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Objectives to describe the increase in orthogeriatrician involvement in hip fracture care in England and its association with improvements in time to surgery and mortality.\ud \ud Study design analysis of Hospital Episode Statistics for 196,401 patients presenting with hip fracture to 150 hospitals in England between 1 April 2010 and 28 February 2014, combined with data on orthogeriatrician hours from a national organisational survey.\ud \ud Methods we examined changes in the average number of hours worked by orthogeriatricians in orthopaedic departments per patient with hip fracture, and their potential effect on mortality within 30 days of presentation. The role of prompt surgery (on day of or day after presentation) was explored as a potential confounding factor. Associations were assessed using conditional Poisson regression models with adjustment for patients’ sex, age and comorbidity and year, with hospitals treated as fixed effects.\ud \ud Results between 2010 and 2013, there was an increase of 2.5 hours per patient in the median number of hours worked by orthogeriatricians—from 1.5 to 4.0 hours. An increase of 2.5 hours per patient was associated with a relative reduction in mortality of 3.4% (95% confidence interval 0.9% to 5.9%, P = 0.01). This corresponds to an absolute reduction of approximately 0.3%. Higher numbers of orthogeriatrician hours were associated with higher rates of prompt surgery, but were independently associated with lower mortality.\ud \ud Conclusion in the context of initiatives to improve hip fracture care, we identified statistically significant and robust associations between increased orthogeriatrician hours per patient and reduced 30-day mortality.

BACKGROUND: Many long-term studies have reported on associations of plasma fibrinogen concentration with cardiovascular disease, but few have been large enough to provide reliable estimates in different circumstances. Moreover, most published prospective studies have related disease risk only to baseline values of plasma fibrinogen (which can lead to substantial underestimation of any risk relationships) and have corrected only for baseline values of possible confounding factors (which can lead to residual biases). OBJECTIVES: By appropriate combination of data from individual participants from all relevant prospective studies in a systematic 'meta-analysis', with correction for regression dilution, the Fibrinogen Studies Collaboration will aim to characterize more precisely than has previously been possible the strength and shape of the age- and sex-specific associations of plasma fibrinogen with coronary heart disease (and, where data are sufficient, with other vascular diseases). It will also help to determine to what extent such associations are independent of possible confounding factors. METHODS: A central database has been established containing data on plasma fibrinogen, sex and other potential confounding factors, age at baseline fibrinogen measurement, age at event or at last follow-up, major vascular morbidity and cause-specific mortality. Information about any repeat measurements of fibrinogen and potential confounding factors is being sought to allow study-specific correction for regression dilution. The analyses will involve age-specific regression models. Synthesis of the available prospective studies of plasma fibrinogen will yield information on more than 10000 incident cardiovascular deaths and events among the approximately 200000 total participants who have been monitored, on average, for about 10 years.

This paper investigates the association between perinatal health and all-cause mortality for specific age intervals, assessing the contribution of maternal socioeconomic characteristics and the presence of maternal-level confounding. Our study is based on a cohort of 12,564 singletons born between 1915 and 1929 at the Uppsala University Hospital. We fitted Cox regression models to estimate age-varying hazard ratios of all-cause mortality for absolute and relative birth weight and for gestational age. We found that associations with mortality vary by age and according to the measure under scrutiny, with effects being concentrated in infancy, childhood or early adult life. For example, the effect of low birth weight was greatest in the first year of life and then continued up to 44 years of age (HR between 2.82 and 1.51). These associations were confirmed in within-family analyses, which provided no evidence of residual confounding by maternal characteristics. Our findings support the interpretation that policies oriented towards improving population health should invest in birth outcomes and hence in maternal health.

Background: Clinical anecdote suggests that rates of eating disorders (ED) vary between schools. Given their high prevalence and mortality, understanding risk factors is important. We hypothesised that rates of ED would vary between schools, and that school proportion of female students and proportion of parents with post-high school education would be associated with ED, after accounting for individual characteristics. Method: Multilevel analysis of register-based, record-linkage data on 55 059 females born in Stockholm County, Sweden, from 1983, finishing high school in 2002-10. Outcome was clinical diagnosis of an ED, or attendance at a specialist ED clinic, aged 16-20 years. Results: The 5-year cumulative incidence of ED diagnosis aged 16-20 years was 2.4%. Accounting for individual risk factors, with each 10% increase in the proportion of girls at a school, the odds ratio for ED was 1.07 (1.01 to 1.13), P = 0.018. With each 10% increase in the proportion of children with at least one parent with post-high school education, the odds ratio for ED was 1.14 (1.09 to 1.19), P < 0.0001. Predicted probability of an average girl developing an ED was 1.3% at a school with 25% girls where 25% of parents have post-high school education, and 3.3% at a school with 75% girls where 75% of parents have post-high school education. Conclusions: Rates of ED vary between schools; this is not explained by individual characteristics. Girls at schools with high proportions of female students, and students with highly educated parents, have higher odds of ED regardless of individual risk factors.

STUDY QUESTION: Can routine antenatal blood pressure measurements between 20 and 36 weeks' gestation contribute to the prediction of pre-eclampsia and its associated adverse outcomes?METHODS: This study used repeated antenatal measurements of blood pressure from 12 996 women in the Avon Longitudinal Study of Parents and Children (ALSPAC) to develop prediction models and validated these in 3005 women from the Southampton Women's Survey (SWS). A model based on maternal early pregnancy characteristics only (BMI, height, age, parity, smoking, existing and previous gestational hypertension and diabetes, and ethnicity) plus initial mean arterial pressure was compared with a model additionally including current mean arterial pressure, a model including the deviation of current mean arterial pressure from a stratified normogram, and a model including both at different gestational ages from 20-36 weeks.STUDY ANSWER AND LIMITATIONS: The addition of blood pressure measurements from 28 weeks onwards improved prediction models compared with use of early pregnancy risk factors alone, but they contributed little to the prediction of preterm birth or small for gestational age. Though multiple imputation of missing data was used to increase the sample size and minimise selection bias, the validation sample might have been slightly underpowered as the number of cases of pre-eclampsia was just below the recommended 100. Several risk factors were self reported, potentially introducing measurement error, but this reflects how information would be obtained in clinical practice.WHAT THIS STUDY ADDS: The addition of routinely collected blood pressure measurements from 28 weeks onwards improves predictive models for pre-eclampsia based on blood pressure in early pregnancy and other characteristics, facilitating a reduction in scheduled antenatal care.FUNDING, COMPETING INTERESTS, DATA SHARING: UK Wellcome Trust, US National Institutes of Health, and UK Medical Research Council. Other funding sources for authors are detailed in the full online paper. With the exceptions of CM-W, HMI, and KMG there were no competing interests.

Study question: Can routine antenatal blood pressure measurements between 20 and 36 weeks’ gestation contribute to the prediction of pre-eclampsia and its associated adverse outcomes?\ud \ud Methods: This study used repeated antenatal measurements of blood pressure from 12 996 women in the Avon Longitudinal Study of Parents and Children (ALSPAC) to develop prediction models and validated these in 3005 women from the Southampton Women’s Survey (SWS). A model based on maternal early pregnancy characteristics only (BMI, height, age, parity, smoking, existing and previous gestational hypertension and diabetes, and ethnicity) plus initial mean arterial pressure was compared with a model additionally including current mean arterial pressure, a model including the deviation of current mean arterial pressure from a stratified normogram, and a model including both at different gestational ages from 20-36 weeks.\ud \ud Study answer and limitations: The addition of blood pressure measurements from 28 weeks onwards improved prediction models compared with use of early pregnancy risk factors alone, but they contributed little to the prediction of preterm birth or small for gestational age. Though multiple imputation of missing data was used to increase the sample size and minimise selection bias, the validation sample might have been slightly underpowered as the number of cases of pre-eclampsia was just below the recommended 100. Several risk factors were self reported, potentially introducing measurement error, but this reflects how information would be obtained in clinical practice.\ud \ud What this study adds: The addition of routinely collected blood pressure measurements from 28 weeks onwards improves predictive models for pre-eclampsia based on blood pressure in early pregnancy and other characteristics, facilitating a reduction in scheduled antenatal care.

The validity and practical utility of observational medical research depends critically on good study design, excellent data quality, appropriate statistical methods and accurate interpretation of results. Statistical methodology has seen substantial development in recent times. Unfortunately, many of these methodological developments are ignored in practice. Consequently, design and analysis of observational studies often exhibit serious weaknesses. The lack of guidance on vital practical issues discourages many applied researchers from using more sophisticated and possibly more appropriate methods when analyzing observational studies. Furthermore, many analyses are conducted by researchers with a relatively weak statistical background and limited experience in using statistical methodology and software. Consequently, even 'standard' analyses reported in the medical literature are often flawed, casting doubt on their results and conclusions. An efficient way to help researchers to keep up with recent methodological developments is to develop guidance documents that are spread to the research community at large. These observations led to the initiation of the strengthening analytical thinking for observational studies (STRATOS) initiative, a large collaboration of experts in many different areas of biostatistical research. The objective of STRATOS is to provide accessible and accurate guidance in the design and analysis of observational studies. The guidance is intended for applied statisticians and other data analysts with varying levels of statistical education, experience and interests. In this article, we introduce the STRATOS initiative and its main aims, present the need for guidance documents and outline the planned approach and progress so far. We encourage other biostatisticians to become involved.

CONTEXT: Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data. DATA SOURCES: Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators. STUDY SELECTION: All identified prospective studies were included with information available on baseline fibrinogen levels and details of subsequent major vascular morbidity and/or cause-specific mortality during at least 1 year of follow-up. Studies were excluded if they recruited participants on the basis of having had a previous history of cardiovascular disease; participants with known preexisting CHD or stroke were excluded. DATA EXTRACTION: Individual records were provided on each of 154,211 participants in 31 prospective studies. During 1.38 million person-years of follow-up, there were 6944 first nonfatal myocardial infarctions or stroke events and 13,210 deaths. Cause-specific mortality was generally available. Analyses involved proportional hazards modeling with adjustment for confounding by known cardiovascular risk factors and for regression dilution bias. DATA SYNTHESIS: Within each age group considered (40-59, 60-69, and > or =70 years), there was an approximately log-linear association with usual fibrinogen level for the risk of any CHD, any stroke, other vascular (eg, non-CHD, nonstroke) mortality, and nonvascular mortality. There was no evidence of a threshold within the range of usual fibrinogen level studied at any age. The age- and sex- adjusted hazard ratio per 1-g/L increase in usual fibrinogen level for CHD was 2.42 (95% confidence interval [CI], 2.24-2.60); stroke, 2.06 (95% CI, 1.83-2.33); other vascular mortality, 2.76 (95% CI, 2.28-3.35); and nonvascular mortality, 2.03 (95% CI, 1.90-2.18). The hazard ratios for CHD and stroke were reduced to about 1.8 after further adjustment for measured values of several established vascular risk factors. In a subset of 7011 participants with available C-reactive protein values, the findings for CHD were essentially unchanged following additional adjustment for C-reactive protein. The associations of fibrinogen level with CHD or stroke did not differ substantially according to sex, smoking, blood pressure, blood lipid levels, or several features of study design. CONCLUSIONS: In this large individual participant meta-analysis, moderately strong associations were found between usual plasma fibrinogen level and the risks of CHD, stroke, other vascular mortality, and nonvascular mortality in a wide range of circumstances in healthy middle-aged adults. Assessment of any causal relevance of elevated fibrinogen levels to disease requires additional research.

Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration has established a central database on over 1.1 million participants from 104 prospective population-based studies, in which subsets have information on lipid and inflammatory markers, other characteristics, as well as major cardiovascular morbidity and cause-specific mortality. Information on repeat measurements on relevant characteristics has been collected in approximately 340,000 participants to enable estimation of and correction for within-person variability. Re-analysis of individual data will yield up to approximately 69,000 incident fatal or nonfatal first ever major cardiovascular outcomes recorded during about 11.7 million person years at risk. The primary analyses will involve age-specific regression models in people without known baseline cardiovascular disease in relation to fatal or nonfatal first ever coronary heart disease outcomes. This initiative will characterize more precisely and in greater detail than has previously been possible the shape and strength of the age-and sex-specific associations of several lipid and inflammatory markers with incident coronary heart disease outcomes (and, secondarily,with other incident cardiovascular outcomes) under a wide range of circumstances. It will, therefore, help to determine to what extent such associations are independent from possible confounding factors and to what extent such markers (separately and in combination) provide incremental predictive value.

Youth unemployment problem is studied with duration models in the framework of the "survival analysis". The time spent searching a job is then modelled with countinuous-time stochastic processes for event history data. At first, a single spell duration model is formulated and estimated for identifying the major variables affecting the probability of getting a job. Then the processes is generalized and a multi-state and multi-episode model is proposed for analysing the dynamics between the states of unemployment, temporary employment and permanent employment. The empirical study is performed on a body of longitudinal data collected in retrospective interviews of a sample of Italian young people and provided by "ISFOL"., Statistica; Vol 45, No 3 (1985)

Background: Estimates of treatment failure, change and interruption are lacking for individuals treated in early HIV infection. Methods: Using CASCADE data, we compared the effect of treatment in early infection (within 12 months of seroconversion) with that seen in chronic infection on risk of virological failure, change and interruption. Failure was defined as two subsequent measures of HIV RNA> 1,000 copies/ml following suppression (< 500 copies/ml), or > 500 copies/ml 6 months following initiation. Treatment change and interruption were defined as modification or interruption lasting > 1 week. In multivariable competing risks proportional subdistribution hazards models, we adjusted for combination antiretroviral therapy (cART) class, sex, risk group, age, CD4(+) T-cell count, HIV RNA and calendar period at treatment initiation. Results: Of 1,627 individuals initiating cART early (median 1.8 months from seroconversion), 159, 395 and 692 failed, changed and interrupted therapy, respectively. For 2,710 individuals initiating cART in chronic infection (median 35.9 months from seroconversion), the corresponding values were 266, 569 and 597. Adjusted hazard ratios (HRs; 95% CIs) for treatment failure and change were similar between the two treatment groups (0.93 [0.72, 1.20] and 1.06 [0.91, 1.24], respectively). There was an increasing trend in rates of interruption over calendar time for those treated early, and a decreasing trend for those starting treatment in chronic infection. Consequently, compared with chronic infection, treatment interruption was similar for early starters in the early cART period, but the relative hazard increased over calendar time (1.54 [1.33, 1.79] in 2000). Conclusions: Individuals initiating treatment in early HIV infection are more likely to interrupt treatment than those initiating later. However, rates of failure and treatment change were similar between the two groups.

One difficulty in performing meta-analyses of observational cohort studies is that the availability of confounders may vary between cohorts, so that some cohorts provide fully adjusted analyses while others only provide partially adjusted analyses. Commonly, analyses of the association between an exposure and disease either are restricted to cohorts with full confounder information, or use all cohorts but do not fully adjust for confounding. We propose using a bivariate random-effects meta-analysis model to use information from all available cohorts while still adjusting for all the potential confounders. Our method uses both the fully adjusted and the partially adjusted estimated effects in the cohorts with full confounder information, together with an estimate of their within-cohort correlation. The method is applied to estimate the association between fibrinogen level and coronary heart disease incidence using data from 154,012 participants in 31 cohorts

One difficulty in performing meta-analyses of observational cohort studies is that the availability of confounders may vary between cohorts, so that some cohorts provide fully adjusted analyses while others only provide partially adjusted analyses. Commonly, analyses of the association between an exposure and disease either are restricted to cohorts with full confounder information, or use all cohorts but do not fully adjust for confounding. We propose using a bivariate random-effects meta-analysis model to use information from all available cohorts while still adjusting for all the potential confounders. Our method uses both the fully adjusted and the partially adjusted estimated effects in the cohorts with full confounder information, together with an estimate of their within-cohort correlation. The method is applied to estimate the association between fibrinogen level and coronary heart disease incidence using data from 154 012 participants in 31 cohorts.† Copyright © 2009 John Wiley & Sons, Ltd.

BACKGROUND: Birth size, perhaps a proxy for prenatal environment, might be a correlate of subsequent breast cancer risk, but findings from epidemiological studies have been inconsistent. We re-analysed individual participant data from published and unpublished studies to obtain more precise estimates of the magnitude and shape of the birth size-breast cancer association. METHODS AND FINDINGS: Studies were identified through computer-assisted and manual searches, and personal communication with investigators. Individual participant data from 32 studies, comprising 22,058 breast cancer cases, were obtained. Random effect models were used, if appropriate, to combine study-specific estimates of effect. Birth weight was positively associated with breast cancer risk in studies based on birth records (pooled relative risk [RR] per one standard deviation [SD] [= 0.5 kg] increment in birth weight: 1.06; 95% confidence interval [CI] 1.02-1.09) and parental recall when the participants were children (1.02; 95% CI 0.99-1.05), but not in those based on adult self-reports, or maternal recall during the woman's adulthood (0.98; 95% CI 0.95-1.01) (p for heterogeneity between data sources = 0.003). Relative to women who weighed 3.000-3.499 kg, the risk was 0.96 (CI 0.80-1.16) in those who weighed < 2.500 kg, and 1.12 (95% CI 1.00-1.25) in those who weighed > or = 4.000 kg (p for linear trend = 0.001) in birth record data. Birth length and head circumference from birth records were also positively associated with breast cancer risk (pooled RR per one SD increment: 1.06 [95% CI 1.03-1.10] and 1.09 [95% CI 1.03-1.15], respectively). Simultaneous adjustment for these three birth size variables showed that length was the strongest independent predictor of risk. The birth size effects did not appear to be confounded or mediated by established breast cancer risk factors and were not modified by age or menopausal status. The cumulative incidence of breast cancer per 100 women by age 80 y in the study populations was estimated to be 10.0, 10.0, 10.4, and 11.5 in those who were, respectively, in the bottom, second, third, and top fourths of the birth length distribution. CONCLUSIONS: This pooled analysis of individual participant data is consistent with birth size, and in particular birth length, being an independent correlate of breast cancer risk in adulthood

Reproductive factors affect breast cancer risk, but less is known of their associations with mammographic density and whether these differ by menopausal status. We report on a cross-sectional study of 1946 pre- and 3047 post-menopausal women who joined a breast screening programme in Northern Greece during 1993-1997. The odds of having a high-density Wolfe pattern (P2/DY) was inversely associated with age (P for linear trend < 0.001) in both pre- and post-menopausal women and, for post-menopausal women, with years since menopause (P < 0.001). The odds of a P2/DY pattern declined with higher parity (P < 0.001) and younger age at first pregnancy (P = 0.05) in both pre- and post-menopausal women. They also decreased with the duration of breast-feeding in pre-menopausal women (P = 0.03 in pre- and P = 0.69 in post-menopausal women; test for interaction with menopausal status: P = 0.07). Age at menarche, age at menopause and the number of miscarriages/abortions were not associated with mammographic density. Age at first pregnancy and parity were strong correlates of mammographic density in pre- and post-menopausal women while duration of breast-feeding appeared to be particularly important in pre-menopausal women. (c) 2005 Elsevier Ltd. All rights reserved.

CONTEXT: Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data. DATA SOURCES: Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators. STUDY SELECTION: All identified prospective studies were included with information available on baseline fibrinogen levels and details of subsequent major vascular morbidity and/or cause-specific mortality during at least 1 year of follow-up. Studies were excluded if they recruited participants on the basis of having had a previous history of cardiovascular disease; participants with known preexisting CHD or stroke were excluded. DATA EXTRACTION: Individual records were provided on each of 154,211 participants in 31 prospective studies. During 1.38 million person-years of follow-up, there were 6944 first nonfatal myocardial infarctions or stroke events and 13,210 deaths. Cause-specific mortality was generally available. Analyses involved proportional hazards modeling with adjustment for confounding by known cardiovascular risk factors and for regression dilution bias. DATA SYNTHESIS: Within each age group considered (40-59, 60-69, and > or =70 years), there was an approximately log-linear association with usual fibrinogen level for the risk of any CHD, any stroke, other vascular (eg, non-CHD, nonstroke) mortality, and nonvascular mortality. There was no evidence of a threshold within the range of usual fibrinogen level studied at any age. The age- and sex- adjusted hazard ratio per 1-g/L increase in usual fibrinogen level for CHD was 2.42 (95% confidence interval [CI], 2.24-2.60); stroke, 2.06 (95% CI, 1.83-2.33); other vascular mortality, 2.76 (95% CI, 2.28-3.35); and nonvascular mortality, 2.03 (95% CI, 1.90-2.18). The hazard ratios for CHD and stroke were reduced to about 1.8 after further adjustment for measured values of several established vascular risk factors. In a subset of 7011 participants with available C-reactive protein values, the findings for CHD were essentially unchanged following additional adjustment for C-reactive protein. The associations of fibrinogen level with CHD or stroke did not differ substantially according to sex, smoking, blood pressure, blood lipid levels, or several features of study design. CONCLUSIONS: In this large individual participant meta-analysis, moderately strong associations were found between usual plasma fibrinogen level and the risks of CHD, stroke, other vascular mortality, and nonvascular mortality in a wide range of circumstances in healthy middle-aged adults. Assessment of any causal relevance of elevated fibrinogen levels to disease requires additional research.

The 5-year relative survival rates of women diagnosed with breast cancer between 1992 and 1994 were compared among the 99 Health Authorities (1999 boundaries) of England. Substantial variation, with evidence of geographical clustering was observed. Part of this variation was explained by differences in deprivation between Health Authorities, in particular by the percentage of class IV and V households. British Journal of Cancer (2004) 90, 2153-2156. doi:10.1038/sj.bjc.6601812 www.bjcancer.com Published online 27 April 2004