In April 2024, two cases of hepatitis A (HA) were linked to the consumption of oysters produced in the same region, which triggered a multidisciplinary study. A network was quickly set up in a one-health approach including epidemiological and clinical data, as well as analysis of locally collected shellfish and wastewater samples. By the end of the outbreak, up to 17 HA cases met the case definition: all shared a same genotype IA strain and have eaten oysters. The prompt response enabled the identification of oyster samples positive for the HAV genome at the start of the monitoring period; these oyster samples subsequently tested negative during the following two months of the sampling campaign. Monitoring three nearby wastewater treatment plants revealed that the contamination was limited to a single area, allowing for more effective monitoring of shellfish. None of the identified cases lived in the area served by the treatment plant, and no clinical cases were detected among the local population, either before or after the outbreak. The decline of HAV concentration in sewage signed the end of the outbreak. While predicting contamination of shellfish growing areas is complicated, sewage surveillance can help establishing an alert system to prevent shellfish contamination, which is an important issue for silent diseases.
LBA4 Background: ESR1 mutations ( ESR1 m) constitutively activate the estrogen receptor (ER) and are the most common mechanism of acquired resistance to aromatase inhibitor (AI) + CDK4/6i. Molecular monitoring by ctDNA analysis can detect the emergence of ESR1 m during 1L AI + CDK4/6i. Camizestrant, the next-generation selective ER degrader (SERD) and complete ER antagonist, has shown anti-tumor activity in pts with and without detectable ESR1 m. SERENA-6 is the first global registrational Phase 3 trial assessing a ctDNA-guided approach to detect the emergence of ESR1 m during 1L AI + CDK4/6i to inform a switch in therapy ahead of disease progression. Methods: Pts with HR+/HER2– ABC who had received ≥6 months of 1L AI (anastrozole/letrozole) + CDK4/6i (abemaciclib/palbociclib/ribociclib) were enrolled and had ctDNA tested for ESR1 m every 2–3 months, coinciding with routine imaging. At ESR1 m detection, pts without evidence of disease progression were randomized 1:1 to switch to camizestrant (75 mg) with continued CDK4/6i (type and dose maintained) + placebo for AI vs continuing AI + CDK4/6i + placebo for camizestrant. The primary endpoint was investigator-assessed PFS (per RECIST v1.1). Prespecified interim analysis data cutoff was Nov 28, 2024. Results: 3,256 eligible pts were surveilled for ESR1 m using ctDNA until 315 eligible pts were randomized to switch to camizestrant (n=157) or continue with AI (n=158). All pts remained on the same CDK4/6i. ~50% of randomized pts had ESR1 m detected at the first ctDNA test. Baseline characteristics were well balanced between treatments. After 171 PFS events, hazard ratio for PFS was 0.44 (95% CI 0.31–0.60, p<0.00001; median PFS 16.0 vs 9.2 months). PFS benefit was consistent across subgroups. PFS rate at 12 months was 60.7% (95% CI 51.1–69.0) vs 33.4% (95% CI 24.9–42.2) and at 24 months was 29.7% (95% CI 19.0–41.2) vs 5.4% (95% CI 0.7–18.2). PFS2 hazard ratio was 0.52 (95% CI 0.33–0.81; 27% maturity). OS is immature (12%). Camizestrant + CDK4/6i was well tolerated with safety consistent with the known profiles of camizestrant, and of each CDK4/6i. Rates of treatment discontinuation due to adverse events were 1.3% for camizestrant and 1.9% for AI. Conclusions: Camizestrant + CDK4/6i guided by emergence of ESR1 m during 1L AI + CDK4/6i in pts with HR+/HER2– ABC resulted in a statistically significant and clinically meaningful improvement in PFS. SERENA-6 is the first global Phase 3 trial to demonstrate clinical utility of using ctDNA to detect and treat emerging resistance, ahead of disease progression. These findings represent a potential new treatment strategy to optimize and improve 1L patient outcomes. Clinical trial information: NCT04964934 .
Important questions remain regarding differences in geographical and age-specific mortality patterns as the COVID-19 pandemic evolved in consecutive waves, and how COVID-19 mortality compares to seasonal influenza. In a pandemic situation, excess all-cause mortality provides a more complete and robust measure than cause-specific mortality. Data submitted by 26 countries participating in the European Mortality Monitoring (EuroMOMO) network between 2020 and 2023 was analysed to quantify excess all-cause mortality during the COVID-19 pandemic. Excess mortality from this period was compared to previous influenza seasons from 2014 to 2019. Pooled estimates of excess mortality showed four main waves during the COVID-19 pandemic period, most markedly in people aged 65 years and above, with timing and magnitude that varied between countries. Here we show that prior to implementation of control measures and COVID-19 vaccination, excess mortality greatly exceeded typical seasonal influenza mortality, but later during the pandemic was at levels comparable to influenza.
OBJECTIVE:Despite their established clinical benefits, breast cancer screening examinations expose women to ionizing radiation (IR) and call for vigilance regarding protocols and practices. This study estimates the population attributable risk (PAR) of radiation-induced breast cancer in France in 2019 that is attributable to past exposure to IR through screening performed in women aged 40 to 74 years old. METHODS:Breast cancer screening practices were reconstituted for the period 1980 to 2019. Records of recent years were built based on French National Health Data System. An estimation was made for earlier years based on the available literature and expert knowledge. Women diagnosed with a history of breast cancer before mammography were excluded. Absorbed glandular doses to the breast were modeled based on existing literature and reports on French practices. Excess breast cancer cases were estimated using 2 radiation-risk models (Biologic Effects of Ionizing Radiation VII and the International Commission on Radiological Protection). RESULTS:Of roughly 55 000 new breast cancer cases diagnosed in 2019 in women at least 40 years old, we estimate that approximately 27 might be attributable to past exposures to IR associated with breast cancer screening between the ages of 50 and 74 years. This leads to a PAR of 0.048%. In addition, about 16 cases might be attributable to screening between ages 40 and 49 years, with a PAR of approximately 0.030%. CONCLUSION:The contribution of breast cancer screening to the breast cancer burden in France is limited. Efforts to limit the dose delivered to the breast must continue.
BACKGROUND:Cardiovascular disease has historically been the most common cause of death (COD) among people with and without diabetes. However, substantial progress has been made in the management of cardiovascular disease. We conducted a multinational analysis to establish whether this trend is still the case. METHODS:In this multinational, population-based study, we assembled aggregated annual mortality data collected during routine clinical care from nationally or regionally representative administrative datasets in high-income jurisdictions between 2000 and 2023. For inclusion, datasets must have ongoing enrolment of new patients with diabetes, cause-specific death counts in people with and without diabetes, and sex-specific and age-specific data. We collected population size, counts of prevalent diabetes (type 1 and type 2), death counts, and person-years of follow-up in people with and without diagnosed diabetes by sex and 10-year age group. We estimated cause-specific trends in mortality rates, proportional mortality, and mortality rate ratios (MRR) for people with versus those without diabetes (type 1 and type 2) using Poisson models standardised for age and sex. FINDINGS:Using data from 11 jurisdictions, we identified 2·7 million deaths in people with diabetes and 11·0 million deaths in people without diabetes during a total of 1·7 billion person-years of follow-up. Cardiovascular disease mortality decreased in all jurisdictions in populations with and without diabetes. Mean 5-year declines in cardiovascular disease mortality among people with diabetes ranged from 8·3% (95% CI 5·9 to 10·7) to 25·4% (22·8 to 28·0). Mortality due to diabetes declined in most jurisdictions. Dementia mortality increased in people with and without diabetes in six (86%) of seven jurisdictions. Cancer mortality declined in people with diabetes in three (33%) of nine jurisdictions and in people without diabetes in six (67%). At the end of the observation period, cancer was the leading COD in people with diabetes in four (36%) of 11 jurisdictions. MRRs were generally stable for all CODs. Exceptions include Lithuania, where the mean 5-year change in MRR for cardiovascular disease was -7·6% (-10·1 to -5·1), indicating a more rapid fall in cardiovascular disease mortality in people with diabetes than in people without. For dementia, the MRR increased in Denmark (5-year change 8·0% [5·0 to 11·1]) and Scotland (11·4% [8·5 to 14·3]). INTERPRETATION:Mortality from cardiovascular disease and diabetes has declined among people with diabetes in most jurisdictions, whereas mortality from dementia has increased markedly, independent of age. Cardiovascular disease is no longer universally the most common COD among people with diabetes in high-income countries. FUNDING:US Centers for Disease Control and Prevention, Diabetes Australia Research Program, and Victoria State Government Operational Infrastructure Support Program.
