Medical Journal News

The philosopher Derek Parfit, introducing his 1984 book Reasons and Persons, sets out a few basic concepts—that we have reasons for acting, that some ways of acting are morally wrong, and that some outcomes are good or bad in a sense that has moral relevance.1 Reaching for what he presumably judged to be an uncontroversial example of a poor outcome, he notes that “it is bad, for example, if people become paralysed.” Whatever hopes one might have about the arc of the moral universe bending towards justice, the US elections have placed enormous power in the hands of a Republican Party intent on sabotaging vaccination programmes and medical research, while withdrawing support from international programmes funded by USAID.2 This threatens the health and wellbeing of millions of people risking the resurgence of polio (and thus paralysis) as well as other existing and novel infectious diseases.While basic human decency calls for...

bmj;389/apr01_2/r614/FAF1faSteve was born in Preston, only two miles from where he would later practice as a consultant physician for 28 years. The maternity ward was hit by an outbreak of neonatal diarrhoea and there were several tragic deaths. Steve teetered on the brink but survived, according to his mother’s account, as a result of copious amounts of Lourdes holy water sprinkled daily on his forehead. Some 60 years later, by complete coincidence, he attended a domiciliary consultation with a lady with a similar birth date—and discovered that she also was one of the Preston outbreak survivors.Steve was the middle of three boys. His father was an engineer, his mother a teacher. Secondary education was at the Bishop Ullathorne School in Coventry. He commenced medical training at University College London, proceeding to Westminster Hospital Medical School in 1968. As a medical student, his artistic talents were in great demand and he...

bmj;389/apr01_1/r621/FAF1faChris Howard studied medicine at Liverpool University, qualifying in 1968. He completed his houseman, senior house officer, and registrar training in medicine and paediatrics at Leeds General Infirmary and in hospitals across Liverpool, obtaining his membership of the Royal College of Physicians in 1973.In 1974 he saw a “positions vacant” advertisement for a paediatrician in a private practice in Hong Kong and immediately applied. He got the job and moved to Hong Kong that summer, joining the Dr Oram and Partners practice where he worked as a paediatrician and GP for the next 23 years. He retired temporarily from medicine in 1997 to embark on a round-the-world sailing trip, returning to practise in his beloved Hong Kong in 2000.Chris had many interests outside of work. He was a keen yachtsman, a member of his university sailing team, and a member of the Royal Hong Kong Yacht Club, where he raced...

by Reina Tonegawa-Kuji, Yuan Hou, Bo Hu, Noah Lorincz-Comi, Andrew A. Pieper, Babak Tousi, James B. Leverenz, Feixiong Cheng

Background

While recently U.S. FDA-approved anti-amyloid beta (anti-Aβ) monoclonal antibodies (mAbs) offer new treatment approaches for patients suffering from Alzheimer’s disease (AD), these medications also carry potential safety concerns and uncertainty about their efficacy for improving cognitive function. This study presents an updated meta-analysis of cognitive outcomes and side effects of anti-Aβ mAbs from phase III randomized controlled trials (RCTs) in patients with sporadic AD.

Methods and Findings

Phase III randomized, placebo-controlled blinded trial evaluating the efficacy and safety of anti-Aβ mAbs in patients with AD were identified through a search in clinical trials.gov, PubMed and Embase on January 14th, 2024. The retrieved studies were further screened from January 15th, 2024, to February 14th, 2024. We included studies that had been published in any language. Quality of trials was assessed using the Jadad score and publication bias was assessed using Egger’s test and Funnel plot. Primary outcomes were mean changes from baseline to post-treatment in Clinical Dementia Rating scale-Sum of Boxes (CDR-SB) and AD Assessment Scale-Cognitive Subscale (ADAS-Cog) scores, and secondary outcomes were adverse events including amyloid-related imaging abnormalities with edema (ARIA-E), and ARIA with hemorrhage (ARIA-H). Random-effects meta-analysis and meta-regression analyses were conducted. The literature search identified 13 phase III RCTs, which included 18,826 patients with mild cognitive impairment or dementia due to AD. Compared with placebo, treatment with mAbs significantly improved cognitive performance on CDR-SB (mean difference −0.25, 95% confidence interval [CI] [−0.38, −0.11]) and ADAS-Cog (standardized mean difference −0.09, 95% CI [−0.12, −0.06]), in which a negative change indicates improvement for both scores. Meta-regression analysis suggested that trials enrolling patients with early-stage AD were associated with better efficacy. Elevated risk of ARIA-E (risk ratio [RR] 9.79, 95% CI [5.32,18.01]), ARIA-H (RR 1.94, 95% CI [1.47,2.57]), and headaches (RR 1.21, 95% CI [1.10,1.32]) were noted. Statistical heterogeneity was relatively high for ARIA-E and ARIA-H, leading to wide confidence intervals and considerable variability in effect sizes, though meta-regression was conducted to address this. Furthermore, differences in trial designs introduce limitations in cross-trial comparisons.

Conclusions

Anti-Aβ mAb therapy slows cognitive decline, but with small effect sizes, and raises potential concerns about ARIA and headaches.

by Melese Siyoum, Rahel Nardos, Biniyam Sirak, Theresa Spitznagle, Wondwosen Teklesilasie, Ayalew Astatkie

Background

Pelvic organ prolapse (POP) is a common condition that can significantly impact a woman’s quality of life. Pelvic floor muscle training (PFMT) is recommended as a first-line conservative treatment for prolapse, but evidence on its effectiveness from low-resource settings is limited. This study aimed to assess the effect of midwife-led PFMT on prolapse symptoms and health-related quality of life (HRQoL) among women with mild-to-moderate POP in Ethiopia.

Methods and findings

A community-based, parallel-groups, two-arm cluster-randomized controlled trial was conducted in Dale and Wonsho districts of Sidama Region, Ethiopia. Women with symptomatic POP stages I–III were randomized by cluster to receive either midwife-led PFMT plus lifestyle counseling (intervention group) or lifestyle counseling alone (control group). The participants and counselors knew what the women were receiving, but they were not aware of the other group. The outcome assessors, who collected data at the end of intervention, were blinded to the participants’ treatment allocation. The primary outcomes were changes in prolapse symptom score (POP-SS) and prolapse quality of life (P-QoL). Mixed-effects generalized linear model was used to determine the effect of PFMT on prolapse symptoms and P-QoL at 99% confidence level. Adjusted β coefficients were used as effect measures. The level of significance was adjusted for multiple comparisons.A total of 187 women were randomized to intervention (n = 86) from four clusters and control (n = 101) arms from another four clusters. At sixth months, the intervention group showed significantly greater improvements both in prolapse symptoms and P-QoL. The mean change difference in POP-SS was −4.11 (99% CI [−5.38, −2.83]; p < 0.001). Similarly, the mean change difference was: −8.86 (99% CI [−13.84, −3.89]; p < 0.001) in physical domain of P-QoL; −11.18 (99% CI [−15.03, −7.32]; p < 0.001) in psychological domain of P-QoL, and −9.01 (99% CI [−10.49, −5.54]; p < 0.001) in personal relationship domain of P-QoL. A significantly higher proportion (83.72%) of women in the intervention group perceived their condition as “better” after the intervention as compared to 41.58% in the control group. Women with earlier stages of prolapse (stages I and II) experienced higher benefits compared to those in stage III.

Conclusions

A midwife-led PFMT combined with lifestyle counseling significantly improves prolapse symptoms and quality of life in mild-to-moderate POP. This strategy can be integrated into the existing maternal and reproductive health programs to address POP in low-income settings where access to trained specialist is limited.

Trial registration

The trial was registered at the Pan African Clinical Trial Registry (https://pactr.samrc.ac.za) database, with the registration number PACTR202302505126575 (https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=24311).

The head of the US Department of Health and Human Services (HHS), Robert F Kennedy Jr, announced on 27 March that he would cut 10 000 employees from department agencies as part of government restructuring by Elon Musk’s Department Government Efficiency. Another 10000 HHS employees left through early retirement and buyouts.1 President Donald Trump had previously told Kennedy to “go wild on health.”2Other major changes are also under way in the agencies that sit under HHS. The Centres for Disease Control and Prevention (CDC) will lose about 3500 employees and get a new head, Susan Monarez, current acting director. Trump’s original choice, David Weldon, was withdrawn when it became clear he didn’t have enough votes for approval.3 The CDC will also conduct a large study to investigate a possible link between vaccines and autism, although many studies have debunked such a link.4 Researcher David Geier, who is not a doctor...

What you need to knowPeople experiencing homelessness face multiple barriers to accessing health care and have high mortality and morbidity from preventable or treatable conditionsClinicians should consider preventive care, harm reduction, and the increased rates of multimorbidity and early onset frailty when caring for people experiencing homelessnessTrauma informed practice provides a framework to enable respectful, safe, collaborative, and empowering relationshipsThere has been a worldwide rise in homelessness over the past 10 years.1 On a single night in 2024 roughly 771 480 people in the United States were experiencing homelessness, the highest figure since reporting began in 2007.2 Equivalent figures in England showed that, on a given night in 2024, an estimated 354 016 people were homeless which is 1 in 160 people.3Health and homelessness are closely interconnected, and there is much that can be done by healthcare professionals to improve the lives of people experiencing homelessness. Here, we explore the...

South Africa, HIV/AIDS hit hardHIV/AIDS researchers in South Africa are reeling from the termination or suspension of grants from the US National Institutes of Health (NIH). Science1 reported that the cuts seem linked to a crackdown on grants with components of diversity, equity, and inclusion. Researchers told Science that grants related to LGBTQ+ health in the US were also terminated. Bhekisisa reported a leaked memo that instructed NIH staff to “hold all awards to entities located in South Africa,” listing it as a “country of concern” alongside China.2Modelling analysis published in TheLancet HIV3 this week estimated “an additional 4.43 to 10.75 million new HIV infections and 0.77 to 2.93 million HIV related deaths between 2025 and 2030” because of international aid cuts proposed by various countries. France, Germany, the Netherlands, the UK, and the US provide over 90% of all international HIV funding.NIH will stop funding climate health researchAn internal...

New England Journal of Medicine, Ahead of Print.

Science is under siege. Political forces are undermining expertise, dismantling research institutions, and replacing evidence based policymaking with ideology. This is a global crisis. The covid-19 pandemic underscored the importance of scientific independence. While vaccines, diagnostics, and therapeutics saved many lives, governments that ignored expert advice and downplayed the threat allowed lives to be lost. Sometimes, it became a political battleground as public health experts were vilified and disinformation flourished, with deadly consequences.1In the US, history is currently being rewritten. Life-saving vaccines are falsely being portrayed as harmful, and researchers are being demonised. Scientific institutions are in disarray, with frozen research grants, staff dismissals, and defunded public health agencies.2 Disinformation is rampant, damaging domestic research and international collaborations. The erosion of scientific credibility threatens global health.This assault on science is also evident in Europe.3 Climate science, vaccine policies, and social research are under attack as populist politicians seek to control...

A New York State county clerk has refused to enforce penalties filed by the state of Texas against a doctor in New York State who posted medication abortion drugs to a Texan woman.1The US constitution requires states to enforce judgments against their citizens by another state, so the dispute is almost certain to go to the Supreme Court. The constitutional right to abortion was overturned in 2022 and the decision left to individual states.2 Texas is one of 19 of the 50 states that have almost completely banned abortion.Despite the bans, abortions have increased as women travel out of their home state for the procedure or receive the medication abortion drugs mifepristone and misoprostol by telemedicine.34 The drugs are now used in around two thirds of US abortions.The doctor at the centre of the Texas lawsuit is Margaret Daley Carpenter of New Paltz, north of New York City. She is...

When Susan Cole was pregnant with her third child her HIV viral load started to rise, even though she was continuing to take her antiretroviral treatment. “Initially I was told I probably wasn’t taking my treatment properly, but that wasn’t the case: there just wasn’t enough research about drug levels during pregnancy,” she says.Cole, a health equity writer and advocate, shared her experiences at a webinar organised by the Message project (Medical Science Sex and Gender Equity).1 The project aims to improve the integration of sex and gender considerations across data collection, analysis, and reporting in the UK’s biomedical, health, and care research.Cole’s lived experiences clearly highlight the problem that Message is trying to tackle. She says that a lack of research involving women affects their experiences of illness and treatment, as well as their outcomes.What is the Message project?When it comes to guidance and policies on sex and gender...

Make them feel safeCatriona McVey, final year medical student, says, “Neurodivergent colleagues often bring unique strengths—such as attention to detail and deep focus in specialised areas—but they can also face additional challenges and barriers to success.“Work with them to identify what they personally find difficult, and explore what accommodations can be made at work. Neurodiversity is a spectrum and something that helps an autistic colleague may not be useful for a colleague with attention deficit/hyperactivity disorder (ADHD). Likewise, some people with ADHD might prefer to work alone when they need to concentrate, whereas others find they’re more productive when they can ‘body double’ by working alongside colleagues.“Culture is an important part of supporting neurodivergent colleagues. Neurodivergent problem solving can be unconventional, but still effective. As long as professional standards are met, focus on outcomes rather than rigid processes by being open to different approaches and communication styles. Lack of eye...

The evolution of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) has been shaped by the continuous challenge of balancing ischaemic protection with bleeding risk. While prolonged DAPT confers thrombotic risk reduction, it invariably increases bleeding complications, which are themselves associated with adverse prognostic implications.1 This dilemma has prompted the exploration of de-escalation strategies—gradual tapering of antiplatelet intensity or duration—as a means of optimising patient outcomes. Currently, the concept of DAPT de-escalation refers to the strategy of discontinuing aspirin after a short period of dual antiplatelet therapy after PCI, leaving patients on monotherapy with a potent P2Y12 inhibitor—typically ticagrelor, as supported by available evidence.234 The rationale behind this approach is to maximise ischaemic protection during the initial months after PCI, when the thrombotic risk is highest, while simultaneously mitigating the bleeding risk, which remains relatively constant and is directly associated with DAPT duration.5 In a previous meta-analysis from our...

Tuberculosis (TB) is the world’s oldest pandemic, accounting for around a billion deaths in the past two centuries.1 In the UK, after more than a decade of declining incidence, numbers are on the rise. In 2024, 5480 people became unwell with TB in England—up 13% from 2023, the largest increase recorded since 1970, and reflecting a trend that started in 2021.2 The TB Action Plan for England 2021-263 commits the country to meet the World Health Organization target of eliminating TB by 2035.4 But achieving the required 18% annual rate reduction from 2025 is not certain.TB is linked to conditions of poverty. People who become unwell with the disease face stigma, financial precarity, digital exclusion, language barriers, and housing insecurity.5 They need the scaffolding provided by support networks to enable them to receive the health and social care required to complete treatment successfully. TB exists on a spectrum between asymptomatic...

Over the past two decades my research has centred on systematic reviews. Developing and evaluating statistical and research methodology for reviews has been a focus, but I have also collaborated on many reviews. These collaborations inevitably reveal the importance of complete, clear, and accurate reporting of primary studies. At best, incomplete and inaccurate reporting wastes research investment—often substantial in the case of large randomised trials—and at worst, it may lead to incorrect conclusions with far reaching consequences.Primary studies that are reported well contribute maximally to the evidence base and can be fairly assessed. The opposite is true when reporting is unclear or incomplete. I have spent countless hours scouring trial reports for information that should be present but is not; trying to decipher unclear text; or trying to decide what to do when the information reported is inconsistent within or across reports of the same study. This time adds up...

AbstractObjectivesTo investigate whether a less intense antiplatelet regimen could be used for people receiving drug coated balloons.DesignMulticentre, randomised, open label, assessor blind, non-inferiority trial (REC-CAGEFREE II).Setting41 hospitals in China between 27 November 2021 and 21 January 2023.Participants1948 adults (18-80 years) with acute coronary syndrome who received treatment exclusively with paclitaxel-coated balloons according to the international drug coated balloon consensus.InterventionsParticipants were randomly assigned (1:1) to either the stepwise dual antiplatelet therapy (DAPT) de-escalation group (n=975) consisting of aspirin plus ticagrelor for one month, followed by five months of ticagrelor monotherapy, and then six months of aspirin monotherapy, or to the standard DAPT group (n=973) consisting of aspirin plus ticagrelor for 12 months.Main outcome measuresThe primary endpoint was net adverse clinical events (all cause death, stroke, myocardial infarction, revascularisation, and Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding) at 12 months in the intention-to-treat population. Non-inferiority was established if the upper limit of the one sided 95% confidence interval (CI) for the absolute risk difference was smaller than 3.2%.ResultsThe mean age of participants was 59.2 years, 74.9% were men, 30.5% had diabetes, and 20.6% were at high bleeding risk. 60.9% of treated lesions were in small vessels, and 17.8% were in-stent restenosis. The mean drug coated balloon diameter was 2.72 mm (standard deviation 0.49). At 12 months, the primary endpoint occurred in 87 (8.9%) participants in the stepwise de-escalation group and 84 (8.6%) in the standard group (difference 0.36%; upper boundary of the one sided 95% CI 2.47%; Pnon-inferiority=0.013). In the stepwise de-escalation versus standard groups, BARC type 3 or 5 bleeding occurred in four versus 16 participants (0.4% v 1.6%, difference −1.19% (95% CI −2.07% to −0.31%), P=0.008), and all cause death, stroke, myocardial infarction, and revascularisation occurred in 84 versus 74 participants (8.6% v 7.6%, difference 1.05% (95% CI −1.37% to 3.47%), P=0.396). Treated as having hierarchical clinical importance by the win ratio method, more wins were noted with the stepwise de-escalation group (14.4% wins) compared with the standard group (10.1% wins) for the predefined hierarchical composite endpoint of all cause death, stroke, myocardial infarction, BARC type 3 bleeding, revascularisation, and BARC type 2 bleeding (win ratio 1.43 (95% CI 1.12 to 1.83), P=0.004). Results from the per-protocol and the intention-to-treat analysis were similar.ConclusionsAmong participants with acute coronary syndrome who could be treated by drug coated balloons exclusively, a stepwise DAPT de-escalation was non-inferior to 12 month DAPT for net adverse clinical events.Trial registrationClinicaltrials.gov NCT04971356

bmj;388/mar31_1/r624/FAF1faSt Bartholomew’s medical school had only been accepting female students for eight years when Coral Sharpe (née Knight) began studying in 1955. Sharpe was not an obvious trailblazer, but in her quiet, resolute way she was determined to study medicine and keep working as a doctor when society might have expected her to concentrate on being a wife and mother.Medicine was in Sharpe’s blood. Her father, Bryant, was a GP in north west London and the whole family was immersed in the practice—Sharpe’s mother, Gladys, was, in effect, the receptionist; the waiting room was in Sharpe’s bedroom; and Sharpe, along with her sister Heather and brother Anthony were born either above or next door to the surgery.Sharpe was, in the parlance of the time, a delicate child. She was prone to ear infections and sudden, mysterious fevers; she was also diagnosed with a heart murmur. Gladys’s letters to Bryant, who...

New England Journal of Medicine, Ahead of Print.

New England Journal of Medicine, Ahead of Print.