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The management regarding metastatic colorectal cancer throughout Europe is not well known. To draw a European comparison of the management and prognosis of metastatic colorectal cancers. Factors associated with chemotherapy administration were identified through logistic regressions. Net survival was estimated and crude probabilities of death related to cancer and other causes using a flexible cumulative hazard model. Among the 13 227 patients with colorectal cancer diagnosed between 2010 and 2013 in cancer registries from 10 European countries, 3140 were metastatic. 62% of metastatic patients received chemotherapy. Compared to Spain, the related adjusted odds ratios ranged from 0.7 to 4.0 (P<0.001) according to country. The 3-year net survival by country ranged between 16% and 37%. The survival gap between countries diminished from 21% to 10% when adjusting for chemotherapy, age and sex. Geographical differences in the crude probability of death related to cancer were large for patients <70 or ≥80 years at diagnosis. Heterogeneity in the application of European guidelines partly explain these differences. General health between populations, accessibility to a reference centre, or provision of health care could also be involved. Further population-based studies are warranted to disentangle between these possible explanations. [ABSTRACT FROM AUTHOR]

Numerous studies have analysed the effect of comorbidity on cancer outcomes, but evidence on the association between multimorbidity and short-term mortality among colorectal cancer patients is limited. We aimed to assess this association and the most frequent patterns of multimorbidity associated with a higher short-term mortality risk among colorectal cancer patients in Spain. Data were obtained from two Spanish population-based cancer registries and electronic health records. We estimated the unadjusted cumulative incidence of death by comorbidity status at 6 months and 1 year. We used a flexible parametric model to derive the excess mortality hazard ratios (HRs) for multimorbidity after adjusting for sex, age at diagnosis, cancer stage and treatment. We estimated the adjusted cumulative incidence of death by comorbidity status and identified multimorbidity patterns. Among the study participants, 1,048 cases were diagnosed with cancers of the colon and rectum, 2 cases with cancer of the anus with overlapping sites of the rectum and 11 cases with anal adenocarcinomas but treated as colorectal cancer patients. Among 1,061 colorectal cancer patients, 171 (16.2%) died before 6 months, 246 (23.3%) died before the 1-year follow-up, and 324 (30.5%) had multimorbidity. Patients with multimorbidity had two times higher mortality risk than those without comorbidities at 6 months (adjusted HR: 2.04; 95% confidence interval [CI]: 1.30–3.20, p = 0.002). The most frequent multimorbidity pattern was congestive heart failure + diabetes. However, patients with rheumatologic disease + diabetes had two times higher 1-year mortality risk than those without comorbidities (HR: 2.23; 95% CI: 1.23–4.07, p = 0.008). Multimorbidity was a strong independent predictor of short-term mortality at 6 months and 1 year among the colorectal cancer patients in Spain. The identified multimorbidity pattern was consistent. Our findings might help identify patients at a higher risk for poor cancer and treatment outcomes. • Multimorbidity was a strong predictor of short-term mortality in colorectal cancer. • Patients with multimorbidity had twice higher mortality risk than those without. • The most frequent multimorbidity pattern was congestive heart failure + diabetes. • Our findings can help identify patients at a higher risk for poor cancer outcomes. [ABSTRACT FROM AUTHOR]

Introduction: The circadian clock plays an important role in several aspects of female reproductive biology. Evidence linking circadian clock-related genes to pregnancy outcomes has been inconsistent. We sought to examine whether variations in single nucleotide polymorphisms (SNPs) of circadian clock genes are associated with PA risk. Methods: Maternal blood samples were collected from 470 PA case and 473 controls. Genotyping was performed using the Illumina Cardio-MetaboChip platform. We examined 119 SNPs in 13 candidate genes known to control circadian rhythms (e.g., CRY2, ARNTL, and RORA). Univariate and penalized logistic regression models were fit to estimate odds ratios (ORs); and the combined effect of multiple SNPs on PA risk was estimated using a weighted genetic risk score (wGRS). Results: A common SNP in the RORA gene (rs2899663) was associated with a 21% reduced odds of PA (P < 0.05). The odds of PA increased with increasing wGRS (Ptrend < 0.001). The corresponding ORs were 1.00, 1.83, 2.81 and 5.13 across wGRS quartiles. Participants in the highest wGRS quartile had a 5.13-fold (95% confidence interval: 3.21-8.21) higher odds of PA compared to those in the lowest quartile. Although the test for interaction was not significant, the odds of PA was substantially elevated for preeclamptics with the highest wGRS quartile (OR = 14.44, 95%CI: 6.62-31.53) compared to normotensive women in the lowest wGRS quartile. Discussion: Genetic variants in circadian rhythm genes may be associated with PA risk. Larger studies are needed to corroborate these findings and to further elucidate the pathogenesis of this important obstetrical complication. [ABSTRACT FROM AUTHOR]

Purpose Data regarding circadian rhythm in the onset of spontaneous preterm premature rupture of membranes (PROM) and placental abruption (PA) cases are conflicting. We modeled the time of onset of preterm PROM and PA cases and examined if the circadian profiles varied based on the gestational age at delivery. Methods We used parametric and nonparametric methods, including trigonometric regression in the framework of generalized linear models, to test the presence of circadian rhythms in the time of onset of preterm PROM and PA cases among 395 women who delivered a singleton between 2009 and 2010 in Lima, Peru. Results We found a diurnal circadian pattern, with a morning peak at 07:32 AM (95% confidence interval, 05:46 AM–09:18 AM) among moderate preterm PROM cases ( P value < .001), and some evidence of a diurnal circadian periodicity among PA cases in term infants ( P value = .067). However, we did not find evidence of circadian rhythms in the time of onset of extremely or very preterm PROM ( P value = .259) and preterm PA ( P value = .224). Conclusions The circadian rhythms of the time of onset of preterm PROM and PA cases varied based on gestational weeks at delivery. Although circadian rhythms were presented among moderate preterm PROM and term PA cases, there was no evidence of circadian rhythms among preterm PA and very or extremely preterm PROM cases, underlying other mechanisms associated with the time of onset. [ABSTRACT FROM AUTHOR]

The targeted maximum likelihood estimation (TMLE) statistical data analysis framework integrates machine learning, statistical theory, and statistical inference to provide a least biased, efficient, and robust strategy for estimation and inference of a variety of statistical and causal parameters. We describe and evaluate the epidemiological applications that have benefited from recent methodological developments. We conducted a systematic literature review in PubMed for articles that applied any form of TMLE in observational studies. We summarized the epidemiological discipline, geographical location, expertize of the authors, and TMLE methods over time. We used the Roadmap of Targeted Learning and Causal Inference to extract key methodological aspects of the publications. We showcase the contributions to the literature of these TMLE results. Of the 89 publications included, 33% originated from the University of California at Berkeley, where the framework was first developed by Professor Mark van der Laan. By 2022, 59% of the publications originated from outside the United States and explored up to seven different epidemiological disciplines in 2021–2022. Double-robustness, bias reduction, and model misspecification were the main motivations that drew researchers toward the TMLE framework. Through time, a wide variety of methodological, tutorial, and software-specific articles were cited, owing to the constant growth of methodological developments around TMLE. There is a clear dissemination trend of the TMLE framework to various epidemiological disciplines and to increasing numbers of geographical areas. The availability of R packages, publication of tutorial papers, and involvement of methodological experts in applied publications have contributed to an exponential increase in the number of studies that understood the benefits and adoption of TMLE. [ABSTRACT FROM AUTHOR]