Benoît Lepage

BACKGROUND: In 2011, WHO member states signed up to the 25 × 25 initiative, a plan to cut mortality due to non-communicable diseases by 25% by 2025. However, socioeconomic factors influencing non-communicable diseases have not been included in the plan. In this study, we aimed to compare the contribution of socioeconomic status to mortality and years-of-life-lost with that of the 25 × 25 conventional risk factors. METHODS: We did a multicohort study and meta-analysis with individual-level data from 48 independent prospective cohort studies with information about socioeconomic status, indexed by occupational position, 25 × 25 risk factors (high alcohol intake, physical inactivity, current smoking, hypertension, diabetes, and obesity), and mortality, for a total population of 1 751 479 (54% women) from seven high-income WHO member countries. We estimated the association of socioeconomic status and the 25 × 25 risk factors with all-cause mortality and cause-specific mortality by calculating minimally adjusted and mutually adjusted hazard ratios [HR] and 95% CIs. We also estimated the population attributable fraction and the years of life lost due to suboptimal risk factors. FINDINGS: During 26·6 million person-years at risk (mean follow-up 13·3 years [SD 6·4 years]), 310 277 participants died. HR for the 25 × 25 risk factors and mortality varied between 1·04 (95% CI 0·98-1·11) for obesity in men and 2 ·17 (2·06-2·29) for current smoking in men. Participants with low socioeconomic status had greater mortality compared with those with high socioeconomic status (HR 1·42, 95% CI 1·38-1·45 for men; 1·34, 1·28-1·39 for women); this association remained significant in mutually adjusted models that included the 25 × 25 factors (HR 1·26, 1·21-1·32, men and women combined). The population attributable fraction was highest for smoking, followed by physical inactivity then socioeconomic status. Low socioeconomic status was associated with a 2·1-year reduction in life expectancy between ages 40 and 85 years, the corresponding years-of-life-lost were 0·5 years for high alcohol intake, 0·7 years for obesity, 3·9 years for diabetes, 1·6 years for hypertension, 2·4 years for physical inactivity, and 4·8 years for current smoking. INTERPRETATION: Socioeconomic circumstances, in addition to the 25 × 25 factors, should be targeted by local and global health strategies and health risk surveillance to reduce mortality. FUNDING: European Commission, Swiss State Secretariat for Education, Swiss National Science Foundation, the Medical Research Council, NordForsk, Portuguese Foundation for Science and Technology.

PURPOSE: HER2 mutations are identified in approximately 2%of non-small-cell lung cancers (NSCLC). There are few data available that describe the clinical course of patients with HER2-mutated NSCLC. PATIENTS AND METHODS: We retrospectively identified 65 NSCLC, diagnosed with a HER2 in-frame insertion in exon 20. We collected clinicopathologic characteristics, patients' outcomes, and treatments. RESULTS: HER2 mutation was identified in 65 (1.7%) of 3,800 patients tested and was almost an exclusive driver, except for one single case with a concomitant KRAS mutation. Our population presented with a median age of 60 years (range, 31 to 86 years), a high proportion of women (45 women v 20 men; 69%), and a high proportion of never-smokers (n= 34; 52.3%). All tumors were adenocarcinomas and 50% were stage IV at diagnosis. For these latter cases, 22 anti-human epidermal growth factor receptor 2 (HER2) treatments were administered after conventional chemotherapy in 16 patients. Subsequently, four patients experienced progressive disease, seven experienced disease stabilizations, and 11 experienced partial responses (overall response rate, 50%; disease control rate [DCR], 82%). Specifically, we observed a DCR of 93% for trastuzumab-based therapies (n = 15) and a DCR of 100% for afatinib (n = 3) but no response to other HER2-targeted drugs (n = 3). Progression-free survival for patients with HER2 therapies was 5.1 months. Median survival was of 89.6 and 22.9 months for early-stage and stage IV patients, respectively. CONCLUSION: This study, the largest to date dedicated to HER2-mutated NSCLC, reinforces the importance of screening for HER2 mutations in lung adenocarcinomas and suggests the potential efficacy of HER2-targeted drugs in this population.

Vertebral osteomyelitis (VO) is a rare event. To estimate the incidence of VO in France for 2002-2003, national hospital-discharge data were used. Hospital stays were categorized as definite, probable or possible VO. Unique patient identification numbers allowed the investigators to link patients with multiple hospital stays and to analyse data for individual patients. A sample of medical records was reviewed to assess the specificity of the VO case definition. In 2002-2003, 1977 and 2036 hospital stays corresponding to 1422 and 1425 patients (median age 59 years, male:female ratio 1.5) were classified as definite (64%), probable (24%) and possible (12%) VO. The overall incidence of VO was 2.4/100,000. Incidence increased with age: 0.3/100,000 (70 years). The main infectious agents reported were Staphylococcus spp. (38%) and Mycobacterium tuberculosis (31%). The most frequent comorbidities were septicaemia (27%) and endocarditis (9%). Three percent of patients died. A review of 90 medical records confirmed the diagnosis of VO in 94% of cases. Using a hospital database and a specific case definition, nationwide surveillance of VO is possible.

Events causing stress responses during sensitive periods of rapid neurological development in childhood may be early determinants of all-cause premature mortality. Using a British birth cohort study of individuals born in 1958, the relationship between adverse childhood experiences (ACE) and mortality≤50 year was examined for men (n=7,816) and women (n=7,405) separately. ACE were measured using prospectively collected reports from parents and the school: no adversities (70%); one adversity (22%), two or more adversities (8%). A Cox regression model was carried out controlling for early life variables and for characteristics at 23 years. In men the risk of death was 57% higher among those who had experienced 2+ ACE compared to those with none (HR 1.57, 95% CI 1.13, 2.18, p=0.007). In women, a graded relationship was observed between ACE and mortality, the risk increasing as ACE accumulated. Women with one ACE had a 66% increased risk of death (HR 1.66, 95% CI 1.19, 2.33, p=0.003) and those with ≥2 ACE had an 80% increased risk (HR 1.80, 95% CI 1.10, 2.95, p=0.020) versus those with no ACE. Given the small impact of adult life style factors on the association between ACE and premature mortality, biological embedding during sensitive periods in early development is a plausible explanatory mechanism.

BACKGROUND: To analyse whether Adverse Childhood Experiences (ACE) are associated with an increased risk of cancer. METHODS: The National child development study (NCDS) is a prospective birth cohort study with data collected over 50 years. The NCDS included all live births during one week in 1958 (n=18558) in Great Britain. Self-reported cancer incidence was based on 444 participants reporting having had cancer at some point and 5694 reporting never having cancer. ACE was measured using reports of: 1) child in care, 2) physical neglect, 3) child's or family's contact with the prison service, 4) parental separation due to divorce, death or other, 5) family experience of mental illness & 6) family experience of substance abuse. The resulting variable had three categories, no ACEs/ one ACE/ 2+ACEs and was used to test for a relationship with cancer. Information on socioeconomic characteristics, pregnancy and birth were extracted as potential confounders. Information on adult health behaviours, socioeconomic environment, psychological state and age at first pregnancy were added to the models. Multivariate models were run using multiply-imputed data to account for missing data in the cohort. RESULTS: The odds of having a cancer before 50 y among women increased twofold for those who had 2+ ACEs versus those with no ACEs, after adjusting for adult factors and early life confounders (OR: 2.1, 95% CI: 1.42-3.21, p<0.001). CONCLUSION: These findings suggest that cancer risk may be influenced by exposure to stressful conditions and events early on in life. This is potentially important in furthering our understanding of cancer aetiology, and consequently in redirecting scientific research and developing appropriate prevention policies.