Efficacy and Safety of Bevacizumab Combined With First-Line Chemotherapy in Elderly (≥75 Years) Patients With Metastatic Colorectal Cancer: A Real-World Study.

BACKGROUND: Although elderly patients are the first concerned by colorectal cancer (CRC), they are underrepresented in clinical trials. The real-world CASSIOPEE study was thus conducted in elderly patients treated for metastatic CRC (mCRC). METHODS: This French prospective, multicenter, noninterventional study aimed to estimate 1-year progression-free survival (PFS) and overall survival (OS), and describe treatments, patient autonomy (Instrumental Activities of Daily Living; Balducci scale), and safety over 24 months, in patients older than 75 with mCRC, starting first-line bevacizumab plus chemotherapy (NCT01555762). RESULTS: From 2012 to 2014, 402 patients were included (safety population: n = 383, efficacy population: n = 358). Patient characteristics were as follows: mean age, 81 ± 4 years (<80 years, 46%; 80-85 years, 44%; >85 years, 10%); men, 52%; colon primary tumor, 80%; main metastatic site, liver 66%; Eastern Cooperative Oncology Group performance 0-1, 81%. Median PFS was 9.1 months (95% confidence interval [CI]: 8.3-10.2). It was superior for patients ≤85 years (<80 years: 9.3 months; 80-85 years: 9.5 months) compared with patients >85 years (8.3 months). Median OS was 19.0 months (95% CI, 16.5-21.5) and decreased in the 2 oldest groups (20.6, 17.8, and 13.0 months). Autonomy assessments decreased over time leading to nonconclusive results. Twenty-six percent of patients experienced serious adverse events (SAEs): 7% bevacizumab-related SAEs, and 6% bevacizumab-targeted SAEs. Two fatal bevacizumab-related adverse events were reported (hemorrhagic stroke and intestinal ischemia). CONCLUSIONS: This large French real-world study showed that medically fit older patients with mCRC could have a benefit/risk balance similar to that of younger patients when treated with first-line bevacizumab plus chemotherapy. Improvements in geriatric assessments are needed to better define this population.

Effect of reminders mailed to general practitioners on colorectal cancer screening adherence: a cluster-randomized trial.

Reminders have been used in various settings, but failed to produce convincing evidence of benefits on patient adherence to colorectal cancer (CRC) screening. The aim of this study was to assess the effectiveness of sending general practitioners (GPs) printed reminders about CRC screening. We conducted a cluster-randomized controlled trial involving 144 GPs in the Val-de-Marne district (France), who provided care for any reason to 20 778 patients eligible for CRC screening between June 2010 and November 2011. Data were collected from the main statutory health-insurance programme and local cancer screening agency. GPs were randomly assigned in a 1 : 1 proportion to the intervention or the control group. Every 4 months, intervention-group GPs received a computer-generated printed list of patients who had not performed scheduled faecal occult blood test (FOBT) screening. The primary outcome was patient adherence to FOBT screening or exclusion from CRC screening for medical reasons. The screening adherence rate was 31.2% [95% confidence interval (CI) 30.3-32.1] in the control group and 32.9% (95% CI 32.0-33.8) in the intervention group [crude relative risk, 1.05 (95% CI 1.01-1.09), P<0.01]. This rate was not significantly different between groups by multilevel modelling accounting for clustering and confounding variables [adjusted relative risk, 1.07 (95% CI 0.95-1.20), P=0.27]. Computer-generated printed reminders sent to GPs did not significantly improve patient adherence to organized CRC screening by the FOBT.

Risk prediction score for severe high altitude illness: a cohort study.

BACKGROUND: Risk prediction of acute mountain sickness, high altitude (HA) pulmonary or cerebral edema is currently based on clinical assessment. Our objective was to develop a risk prediction score of Severe High Altitude Illness (SHAI) combining clinical and physiological factors. Study population was 1017 sea-level subjects who performed a hypoxia exercise test before a stay at HA. The outcome was the occurrence of SHAI during HA exposure. Two scores were built, according to the presence (PRE, n = 537) or absence (ABS, n = 480) of previous experience at HA, using multivariate logistic regression. Calibration was evaluated by Hosmer-Lemeshow chisquare test and discrimination by Area Under ROC Curve (AUC) and Net Reclassification Index (NRI). RESULTS: The score was a linear combination of history of SHAI, ventilatory and cardiac response to hypoxia at exercise, speed of ascent, desaturation during hypoxic exercise, history of migraine, geographical location, female sex, age under 46 and regular physical activity. In the PRE/ABS groups, the score ranged from 0 to 12/10, a cut-off of 5/5.5 gave a sensitivity of 87%/87% and a specificity of 82%/73%. Adding physiological variables via the hypoxic exercise test improved the discrimination ability of the models: AUC increased by 7% to 0.91 (95%CI: 0.87-0.93) and 17% to 0.89 (95%CI: 0.85-0.91), NRI was 30% and 54% in the PRE and ABS groups respectively. A score computed with ten clinical, environmental and physiological factors accurately predicted the risk of SHAI in a large cohort of sea-level residents visiting HA regions.

Long-term effects of an educational seminar on antibiotic prescribing by GPs: a randomised controlled trial.

BACKGROUND: High levels of outpatient antibiotic use remain observed in many European countries. Several studies have shown a strong relationship between antibiotic use and bacterial resistance. AIM: To assess the long-term effect of a standardised educational seminar on antibiotic prescriptions by GPs. DESIGN AND SETTING: Randomised controlled trial of 171 GPs (of 203 initially randomised) in France. METHOD: GPs in the control group (n = 99) received no antibiotic prescription recommendation. Intervention group GPs (n = 72) attended an interactive seminar presenting evidence-based guidelines on antibiotic prescription for respiratory infections. The proportion of prescriptions containing an antibiotic in each group and related costs were compared to the baseline up to 30 months following the intervention. Data were obtained from the National Health Insurance System database. RESULTS: In the intervention group, 4-6 months after the intervention, there was a significant decrease in the proportion of prescriptions containing an antibiotic from 15.2 ± 5.4% to 12.3 ± 5.8% (-2.8% [95% CI = -3.8 to -1.9], P<0.001). By contrast, an increase was observed in controls from 15.3 ± 6.0 to 16.4 ± 6.7% (+1.1% [95% CI = +0.4 to +1.8], P<0.01), resulting in a between-group difference of 3.93% ([95% CI = 2.75 to 5.11], P<0.001). The between-group difference was maintained 30 months after intervention (1.99% [95% CI = 0.56 to 3.42], P<0.01). Persistence of the intervention effect over the entire study period was confirmed in a hierarchical multivariate analysis. CONCLUSION: This randomised trial shows that a standardised and interactive educational seminar results in a long-term reduction in antibiotic prescribing and could justify a large-scale implementation of this intervention.

Understanding barriers to organized breast cancer screening in France: women's perceptions, attitudes, and knowledge.

BACKGROUND: The participation rate in organized breast cancer screening in France is lower than recommended. Non-participants either use opportunistic screening or do not use either screening modality. OBJECTIVE: To assess any differences in perceptions, attitudes and knowledge related to breast cancer screening between users of opportunistic screening and non-users of any screening mammograms and to identify potential barriers to participation in organized screening. METHODS: Six focus groups were conducted in May 2010 with 34 French non-participants in organized screening, 15 who used opportunistic screening (OpS group) and 19 who used no screening (NoS group). The guide used for both groups explored perceptions and attitudes related to health, cancer and screening; perceptions of femininity; and knowledge about breast cancer screening. Thematic content analysis was performed. RESULTS: Perceptions, attitudes and knowledge differed between the two groups. Women in the OpS group perceived a high susceptibility to breast cancer, visited their gynaecologist regularly, were unfamiliar with organized screening modalities and had doubts about its quality. NoS women had very high- or low-perceived susceptibility to breast cancer, knew about screening modalities, had doubts about its usefulness and expressed negative opinions of mammograms. CONCLUSIONS: Differences in perceptions and attitudes related to breast cancer screening partially explain why some women choose opportunistic screening or no screening. General practitioners and gynaecologists are in a unique position to provide individually tailored preventative messages to improve participation in organized screening.

Low skeletal muscle mass and risk of functional decline in elderly community-dwelling women: the prospective EPIDOS study.

OBJECTIVES: To assess relationships between low skeletal muscle mass (SMM) and functional decline in community-dwelling elderly women. DESIGN: Secondary analysis of data from EPIDOS, a French prospective observational multicenter cohort study of osteoporosis epidemiology. SETTING: One center in France between 1992 and 1994. PARTICIPANTS: Women aged 75 years or older without disability and with available baseline SMM measurements. MEASUREMENTS: SMM was assessed using dual-energy X-ray absorptiometry and functional decline was defined as loss of at least one Instrumental Activity of Daily Living component. Associations linking low SMM to functional decline were estimated using the Cox proportional hazards model. RESULTS: Of 975 women followed for 4 years, 452 (46.4%) experienced functional decline. Factors independently associated with functional decline were decreased SMM (adjusted hazard ratio [aHR] per SD decrease, 1.12; 95% confidence interval [95% CI], 1.01-1.24), older age (aHR per SD increase, 1.28; 95% CI, 1.17-1.39), one or more comorbidities (aHR, 1.65; 95%CI, 1.05-2.59), and impaired chair-stand test (aHR, 1.35; 95% CI, 1.01-1.82). The second SMM quartile was associated with functional decline (aHR, 1.39; 95% CI, 1.06-1.84) and the lowest quartile showed a nearly significant association (aHR, 1.29; 95% CI, 0.98-1.72). Factors negatively associated with functional decline were living alone (aHR, 0.76; 95% CI, 0.59-0.96), higher handgrip strength (aHR per SD increase, 0.88; 95% CI, 0.78-0.88), and walking speed (aHR per SD increase, 0.86; 95% CI, 0.77-0.96). CONCLUSION: Low SMM was independently associated with functional decline within 4 years after adjustment for age, muscle strength, physical performance, and comorbidities in community-dwelling elderly women.