Most epidemiology textbooks that discuss models are vague on details of model selection. This lack of detail may be understandable since selection should be strongly influenced by features of the ...particular study, including contextual (prior) information about covariates that may confound, modify, or mediate the effect under study. It is thus important that authors document their modeling goals and strategies and understand the contextual interpretation of model parameters and model selection criteria. To illustrate this point, we review several established strategies for selecting model covariates, describe their shortcomings, and point to refinements, assuming that the main goal is to derive the most accurate effect estimates obtainable from the data and available resources. This goal shifts the focus to prediction of exposure or potential outcomes (or both) to adjust for confounding; it thus differs from the goal of ordinary statistical modeling, which is to passively predict outcomes. Nonetheless, methods and software for passive prediction can be used for causal inference as well, provided that the target parameters are shifted appropriately.
There are two common misconceptions about case-control studies: that matching in itself eliminates (controls) confounding by the matching factors, and that if matching has been performed, then a ...“matched analysis” is required. However, matching in a case-control study does not control for confounding by the matching factors; in fact it can introduce confounding by the matching factors even when it did not exist in the source population. Thus, a matched design may require controlling for the matching factors in the analysis. However, it is not the case that a matched design requires a matched analysis. Provided that there are no problems of sparse data, control for the matching factors can be obtained, with no loss of validity and a possible increase in precision, using a “standard” (unconditional) analysis, and a “matched” (conditional) analysis may not be required or appropriate.
Dementia and obesity are increasingly important public health issues. Obesity in middle age has been proposed to lead to dementia in old age. We investigated the association between BMI and risk of ...dementia.
For this retrospective cohort study, we used a cohort of 1,958,191 individuals derived from the United Kingdom Clinical Practice Research Datalink (CPRD) which included people aged 40 years or older in whom BMI was recorded between 1992 and 2007. Follow-up was until the practice's final data collection date, patient death or transfer out of practice, or first record of dementia (whichever occurred first). People with a previous record of dementia were excluded. We used Poisson regression to calculate incidence rates of dementia for each BMI category.
Our cohort of 1,958,191 people from UK general practices had a median age at baseline of 55 years (IQR 45-66) and a median follow-up of 9·1 years (IQR 6·3-12·6). Dementia occurred in 45,507 people, at a rate of 2·4 cases per 1000 person-years. Compared with people of a healthy weight, underweight people (BMI <20 kg/m(2)) had a 34% higher (95% CI 29-38) risk of dementia. Furthermore, the incidence of dementia continued to fall for every increasing BMI category, with very obese people (BMI >40 kg/m(2)) having a 29% lower (95% CI 22-36) dementia risk than people of a healthy weight. These patterns persisted throughout two decades of follow-up, after adjustment for potential confounders and allowance for the J-shape association of BMI with mortality.
Being underweight in middle age and old age carries an increased risk of dementia over two decades. Our results contradict the hypothesis that obesity in middle age could increase the risk of dementia in old age. The reasons for and public health consequences of these findings need further investigation.
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Summary Background The UK has had universal free health care and public health programmes for more than six decades. Several policy initiatives and structural reforms of the health system have been ...undertaken. Health expenditure has increased substantially since 1990, albeit from relatively low levels compared with other countries. We used data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2010 (GBD 2010) to examine the patterns of health loss in the UK, the leading preventable risks that explain some of these patterns, and how UK outcomes compare with a set of comparable countries in the European Union and elsewhere in 1990 and 2010. Methods We used results of GBD 2010 for 1990 and 2010 for the UK and 18 other comparator nations (the original 15 members of the European Union, Australia, Canada, Norway, and the USA; henceforth EU15+). We present analyses of trends and relative performance for mortality, causes of death, years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE). We present results for 259 diseases and injuries and for 67 risk factors or clusters of risk factors relevant to the UK. We assessed the UK's rank for age-standardised YLLs and DALYs for their leading causes compared with EU15+ in 1990 and 2010. We estimated 95% uncertainty intervals (UIs) for all measures. Findings For both mortality and disability, overall health has improved substantially in absolute terms in the UK from 1990 to 2010. Life expectancy in the UK increased by 4·2 years (95% UI 4·2–4·3) from 1990 to 2010. However, the UK performed significantly worse than the EU15+ for age-standardised death rates, age-standardised YLL rates, and life expectancy in 1990, and its relative position had worsened by 2010. Although in most age groups, there have been reductions in age-specific mortality, for men aged 30–34 years, mortality rates have hardly changed (reduction of 3·7%, 95% UI 2·7–4·9). In terms of premature mortality, worsening ranks are most notable for men and women aged 20–54 years. For all age groups, the contributions of Alzheimer's disease (increase of 137%, 16–277), cirrhosis (65%, −15 to 107), and drug use disorders (577%, 71–942) to premature mortality rose from 1990 to 2010. In 2010, compared with EU15+, the UK had significantly lower rates of age-standardised YLLs for road injury, diabetes, liver cancer, and chronic kidney disease, but significantly greater rates for ischaemic heart disease, chronic obstructive pulmonary disease, lower respiratory infections, breast cancer, other cardiovascular and circulatory disorders, oesophageal cancer, preterm birth complications, congenital anomalies, and aortic aneurysm. Because YLDs per person by age and sex have not changed substantially from 1990 to 2010 but age-specific mortality has been falling, the importance of chronic disability is rising. The major causes of YLDs in 2010 were mental and behavioural disorders (including substance abuse; 21·5% 95 UI 17·2–26·3 of YLDs), and musculoskeletal disorders (30·5% 25·5–35·7). The leading risk factor in the UK was tobacco (11·8% 10·5–13·3 of DALYs), followed by increased blood pressure (9·0 % 7·5–10·5), and high body-mass index (8·6% 7·4–9·8). Diet and physical inactivity accounted for 14·3% (95% UI 12·8–15·9) of UK DALYs in 2010. Interpretation The performance of the UK in terms of premature mortality is persistently and significantly below the mean of EU15+ and requires additional concerted action. Further progress in premature mortality from several major causes, such as cardiovascular diseases and cancers, will probably require improved public health, prevention, early intervention, and treatment activities. The growing burden of disability, particularly from mental disorders, substance use, musculoskeletal disorders, and falls deserves an integrated and strategic response. Funding Bill & Melinda Gates Foundation.
Background Surgical management of liver lesions has moved toward “parenchymal-sparing” strategies. Although open parenchymal-sparing liver resections are supported by encouraging results, the ...applicability of the laparoscopic approach for nonperipheral tumors is still questionable. Our aim was to assess the feasibility, safety, and oncologic adequacy of laparoscopic parenchymal-sparing liver resection for nonperipheral lesions with a description of the technique adopted in this setting. Study Design A prospectively collected single-center database of 517 laparoscopic liver resections was reviewed. Laparoscopic nonperipheral parenchymal-sparing liver resections (LapPSLRs), that is, entirely intraparenchymal limited resections performed on nonperipheral lesions, were selected. Intra- and perioperative outcomes were analyzed along with 3-year actuarial survival for patients with colorectal liver metastases. Results The group comprised 49 LapPSLRs. Colorectal liver metastases were the most frequent diagnosis (n = 24 patients). Lesions were located in segments 8, 7, 4a, and 3 in 51%, 8.2%, 36.7%, and 4.1% of cases, respectively. Conversion occurred in 4 patients (8%). Intra- and postoperative short-term outcomes were calculated for the 24 isolated LapPSLR (not associated with any concurrent liver resection). Median operative time and blood loss were 215 minutes and 225 mL, respectively. Pringle maneuver was used in 75% of cases. Postoperative 90-day mortality was nil and morbidity rate was 12.5%. Median postoperative stay was 3 days. Median tumor-free margin was 4 mm and 100% R0 rate was achieved for all LapPSLRs with curative intent. Three-year overall, recurrence-free, and disease-free survival rates were 100%, 65.2%, and 69.6%, respectively. Conclusions Laparoscopic parenchymal-sparing liver resections for nonperipheral liver lesions are feasible and can be performed safely without compromising perioperative and oncological outcomes.
The Global Asthma Network (GAN), established in 2012, followed the International Study of Asthma and Allergies in Childhood (ISAAC). ISAAC Phase One involved over 700 000 adolescents and children ...from 156 centres in 56 countries; it found marked worldwide variation in symptom prevalence of asthma, rhinitis and eczema that was not explained by the current understanding of these diseases; ISAAC Phase Three involved over 1 187 496 adolescents and children (237 centres in 98 countries). It found that asthma symptom prevalence was increasing in many locations especially in low- and middle-income countries where severity was also high, and identified several environmental factors that required further investigation.GAN Phase I, described in this article, builds on the ISAAC findings by collecting further information on asthma, rhinitis and eczema prevalence, severity, diagnoses, asthma emergency room visits, hospital admissions, management and use of asthma essential medicines. The subjects will be the same age groups as ISAAC, and their parents. In this first global monitoring of asthma in children and adults since 2003, further evidence will be obtained to understand asthma, management practices and risk factors, leading to further recognition that asthma is an important non-communicable disease and to reduce its global burden.
Widespread implementation of laparoscopic hemihepatectomy is currently limited by its technical difficulty, paucity of training opportunities, and perceived long and harmful learning curve. Studies ...confirming the possibility of a short and safe learning curve for laparoscopic hemihepatectomy could potentially benefit the further implementation of the technique.
To evaluate the extent and safety of the learning curve for laparoscopic hemihepatectomy.
A prospectively collected single-center database containing all laparoscopic liver resections performed in our unit at the University Hospital Southampton National Health Service Foundation Trust between August 2003 and March 2015 was retrospectively reviewed; analyses were performed in December 2015. The study included 159 patients in whom a total laparoscopic right or left hemihepatectomy procedure was started (intention-to-treat analysis), including laparoscopic extended hemihepatectomies and hemihepatectomies with additional wedge resections, at a tertiary referral center specialized in laparoscopic hepato-pancreato-biliary surgery.
Primary end points were clinically relevant complications (Clavien-Dindo grade ≥III). The presence of a learning curve effect was assessed with a risk-adjusted cumulative sum analysis.
Of a total of 531 consecutive laparoscopic liver resections, 159 patients underwent total laparoscopic hemihepatectomy (105 right and 54 left). In a cohort with 67 men (42%), median age of 64 years (interquartile range IQR, 51-73 years), and 110 resections (69%) for malignant lesions, the overall median operation time was 330 minutes (IQR, 270-391 minutes) and the median blood loss was 500 mL (IQR, 250-925 mL). Conversion to an open procedure occurred in 17 patients (11%). Clinically relevant complications occurred in 17 patients (11%), with 1% mortality (death within 90 days of surgery, n = 2). Comparison of outcomes over time showed a nonsignificant decrease in conversions (right: 14 13% and left: 3 6%), blood loss (right: 550 mL IQR, 350-1150 mL and left: 300 mL IQR, 200-638 mL), complications (right: 15 14% and left: 4 7%), and hospital stay (right: 5 days IQR, 4-7 days and left: 4 days IQR, 3-5 days). Risk-adjusted cumulative sum analysis demonstrated a learning curve of 55 laparoscopic hemihepatectomies for conversions.
Total laparoscopic hemihepatectomy is a feasible and safe procedure with an acceptable learning curve for conversions. Focus should now shift to providing adequate training opportunities for centers interested in implementing this technique.
•Environmental conditions influence the emergence and spread of SARS-CoV-2.•The contribution of climate and air pollution requires additional studies.•Environmental stressors may contribute to the ...severity of COVID-19.•Behavioural and societal changes may remain long after the pandemic.•COVID-19 will have a long-lasting impact on the environmental health field.
The outbreak of COVID-19 raised numerous questions on the interactions between the occurrence of new infections, the environment, climate and health. The European Union requested the H2020 HERA project which aims at setting priorities in research on environment, climate and health, to identify relevant research needs regarding Covid-19. The emergence and spread of SARS-CoV-2 appears to be related to urbanization, habitat destruction, live animal trade, intensive livestock farming and global travel. The contribution of climate and air pollution requires additional studies. Importantly, the severity of COVID-19 depends on the interactions between the viral infection, ageing and chronic diseases such as metabolic, respiratory and cardiovascular diseases and obesity which are themselves influenced by environmental stressors. The mechanisms of these interactions deserve additional scrutiny. Both the pandemic and the social response to the disease have elicited an array of behavioural and societal changes that may remain long after the pandemic and that may have long term health effects including on mental health. Recovery plans are currently being discussed or implemented and the environmental and health impacts of those plans are not clearly foreseen. Clearly, COVID-19 will have a long-lasting impact on the environmental health field and will open new research perspectives and policy needs.
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