Does adequate physical activity attenuate the associations of alcohol and alcohol-related cancer mortality? A pooled study of 54 686 British adults.

The potential of physical activity (PA) to attenuate the effects of alcohol consumption on the risks of alcohol-related cancer mortality is unknown. We used data from participants aged 30 years and over in 10 British population-based surveys (Health Surveys for England 1994, 1997, 1998, 1999, 2003, 2004, 2006 and 2008 and the Scottish Health Surveys 1998 and 2003). Alcohol-related cancer mortality included oral cavity, throat, larynx, oesophagus, liver, colorectal, stomach and female breast (conservative definition), and additionally pancreas and lung (broad definition). Alcohol consumption was categorised into six groups based on the UK units/week: (a) never-drinkers, (b) ex-drinkers, (c) occasional drinkers, (d) within guidelines (<14 UK units/week [women]; <21 UK units/week [men]), (e) hazardous (14-35 [women]; 21-49 [men]) and (f) harmful (>35 [women]; >49 [men]). PA was categorised using two dichotomous classifications based on the lower (7.5 Metabolic Equivalent Task [MET]-hours/week) and upper (15 MET-hours/week) recommended limits. Using Cox proportional hazard models, we found a strong direct association between alcohol consumption and mortality risk of alcohol-related cancers, with a significantly higher risk among ex-drinkers (Hazard ratio [HR] = 1.46, 95% confidence interval [CI] = [1.09, 1.94]), drinkers who consumed hazardous (HR = 1.39, 95% CI = [1.06, 1.83]) and harmful amounts of alcohol (HR = 1.62, 95% CI = [1.13, 2.30]) compared to never-drinkers in the fully adjusted model. The increased mortality risks were substantially attenuated when participants in these drinking groups exercised >7.5 MET-hours/week. PA could be promoted as an adjunct risk minimisation measure for alcohol-related cancer prevention.

Does a physically active lifestyle attenuate the association between alcohol consumption and mortality risk? Findings from the UK biobank.

Alcohol consumption is common across Western culture, despite its associations with adverse health outcomes, including cancer and cardiovascular disease (CVD). Physical activity (PA) has beneficial effects on many alcohol related outcomes, with data suggesting PA may offset the association between alcohol consumption and mortality. This study examined the joint associations of PA and alcohol on all-cause, CVD and cancer mortality. Participants were recruited between 2006 and 2010 in the United Kingdom. Alcohol consumption was categorised based on current UK guidelines (14 units/week). PA was categorised based on the Metabolic Task Equivalent of PA as low, moderate and high. Data were analysed using Cox proportional-hazard models. The final analysis, conducted in 2019, included 297,988 adults aged ≥40. Over an average follow-up of 6.9 years, 6079 deaths were recorded, including 1219 CVD deaths and 3112 cancer deaths. We observed greater point estimates for risk of all-cause mortality among low PA individuals who consumed alcohol at the same level as active individuals. For example, low PA participants who reported alcohol consumption ≥double guidelines had a greater HR (1.55, 95% CI 1.25, 1.93) than active individuals (moderate PA HR 1.21, 95% CI 0.95, 1.54; high PA HR 1.21, 95% CI 1.00, 1.46). Considering CVD, we observed a similar trend with lower point estimates of risk of mortality among active individuals. We found some evidence that PA modified the associations of alcohol and all-cause and CVD mortality in this large population sample of British adults.

Patterns of immediate breast reconstruction in New South Wales, Australia: a population-based study.

BACKGROUND: The rate of immediate breast reconstruction (IBR) following mastectomy for breast cancer in Australia is low and varies between regions. To date, no previous Australian studies have examined IBR rates between all hospitals within a particular jurisdiction, despite hospitals being an important known contributor to variation in IBR rates in other countries. METHODS: We used cross-classified random-effects logistic regression models to examine the inter-hospital variation in IBR rates by using data on 7961 women who underwent therapeutic mastectomy procedures in New South Wales (NSW) between January 2012 and June 2015. We derived IBR rates by patient-, residential neighbourhood- and hospital-related factors and investigated the underlying drivers for the variation in IBR. RESULTS: We estimated the mean IBR rate across all hospitals performing mastectomy to be 17.1% (95% Bayesian credible interval (CrI) 12.1-23.1%) and observed wide inter-hospital variation in IBR (variance 4.337, CrI 2.634-6.889). Older women, those born in Asian countries (odds ratio (OR) 0.5, CrI 0.4-0.6), residing in neighbourhoods with lower socioeconomic status (OR 0.7, CrI 0.5-0.8 for the most disadvantaged), and who underwent surgery in public hospitals (OR 0.4, CrI 0.1-1.0) were significantly less likely to have IBR. Women residing in non-metropolitan areas and attending non-metropolitan hospitals were significantly less likely to undergo IBR than their metropolitan counterparts attending metropolitan hospitals. CONCLUSION: Wide inter-hospital variation raises concerns about potential inequities in access to IBR services and unmet demand in certain areas of NSW. Explaining the underlying drivers for IBR variation is the first step in identifying policy solutions to redress the issue.

Exploring variation in low-value care: a multilevel modelling study.

BACKGROUND: Whether patients receive low-value hospital care (care that is not expected to provide a net benefit) may be influenced by unmeasured factors at the hospital they attend or the hospital's Local Health District (LHD), or the patients' areas of residence. Multilevel modelling presents a method to examine the effects of these different levels simultaneously and assess their relative importance to the outcome. Knowing which of these levels has the greatest contextual effects can help target further investigation or initiatives to reduce low-value care. METHODS: We conducted multilevel logistic regression modelling for nine low-value hospital procedures. We fit a series of six models for each procedure. The baseline model included only episode-level variables with no multilevel structure. We then added each level (hospital, LHD, Statistical Local Area [SLA] of residence) separately and used the change in the c statistic from the baseline model as a measure of the contribution of the level to the outcome. We then examined the variance partition coefficients (VPCs) and median odds ratios for a model including all three levels. Finally, we added level-specific covariates to examine if they were associated with the outcome. RESULTS: Analysis of the c statistics showed that hospital was more important than LHD or SLA in explaining whether patients receive low-value care. The greatest increases were 0.16 for endoscopy for dyspepsia, 0.13 for colonoscopy for constipation, and 0.14 for sentinel lymph node biopsy for early melanoma. SLA gave a small increase in c compared with the baseline model, but no increase over the model with hospital. The VPCs indicated that hospital accounted for most of the variation not explained by the episode-level variables, reaching 36.8% (95% CI, 31.9-39.0) for knee arthroscopy. ERCP (8.5%; 95% CI, 3.9-14.7) and EVAR (7.8%; 95% CI, 2.9-15.8) had the lowest residual variation at the hospital level. The variables at the hospital, LHD and SLA levels that were available for this study generally showed no significant effect. CONCLUSIONS: Investigations into the causes of low-value care and initiatives to reduce low-value care might best be targeted at the hospital level, as the high variation at this level suggests the greatest potential to reduce low-value care.

Exendin-4 promotes proliferation and differentiation of MC3T3-E1 osteoblasts by MAPKs activation.

Glucagon-like peptide-1 (GLP1) and its receptor agonist have been previously reported to play a positive role in bone metabolism in aged ovariectomized rats and insulin-resistant models. However, whether GLP1 has a direct effect on the proliferation and differentiation of osteoblasts or any cellular mechanism for this potential role is unknown. We examined the effects of the GLP1 receptor agonist exendin-4 on the proliferation, differentiation, and mineralization of mouse osteoblastic MC3T3-E1 cells. GLP1 receptor was detected in MC3T3-E1 cells by polymerase chain reaction (PCR) and Western blot assay. Cell proliferation was assessed using MTT assay, revealing that exendin-4 increased cell proliferation at effective concentrations between 10(-10) and 10(-5) M. Quantitative PCR analysis showed that exendin-4 increased the mRNA expression of the differentiation markers alkaline phosphatase (ALP), collagen-1 (COL1), osteocalcin (OC), and runt-related transcription factor 2 (RUNX2) under osteogenic conditions. Alizarin red staining confirmed that 10(-7) M exendin-4 increased osteoblast mineralization by 18.7%. Exendin-4 upregulated the phosphorylation of ERK1/2, p38, and JNK, with the peak effect at 1.5 h in the Western blot analysis. The use of selective MAPK inhibitors, namely PD98059, SB203580, and SP600125, blocked the effects of exendin-4 on kinase activation (ERK1/2, p38, and JNK), as well as cell proliferation and differentiation in MC3T3-E1 cells. These findings demonstrate that exendin-4 promotes both the proliferation and differentiation of preosteoblasts MC3T3-E1 via activation of the MAPK pathway.