdown report found that between 2015 and 2019, <a href="https://www.nejm.org/doi/full/10.1056/NEJMsr2028985">the number of people exposed to bushfires</a> increased in 128 countries, compared with a 2001-2004 baseline. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/climate-change-is-bringing-a-new-world-of-bushfires-123261">Climate change is bringing a new world of bushfires</a>
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</em>
</p>
<hr>
<p>Climate change worsens <a href="https://theconversation.com/climate-change-is-bringing-a-new-world-of-bushfires-123261">risk factors</a> for more frequent and intense bushfires. We need only look to last summer’s unprecedented bushfires in Australia as a stark illustration. The number of people exposed to the bushfires was amplified by expanding settlements and inadequate risk reduction measures. </p>
<h2>Sea level rise, human migration and health</h2>
<p>As the world warms and the sea rises, millions of people will be exposed to coastal changes, including inundation and erosion. </p>
<p>Sea-level rise has direct and indirect consequences for human health. In some places, water and soil quality and supply will be compromised due to the intrusion of saltwater. Flooding and wave power will damage infrastructure, including drinking water and sanitation services. And disease vector ecology will also change, such as <a href="https://bmcinfectdis.biomedcentral.com/articles/10.1186/1471-2334-11-18">higher mosquito densities</a> in coastal habitats, potentially causing greater transmission of infectious diseases like dengue or malaria. </p>
<p>However, people and communities may adapt by moving away. In Fiji, for example, <a href="https://theconversation.com/climate-change-forced-these-fijian-communities-to-move-and-with-80-more-at-risk-heres-what-they-learned-116178">at least four communities</a> have relocated in response to coastal changes. The Fijian government notes planned relocation will be <a href="https://www.pacificclimatechange.net/document/planned-relocation-guidelines-framework-undertake-climate-change-related-relocation">a last resort</a> only when other adaptation options are exhausted.</p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/climate-change-forced-these-fijian-communities-to-move-and-with-80-more-at-risk-heres-what-they-learned-116178">Climate change forced these Fijian communities to move – and with 80 more at risk, here's what they learned</a>
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</p>
<hr>
<p><a href="https://www.weforum.org/agenda/2019/04/how-will-retreating-from-the-sea-affect-our-health">Relocation might also lead to health threats </a>. This includes physical health consequences from altered diets, as fishing and subsistence agriculture may be disrupted. There are also mental health impacts from people losing their attachments and connections to their places of belonging. </p>
<p>But sometimes, migration responses to climate change can have health benefits. Moving from vulnerable coastlines might reduce exposure to environmental hazards such as flooding, be an impetus to seek healthier livelihoods and lifestyles, and improve access to health services.</p>
<p>Our estimation of the number of people facing potential inundation is based on projections of global mean sea-level rise and on current population data. </p>
<p>In a high emissions scenario with <a href="https://www.ipcc.ch/srocc/chapter/chapter-4-sea-level-rise-and-implications-for-low-lying-islands-coasts-and-communities">warming of 4.5°C</a>, seas could rise by one metre by 2100 relative to 1986–2005. This would see 145 million people face potential inundation. </p>
<p>A collapse of the Western Antarctic Ice Sheet could cause <a href="https://www.tandfonline.com/doi/abs/10.1080/13669870600717632">five to six metres</a> of sea level rise. Under this extreme scenario, 565 million people may be inundated. </p>
<hr>
<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/how-many-people-will-migrate-due-to-rising-sea-levels-why-our-best-guesses-arent-good-enough-145776">How many people will migrate due to rising sea levels? Why our best guesses aren't good enough</a>
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</em>
</p>
<hr>
<p>It is important to note, however, that uncertainties constrain our ability to forecast migration numbers due to sea-level rise. These uncertainties include future environmental and demographic factors and potential adaptation (and maladaptation) responses, such as living with water or coastal fortification. </p>
<h2>So is there any good news?</h2>
<p>The 2020 Lancet Countdown report notes improvements in some instances, as some sectors and countries take bold steps to respond to climate change. </p>
<p>We are seeing, for example, health benefits emerging from the transition to clean energy. Deaths from air pollution attributed to coal-fired power have declined from 440,000 in 2015 to 400,000 in 2018, despite overall population increases. </p>
<p>But more must be done: we need sustained greenhouse gas emission cuts, increased greenhouse gas absorption and proactive adaptation actions. Yet global efforts to address climate change still fall short of the commitments made in the Paris Agreement five years ago. </p>
<p>We cannot afford to focus attention on the COVID-19 pandemic at the expense of climate action. </p>
<p>If responses to the economic impacts of COVID-19 align with an effective response to climate change, we’ll see immense benefits for human health, with cleaner air, healthier diets and more liveable cities.</p><img src="https://counter.theconversation.com/content/151027/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Celia McMichael is a Senior Lecturer in The School of Geography, The University of Melbourne. She is currently collaborating with national and international colleagues and partner agencies on two Australian Research Council Grants, both with a focus on climate change and human mobility in Small Island States. She works on the Lancet Countdown on Health and Climate Change, as part of a small working group focused on climate change, migration and health that also includes Prof Ilan Kelman (University College London, UK), Dr Shouro Dasgupta (Università Ca' Foscari Venezia, Italy), and Dr Sonja Ayeb-Karlsson (United Nations University Institute for Environment and Human Security, Germany).
<a href="https://orcid.org/0000-0002-4572-602X">https://orcid.org/0000-0002-4572-602X</a></span></em></p><p class="fine-print"><em><span>Dr Sonja Ayeb-Karlsson works for UNU-EHS. She is also affiliated with University of Sussex, a part of WG1 of the Lancet Countdown, and an editorial board member for Climate and Development, UCL Open: Environment and SEI WeAdapt. </span></em></p><p class="fine-print"><em><span>Ilan Kelman receives funding from research councils in the UK and Norway, as well as from the Wellcome Trust (which funded the Lancet Countdown project on which this article is based) and internal UCL funding. He is also Professor II at the University of Agder in Norway and co-directs the non-profit organisation Risk RED (Risk Reduction Education for Disasters).</span></em></p><p class="fine-print"><em><span>Shouro Dasgupta does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>A major new report presents the latest data on the health impacts in a warming world. It found there were 296,000 heat-related deaths in people over 65 years in 2018.Celia McMichael, Senior Lecturer in Geography, The University of MelbourneDr Sonja Ayeb-Karlsson, Senior Researcher, Institute for Environment and Human Security (UNU-EHS), United Nations UniversityIlan Kelman, Professor of Disasters and Health, UCLShouro Dasgupta, Lecturer in Environmental Economics, Ca' Foscari University of VeniceLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1403262020-07-06T12:12:40Z2020-07-06T12:12:40ZRetractions and controversies over coronavirus research show that the process of science is working as it should<figure><img src="https://images.theconversation.com/files/345365/original/file-20200702-111359-13unxc9.jpg?ixlib=rb-1.1.0&rect=0%2C26%2C3576%2C2344&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">A high-profile paper
on the risks of hyrdoxychloroquine was recently and rightfully retracted.</span> <span class="attribution"><a class="source" href="http://www.apimages.com/metadata/Index/Virus-Outbreak-Malaria-Drug-States/195f1b7599b54c8abc2d3cf2da592672/67/0">AP Photo/John Locher,</a></span></figcaption></figure><p><em>Leer <a href="https://theconversation.com/controversias-en-la-investigacion-del-coronavirus-muestran-que-la-ciencia-esta-funcionando-como-deberia-143391">en español</a></em></p>
<p>Several high-profile papers on COVID-19 research have come under fire from people in the scientific community in recent weeks. Two articles addressing the safety of certain drugs when taken by COVID-19 patients were <a href="https://www.nytimes.com/2020/06/04/health/coronavirus-hydroxychloroquine.html">retracted</a>, and researchers are calling for the retraction of a third paper that evaluated behaviors that <a href="https://metrics.stanford.edu/PNAS%20retraction%20request%20LoE%20061820">mitigate coronavirus transmission</a>.</p>
<p>Some people are viewing the retractions as an <a href="https://www.wsj.com/articles/the-lancets-politicized-science-on-antimalarial-drugs-11591053222?cx_testId=3&cx_testVariant=cx_4&cx_artPos=0#cxrecs_s">indictment of the scientific process</a>. Certainly, the overturning of these papers is bad news, and there is plenty of blame to go around. </p>
<p>But despite these short-term setbacks, the scrutiny and subsequent correction of the papers actually show that science is working. Reporting of the pandemic is allowing people to see, many for the first time, the messy business of scientific progress. </p>
<h2>Scientific community quickly responds to flawed research</h2>
<p>In May, two papers were published on the safety of certain drugs for COVID-19 patients. The first, published in the New England Journal of Medicine, claimed that a particular heart medication <a href="http://doi.org/10.1056/NEJMoa2007621">was in fact safe for COVID-19 patients</a>, despite previous concerns. The second, published in The Lancet, claimed that the antimalarial drug <a href="https://doi.org/10.1016/S0140-6736(20)31180-6">hydroxychloroquine increased the risk of death</a> when used to treat COVID-19. </p>
<p>The Lancet paper caused the World Health Organization to briefly <a href="https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---25-may-2020">halt studies investigating hydroxychloroquine</a> for COVID-19 treatment.</p>
<figure class="align-right zoomable">
<a href="https://images.theconversation.com/files/345113/original/file-20200701-159824-g2k6ku.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/345113/original/file-20200701-159824-g2k6ku.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/345113/original/file-20200701-159824-g2k6ku.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=806&fit=crop&dpr=1 600w, https://images.theconversation.com/files/345113/original/file-20200701-159824-g2k6ku.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=806&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/345113/original/file-20200701-159824-g2k6ku.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=806&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/345113/original/file-20200701-159824-g2k6ku.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1012&fit=crop&dpr=1 754w, https://images.theconversation.com/files/345113/original/file-20200701-159824-g2k6ku.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1012&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/345113/original/file-20200701-159824-g2k6ku.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1012&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">The paper published in The Lancet claimed that hydroxychloroquine increased risk of death in COVID-19 patients, but was retracted when other scientists discovered the data used for the study was unreliable.</span>
<span class="attribution"><a class="source" href="https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(20)31180-6.pdf">The Lancet/Mandeep R Mehra, Sapan S Desai, Frank Ruschitzka, Amit N Patel</a></span>
</figcaption>
</figure>
<p>Within days, over 200 scientists signed an <a href="https://doi.org/10.5281/zenodo.3871094">open letter</a> highly critical of the paper, noting that some of the findings were simply implausible. The database provided by the tiny company Surgisphere – whose website is no longer accessible – was unavailable during peer review of the paper or to scientists and the public afterwards, preventing anyone from evaluating the data. Finally, the letter suggested that it was unlikely this company was able to obtain the hospital records alleged to be in the database when no one else had access to this information.</p>
<p>[<em>The Conversation’s science, health and technology editors pick their favorite stories.</em> <a href="https://theconversation.com/us/newsletters/science-editors-picks-71/?utm_source=TCUS&utm_medium=inline-link&utm_campaign=newsletter-text&utm_content=science-favorite">Weekly on Wednesdays</a>.]</p>
<p>By early June, both <a href="https://doi.org/10.1016/S0140-6736(20)31324-6">the Lancet</a> and <a href="https://doi.org/10.1056/NEJMc2021225">New England Journal of Medicine</a> articles were retracted, citing concerns about the integrity of the database the researchers used in the studies. A retraction is the withdrawal of a published paper because the data underlying the major conclusions of the work are found to be seriously flawed. These flaws are sometimes, but not always, due to intentional scientific misconduct. </p>
<p>The urgency to find solutions to the COVID-19 pandemic certainly contributed to the publication of <a href="https://theconversation.com/coronavirus-research-done-too-fast-is-testing-publishing-safeguards-bad-science-is-getting-through-134653">sloppy and possibly fraudulent science</a>. The quality control measures that minimize the publication of bad science failed miserably in these cases.</p>
<h2>Imperfect and iterative</h2>
<p>The retraction of the hydroxychloroquine paper in particular drew immediate attention not only because it placed science in a bad light, but also because <a href="https://www.forbes.com/sites/andrewsolender/2020/05/22/all-the-times-trump-promoted-hydroxychloroquine/#20668b474643">President Trump had touted the drug</a> as an effective treatment for COVID-19 despite the lack of strong evidence.</p>
<p>Responses in the media were harsh. The New York Times declared that “<a href="https://www.nytimes.com/2020/06/14/health/virus-journals.html?searchResultPosition=1">The pandemic claims new victims: prestigious medical journals</a>.” The Wall Street Journal accused the Lancet of “<a href="https://www.wsj.com/articles/the-lancets-politicized-science-on-antimalarial-drugs-11591053222?mod=searchresults&page=1&pos=9">politicized science</a>,” and the Los Angeles Times claimed that the retracted papers “<a href="https://www.latimes.com/business/story/2020-06-08/coronavirus-retracted-paper">contaminated global coronavirus research</a>.” </p>
<p>These headlines may have merit, but perspective is also needed. <a href="https://doi.org/10.1126/science.aav8384">Retractions are rare</a> – only about 0.04% of published papers are withdrawn – but scrutiny, update and correction are common. It is how science is supposed to work, and it is happening in all areas of research relating to SARS-CoV-2. </p>
<p>Doctors have learned that the disease <a href="https://doi.org/10.1126/science.abc3208">targets numerous organs</a>, not just the lungs as was initially thought. Scientists are still working on understanding whether COVID-19 patients <a href="https://doi.org/10.1038/s41591-020-0897-1">develop immunity</a> to the disease.
As for hydroxychloroquine, <a href="https://doi.org/doi:10.1126/science.abd2496">three new large studies</a> published after the Lancet retraction indicate that the malaria drug is indeed ineffective in preventing or treating COVID-19. </p>
<figure class="align-left zoomable">
<a href="https://images.theconversation.com/files/345366/original/file-20200702-111318-a1ncb4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/345366/original/file-20200702-111318-a1ncb4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=237&fit=clip" srcset="https://images.theconversation.com/files/345366/original/file-20200702-111318-a1ncb4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=874&fit=crop&dpr=1 600w, https://images.theconversation.com/files/345366/original/file-20200702-111318-a1ncb4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=874&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/345366/original/file-20200702-111318-a1ncb4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=874&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/345366/original/file-20200702-111318-a1ncb4.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=1098&fit=crop&dpr=1 754w, https://images.theconversation.com/files/345366/original/file-20200702-111318-a1ncb4.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=1098&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/345366/original/file-20200702-111318-a1ncb4.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=1098&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Since the beginning of scientific publishing, peer review has helped weed out bad science, but public discourse between researchers has easily played as big a role.</span>
<span class="attribution"><a class="source" href="https://commons.wikimedia.org/wiki/File:Nature_cover,_November_4,_1869.jpg">Public Domain</a></span>
</figcaption>
</figure>
<h2>Science is self-correcting</h2>
<p>Before a paper is published, it undergoes peer review by experts in the field who recommend to the journal editor whether it should be accepted for publication, rejected or reconsidered after modification. The reputation of the journal is dependent on high-quality peer review, and once a paper is published, it is in the public domain, where it can then be evaluated and judged by other scientists. </p>
<p>The publication of the Lancet and the New England Journal of Medicine papers failed at the level of peer review. But scrutiny by the scientific community – likely spurred on by the public spotlight on coronavirus research – caught the mistakes in record time.</p>
<p>The hydroxychloroquine article published in The Lancet was retracted only 13 days after it was published. By contrast, it took 12 years for the Lancet to retract the fraudulent article that <a href="https://doi.org/10.1016/S0140-6736(97)11096-0">incorrectly claimed vaccinations cause autism</a>.</p>
<p>It is not yet known whether these papers involved deliberate scientific misconduct, but mistakes and corrections are common, even for top scientists. For example, <a href="https://www.nobelprize.org/prizes/chemistry/1954/pauling/facts/">Linus Pauling</a>, who won the Nobel Prize for discovering the structure of proteins, later published an <a href="https://doi.org/10.1073/pnas.39.2.84">incorrect structure of DNA</a>. It was subsequently corrected by <a href="https://doi.org/10.1038/171737a0">Watson and Crick</a>. Mistakes and corrections are a hallmark of progress, not foul play.</p>
<p>Importantly, these errors were exposed by other scientists. They were not uncovered by some policing body or watchdog group. </p>
<p>This back-and-forth between academics is foundational to science. There is no reason to believe that scientists are more virtuous than anyone else. Rather, the mundane human traits of curiosity, competitiveness, self-interest and reputation come into play before and after publication are what allow science to regulate itself. A model based on robust evidence emerges while the weaker one is abandoned.</p>
<h2>Living with uncertainty</h2>
<p>From high school classes and textbooks, science seems like a body of well-known facts and principles that are straightforward and incontrovertible. These sources view science in hindsight and often make discoveries seem inevitable, even dull. </p>
<p>In reality, scientists learn as they go. Uncertainty is inherent to the path of discovery, and success is not guaranteed. <a href="https://doi.org/10.1093/biostatistics/kxx069">Only 14% of drugs and therapies</a> that go through human clinical trials ultimately win FDA approval, with less than a 4% success rate for cancer drugs. </p>
<p>The process of science generally takes place below the radar of public awareness, and so this uncertainty is not generally in view. However, Americans are <a href="https://www.journalism.org/2020/04/29/1-americans-are-turning-to-media-government-and-others-for-covid-19-news/">paying close attention</a> to the COVID-19 pandemic, and many are, for the first time, seeing the sausage as it is being made. </p>
<p>Although the recent retractions may be unappetizing, medical science has been very successful over the long run. Smallpox has been eradicated, infections are treated with antibiotics rather than amputation and pain management during surgery has advanced well beyond biting on a stick. </p>
<p>The system is by no means perfect, but it is pretty darned good.</p>
<p><em>This story was edited on July 9 to more precisely describe the state of hydroxychloroquine research.</em></p><img src="https://counter.theconversation.com/content/140326/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Mark R. O'Brian receives funding from the National Institutes of Health</span></em></p>Severe scrutiny of two major papers, including one about the effectiveness of hydroxychloroquine, is part of science’s normal process of self-correction.Mark R. O'Brian, Professor and Chair of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, University at BuffaloLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1393092020-05-29T02:05:27Z2020-05-29T02:05:27ZCould taking hydroxychloroquine for coronavirus be more harmful than helpful?<figure><img src="https://images.theconversation.com/files/337900/original/file-20200527-20229-1imk34p.jpg?ixlib=rb-1.1.0&rect=0%2C0%2C7951%2C5304&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><span class="source">Shutterstock</span></span></figcaption></figure><p><em><strong>UPDATE</strong>: Since this Research Check was published, The Lancet has <a href="https://www.thelancet.com/lancet/article/s0140673620313246">retracted</a> the study it published (and which is evaluated in this article), explaining that three of the study’s authors said they “can no longer vouch for the veracity of the primary data sources” and were unable to independently audit the data.</em></p>
<p><em>The journal previously issued an <a href="https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(20)31290-3.pdf">expression of concern</a> over the study, referring to “serious scientific questions” over the provenance of the data. The World Health Organisation has also announced it will <a href="https://www.statnews.com/2020/06/03/who-resuming-hydroxychloroquine-study-for-covid-19/">resume</a> its trial of hydroxychloroquine for COVID-19, after temporarily suspending it in response to the Lancet study.</em></p>
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<p><em>In response to the initial expression of concern, Andrew McLachlan, lead author of this Research Check, <a href="https://www.scimex.org/newsfeed/expert-reaction-who-restarts-hydroxychloroquine-trials-after-study-data-raises-concerns">told the Australian Science Media Centre</a>:</em> </p>
<p><em>“The study used data from an international registry curated by a US company including 96,000 people with COVID-19, 671 hospitals across 6 continents. People treated with hydroxychloroquine or chloroquine had a higher death rate. This was a surprising and controversial finding (hydroxychloroquine has been used safely for malaria and autoimmune diseases for decades). On the back of these results a number of trials investigating hydroxychloroquine in COVID-19, including a WHO trial, were suspended, after a reassessment of the possible harms from hydroxychloroquine. Subsequently, many commentators and groups called into question the veracity of the registry data in the Lancet study, how it was collected, and aspects of the analysis. While the authors published a clarification, it failed to address major issues.</em></p>
<p><em>"The study itself (and most commentators) concluded that high-quality randomised controlled trials of hydroxychloroquine in COVID-19 were needed – especially to clarify possible harms and establish which COVID-19 patients would benefit. Many considered suspending ongoing clinical trials involving hydroxychloroquine in COVID-19 as premature. All the ongoing randomised controlled trials involve careful screening and monitoring of well-known adverse effects (on heart rhythm and eye toxicity). The numerous trials should continue; they can be conducted safely and when complete will answer the important question of whether hydroxychloroquine is a safe and effective drug to treat or prevent COVID-19 in the global pandemic.”</em></p>
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<p>A <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31180-6/fulltext">paper published in The Lancet</a> has cast fresh controversy on the use of the malaria drug hydroxychloroquine as a potential treatment for COVID-19. </p>
<p>The study’s authors reported they were “unable to confirm a benefit” of using the drug, while also finding COVID-19 patients in hospital treated with hydroxychloroquine were more likely to die or suffer life-threatening heart rhythm complications.</p>
<p>The publication prompted the World Health Organisation to <a href="https://www.abc.net.au/news/2020-05-26/who-pauses-trial-of-hydroxychloroquine-for-coronavirus-patients/12285652">suspend its testing of hydroxychloroquine to treat COVID-19</a>, while a <a href="https://www.ascot-trial.edu.au/blogs/news/statement-on-the-status-of-australasian-covid-19-trial-ascot">similar Australian trial</a> has paused recruitment.</p>
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Read more:
<a href="https://theconversation.com/donald-trump-is-taking-hydroxychloroquine-to-ward-off-covid-19-is-that-wise-139031">Donald Trump is taking hydroxychloroquine to ward off COVID-19. Is that wise?</a>
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<h2>A bit of background</h2>
<p>Hydroxychloroquine has been used since the 1940s to treat malaria, but has been making headlines as a <a href="https://www.nps.org.au/media/hydroxychloroquine-and-covid-19">potential treatment for COVID-19</a>. US President Donald Trump recently declared <a href="https://theconversation.com/donald-trump-is-taking-hydroxychloroquine-to-ward-off-covid-19-is-that-wise-139031">he was taking it daily</a>, while Australian businessman and politician Clive Palmer <a href="https://www.sbs.com.au/news/the-feed/clive-palmer-has-bought-30-million-doses-of-an-anti-malaria-drug-to-fight-covid-19-but-experts-warn-this-may-not-be-the-cure-all">pledged to create a national stockpile</a> of the drug.</p>
<p>The drug alters the human immune system (it’s an <a href="https://www.nps.org.au/hcq-and-covid-19">immunomodulator, not an immunosuppressant</a>) and has an important role in helping people with rheumatoid arthritis and lupus. </p>
<p>It does have a range of serious <a href="https://www.tga.gov.au/alert/new-restrictions-prescribing-hydroxychloroquine-covid-19">possible side-effects</a>, including eye damage and altered heart rhythm, which require monitoring. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/338096/original/file-20200528-20229-1lfsj4s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/338096/original/file-20200528-20229-1lfsj4s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/338096/original/file-20200528-20229-1lfsj4s.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/338096/original/file-20200528-20229-1lfsj4s.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/338096/original/file-20200528-20229-1lfsj4s.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/338096/original/file-20200528-20229-1lfsj4s.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/338096/original/file-20200528-20229-1lfsj4s.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">We don’t know the patients in this study died because they took hydroxychloroquine.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
</figcaption>
</figure>
<p><a href="https://www.nature.com/articles/s41421-020-0156-0">Laboratory studies</a> suggest hydroxychloroquine may disrupt replication of the SARS-CoV-2 virus that causes COVID-19. It’s also possible hydroxychloroquine could reduce “<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7161506/">cytokine storm</a>” – the catastrophic immune system overreaction that happens in some people with severe COVID-19.</p>
<p>A huge global effort is underway to investigate whether hydroxychloroquine is safe and effective for preventing or treating COVID-19, especially to improve recovery and reduce the risk of death. Previous studies have been inconclusive as they were anecdotal, observational or small randomised trials. </p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/in-the-fight-against-coronavirus-antivirals-are-as-important-as-a-vaccine-heres-where-the-science-is-up-to-133926">In the fight against coronavirus, antivirals are as important as a vaccine. Here's where the science is up to</a>
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<p>Doubts about hydroxychloroquine’s effectiveness have been increasing, with a large observational study from New York <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2012410">showing it had no benefit</a> in treating people with COVID-19.</p>
<p>The new <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31180-6/fulltext">Lancet study</a>, published last week, has found it could increase the risk of death among COVID-19 patients in hospital. But there’s more to the story. </p>
<h2>What did the new study do?</h2>
<p>The <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31180-6/fulltext">Lancet study</a> collected real-world data on more than 96,000 hospitalised patients with COVID-19 from more than 600 hospitals across six continents. </p>
<p>About 15,000 patients were treated with hydroxychloroquine (or a closely related drug, chloroquine) alone or in combination with an antibiotic.</p>
<p>Using a global registry the researchers investigated the safety of these treatments. They looked at whether people died in hospital, as well as the risk of developing life-threatening heart rhythm problems (called ventricular arrhythmias).</p>
<h2>What did the study find?</h2>
<p>Treatment with hydroxychloroquine was associated with increased rates of death in people with COVID-19, even after the researchers adjusted for other factors (age, other health conditions, suppressed immune system, smoking, and severity of the COVID-19 infection) that might increase the risk of death. </p>
<p>About 18% of people who received hydroxychloroquine died in hospital, compared with 9% of people with COVID-19 who did not receive these treatments. The risk of death was even higher (24%) in people receiving hydroxychloroquine in combination with either of the antibiotics azithromycin or clarithromycin.</p>
<p>Hydroxychloroquine (6%) and chloroquine (4%) treatment was also associated with more cases of dangerous heart rhythm problems when compared with untreated people with COVID-19 (0.3%).</p>
<p>Any evidence of benefit, while not the focus of this study, was unclear.</p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/why-are-there-so-many-drugs-to-kill-bacteria-but-so-few-to-tackle-viruses-137480">Why are there so many drugs to kill bacteria, but so few to tackle viruses?</a>
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<h2>How can we interpret the results?</h2>
<p>This was an observational study, so it can only explore the association between treatments and death – rather than telling us hydroxychloroquine <em>caused</em> these patients to die.</p>
<p>It is <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31174-0/fulltext">unclear</a> why the death rate for patients treated with hydroxychloroquine and chloroquine was double that of those who weren’t, as the cause of death was not reported in this study.</p>
<p>Importantly, the study cannot account for all the factors that might contribute to death in these hospitalised patients and how these factors interact with each other. However, the researchers did a good job of “<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3144483/">matching</a>” the characteristics of people who were receiving hydroxychloroquine with those who were not receiving the drug, which makes the results more reliable. </p>
<p>But there may still be other factors, or medicines, that contributed to these findings. So there remains uncertainly about whether hydroxychloroquine causes, or even contributes to, the death of people with COVID-19. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/338100/original/file-20200528-20245-ml466p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/338100/original/file-20200528-20245-ml466p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/338100/original/file-20200528-20245-ml466p.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/338100/original/file-20200528-20245-ml466p.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/338100/original/file-20200528-20245-ml466p.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/338100/original/file-20200528-20245-ml466p.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/338100/original/file-20200528-20245-ml466p.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">While the Lancet study has seen some hydroxychloroquine trials halted, others are continuing under careful monitoring.</span>
<span class="attribution"><span class="source">Shutterstock</span></span>
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</figure>
<p>Further, it was not possible to have careful control over the hydroxychloroquine dose people received – or other medicines people might be taking such as antivirals or other medicines for heart conditions (which potentially interact in sick hospitalised patients). </p>
<p>The average dose of hydroxychloroquine in this study was at the upper end of the regular recommended dose range for rheumatoid arthritis and lupus. But the wide range of hydroxychloroquine (and chloroquine) doses in this study makes interpretation of the findings difficult, especially when we know <a href="https://www1.racgp.org.au/ajgp/coronavirus/hydroxychloroquine-use-during-the-covid-19-pandemi">harmful effects</a> are associated with larger doses.</p>
<h2>Broader implications</h2>
<p>This study provides important information about the safety of hydroxychloroquine in treating vulnerable people with COVID-19 receiving hospital care.</p>
<p>While the implications for using hydroxychloroquine to treat COVID-19 in the community or for prevention of COVID-19 remain unclear, if nothing else this study highlights the need to carefully monitor people receiving the drug. </p>
<p>Some hydroxychloroquine trials are continuing, such as the very large <a href="https://www.recoverytrial.net/for-site-staff/site-staff/#alert">RECOVERY trial</a> in the UK. </p>
<p>This new information must be considered when balancing harm and potential benefit of these trials and will likely result in renewed safety monitoring.</p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/coronavirus-scientists-promoting-chloroquine-and-remdesivir-are-acting-like-sports-rivals-138051">Coronavirus: scientists promoting chloroquine and remdesivir are acting like sports rivals</a>
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<p>We’ll need to see results from <a href="https://www.mja.com.au/journal/2020/clinical-trials-prevention-and-treatment-coronavirus-disease-2019-covid-19-current">ongoing</a> high-quality randomised controlled trials to truly know if hydroxychloroquine is effective and safe in treating or preventing COVID-19. </p>
<p>Further questions about what dose should be used, and which patients will benefit most, are topics under active investigation. </p>
<p>You <a href="https://www.tga.gov.au/alert/new-restrictions-prescribing-hydroxychloroquine-covid-19">should not take hydroxychloroquine</a> for COVID-19 unless you’re part of a clinical trial. <strong>– Andrew McLachlan and Ric Day</strong></p>
<h2>Blind peer review</h2>
<p><em>This review was written before further questions were raised about the Lancet study. See update below.</em></p>
<p>This is a fair and reasonable review of the Lancet paper, its relationship to previous studies, and its impact on ongoing clinical trials. </p>
<p>As stated in the review the Lancet article adds to the body of knowledge, including recent substantial studies in the <a href="https://www.nejm.org/doi/full/10.1056/NEJMoa2012410">New England Journal of Medicine</a> and the <a href="https://www.bmj.com/content/369/bmj.m1849">British Medical Journal</a>, that hydroxychloroquine is without significant effect in treatment trials. </p>
<p>The high death rate is concerning but not unprecedented, given that a clinical trial in Brazil was <a href="https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2765499">halted</a> because of adverse effects on the heart. However, recent <a href="https://www.theguardian.com/science/2020/may/28/questions-raised-over-hydroxychloroquine-study-which-caused-who-to-halt-trials-for-covid-19?CMP=share_btn_tw">media reports</a> suggest the data may have to be revised due to <a href="https://statmodeling.stat.columbia.edu/2020/05/25/hydroxychloroquine-update/">misclassification</a> of the participating hospitals. <strong>– Ian Musgrave</strong></p>
<p><em><strong>UPDATE</strong>: Ian Musgrave has provided the following comments (with thanks to the <a href="https://www.smc.org.au/">Australian Science Media Centre</a>) in response to The Lancet’s earlier expression of concern about the study:</em></p>
<p><em>“The news of the WHO restarting clinical trials ironically comes as another study was <a href="https://www.nejm.org/doi/pdf/10.1056/NEJMoa2016638">published in the New England Journal of Medicine</a> which showed no effect of hydroxychloroquine as pre-exposure prophylaxis for COVID-19. The decision by the WHO to pause trials was appropriate at the time, and the decision to reopen after careful review is also appropriate.</em></p>
<p><em>"Even if we completely discount the Lancet studies, there is still significant evidence of lack of efficacy and potential harm that restarting clinical trials should be done carefully. And clinical trials are still needed. The rapid pace of the COVID-19 outbreak means the early data we collect may be misleading or incomplete. While hydroxychloroquine has been given undue attention (and its potential harms minimised) there may still be some benefit to its judicious use. The Lancet case shows us that the scientific community must remain vigilant even with results we agree with and that data transparency and data sharing are even more important when we need to make good conclusions quickly in uncertain times.”</em></p>
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<p><em>Research Checks interrogate newly published studies and how they’re reported in the media. The analysis is undertaken by one or more academics not involved with the study, and reviewed by another, to make sure it’s accurate.</em></p><img src="https://counter.theconversation.com/content/139309/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Andrew McLachlan receives research funding from the NHMRC, research scholarship funding from GSK for a PhD student under his supervision and has previously received (and disclosed) in kind research support from Pfizer and GSK for investigator initiated research projects. Andrew serves and is paid as an expert on Australian government committees related to medicines regulation and anti-doping.</span></em></p><p class="fine-print"><em><span>IIan Musgrave has previously received funding from the National Health and Medical Research Council to study adverse reactions to herbal medicines and has previously been funded by the Australian Research Council to study potential natural product treatments for Alzheimer's disease. He has collaborated with SA water on studies of cyanobacterial toxins and their implication for drinking water quality. He has no funding from nor shares in any companies that have financial interests in COVID-19 therapies. He is a member of Friends of Science in Medicine.</span></em></p><p class="fine-print"><em><span>Ric Day does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>People taking hydroxychloroquine for coronavirus may be more likely to die, according to new research. But that doesn’t mean the drug is killing them.Andrew McLachlan, Head of School and Dean of Pharmacy, University of SydneyRic Day, Professor of Clinical Pharmacology, UNSW SydneyLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1205002020-01-30T23:36:02Z2020-01-30T23:36:02ZHeat kills. We need consistency in the way we measure these deaths<figure><img src="https://images.theconversation.com/files/312380/original/file-20200129-93030-1l4yoju.jpg?ixlib=rb-1.1.0&rect=46%2C0%2C5184%2C3437&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Heat increases the risk of death, but the question of how much has been a topic of debate.</span> <span class="attribution"><span class="source">From shutterstock.com</span></span></figcaption></figure><p>One of the most confronting impacts of climate change is the risk of more deaths from hot weather. Heat stress <a href="https://theconversation.com/hot-and-bothered-heat-affects-all-of-us-but-older-people-face-the-highest-health-risks-123769">can exacerbate</a> existing health conditions including diabetes, kidney disease and heart disease. Older people are particularly vulnerable.</p>
<p>It may then surprise you to learn a <a href="https://doi.org/10.1016/j.envint.2019.105027">few</a> <a href="https://www.thelancet.com/journals/lanplh/article/PIIS2542-5196(17)30156-0/fulltext">recent</a> <a href="https://link.springer.com/article/10.1007/s10584-018-2274-3">studies</a> have suggested climate change will decrease temperature-related deaths in Australia. And a related study published in <a href="https://doi.org/10.1016/S0140-6736(14)62114-0">The Lancet</a> found the cold kills more people in Sydney, Melbourne and Brisbane than the heat.</p>
<p>But my research, published in <a href="https://link.springer.com/article/10.1007%2Fs10584-019-02519-1">Climatic Change</a>, disputes these results.</p>
<p>Using a similar methodology as that used in the study published in <a href="https://doi.org/10.1016/S0140-6736(14)62114-0">The Lancet</a>, I found the majority of deaths related to temperature in Australia are caused by heat.</p>
<p>As temperature-related deaths are one of the main measures we use to assess the effects of climate change, it’s important we measure them accurately and consistently.</p>
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<strong>
Read more:
<a href="https://theconversation.com/hot-and-bothered-heat-affects-all-of-us-but-older-people-face-the-highest-health-risks-123769">Hot and bothered: heat affects all of us, but older people face the highest health risks</a>
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<h2>How do researchers measure temperature-related deaths?</h2>
<p>An important part of the process is estimating the proportion of deaths that occurred during cold weather and hot weather. </p>
<p>To determine this many studies use a reference (or baseline) temperature. This reference temperature should be a day where people in a region feel comfortable and their health is unlikely to be affected by cold or heat. Temperature-related deaths falling below this temperature are classified as cold-related, and deaths above will be heat-related.</p>
<p>We use statistical techniques to distinguish temperature-related deaths from deaths due to unrelated causes.</p>
<p>For example, estimates should adjust for the severity of seasonal factors, including flu seasons. Flu and pneumonia deaths do <a href="https://theconversation.com/there-are-lots-of-myths-about-flu-we-debunk-six-of-them-120444">rise in winter</a>, but they’re not directly caused by the cold.</p>
<p>Temperature-related death estimates vary depending on the underlying assumptions made, and the modelling techniques used. But a key issue causing a discrepancy between results is the use of different reference temperatures. This influences the proportion of deaths classified as being related to cold and heat.</p>
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<em>
<strong>
Read more:
<a href="https://theconversation.com/how-rising-temperatures-affect-our-health-123016">How rising temperatures affect our health</a>
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</em>
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<h2>The importance of the reference temperature</h2>
<p>The relationship between temperature and death can be shown as a curve of the risk of death from high/low temperatures in relation to the reference temperature.</p>
<p>The figure below shows how the estimated curves, called temperature-mortality curves, can differ when the reference temperature is changed. It compares temperature-mortality curves from <a href="https://doi.org/10.1007/s10584-019-02519-1">my latest study</a> (the bottom row), to those from the <a href="https://www.sciencedirect.com/science/article/pii/S0140673614621140">study published in The Lancet</a> (the top row).</p>
<p>Red and blue shading show the parts of the curve defined as heat and cold. Arrows point to the reference temperature used to estimate the curves. </p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/298524/original/file-20191024-170458-ewz2bm.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/298524/original/file-20191024-170458-ewz2bm.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/298524/original/file-20191024-170458-ewz2bm.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=448&fit=crop&dpr=1 600w, https://images.theconversation.com/files/298524/original/file-20191024-170458-ewz2bm.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=448&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/298524/original/file-20191024-170458-ewz2bm.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=448&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/298524/original/file-20191024-170458-ewz2bm.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=562&fit=crop&dpr=1 754w, https://images.theconversation.com/files/298524/original/file-20191024-170458-ewz2bm.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=562&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/298524/original/file-20191024-170458-ewz2bm.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=562&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">A comparison of temperature-mortality curves.</span>
<span class="attribution"><span class="source">Gasparrini et al. (2015) and Longden (2019)</span></span>
</figcaption>
</figure>
<p>Numerous studies, including the Lancet study, have estimated the number of deaths attributable to heat and cold using what’s called a minimum mortality temperature (MMT) as the reference temperature. </p>
<p>The MMT is the lowest point of a temperature-mortality curve and is often interpreted as the daily average temperature at which there’s the lowest risk of death.</p>
<p>Based on the findings for Australia, I’m concerned the reference temperature (the MMT) used in <a href="https://www.sciencedirect.com/science/article/pii/S0140673614621140">The Lancet study</a> was too high. For example, a reference temperature of 22.4°C (shown in the figure above) meant almost 90% of Melbourne’s historical daily average temperatures were classified as cold. This could be equivalent to a day with a maximum of 31.4°C and a night minimum of 13.4°C.</p>
<p>I’ve used a different reference temperature in <a href="https://doi.org/10.1007/s10584-019-02519-1">my latest study</a>. I used the median of historical daily average temperatures as the reference temperature. For example, in my study cold days in Melbourne are those below a daily average temperature of 14.7°C. All daily average temperatures above 14.7°C are considered hot.</p>
<p>Using the median as the reference temperature creates a 50/50 split between what’s considered hot and cold.</p>
<h2>Comparing the results</h2>
<p>As well as using a different reference temperature, I used <a href="https://www.qld.gov.au/law/births-deaths-marriages-and-divorces/data/national-data">national death record data</a> to estimate temperature-related deaths for six climate zones. They range from areas with a “hot humid summer” in the north and areas of “mild/warm summers and cold winters” in Tasmania, the ACT and parts of NSW and Victoria.</p>
<p>The other studies I mentioned used data for many cities from around the world, but only included the three largest Australian capitals (Sydney, Melbourne and Brisbane).</p>
<figure class="align-center zoomable">
<a href="https://images.theconversation.com/files/284453/original/file-20190717-147307-j7e065.png?ixlib=rb-1.1.0&q=45&auto=format&w=1000&fit=clip"><img alt="" src="https://images.theconversation.com/files/284453/original/file-20190717-147307-j7e065.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/284453/original/file-20190717-147307-j7e065.png?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=425&fit=crop&dpr=1 600w, https://images.theconversation.com/files/284453/original/file-20190717-147307-j7e065.png?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=425&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/284453/original/file-20190717-147307-j7e065.png?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=425&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/284453/original/file-20190717-147307-j7e065.png?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=534&fit=crop&dpr=1 754w, https://images.theconversation.com/files/284453/original/file-20190717-147307-j7e065.png?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=534&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/284453/original/file-20190717-147307-j7e065.png?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=534&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px"></a>
<figcaption>
<span class="caption">Climate zones across Australia.</span>
<span class="attribution"><span class="source">Longden (2019)</span></span>
</figcaption>
</figure>
<p>In <a href="https://link.springer.com/article/10.1007/s10584-019-02519-1">my study</a>, I estimated 2% of deaths in Australia between 2006 and 2017 were due to the heat.</p>
<p>In the three warmer climate zones this number was higher, ranging from 4.5% to 9.1% of deaths. However, as the majority of the population lives in the second coldest climate zone (warm summer, cold winter), this brings down the national estimate.</p>
<p>In the coldest climate zone, 3.6% of deaths were due to the cold and the heat was less dangerous.</p>
<p>These estimates are notably different to those in <a href="https://doi.org/10.1016/S0140-6736(14)62114-0">The Lancet</a> study where the total for Sydney, Melbourne and Brisbane had 6.5% of deaths associated with cold temperatures, but only 0.5% of deaths due to the heat.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/car-accidents-drownings-violence-hotter-temperatures-will-mean-more-deaths-from-injury-129628">Car accidents, drownings, violence: hotter temperatures will mean more deaths from injury</a>
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<p>The difference between these results suggests the need to explore alternative approaches for estimating temperature-related deaths.</p>
<p>Future research should assess whether changing the reference temperature impacts the estimates of temperature-related deaths for other countries.</p>
<p>Finally, accounting for climate zones is another important factor that will affect the balance between the danger of cold and heat.</p><img src="https://counter.theconversation.com/content/120500/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>This research was conducted by Thomas Longden at the Centre for Health Economics Research and Evaluation (CHERE) at the University of Technology Sydney (UTS). At UTS he received funding from the Lord Mayor's Charitable Foundation, Sustainability Victoria, the Independent Hospital Pricing Authority (IHPA) and the Commonwealth Dept. of Health.
At ANU he is a Grand Challenge Fellow working on the ANU Energy Change Institute’s Grand Challenge – Zero-Carbon Energy for the Asia-Pacific. He is based at the Crawford School of Public Policy. </span></em></p>A warming climate leads to more heat-related deaths. The fact some research is showing the opposite indicates we need to refine the way we measure heat-related mortality.Thomas Longden, Research Fellow, Australian National UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1227212019-09-03T05:15:35Z2019-09-03T05:15:35ZWe don’t know menopausal hormone therapy causes breast cancer, but the evidence continues to suggest a link<figure><img src="https://images.theconversation.com/files/290465/original/file-20190902-175673-1xmww2h.jpg?ixlib=rb-1.1.0&rect=67%2C33%2C5540%2C3699&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">This isn't the first time scientific research has found a link between menopausal hormone therapy and breast cancer.</span> <span class="attribution"><span class="source">From shutterstock.com</span></span></figcaption></figure><p>Menopause is a normal life stage for women at <a href="https://www.ncbi.nlm.nih.gov/pubmed/22198658">around 51 years</a>. Most women don’t need treatment for their symptoms, but around <a href="https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0146494">13% of Australian women</a> aged 50-69 take menopausal hormone therapy (sometimes called “hormone replacement therapy”).</p>
<p>This medication contains hormones that are normally low or absent after menopause, and reduces symptoms such as hot flushes and night sweats, which can be troublesome and persistent for some women. </p>
<p>But growing evidence over recent years has pointed to <a href="https://www.ncbi.nlm.nih.gov/pubmed/12117397">an increased risk</a> of breast cancer associated with menopausal hormone therapy. This has already led some women to stop or avoid the treatment.</p>
<p>Now a new study, published in the leading medical journal <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31709-X/fulltext">The Lancet</a>, strengthens the existing evidence, and suggests the risks are greater than we previously thought.</p>
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<p>
<em>
<strong>
Read more:
<a href="https://theconversation.com/heres-what-you-need-to-know-about-menopausal-hormone-therapy-and-cancer-risk-51305">Here's what you need to know about menopausal hormone therapy and cancer risk</a>
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<p>This study only measured the risk of breast cancer, not potential benefits such as improved symptoms, sleep and quality of life.</p>
<p>However, it provides important information to help women decide whether to take menopausal hormone therapy and how long for.</p>
<h2>What the study found</h2>
<p>This paper combined data from 58 international studies conducted between 1992 and 2018 to measure the association between menopausal hormone therapy and breast cancer. Cumulatively, the studies included more than 100,000 women with breast cancer and 400,000 women without breast cancer.</p>
<p>The authors found women taking any type of menopausal hormone therapy, except topical (vaginal) oestrogen, had a higher risk of breast cancer compared with women of a similar age who did not take menopausal hormone therapy, taking into account other known risk factors for breast cancer.</p>
<p>The increased risk of breast cancer was apparent after only one year on menopausal hormone therapy, and increased steadily with longer duration of use. </p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/290594/original/file-20190902-175686-1v5jb1d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/290594/original/file-20190902-175686-1v5jb1d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/290594/original/file-20190902-175686-1v5jb1d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/290594/original/file-20190902-175686-1v5jb1d.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/290594/original/file-20190902-175686-1v5jb1d.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/290594/original/file-20190902-175686-1v5jb1d.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/290594/original/file-20190902-175686-1v5jb1d.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
<figcaption>
<span class="caption">About 13% of Australian women of menopausal age take menopausal hormone therapy.</span>
<span class="attribution"><span class="source">From shutterstock.com</span></span>
</figcaption>
</figure>
<p>Menopausal hormone therapy contains oestrogen to treat the symptoms of menopause, plus progesterone (or a progestogen which acts like progesterone), to prevent endometrial (uterine) cancer. This is called combined menopausal hormone therapy.</p>
<p>Given that progestogen is added to oestrogen to prevent uterine cancer, it’s somewhat ironic that it may increase the risk of breast cancer. </p>
<p>A previous <a href="https://www.ncbi.nlm.nih.gov/pubmed/12117397">large randomised controlled trial</a> showed more than five years of combined menopausal hormone therapy increased the risk of breast cancer. New data from this study suggest oestrogen alone also increases breast cancer risk, although much less than combined menopausal hormone therapy.</p>
<p>The authors estimated for every 50-70 women taking combined (oestrogen and progestogen) menopausal hormone therapy, there would be one additional case of breast cancer. For oestrogen alone, they predicted one additional case for every 200 women taking menopausal hormone therapy. </p>
<p>The study also found taking progestogen every day in menopausal hormone therapy (called “continuous combined”) may increase breast cancer risk more than taking progestogen on an intermittent, or “cyclical” basis. Cyclical regimens are less popular in Australia because they are more likely to cause bleeding. This study may change practice towards using cyclical rather than daily progestogen.</p>
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Read more:
<a href="https://theconversation.com/science-or-snake-oil-do-meds-like-remifemin-ease-hot-flushes-and-night-sweats-in-menopausal-women-70339">Science or Snake Oil: do meds like Remifemin ease hot flushes and night sweats in menopausal women?</a>
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<p>The studies included in this review are observational, so while they demonstrate a correlation, they cannot prove menopausal hormone therapy causes breast cancer. However, the associations are strong, there is no other apparent reason for the observed association – and the link is biologically plausible. </p>
<p>Most breast cancers are sensitive to oestrogen and progesterone. We know postmenopausal women with higher circulating levels of oestrogen are <a href="https://link.springer.com/article/10.1007/s10552-011-9729-4">at higher risk</a> of breast cancer, and that blocking oestrogen reduces breast cancer risk. </p>
<p>Taking menopausal hormone therapy increases the levels of oestrogen and taking progesterone increases exposure to a hormone not normally produced after menopause. </p>
<h2>Length of use</h2>
<p>Previously it was thought that up to five years of menopausal hormone therapy <a href="https://www.ncbi.nlm.nih.gov/pubmed/12117397">did not increase breast cancer risk</a>. This study challenges that assumption by showing risk increased after one year of use. The longer women took menopausal hormone therapy, the greater the risk. </p>
<p>The estimated risk of breast cancer was 6.3% in postmenopausal women who did not take menopausal hormone therapy compared to 8.3% for five years of combined menopausal hormone therapy. This is an absolute increase of 2%, or one extra breast cancer case for every 50 users. That’s approximately twice as high as indicated in <a href="https://www.ncbi.nlm.nih.gov/pubmed/12117397">earlier studies</a>.</p>
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<img alt="" src="https://images.theconversation.com/files/290602/original/file-20190903-175700-7jsc1r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/290602/original/file-20190903-175700-7jsc1r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=400&fit=crop&dpr=1 600w, https://images.theconversation.com/files/290602/original/file-20190903-175700-7jsc1r.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=400&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/290602/original/file-20190903-175700-7jsc1r.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=400&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/290602/original/file-20190903-175700-7jsc1r.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=503&fit=crop&dpr=1 754w, https://images.theconversation.com/files/290602/original/file-20190903-175700-7jsc1r.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=503&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/290602/original/file-20190903-175700-7jsc1r.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=503&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Uniform national guidelines would assist doctors and patients in deciding the most appropriate way to manage menopausal symptoms.</span>
<span class="attribution"><span class="source">From shutterstock.com</span></span>
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<p>This new information raises questions about <a href="https://journals.lww.com/menopausejournal/Abstract/2017/07000/The_2017_hormone_therapy_position_statement_of_The.5.aspx">international guidelines</a>, which suggest healthy women around the average age of menopause can safety take menopausal hormone therapy for up to ten years. </p>
<p>Another important finding was the persistent increased risk of breast cancer for up to ten years after stopping menopausal hormone therapy. This is considerably longer than <a href="https://link.springer.com/article/10.1007/s10549-014-2934-6">was previously thought</a>. </p>
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<a href="https://theconversation.com/chemical-messengers-how-hormones-change-through-menopause-56921">Chemical messengers: how hormones change through menopause</a>
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<p>Follow-up from another <a href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)32033-1/fulltext">large observational study</a> of over one million women published in the same edition of The Lancet showed menopausal hormone therapy also increases the risk of dying from breast cancer.</p>
<p>In postmenopausal women who had never taken menopausal hormone therapy, one in 135 died from breast cancer, compared with one in 120 women taking oestrogen alone for five years or more, and one in 95 women taking combined menopausal hormone therapy for five years or more. </p>
<p>Together, these findings suggest taking menopausal hormone therapy for more than five years may increase the number of women diagnosed with and dying from breast cancer. Natural or “biodentical” preparations contain similar hormones, and are likely to carry the same risk.</p>
<h2>Not the only treatment</h2>
<p>While menopausal hormone therapy may be an effective treatment for menopausal symptoms, it’s not the only one. There’s growing evidence drug free and non-hormonal therapies <a href="https://www.bmj.com/content/359/bmj.j5101">are also effective</a> for hot flushes and night sweats. </p>
<p>For genitourinary symptoms, such as vaginal dryness, topical oestrogen is effective and has shown <a href="https://www.ncbi.nlm.nih.gov/pubmed/27577677">no increase in breast cancer risk</a>.</p>
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Read more:
<a href="https://theconversation.com/what-causes-breast-cancer-in-women-what-we-know-dont-know-and-suspect-86314">What causes breast cancer in women? What we know, don't know and suspect</a>
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<p>Unfortunately, advice and information about the risks and benefits of menopausal hormone therapy have been inconsistent in Australia to date. This makes it more difficult to translate new evidence into safer prescribing and practice, and to guide doctors and patients in deciding whether menopausal hormone therapy is the right choice. </p>
<p>For women going through menopause at the average age, menopausal hormone therapy should only be used to treat troublesome menopausal symptoms, not for the <a href="https://jamanetwork.com/journals/jama/fullarticle/2665782">prevention or treatment</a> of other conditions.</p>
<p>Women with troublesome symptoms need high quality information to weigh up the risks and benefits of hormonal therapy. </p>
<p>We urgently need national consensus guidelines, incorporating the most up-to-date evidence, to better support women and their health-care providers to make informed decisions about safe and effective ways to manage menopausal symptoms.</p><img src="https://counter.theconversation.com/content/122721/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Martha Hickey receives funding from the National Health and Medical Research Foundation as a Practitioner Fellowship and project grant funding for menopause research. She is an editor for the Cochrane Gynaecology and Fertility Group</span></em></p><p class="fine-print"><em><span>Mark Jenkins does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>A study published recently in The Lancet indicated menopausal hormone therapy is associated with an increased risk of breast cancer. How can we interpret the results?Martha Hickey, Professor of Obstetrics and Gynaecology, The University of MelbourneMark Jenkins, Director of the Centre for Epidemiology and Biostatistics, The University of MelbourneLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/1049932018-10-17T13:07:41Z2018-10-17T13:07:41ZTerrorism research: we’re missing the bigger picture by focusing too much on PTSD<p>The terrorist attacks of September 11, 2001 left almost 3,000 fatalities and more than 6,000 people injured. They also occurred at a time when there was a surge of interest in emotional and psychological trauma.</p>
<p>It is hardly surprising, therefore, that many researchers actively sought to uncover PTSD associated with the aftermath of 9/11. But in a study published in <a href="https://www.thelancet.com/pb/assets/raw/Lancet/pdfs/S2215-0366(18)30335-3.pdf">The Lancet Psychiatry</a>, my colleague, David Wainwright, from University of Bath, and I propose that there has been an overemphasis on uncovering psychological trauma. This is potentially harmful to the minority of victims who are in real need. It also elides significant evidence that, when confronted by terrorism, people often show resilience and defiance.</p>
<h2>Our method</h2>
<p>Our purpose was to review the history of academic inquiry into the association between terrorism and mental health, and to explore its consequences. To do so we first compiled a list from psychological and medical databases of all the research literature we could find that linked these concepts together in their titles or abstracts. After removing less relevant papers we were left with some 330, all of which were read and analysed.</p>
<p>The tendency to look for any such connection actually only emerged <a href="https://www.wiley.com/en-gb/Terrorists,+Victims+and+Society:+Psychological+Perspectives+on+Terrorism+and+its+Consequences-p-9780471494621">quite recently</a>. Research on terrorism, historically, focused more on politics or physical damage. That changed shortly before the 2001 terrorist attacks on the World Trade Centre in New York. The growing recognition of PTSD encouraged a social and cultural climate more attuned to the possibility and consequences of psychological damage.</p>
<p>Most of the pieces we reviewed appeared after 9/11 but, notably, there had been an emerging interest in the field driven by earlier incidents in <a href="http://www.bbc.co.uk/history/events/omagh_bomb">Omagh (1998)</a>, <a href="http://news.bbc.co.uk/onthisday/hi/dates/stories/april/19/newsid_2733000/2733321.stm">Oklahoma</a> and <a href="https://theconversation.com/uk/topics/tokyo-sarin-gas-attack-36236">Tokyo (1995)</a>, as well as in Israel both during and after the first Gulf War (1991).</p>
<p>The most striking lesson we drew was that overall, right across the board, terrorism is not terrorising – at least not in the sense understood by much of the research conducted after 9/11 that actively sought evidence of PTSD. The actual rate of PTSD was on a par with that after any other potentially traumatic event – typically less than 5% for civilian populations. That ought to be a cause for celebration.</p>
<p>But that’s not how the evidence was reported. Instead, across a range of high profile, peer reviewed journals, we found studies that, while referring to PTSD, were actually drawn to measuring a subset of its criteria, in effect expanding the bounds of what they reported.</p>
<p>For instance, <a href="https://www.estss.org/learn-about-trauma/dsm-iv-definition/">the first criterion to assess PTSD</a> from the then Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) is the need to have experienced an event “that involved actual or threatened death or serious injury, or a threat to the physical integrity of self or others”. This has been described by some as the <a href="https://onlinelibrary.wiley.com/doi/epdf/10.1046/j.1365-2850.2001.00358.x">“gatekeeper”</a> to the diagnosis and was absent from most of the surveys. These were often conducted over the phone by volunteers with limited training. And, as they could check just a few items from the then standard <a href="https://www.mirecc.va.gov/docs/visn6/3_ptsd_checklist_and_scoring.pdf">17-point checklist for PTSD</a>, the researchers would report finding what they then variously described as “pre-PTSD” or “PTSD symptoms” instead.</p>
<p>As different research teams applied distinct symptom checklists in their surveys – rarely using diagnostic interviews – the results and conclusions from these were <a href="https://jamanetwork.com/journals/jama/fullarticle/195157">“virtually impossible to compare”</a>. </p>
<p>To then describe what was found as being “partial PTSD” or “spectrum PTSD” could only serve to confuse matters. It is akin to labelling nausea and vomitting – which are both possible symptoms of bubonic plague – as bubonic plague symptoms.</p>
<h2>Responding to a cultural mood?</h2>
<p>Why did this happen and what are the consequences? Well we certainly do not propose that anybody misrepresented their data. Rather, we suggest that the cultural mood or script today increasingly predisposes people to looking for mental health impacts. They then fail to notice when their own evidence points the other way.</p>
<p>For instance, examples of people relying on their own social and community networks to recover were read as reflecting a lack of awareness about psychological services rather than signs of resilience. But it does not help the minority who truly need such support when many more are referred for counselling. The vast majority of people affected by terrorism continued about their everyday lives relatively unimpaired and, in many instances, defiant.</p>
<p>Overall, we concluded, the evidence pointed to a considerable degree of coping with extreme adversity. And this was despite a dominant social narrative often promoted by politicians and officials, as well as media commentators and academics, to the effect that terrorism is somehow bound to impact our mental well-being adversely.</p>
<p>If anything, this shows some limits to those who presume that language or discourse can significantly shape or determine our existence. Researchers, particularly in Israel, noted the possibility for <a href="https://bmcmedicine.biomedcentral.com/articles/10.1186/1741-7015-4-21">resilience</a> and even healing at such times, as well as the problematic deployment of the PTSD label as a call for resources and recognition, or alternatively to <a href="https://link.springer.com/article/10.1007%2Fs11013-010-9187-6">demand professional intervention</a>.</p>
<p>Europe and America, <a href="https://link.springer.com/article/10.1007/s10597-013-9631-5">they averred</a>, within which such individualised mental health categories arose, are particularly obsessed with the self and identity. In fact, we are all relational constructs of families and communities. So a proper understanding of mental health requires a greater appreciation of culture and its transformation over recent times that a narrow empiricism is unable to provide.</p>
<p>It may be more useful for government, academics and commentators to focus on what really happens at such times than to emphasise a narrative of vulnerability which, while of little direct effect, reflects rather more their insecurities than those affected by adversity.</p><img src="https://counter.theconversation.com/content/104993/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Bill Durodie gratefully acknowledges the support of the Gerda Henkel Stiftung in Germany for their provision of funds under their Special Programme for Security, Society and the State that has assisted his work.</span></em></p>After 9/11, academic investigation seemed to seek out trauma rather than signs of resilience.Bill Durodie, Professor and Chair of International Relations, University of BathLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/696602016-12-06T11:42:33Z2016-12-06T11:42:33ZEconomies grow when early childhood development is a priority<figure><img src="https://images.theconversation.com/files/148589/original/image-20161205-19367-ubljcr.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">Healthy, supported children can be a boon to their countries' economies. </span> <span class="attribution"><span class="source">Reuters/Tiksa Negeri</span></span></figcaption></figure><p>The <a href="http://thousanddays.org/the-issue/why-1000-days/">first 1000 days</a> of life – the period from conception to the age of two – are pivotal for any human being’s development. This has been shown repeatedly by every science that studies early childhood development: anatomy, epidemiology, genetics, immunology, physiology, psychology and public health.</p>
<p>And it is confirmed in several papers and commentaries in a <a href="http://www.thelancet.com/series/ECD2016">Lancet series</a> I led in my capacity as a distinguished professor at the University of the Witwatersrand and Director of the DST-NRF <a href="http://www.wits.ac.za/coe-human/">Centre of Excellence in Human Development</a>. Our newest work <a href="http://www.thelancet.com/series/ECD2016">powerfully demonstrates</a> that low-cost interventions which facilitate and support nurturing care for infants in their first years of life contribute to lifelong health, wellbeing and productivity. The economic benefits of these interventions far outweigh the investment costs.</p>
<p>Simply put, we need to intervene earlier than we currently do. In South Africa for instance, a great deal of emphasis in early childhood development (ECD) is placed on subsidising three and four-year-olds to attend creches and play centres. Early learning in preschool is important. But it is less effective than it could be because children’s foundational skills and capacities are laid down at a younger age – in the first 1000 days. </p>
<h2>A cycle of poverty</h2>
<p>Poor childhood conditions, such as exposure to poverty and stunting, are associated with long-term disadvantages to health, education, social adjustment and earnings.</p>
<p>In South Africa, <a href="http://www.dailymaverick.co.za/article/2016-05-17-suffer-the-children-sas-inequality-strikes-hardest-where-it-hurts-the-most/">63% of children</a> younger than 18 live in poverty: that is, on less than R923 a month or R31 a day. <a href="https://theconversation.com/why-child-malnutrition-is-still-a-problem-in-south-africa-22-years-into-democracy-60224">And 27%</a> of 0-3 year olds are <a href="https://theconversation.com/why-child-malnutrition-is-still-a-problem-in-south-africa-22-years-into-democracy-60224">stunted</a>, a condition which results from long-term undernutrition, mainly of essential vitamins and minerals. This hampers the development of lean mass – skeleton, brain, internal organ size and function. </p>
<p>Children living in poverty and who are stunted tend to <a href="http://www.thelancet.com/journals/langlo/article/PIIS2214-109X(16)30266-2/fulltext">go to school later</a>. They also tend to learn less, pass fewer grades, leave school earlier and earn less as adults. In turn, their children are more likely to grow up in poverty, lacking essential nutrients and learning experiences, trapping families and children in poverty for generations.</p>
<p>It is this negative cycle that most concerns <a href="http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)31574-4/fulltext">politicians and economists</a>. Countries can’t grow at the pace of their most able people because too many children and adults are left behind. The Lancet series estimates, globally, that individuals who experienced poor early development suffer a loss of about a quarter of adult average income a year. This makes their families poor too.</p>
<p>Importantly, these negative individual effects add up. <a href="http://www.costofhungerafrica.com/kypmd1u0vmrf5iro3c0prngjdftu5u">Studies</a> in several African countries estimate that the cost of hunger – the knock on effects of stunting on learning and earning – is 10.3% of GDP in Malawi, <a href="https://www.wfp.org/stories/hunger-costs-rwanda-us820-million-annually">11.5% in Rwanda</a> and 16.5% in Ethiopia. In South Africa we estimate that stunting results in a loss of future earnings of 1.3% of GDP, or R62 billion per year.</p>
<p>The series also <a href="http://www.thelancet.com/series/ECD2016">estimates</a> what poor early development costs countries, by comparing the future costs to current expenditure on health and education. For example, Pakistan is estimated to lose 8.2% of future GDP to poor child growth. This is three times what it currently spends on health as a percentage of GDP (2.8%). Countries that do not improve early childhood development are fighting a losing battle.</p>
<h2>Nurturing care</h2>
<p>Babies need love, care, protection and stimulation by stable parents and caregivers. In The Lancet series, this is referred to as “nurturing care”. Breastfeeding is a good example of nurturing care. Nurturing care can break down under conditions of severe stress and struggle. </p>
<p>Extremely poor families find it hard to provide nurturing care for young children. They sometimes don’t have the means for health care or nutritious food. They may be so emotionally drained by daily struggles that they feel unable to show interest in or encourage a young child. There are several ways in which governments and social services could support such families.</p>
<p>For instance, national policies can support families financially, give them time to spend with their young children and improve access to health and other services. Minimum wages and social grants protect families against the worst effects of poverty. Maternity leave, breastfeeding breaks at work and time for working mothers to take their children to clinics and doctors are also crucial.</p>
<p>Other meaningful interventions include free or subsidised health care, quality and affordable child care and preschool education.</p>
<p>Many politicians and policymakers may fear that dedicated early child development are beyond their budgets. As I’ve already pointed out, the return on investment of such programmes is substantially more than the cost of implementing them. But The Lancet series went further: we modelled the cost of adding two early child development programmes to existing packages of maternal and child health services. </p>
<h2>A worthwhile investment</h2>
<p>The first programme is community-based group treatment for maternal depression. Addressing maternal depression is important because it <a href="http://www.who.int/bulletin/volumes/89/8/11-088187/en/">adversely affects</a> a mother’s ability to provide nurturing care. The second programme is a child development stimulation programme, <a href="http://www.who.int/maternal_child_adolescent/documents/care_child_development/en/">Care for Child Development</a>, which can be implemented in health care facilities or in community programmes. </p>
<p>Our research modelled the cost of expanding these programmes to universal levels in 73 countries that experience a high burden of child mortality, growth and development. The cost of bringing both programmes to 98% coverage over the next 15 years is US$34 billion. </p>
<p>The additional cost for the supply-side of the programmes in the year 2030 is on average, 50 US cents per capita. This varies from 20c in low income countries where costs are lower, to 70c per capital in middle income countries. </p>
<p>The evidence consolidated in this series points to effective interventions and delivery approaches at a scale that was not envisaged before. During the next 15 years, world leaders have a unique opportunity to invest in the early years for long-term individual and societal gains and for the achievement of the <a href="http://www.un.org/sustainabledevelopment/sustainable-development-goals/">sustainable development goals</a>.</p><img src="https://counter.theconversation.com/content/69660/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>The Lancet Series "Advancing Early Child Development: From Science to Scale" was supported by grants from the Bill and Melinda Gates Foundation and the Conrad N Hilton Foundation through the World Health Organization and UNICEF</span></em></p>Poor childhood conditions, such as exposure to poverty and stunting, are associated with long-term disadvantages to health, education, social adjustment and earnings.Linda M. Richter, Director, DST-NRF Centre of Excellence in Human Development, University of the WitwatersrandLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/655932016-09-28T13:27:41Z2016-09-28T13:27:41ZBMJ vs The Lancet: there are no winners in the ‘statins war’<figure><img src="https://images.theconversation.com/files/139556/original/image-20160928-552-179ioji.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">
</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/pic-199388345/stock-photo-a-generic-pack-of-the-controversial-cholesterol-preventative-drug-statin-with-logos-removed.html?src=g8wiEQZT6Gf7RP9mbPdybQ-1-1">roger ashford/Shutterstock.com</a></span></figcaption></figure><p>The editors of the BMJ and The Lancet – two heavyweight medical journals – have been arguing about statins for nearly three years. The tabloid press have dubbed the spat “<a href="http://www.dailymail.co.uk/health/article-2700573/Statin-wars-Doctors-bitterly-divided-calls-half-adults-pills-cut-cholesterol-Heres-need-know.html">statin wars</a>”. </p>
<p>The gist of the debate is: should statins be offered to a wider swathe of the public? And how extensive and serious are the side effects of these cholesterol-lowering drugs?</p>
<p>The row kicked-off in 2013 when the BMJ published two articles claiming that the side effects from statins are <a href="http://www.bmj.com/content/347/bmj.f6340">much higher</a> than <a href="http://www.bmj.com/content/347/bmj.f6123">clinical trials reported</a>. In early 2014, <a href="https://www.theguardian.com/society/2014/mar/21/-sp-doctors-fears-over-statins-may-cost-lives-says-top-medical-researcher">Rory Collins</a>, professor of medicine and epidemiology at the University of Oxford and a statin trial leader, hit back. He described the BMJ papers as flawed and misleading. </p>
<p>A subsequent review by an independent panel of experts found that the BMJ papers <a href="http://www.bmj.com/about-bmj/independent-statins-review-panel">did not warrant retraction</a>. As a response, the statin trial leaders published a review identifying the <a href="http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(16)31357-5/abstract">benefits of statins</a> in the Lancet in 2016. </p>
<p>The latest news from the front line is that Fiona Godlee, editor of the BMJ, has written to the UK’s chief medical officer, Sally Davies, asking for an <a href="http://www.bmj.com/content/354/bmj.i4992">independent review</a> of statin risks and benefits.</p>
<p>Unfortunately, the point of the debate is lost when reading articles in the mainstream media on this topic. Given the frequency of statin coverage in the news, it is not uncommon for people on statins to say to their GP: “I heard they’re bad, so I stopped taking them,” or “My mum took them all her life but still had a heart attack.” A <a href="http://www.bmj.com/content/353/bmj.i3283">recent paper</a> in the BMJ showed that significant numbers of patients stopped taking statins as a result of the media coverage after the BMJ published the articles in 2013. </p>
<h2>Muddying the water</h2>
<p>Confusingly, <a href="http://www.dailymail.co.uk/health/article-3780760/Statins-safe-six-million-people-benefits-outweigh-harm-says-biggest-study-ever.html">newspaper</a> and TV reports seem to point to statins being either entirely good or bad. They are not miracle medications, nor are they poison, yet the media continues to portray them as one or the other. </p>
<p>Buried in the depths of this argument between the BMJ and the Lancet, there is one truth accepted by both parties: statins have prevented heart attacks, strokes and other cardiovascular diseases. The extent to which they benefited patients, the prevalence of the side effects and the evidence for prescribing statins to wider groups of patients to benefit the health of the population is the point of this debate. </p>
<p>The BMJ and the Lancet both seem to argue from opposing corners, using the term “data” as a weapon. In reality, the Lancet has not published significant amounts of new data in their recently published review on statins. The BMJ editor’s calls for making the statin-trial data public and for the scrutiny of an independent review is unlikely to give a clearer picture of the incidence of side effects. </p>
<p>The statin trials were performed on specific groups of patients. The numbers and types of patients where statins are currently used is extrapolated from this trial evidence. There have not been clinical trials addressing every specific type of patient where statins are being used, especially in the elderly population. Relating the benefits and side effects reported from the clinical trials to the current use of statins is not likely to be accurate. So, any expensive independent review is not likely to inform us better about true statin side effects which should be the aim of any such review. </p>
<p>New observational studies lack the vigour of clinical trials and while they can suggest patterns and trends, are seldom conclusive. Academics debate who should receive statins based on health-economics arguments, telling us about numbers of patients who have been harmed or the number of lives that have been saved. Relating such numbers and quoting these to a patient who is having statin-related myopathy (muscle weakness) or to a patient who has had a heart attack despite taking statins is not likely to be helpful to that patient.</p>
<p>Perhaps more data can truly answer this question but, for this, new research is needed and funding statin studies when most statins are off-patent is difficult because there is no incentive for pharmaceutical companies to fund such studies. New studies are needed to update us about the benefits and side effects of statins with modern use but the risk of misinterpretation of the results in the media must be acknowledged. What we know is this: statins are good for most patients.</p><img src="https://counter.theconversation.com/content/65593/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Rahul Potluri does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.</span></em></p>Misreporting on the ongoing debate is likely to lead to more deaths from cardiovascular disease.Rahul Potluri, Clinical lecturer, Aston UniversityLicensed as Creative Commons – attribution, no derivatives.tag:theconversation.com,2011:article/594792016-05-17T10:04:10Z2016-05-17T10:04:10ZAre NHS patients really more likely to die at weekends? Here are the facts<figure><img src="https://images.theconversation.com/files/122698/original/image-20160516-15924-1qzze24.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=496&fit=clip" /><figcaption><span class="caption">People admitted to hospital on the weekend tend to be sicker.</span> <span class="attribution"><a class="source" href="http://www.shutterstock.com/dl2_lim.mhtml?src=kSbwT8GtuWbq0uWOvABszA-1-1&clicksrc=download_btn_inline&id=406082761&size=medium_jpg&submit_jpg=">spatuletail/shutterstock.com</a></span></figcaption></figure><p>Jeremy Hunt, secretary of state for health, and Philippa Whitford, a Scottish surgeon and MP, had a row about seven-day services during Hunt’s appearance before the Health Select Committee on <a href="http://www.parliament.uk/business/committees/committees-a-z/commons-select/health-committee/news-parliament-20151/spending-review-health-minister-evidence-15-16/">May 9</a>. The issue has also featured in the acrimonious dispute about the junior doctors’ contract <a href="http://www.nhsemployers.org/your-workforce/need-to-know/junior-doctors-contract">negotiations</a> which reopened on the same day. </p>
<p>Hunt and Whitford tussled about the quality and interpretation of evidence about weekend mortality rates and whether we need a seven-day hospital service to set things right. Hunt referred to <a href="https://www.gov.uk/government/publications/research-into-the-weekend-effect-on-hospital-mortality/research-into-the-weekend-effect-on-patient-outcomes-and-mortality">evidence</a> compiled by the Department of Health. It comprises eight studies, of which only four are peer-reviewed articles, the others being reports. Hunt claims that these studies prove that hospital mortality rates are higher for those admitted over the weekend than during the week. Other studies have also found a “weekend effect”. But the effect is smaller when accounting for how sick patients are and it isn’t evident for all conditions. For instance, there is no weekend effect for <a href="http://bit.ly/1TgrYRj">stroke care</a>.</p>
<p>Whitford didn’t dispute the existence of a weekend effect, but said the higher weekend mortality rate is not because more people are dying. Rather the rate is higher because fewer people are admitted at the weekend and they tend to be sicker. This was the conclusion drawn by authors of a <a href="http://hsr.sagepub.com/content/early/2016/05/05/1355819616649630.full.pdf+html">study</a> published a few days before the committee hearing. Unlike other studies, this made use of both accident and emergency and hospital data. It found a weekend effect only among those admitted to hospital, and it was mainly because they are sicker. The authors conclude that expanding services to seven days a week may cause the mortality rate to fall, but most likely because admissions will increase, not because fewer people will die.</p>
<h2>Hunt’s solution</h2>
<p>Hunt brought out a different message from the same study, saying that more stringent admission criteria shouldn’t be applied at the weekend. He wants four <a href="http://www.parliament.uk/documents/commons-committees/Health/Correspondence/2015-16/Letter-from-the-Secretary-of-State-for-Health-to-the-Chair-on-seven-day-NHS-hospital-services.pdf">priority clinical standards</a> to be met every day for all patients requiring urgent and emergency care. All emergency admissions should have a thorough assessment by a consultant within 14 hours of arrival at hospital; everyone in hospital should have access to consultant-directed diagnostic tests, and to consultant-directed interventions; and high dependency patients must be seen and reviewed by a consultant twice daily, and once a day after transfer to a general ward.</p>
<p>Notably, these standards all relate to the presence of consultants (senior doctors). But, to meet them, a whole range of diagnostic and support services must be made available as well as clinical cover provided by junior doctors. Junior doctors, however, object to plans to consider Saturday a <a href="https://fullfact.org/health/junior-doctors-pay-short-introduction-dispute/">normal working day</a> for calculating their pay.</p>
<figure class="align-center ">
<img alt="" src="https://images.theconversation.com/files/122701/original/image-20160516-15899-o6xye5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&fit=clip" srcset="https://images.theconversation.com/files/122701/original/image-20160516-15899-o6xye5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=600&h=458&fit=crop&dpr=1 600w, https://images.theconversation.com/files/122701/original/image-20160516-15899-o6xye5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=600&h=458&fit=crop&dpr=2 1200w, https://images.theconversation.com/files/122701/original/image-20160516-15899-o6xye5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=600&h=458&fit=crop&dpr=3 1800w, https://images.theconversation.com/files/122701/original/image-20160516-15899-o6xye5.jpg?ixlib=rb-1.1.0&q=45&auto=format&w=754&h=576&fit=crop&dpr=1 754w, https://images.theconversation.com/files/122701/original/image-20160516-15899-o6xye5.jpg?ixlib=rb-1.1.0&q=30&auto=format&w=754&h=576&fit=crop&dpr=2 1508w, https://images.theconversation.com/files/122701/original/image-20160516-15899-o6xye5.jpg?ixlib=rb-1.1.0&q=15&auto=format&w=754&h=576&fit=crop&dpr=3 2262w" sizes="(min-width: 1466px) 754px, (max-width: 599px) 100vw, (min-width: 600px) 600px, 237px">
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<span class="caption">Seven-day service is a central feature of the dispute about the junior doctors’ contract.</span>
<span class="attribution"><a class="source" href="http://www.shutterstock.com/dl2_lim.mhtml?src=7rfstA2OwnA3TqQS_KUN3g-1-27&clicksrc=download_btn_inline&id=412141594&size=medium_jpg&submit_jpg=">Ms Jane Campbell / Shutterstock.com</a></span>
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<p>The four standards were chosen as priorities by NHS England and the Academy of Medical Royal colleges set out by NHS England’s <a href="https://www.england.nhs.uk/wp-content/uploads/2013/12/evidence-base.pdf">Seven Days a Week Forum</a>. These are being rolled out across the country, the aim being that they will have been adopted by all hospitals by March 2020.</p>
<p>The standards have already been implemented in some hospitals. The day after the Hunt-Whitford debate, a <a href="http://bit.ly/22dn4tW">study</a> was published in The Lancet comparing hospitals that have implemented the standards with those that have not. This found that patients admitted on Sundays get less than half the attention from consultants than those admitted on Wednesdays. But it also found that variation across hospitals in how much time consultants spend with patients is not associated with the hospital’s mortality rate. So it cannot be said that mortality rates can be reduced simply by increasing consultant cover.</p>
<h2>Where does this leave us?</h2>
<p>Clearly, more evidence is required. First, it remains unclear whether the weekend effect is just a <a href="http://hsr.sagepub.com/content/early/2016/05/05/1355819616649630.full.pdf+html">statistical artefact</a> or whether there is a real problem with a clear cause. </p>
<p>Second, studies should capture a broader array of <a href="http://bit.ly/1YuC6cw">outcomes</a> than just mortality. Even if seven-day services don’t reduce mortality rates, patients may still be better off.</p>
<p>Third, we need to know the costs of the policy. On May 11, the Public Accounts Committee offered <a href="http://bit.ly/1ZEdLBt">harsh criticism</a>, saying: </p>
<blockquote>
<p>no coherent attempt has been made to assess the headcount implications of major policy initiatives such as the seven-day NHS … It beggars belief that such a major policy should be advanced with so flimsy a notion of how it will be funded…</p>
</blockquote>
<p>Finally, implementation of seven-day services was a <a href="https://www.gov.uk/government/news/prime-minister-pledges-to-deliver-7-day-gp-services-by-2020">manifesto commitment</a>. But mortality rates for patients admitted <a href="http://bit.ly/1TgrYRj">overnight</a> are higher than for those admitted during the day; and they are higher for <a href="http://www.nets.nihr.ac.uk/projects/hsdr/11200439">poorer</a> than richer patients. If we want to reduce hospital mortality, perhaps policy could be directed at correcting these differences as well.</p><img src="https://counter.theconversation.com/content/59479/count.gif" alt="The Conversation" width="1" height="1" />
<p class="fine-print"><em><span>Andrew Street receives funding from the National Institute of Health Research and the Department of Health's Policy Research Programme but the views expressed are his own.</span></em></p>While politicians and doctors argue over the data on the weekend effect, it’s important to remember that there are other ways to reduce hospital deaths.Andrew Street, Professor, Centre for Health Economics, University of YorkLicensed as Creative Commons – attribution, no derivatives.