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Monitoring outcomes of health care providers, such as patient deaths, hospitalizations, and hospital readmissions, helps in assessing the quality of health care. We consider a large database on patients being treated at dialysis facilities in the United States, and the problem of identifying facilities with outcomes that are better than or worse than expected. Analyses of such data have been commonly based on random or fixed facility effects, which have shortcomings that can lead to unfair assessments. A primary issue is that they do not appropriately account for variation between providers that is outside the providers' control due, for example, to unobserved patient characteristics that vary between providers. In this article, we propose a smoothed empirical null approach that accounts for the total variation and adapts to different provider sizes. The linear model provides an illustration that extends easily to other non-linear models for survival or binary outcomes, for example. The empirical null method is generalized to allow for some variation being due to quality of care. These methods are examined with numerical simulations and applied to the monitoring of survival in the dialysis facility data. [ABSTRACT FROM AUTHOR]

Background: Immunotherapies targeting ligand-receptor interactions (LRIs) are advancing rapidly in the treatment of colorectal cancer (CRC), and LRIs also affect many aspects of CRC development. However, the pattern of LRIs in CRC and their effect on tumor microenvironment and clinical value are still unclear.Methods: We delineated the pattern of LRIs in 55,539 single-cell RNA sequencing (scRNA-seq) samples from 29 patients with CRC and three bulk RNA-seq datasets containing data from 1411 CRC patients. Then the influence of tumor microenvironment, immunotherapy and prognosis of CRC patients were comprehensively investigated.Results: We calculated the strength of 1893 ligand-receptor pairs between 25 cell types to reconstruct the spatial structure of CRC. We identified tumor subtypes based on LRIs, revealed the relationship between the subtypes and immunotherapy efficacy and explored the ligand-receptor pairs and specific targets affecting the abundance of tumor-infiltrating lymphocytes. Finally, a prognostic model based on ligand-receptor pairs was constructed and validated.Conclusion: Overall, through the comprehensive and in-depth investigation of the existing ligand-receptor pairs, this study provides new ideas for CRC subtype classification, a new risk screening tool for CRC patients, and potential ligand-receptor pair targets and pathways for CRC therapy. [ABSTRACT FROM AUTHOR]

Background: Cancer poses a huge disease burden, which could be reduced by adopting healthy lifestyles mainly composed of healthy diet, body weight, physical activity, limited alcohol consumption, and avoidance of smoking. However, no systematic review has summarised the relations of combined lifestyle factors with cancer morbidity and mortality.Methods: EMBASE and PubMed were searched up to April 2019. Cohort studies investigating the association of combined lifestyle factors with risks of incident cancer and cancer mortality were selected. Summary hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using random-effects models. Heterogeneity and publication bias tests were conducted.Results: The HRs (95% CIs) comparing individuals with the healthiest versus the least healthy lifestyles were 0.71 (0.66-0.76; 16 studies with 1.9 million participants) for incident cancer and 0.48 (0.42-0.54; 30 studies with 1.8 million participants) for cancer mortality. Adopting the healthiest lifestyles was also associated with 17 to 58% lower risks of bladder, breast, colon, endometrial, oesophageal, kidney, liver, lung, rectal, and gastric cancer. The relations were largely consistent and significant among participants with different characteristics in the subgroup analyses.Conclusions: Adopting healthy lifestyles is associated with substantial risk reduction in cancer morbidity and mortality, and thus should be given priority for cancer prevention. [ABSTRACT FROM AUTHOR]

Background: Cows' milk generally contains two types of β-casein, A1 and A2 types. Digestion of A1 type can yield the peptide β-casomorphin-7, which is implicated in adverse gastrointestinal effects of milk consumption, some of which resemble those in lactose intolerance. This study aimed to compare the effects of milk containing A1 β-casein with those of milk containing only A2 β-casein on inflammation, symptoms of post-dairy digestive discomfort (PD3), and cognitive processing in subjects with self-reported lactose intolerance.Methods: Forty-five Han Chinese subjects participated in this double-blind, randomized, 2 × 2 crossover trial and consumed milk containing both β-casein types or milk containing only A2 β-casein. Each treatment period was 14 days with a 14-day washout period at baseline and between treatment periods. Outcomes included PD3, gastrointestinal function (measured by smart pill), Subtle Cognitive Impairment Test (SCIT), serum/fecal laboratory biomarkers, and adverse events.Results: Compared with milk containing only A2 β-casein, the consumption of milk containing both β-casein types was associated with significantly greater PD3 symptoms; higher concentrations of inflammation-related biomarkers and β-casomorphin-7; longer gastrointestinal transit times and lower levels of short-chain fatty acids; and increased response time and error rate on the SCIT. Consumption of milk containing both β-casein types was associated with worsening of PD3 symptoms relative to baseline in lactose tolerant and lactose intolerant subjects. Consumption of milk containing only A2 β-casein did not aggravate PD3 symptoms relative to baseline (i.e., after washout of dairy products) in lactose tolerant and intolerant subjects.Conclusions: Consumption of milk containing A1 β-casein was associated with increased gastrointestinal inflammation, worsening of PD3 symptoms, delayed transit, and decreased cognitive processing speed and accuracy. Because elimination of A1 β-casein attenuated these effects, some symptoms of lactose intolerance may stem from inflammation it triggers, and can be avoided by consuming milk containing only the A2 type of beta casein.Trial Registration: ClinicalTrials.gov/NCT02406469. [ABSTRACT FROM AUTHOR]