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The main objective of this study was to evaluate the association of the insomnia-anxiety comorbidity with incident type 2 diabetes (T2D) in a large prospective cohort. We selected adults without diabetes at baseline from the French NutriNet-Santé cohort who had completed the trait anxiety subscale of the Spielberger State-Trait Anxiety Inventory (STAI-T, 2013–2016) and a sleep questionnaire (2014); insomnia was defined according to established criteria. Using multivariable Cox models, we compared T2D risk across 4 groups: no insomnia or anxiety (reference), insomnia alone, anxiety alone (STAI-T ≥ 40), and comorbid anxiety and insomnia. Among 35,014 participants (mean baseline age: 52.4 ± 14.0 years; 76% women), 378 (1.1%) developed T2D over a mean follow-up of 5.9 ± 2.1 years. Overall, 28.5% of the sample had anxiety alone, 7.5%—insomnia alone, and 12.5%—both disorders. In the fully-adjusted model, a higher T2D risk was associated with anxiety-insomnia comorbidity (HR = 1.40; 95% CI 1.01, 1.94), but not with each disorder separately, compared to the group without insomnia or anxiety. The findings supported a positive association between anxiety-insomnia comorbidity and incident T2D among general-population adults. Future research using clinical diagnoses of mental disorders could confirm the findings and guide diabetes prevention programs.

The objectives of this study were to assess the associations among various physical and mental chronic conditions and napping. A cross-sectional epidemiological survey was proposed within the NutriNet-Santé population-based e-cohort launched in France in 2009. Participants were 43,060 French volunteers aged 18 y and over with Internet access. A self-report questionnaire assessing sleep characteristics was administered in 2014. The main outcome (dependent) variable was weekday or weekend napping (yes/no). The main exposure (independent) variables were overweight/obesity, hypertension, diabetes, anxiety and depressive disorders, incident major cardiovascular diseases (myocardial infarction, stroke, unstable angina), and incident cancer (breast and prostate). The associations of interest were investigated with multivariable logistic regression analysis. No significant associations were found between major cardiovascular diseases or breast or prostate cancer and napping. Instead, we found that napping was more common among males (46.1%) than among females 36.9% (p < 0.0001). Individuals who were overweight or obese or had hypertension, diabetes, depression or anxiety disorders had an increased likelihood of napping compared with their healthy peers. The adjusted ORs ranged from 1.14 to 1.28″. In conclusion, most chronic conditions were independently associated with napping. Future longitudinal analyses are needed to elucidate causality.

This study reports characteristics and outcomes in patients with locally advanced or metastatic non-small cell lung cancer (aNSCLC) receiving nivolumab in second-line or later (2L+) in France and Germany between 2015 and 2020. Patients with aNSCLC (stage IIIB–C/IV) receiving nivolumab in 2L+ were included from the retrospective Epidemiological Strategy and Medical Economics of Advanced and Metastatic Lung Cancer cohort (ESME-AMLC, France; 2015–2019) and Clinical Research platform Into molecular testing, treatment and outcome of non-Small cell lung carcinoma Patients (CRISP, Germany; 2016–2020). Overall, 2262 ESME-AMLC and 522 CRISP patients were included. Median treatment duration (95% confidence intervals) was 2.8 months (2.5–3.2) in squamous and 2.5 months (2.3–2.8) in non-squamous/others patients in ESME-AMLC, and 2.3 months (1.4–3.1) and 2.3 months (2.0–2.8), respectively in CRISP. One-year and two-year overall survival (OS) were 47.2% and 26.7% in squamous and 50.8% and 32.8% in non-squamous/others patients in ESME-AMLC, and 43.1% and 20.9%, and 37.7% and 18.9%, respectively in CRISP. Poorer performance score and shorter time from start of previous line of therapy initiation were significantly associated with shorter treatment duration and OS. This study confirms, in real-world clinical databases, the efficacy of nivolumab previously observed in clinical trials.

Purpose We assessed the association of long-term weight change ae5 kg with total sleep time (TST), investigating effect modification by sex and overweight/obesity. In a cross-sectional context, we studied 41,610 adults from the general population-based NutriNet-Sant, e-cohort. A sleep questionnaire was self-administered in 2014. It included sleep logs for the estimation of average TST at night, and items for the calculation of major weight change as experienced over the previous 5 years. We fit multivariate polytomous logistic regression models. Overall, women with major weight loss had an increased likelihood of short TST (ae6 h) when compared with women with stable weight (OR = 1.15, 95% CI: 1.05-1.25). Individuals with major weight gain had an increased likelihood of short TST compared with their counterparts with stable weight (men: OR = 1.20, 95% CI: 1.05-1.37; women: OR = 1.24, 95% CI: 1.15-1.33). Men with major weight gain were less likely to report long TST compared with men with stable weight (OR = 0.83, 95% CI: 0.70-0.97). Overweight or obesity did not moderate the associations. The study advances knowledge in the fields of public health and nutrition by providing some evidence of a sex-specific association of major weight change with both short and long TST. These associations merit future investigation in a longitudinal context with repeated, objective measures of both weight and sleep time, while applying more stringent interaction test criteria and accounting for changes in health behaviors.

ObjectiveTo develop a composite responder index in primary Sjögren’s syndrome (pSS): the Sjögren’s Tool for Assessing Response (STAR).MethodsTo develop STAR, the NECESSITY (New clinical endpoints in primary Sjögren’s syndrome: an interventional trial based on stratifying patients) consortium used data-driven methods based on nine randomised controlled trials (RCTs) and consensus techniques involving 78 experts and 20 patients. Based on reanalysis of rituximab trials and the literature, the Delphi panel identified a core set of domains with their respective outcome measures. STAR options combining these domains were proposed to the panel for selection and improvement. For each STAR option, sensitivity to change was estimated by the C-index in nine RCTs. Delphi rounds were run for selecting STAR. For the options remaining before the final vote, a meta-analysis of the RCTs was performed.ResultsThe Delphi panel identified five core domains (systemic activity, patient symptoms, lachrymal gland function, salivary gland function and biological parameters), and 227 STAR options combining these domains were selected to be tested for sensitivity to change. After two Delphi rounds, a meta-analysis of the 20 remaining options was performed. The candidate STAR was then selected by a final vote based on metrological properties and clinical relevance.ConclusionThe candidate STAR is a composite responder index that includes all main disease features in a single tool and is designed for use as a primary endpoint in pSS RCTs. The rigorous and consensual development process ensures its face and content validity. The candidate STAR showed good sensitivity to change and will be prospectively validated by the NECESSITY consortium in a dedicated RCT.

Background: Participation in randomized controlled trials (RCTs) may be quite demanding and could represent an important burden for patients. We aimed to explore this research burden (i.e., the psychological, physical, and financial burdens) experienced by patients through their participation in a RCT.Methods: We conducted a systematic review of qualitative studies exploring adult patients' experiences with RCT participation. We searched MEDLINE (PubMed), CINAHL, PSYCHINFO, and Embase (search date March 2018) for eligible reports. Qualitative data coding and indexing were assisted by NVivo. The quality of reports was assessed by using the Critical Appraisal Skills Program (CASP) tool.Results: We included 45 qualitative studies that involved 1732 RCT participants. Important psychological burdens were identified at every stage of the trial process. Participants reported feeling anxiety and being afraid of \"being a 'guinea pig'\" and described undergoing randomization and allocation to a placebo as particularly difficult resulting in disappointment, anger, and depression. Patients' follow-up and trial closure were also responsible for a wide range of psychological, physical, and financial burdens. Furthermore, factors related to burdensome impacts and consequences were discerned. These factors involved trial information, poorly organized and too-demanding follow-up, and lack of appropriate management when the patient's participation ended. Trial participation was also associated with beneficial effects such as the satisfaction of feeling \"useful,\" gaining \"a sense of control,\" and receiving special attention.Conclusions: Our finding provides a detailed description of research burden across the whole RCT process. Many of the burdens described could be anticipated, and some avoided in a movement toward minimally disruptive clinical research. Such an approach could improve trial recruitment and retention.

OBJECTIVE Obesity alters gut microbiota ecology and associates with low-grade inflammation in humans. Roux-en-Y gastric bypass (RYGB) surgery is one of the most efficient procedures for the treatment of morbid obesity resulting in drastic weight loss and improvement of metabolic and inflammatory status. We analyzed the impact of RYGB on the modifications of gut microbiota and examined links with adaptations associated with this procedure. RESEARCH DESIGN AND METHODS Gut microbiota was profiled from fecal samples by real-time quantitative PCR in 13 lean control subjects and in 30 obese individuals (with seven type 2 diabetics) explored before (M0), 3 months (M3), and 6 months (M6) after RYGB. RESULTS Four major findings are highlighted: 1) Bacteroides/Prevotella group was lower in obese subjects than in control subjects at MO and increased at M3. It was negatively correlated with corpulence, but the correlation depended highly on caloric intake; 2) Escherichia coli species increased at M3 and inversely correlated with fat mass and leptin levels independently of changes in food intake; 3) lactic acid bacteria including Lacto-bacillus/Leuconostoc/Pediococcus group and Bifidobacterium genus decreased at M3; and 4) Faecalibacterium prausnitzii species was lower in subjects with diabetes and associated negatively with inflammatory markers at MO and throughout the follow-up after surgery independently of changes in food intake. CONCLUSIONS These results suggest that components of the dominant gut microbiota rapidly adapt in a starvation-like situation induced by RYGB while the F. prausnitzii species is directly linked to the reduction in low-grade inflammation state in obesity and diabetes independently of calorie intake. Diabetes 59:3049-3057, 2010

The objective of the present study was to conduct the first systematic review and meta-analysis of prospective studies investigating the associations between total cholesterol (TC), HDL-cholesterol (HDL-C) and LDL-cholesterol (LDL-C) levels and the risk of breast cancer. Relevant studies were identified in PubMed (up to January 2014). Inclusion criteria were original peer-reviewed publications with a prospective design. Random-effects models were used to estimate summary hazard ratios (HR) and 95 % CI. Distinction was made between studies that did or did not exclude cancer cases diagnosed during the first years of follow-up, thereby eliminating potential preclinical bias. Overall, the summary HR for the association between TC and breast cancer risk was 0·97 (95 % CI 0·94, 1·00; dose–response per 1 mmol/l increment, thirteen studies), and that between HDL-C and breast cancer risk was 0·86 (95 % CI 0·69, 1·09; dose–response per 1 mmol/l increment, six studies), with high heterogeneity (I 2= 67 and 47 %, respectively). For studies that eliminated preclinical bias, an inverse association was observed between the risk of breast cancer and TC (dose–response HR 0·94 (95 % CI 0·89, 0·99), seven studies, I 2= 78 %; highest v. lowest HR 0·82 (95 % CI 0·66, 1·02), nine studies, I 2= 81 %) and HDL-C (dose–response HR 0·81 (95 % CI 0·65, 1·02), five studies, I 2= 30 %; highest v. lowest HR 0·82 (95 % CI 0·69, 0·98), five studies, I 2= 0 %). There was no association observed between LDL-C and the risk of breast cancer (four studies). The present meta-analysis confirms the evidence of a modest but statistically significant inverse association between TC and more specifically HDL-C and the risk of breast cancer, supported by mechanistic plausibility from experimental studies. Further large prospective studies that adequately control for preclinical bias are needed to confirm the results on the role of cholesterol level and its fractions in the aetiology of breast cancer.

Background: To assess the completeness of reporting, research transparency practices, and risk of selection and immortal bias in observational studies using routinely collected data for comparative effectiveness research. Method: We performed a meta-research study by searching PubMed for comparative effectiveness observational studies evaluating therapeutic interventions using routinely collected data published in high impact factor journals from 01/06/2018 to 30/06/2020. We assessed the reporting of the study design (i.e., eligibility, treatment assignment, and the start of follow-up). The risk of selection bias and immortal time bias was determined by assessing if the time of eligibility, the treatment assignment, and the start of follow-up were synchronized to mimic the randomization following the target trial emulation framework. Result: Seventy-seven articles were identified. Most studies evaluated pharmacological treatments (69%) with a median sample size of 24,000 individuals. In total, 20% of articles inadequately reported essential information of the study design. One-third of the articles (n = 25, 33%) raised some concerns because of unclear reporting (n = 6, 8%) or were at high risk of selection bias and/or immortal time bias (n = 19, 25%). Only five articles (25%) described a solution to mitigate these biases. Six articles (31%) discussed these biases in the limitations section. Conclusion: Reporting of essential information of study design in observational studies remained suboptimal. Selection bias and immortal time bias were common methodological issues that researchers and physicians should be aware of when interpreting the results of observational studies using routinely collected data.

Background Resveratrol is a natural compound found in red wine. It has demonstrated anti-inflammatory properties in preclinical models. We compared the effect of oral resveratrol in a new patented formulation to oral placebo for individuals with painful knee osteoarthritis. Methods and findings ARTHROL was a double-blind, randomized, placebo-controlled, Phase 3 trial conducted in 3 tertiary care centers in France. We recruited adults who fulfilled the 1986 American College of Rheumatology criteria for knee osteoarthritis and reported a pain intensity score of at least 40 on an 11-point numeric rating scale (NRS) in 10-point increments (0, no pain, to 100, maximal pain). Participants were randomly assigned (1:1) by using a computer-generated randomization list with permuted blocks of variable size (2, 4, or 6) to receive oral resveratrol (40 mg [2 caplets] twice a day for 1 week, then 20 mg [1 caplet] twice a day; resveratrol group) or matched oral placebo (placebo group) for 6 months. The primary outcome was the mean change from baseline in knee pain on a self-administered 11-point pain NRS at 3 months. The trial was registered at ClinicalTrials.gov : (NCT02905799). Between October 20, 2017 and November 8, 2021, we assessed 649 individuals for eligibility, and from November 9, 2017, we recruited 142 (22%) participants (mean age 61.4 years [standard deviation (SD) 9.6] and 101 [71%] women); 71 (50%) were randomly assigned to the resveratrol group and 71 (50%) to the placebo group. At baseline, the mean knee pain score was 56.2/100 (SD 13.5). At 3 months, the mean reduction in knee pain was −15.7 (95% confidence interval (CI), −21.1 to −10.3) in the resveratrol group and −15.2 (95% CI, −20.5 to −9.8) in the placebo group (absolute difference −0.6 [95% CI, −8.0 to 6.9]; p = 0.88). Serious adverse events (not related to the interventions) occurred in 3 (4%) in the resveratrol group and 2 (3%) in the placebo group. Our study has limitations in that it was underpowered and the effect size, estimated to be 0.55, was optimistically estimated. Conclusions In this study, we observed that compared with placebo, oral resveratrol did not reduce knee pain in people with painful knee osteoarthritis. Trial registration ClinicalTrials.gov ID: NCT02905799 .