Philippe Autier’s research while affiliated with International Prevention Research Institute and other places

Background Randomised trials conducted from 2006 to 2021 indicated that vitamin D supplementation (VDS) was able to prevent severe COVID-19 and acute respiratory infections (ARI). However, larger randomised trials published in 2022 did not confirm the health benefits of VDS in COVID-19 patients. Objective To examine through a systematic review with meta-analysis the characteristics of randomised trials on VDS to COVID-19 patients and admission to intensive care unit (ICU), and of randomised trials on VDS for the prevention of ARI. Method A systematic search retrieved randomised trials on VDS to COVID-19 patients and admission to ICU. Data on VDS and ARI were extracted from the meta-analysis of Jolliffe et al. 2021. Groups were formed including trials with total numbers of patients below or above the median size of all trials. The associations between VDS vs no VDS, and admission to ICU were evaluated using random-effects models from which summary odds ratios (SOR) and 95% confidence intervals (CI) were obtained. Meta-analyses were done for all trials and for each group of trials, which allowed testing a possible effect modification of trial size. Publication bias was assessed using the Louis-Furuya-Kanaruori (LFK) index (no bias if index between -1 and +1) and the trim and fill method. Results Nine trials on VDS for preventing admission to ICU were identified, including 50 to 548 patients. The summary odds ratio (SOR) was 0.61 (95% CI: 0.39–0.95) for all trials, 0.34 (0.13–0.93) for trials including 50 to <106 patients and 0.88 (0.62–1.24) for trials including 106 to 548 patients (interaction p = 0.04). The LFK index was -3.79, and after trim and fill, the SOR was 0.80 (0.40–1.61). The SOR for the 37 trials on VDS for ARI prevention included 25 to 16,000 patients. The SOR was 0.92 (0.86–0.99) for all trials, 0.69 (0.57–0.83) for trials including 25 to <248 patients and 0.98 (0.94–1.03) for trials including 248 to 16,000 patients (interaction p = 0.0001). The LFK index was -3.11, and after trim and fill, the SOR was 0.96 (0.88–1.05). Conclusion Strong publication bias affected small randomised trials on VDS for the prevention of severe COVID-19 and of ARI. Systematic reviews should beware of small-size randomised trials that generally exaggerate health benefits.

One in every three cancers diagnosed is a skin cancer. Europe has the global lead in the number of UV‐attributable cancer cases with the highest number of melanoma cases worldwide and the second highest number of keratinocyte cancers (KC). Further increases are expected in Europe for the coming decades. Projected increases are highest for KC with increases in incidence around 40% and increases in mortality around 50%, with KC mortality in males approximating melanoma mortality in females. The two main drivers for this skin cancer epidemic are ageing of the population but especially UV exposure. In conclusion, skin cancer represents a major challenge in the cancer field in Europe today and will continue to do so in the coming decades. This calls for a European skin cancer action plan intended to reduce avoidable UV exposure and to prepare the healthcare system to safeguard early diagnosis and treatment of skin cancer.

Background and Objectives Teriflunomide is a disease‐modifying therapy (DMT) for multiple sclerosis (MS). This post authorisation safety study assessed risks of adverse events of special interest (AESI) associated with teriflunomide use. Methods Secondary use of individual data from the Danish MS Registry (DMSR), the French National Health Data System (SNDS), the Belgian national database of health care claims (AIM‐IMA) and the Belgian Treatments in MS Registry (Beltrims). We included patients treated with a DMT at the date of teriflunomide reimbursement or initiating another DMT. Adjusted hazard rates (aHR) and 95% confidence intervals were derived from Cox models with time‐dependent exposure comparing teriflunomide treatment with another DMT. Results Of 81 620 patients (72% women) included in the cohort, 22 324 (27%) were treated with teriflunomide. After a median follow‐up of 4 years, teriflunomide use compared to other DMT was not associated with a risk of all‐cause mortality, severe infection, pneumoniae, herpes zoster reactivation, pancreatitis, cardiovascular condition and cancers. For opportunistic infections, aHR for teriflunomide versus other DMT was 2.4 (1.2–4.8) in SNDS, which was not bound to a particular opportunistic agent. The aHR was 2.0 (1.1–3.7) for renal failures in the SNDS, but no association was found in other data sources. A total of 187 SNDS patients had a history of renal failure prior to cohort entry. None of these patients (0%) had a renal failure recurrence when treated with teriflunomide for 19 (13%) recurrences reported for patients on another DMT. Discussion We found no evidence that teriflunomide use would be associated with an increased risk of AESI. Trial Registration EUPAS register: EU PAS 19610.

Background To assess the amount of breast cancer overdiagnosis associated with the National Health Service Breast Screening Programme (NHSBSP) that started in 1988 in England. Methods First, numbers of breast cancers in women eligible for breast screening not attending screening were estimated for the period 1995–2019, which were extrapolated to all women. A second method was based on ratios of incidence rates of breast cancers in women aged 50–69 to women aged 70 years or more in 1971–1985. The ratio was used for estimating expected numbers of cancers in 1988–2019, and 1995–2019. Results From 1995 to 2019, 506,607 non-invasive and invasive breast cancers were diagnosed among women aged 50–64 years (1995–2001) and 50–70 years (2002–2019). A first method estimated that 95,297 cancers were in excess to the number of cancers that would be expected had the NHSBSP not existed. 42,567 screen-detected non-invasive and micro-invasive cancers represented 45.8% of the total excess cancer. 18.8% of all cancers diagnosed among women invited to screening, 25.1% of cancers found in women attending screening, and 35.1% of cancers detected by screening would represent overdiagnosis. A second method estimated that, 18.0% of all cancers diagnosed in 1988–2019, and 18.2% of all cancers diagnosed in 1995–2019 among women invited to screening would represent overdiagnosis. Conclusion The two independent methods obtained similar estimates of overdiagnosis. The NHS Breast Screening Programme in England is associated with substantial amount of overdiagnosis.

Background: Randomised trials conducted before 2021 indicated that vitamin D supplementation (VDS) was able to prevent severe COVID-19 and acute respiratory infections (ARI). However, these health benefits were not confirmed by larger randomised trials published after 2021. Objective: To examine the characteristics of randomised trials on VDS to COVID-19 patients and admission to intensive care unit (ICU), and on VDS for the prevention of ARI. Method: A systematic search retrieved randomised trials on VDS to COVID-19 patients and admission to ICU. Data on VDS and ARI were extracted from the meta-analysis of Jolliffe et al., 2021. The associations between VDS vs no VDS, and admission to ICU were evaluated using random effect models. Meta-analyses were done for all trials and by groups trial size. Publication bias was assessed using the LFK index (no bias if index between -1 and +1) and the Trim and Fill method. Results: Nine trials on VDS for preventing admission to ICU were identified. The summary odds ratio (SOR) was 0.61 (95%CI: 0.39-0.95) for all trials, 0.34 (0.13-0.93) for trials including 50 to <106 patients and 0.88 (0.62-1.24) for trials including 106 to 548 patients (effect modification: p=0.04). The LFK index was -3.79, and after Trim and Fill, the SOR was 0.80 (0.40-1.61). The SOR for the 37 trials on VDS for ARI prevention was 0.92 (0.86-0.99) for all trials, 0.69 (0.57-0.83) for trials including 25 to <248 patients and 0.98 (0.94-1.03) for trials including 248 to 16,000 patients (effect modification p=0.0001). The LFK index was -3.11, and after Trim and Fill, the SOR was 0.96 (0.88-1.05). Conclusion: Strong publication bias affected randomised trials on VDS for the prevention of severe COVID-19 and of ARI. Systematic reviews should beware of small-size randomised trials that generally exaggerate health benefits.