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Glucagon-Like Peptide-1 Receptor Agonists and Cancer

To the Editor Dai and colleagues, along with others, have recently highlighted the potential role of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on cancer prevention. Specifically, the study by Dai et al used a target trial emulation (TTE) method, which enhances causal inference and has the potential to inform clinical guidelines and policy. The TARGET Statement on reporting of observational studies of emulating a target trial states that TTE studies can be used to answer causal questions about the comparative effects of interventions when randomized clinical trials are unavailable or not feasible. This is the case here because there are no available cancer prevention trials using GLP-1RAs. Because clinical trials would require large sample sizes, long-term follow-up, prohibitive costs, and risk of contamination, this direct evidence is unlikely to ever materialize. A TTE approach is therefore justified, but we believe there are 2 major deviations of the TTE methodology in the study by Dai et al that weaken the presented evidence.

Glucagon-Like Peptide-1 Receptor Agonists and Cancer

To the Editor Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have become among the most widely used medications worldwide, though their use has raised concerns regarding a potential increased risk of cancer. Dai et al conducted a retrospective cohort study assessing the incidence of 13 distinct cancers, which yielded a pooled hazard ratio (HR) of 0.83 (95% CI, 0.76-0.91), suggesting an overall decreased risk, although a notable increase in risk was identified for kidney cancer. The authors described the risk as follows: “However, GLP-1RAs were associated with a marginally nonsignificant increased risk of kidney cancer (HR, 1.38; 95% CI, 0.99-1.93; P =.04).” The term marginally nonsignificant likely reflects the fact that the lower bound of the CI was 1.0, despite the P value of.04, which is conventionally considered statistically significant. This apparent discrepancy may be attributable to differences in the statistical methods used to calculate the CIs vs the P value.

Aflibercept 8 mg in Polypoidal Choroidal Vasculopathy

This secondary analysis of the Study of the Effects of High-Dose Aflibercept Injected Into the Eye of Patients With an Age-Related Disorder That Causes Loss of Vision Due to Growth of Abnormal Blood Vessels at the Back of the Eye (PULSAR) randomized clinical trial investigates the efficacy and safety of aflibercept 8 mg vs aflibercept 2 mg in participants with indocyanine green angiography–confirmed polypoidal choroidal vasculopathy.

The shortest day of the year is descending on the Northern Hemisphere. Here's what to know

Yes the darkest day of the year is here, but that means brighter days are ahead. Sunday is the shortest day of the year north of the equator, where the solstice marks the start of astronomical winter. It's the opposite in the Southern Hemisphere, where it is the longest day of the year and summer will start.

Nearly three-quarters of western US overdue for wildfires, research indicates

Wildfires can benefit forests by clearing old debris, leaving behind fertilizer, and more. For over a century, the United States has poured billions of dollars into fire suppression tactics to keep people, homes and critical environments safe, but suppression can deprive landscapes of necessary burns and increase potential fuel for large fires in the future.

[Clinical Picture] Unexpected finding in a 17-year-old female undergoing screening colonoscopy

A 17-year-old female was referred to a gastroenterologist for an elective screening colonoscopy because of a diagnosis of sessile serrated polyposis syndrome in her older brother. He also had severe ileocolonic Crohn's disease, which was diagnosed 14 months previously. The patient was asymptomatic, with no clinically significant medical history and was not taking any medication. Initial colonoscopy revealed multiple flat lesions with altered pit patterns measuring 30–50 mm in diameter located in the caecum, ascending colon, transverse colon, sigmoid colon, and rectum.

[Personal View] Azithromycin mass drug administration: balancing survival benefits and risks in children

Childhood mortality remains a major public health challenge in low-income and middle-income countries, particularly in sub-Saharan Africa, despite major advances in universal sanitation and immunisations. Mass drug administration (MDA) of azithromycin, a broad-spectrum antibiotic, has shown promise in reducing under-5 mortality in high-risk regions, although its mechanism of protection remains largely unknown. In this Personal View, we analyse current evidence, potential effect of MDA on antimicrobial resistance, and relevant ethical principles, and propose priorities for future public health interventions.

[Review] Unveiling the incidences and trends of alveolar echinococcosis in Europe: a systematic review from the KNOW-PATH project

Human alveolar echinococcosis is a notifiable parasitic infectious disease in most European countries; however, in practice, it is under-reported by national health systems. To fill this knowledge gap, data on the number, incidence, and trend of cases in Europe were extracted through a systematic review approach from both the scientific and grey literature, covering 1997–2023. This systematic review identified 4207 human alveolar echinococcosis cases from 28 of the 40 European countries investigated.

[Series] Tackling antimicrobial resistance in people who are immunocompromised: leveraging diagnostic and antimicrobial stewardship

Antimicrobial resistance (AMR) disproportionately affects people who are immunocompromised due to their frequent encounters with the health-care system and repeated, prolonged exposure to antibiotics. AMR threatens to undermine continued advances in cancer care, haematopoietic cell transplantation, and solid organ transplantation by severely restricting therapeutic options. The convergence of several factors in the diagnostic evaluation of infection among individuals with immunocompromising conditions contributes to excess and inappropriate antibiotic use.

[Series] Innovation in active and passive immunisation of people who are immunocompromised: a call to action

The proportion of the population with immunocompromising conditions, who are at increased risk for complications from infectious diseases, continues to grow. Concurrently, outbreaks due to known and emerging pathogens are increasing. Vaccines are the foundation of infection prevention; however, attenuated immune responses in people who are immunocompromised necessitates innovation in design and delivery strategies. Passive immunisation, whereby the desired immunity is directly transferred to an individual, albeit transiently, could be valuable for patients who are unable to generate robust immune responses with vaccination or infection.

[Articles] Global policy responses to antimicrobial resistance, 2021–22: a systematic governance analysis of 161 countries and territories

The global response to antimicrobial resistance was greatly affected by the income level of the nation, highlighting global disparities in antimicrobial resistance governance capacity. Lower scores in lower-income regions likely reflect systemic challenges, such as less public health spending and less access clean water and santiation. Implementation tools should be prioritised in the design and execution of NAPs, especially measures that improve infection prevention and control, surveillance systems for antimicrobial use, and stewardship programmes.

[Articles] A 3-month clofazimine–rifapentine-containing regimen for drug-susceptible tuberculosis versus standard of care (Clo-Fast): a randomised, open-label, phase 2c clinical trial

Although the trial was stopped early, we found that a 3-month regimen containing clofazimine and rifapentine had 12-week culture conversion rates that did not differ statistically from the standard of care. The regimen was associated with an unacceptably high proportion of participants with unfavourable composite clinical outcomes and grade 3 or worse adverse events.

[Articles] Sotrovimab versus usual care in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

In patients admitted to hospital with COVID-19 pneumonia, sotrovimab was associated with reduced mortality in the primary analysis population who had a high serum SARS-CoV-2 antigen concentration at baseline, but not in the overall population. Treatment options for patients admitted to hospital are limited, and mortality in those receiving current standard of care was high. The emergence of high-level resistance to sotrovimab among subsequent SARS-CoV-2 variants restricts its current usefulness, but these results indicate that targeted neutralising antibody therapy could potentially still benefit some patients admitted to hospital who are at high risk of death in an era of widespread vaccination and omicron infection.

[Articles] Dynamics of endemic virus re-emergence in children in the USA following the COVID-19 pandemic (2022–23): a prospective, multicentre, longitudinal, immunoepidemiological surveillance study

In this study, we captured immunological evidence of endemic virus re-emergence in children following lifting of pandemic NPIs, which revealed high rates of exposure to endemic respiratory pathogens in a large group of seronegative, predominantly younger, children. This study demonstrates the feasibility and utility of immunoepidemiological surveillance to enable more precise and accurate modelling of pathogen circulation dynamics to predict and prepare for future waves of disease.

[Media Watch] The social and political drivers behind pandemics

The global awareness of pandemics has been higher than ever in recent years due to the COVID-19 pandemic, but what set of factors allows pandemics to develop in the first place? Tyler B Evans seeks to answer this question in his book Pandemics, Poverty, and Politics: Decoding the Social and Political Drivers of Pandemics from Plague to COVID-19, by using his experiences of a life spent in public health across the globe to analyse the underlying social and structural systems that lead to pandemics.