An Epidemiological Study of Lung Cancer and Selected Other Cancers among Namibian Uranium Workers.

The Rössing Uranium Limited (RUL) open-cast uranium mine in Namibia has operated since 1976. Studies of underground uranium miners from Europe and North America have shown increased cancer risks (principally lung cancer). We explored the association between radiation doses and selected cancers in RUL mineworkers. Employees with at least one-year of continuous employment between 1976 and 2010 were included. Incident cancer cases [lung, extra-thoracic airways (ETA), leukemia, brain and kidney] occurring before the end of 2015 were identified from the Namibian and South African National Cancer Registries, and RUL's occupational health provider. Using a case-cohort design, data on exposure and confounding factors were collected for all cancer cases among the study cohort and a stratified random sample (sub-cohort) of the cohort, including cases. Radiation doses were estimated based on annual dose records held by RUL. In total, 76 cancer cases (32 lung, 18 ETA, 8 leukemia, 9 brain, 9 kidney) and a sub-cohort of 1,121 sampled from 7,901 RUL employees were included. A weighted Cox model, adjusted for available known confounders, produced a rate ratio (95% CI) for lung cancer of 1.42 (0.42, 4.77) and 1.22 (0.26, 5.68), respectively, for medium and higher cumulative lung dose categories compared to the lower category, and 1.04 (0.95, 1.13) for a dose increase of 10 mSv. This study faced considerable challenges with respect to case ascertainment, exposure estimates, and ensuring accuracy of key variables. Persuasive consistent evidence for elevated cancer risk was not found for radiation or other exposures studied at the Rössing uranium mine.

Phytoestrogen intake and other dietary risk factors for low motile sperm count and poor sperm morphology.

BACKGROUND: Few potentially modifiable risk factors of male infertility have been identified, and while different diets and food groups have been associated with male infertility, evidence linking dietary factors including phytoestrogens and semen quality is limited and contradictory. OBJECTIVES: To study the associations between phytoestrogen intake and other dietary factors and semen quality. MATERIALS AND METHODS: A case-referent study was undertaken of the male partners, of couples attempting conception with unprotected intercourse for 12 months or more without success, recruited from 14 UK assisted reproduction clinics. A total of 1907 participants completed occupational, lifestyle and dietary questionnaires before semen quality (concentration, motility and morphology) were assessed. Food intake was estimated by a 65-item food frequency questionnaire (FFQ) covering the 12 months prior to recruitment. Analyses of dietary risk factors for low motile sperm concentration (MSC: <4.8 × 106 /mL) and poor sperm morphology (PM: <4% normal morphology) used unconditional logistic regression, accounting for clustering of subjects within the clinics, first without, and then with, adjustment for confounders associated with that outcome. RESULTS: High consumption of daidzein (≥13.74 µg/d), a phytoestrogen found in soy products, was a protective factor for MSC with an odds ratio (95%CI) of 0.58 (0.42-0.82) after adjustment for clustering and potential confounding. Dietary risk factors for PM after similar adjustment showed that drinking whole milk (OR 0.67, 95%CI 0.47-0.96) and eating red meat were protective with an OR 0.67 (0.46-0.99) for eating red meat >3 times/wk. DISCUSSION: In this case-referent study of men attending an infertility clinic for fertility diagnosis, we have identified that low MSC is inversely associated with daidzein intake. In contrast, daidzein intake was not associated with PM but eating red milk and drinking whole milk were protective. CONCLUSIONS: Dietary factors associated with semen quality were identified, suggesting that male fertility might be improved by dietary changes.

Scores Obtained from a Simple Cognitive Test of Visuospatial Episodic Memory Performed Decades before Death Are Associated with the Ultimate Presence of Alzheimer Disease Pathology.

BACKGROUND: Community- or population-based longitudinal studies of cognitive ability with a brain donation end point offer an opportunity to examine relationships between pathology and cognitive state prior to death. Discriminating the earliest signs of dementing disorders, such as Alzheimer disease (AD), is necessary to undertake early interventions and treatments. METHODS: The neuropathological profile of brains donated from The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age, including CERAD (Consortium to Establish a Registry for Alzheimer's Disease) and Braak stage, was assessed by immunohistochemistry. Cognitive test scores collected 20 years prior to death were correlated with the extent of AD pathology present at death. RESULTS: Baseline scores from the Memory Circle test had the ability to distinguish between individuals who developed substantial AD pathology and those with no, or low, AD pathology. Predicted test scores at the age of 65 years also discriminated between these pathology groups. The addition of APOE genotype further improved the discriminatory ability of the model. CONCLUSIONS: The results raise the possibility of identifying individuals at future risk of the neuropathological changes associated with AD over 20 years before death using a simple cognitive test. This work may facilitate early interventions, therapeutics and treatments for AD by identifying at-risk and minimally affected (in pathological terms) individuals.

The Health and Occupation Research Network: An Evolving Surveillance System.

Vital to the prevention of work-related ill-health (WRIH) is the availability of good quality data regarding WRIH burden and risks. Physician-based surveillance systems such as The Health and Occupation Research (THOR) network in the UK are often established in response to limitations of statutory, compensation-based systems for addressing certain epidemiological aspects of disease surveillance. However, to fulfil their purpose, THOR and others need to have methodologic rigor in capturing and ascertaining cases. This article describes how data collected by THOR and analogous systems can inform WRIH incidence, trends, and other determinants. An overview of the different strands of THOR research is provided, including methodologic advancements facilitated by increased data quantity/quality over time and the value of the research outputs for informing Government and other policy makers. In doing so, the utility of data collected by systems such as THOR to address a wide range of research questions, both in relation to WRIH and to wider issues of public and social health, is demonstrated.

How serious is bias in effect estimation in randomised trials with survival data given risk heterogeneity and informative censoring?

It is often assumed that randomisation will prevent bias in estimation of treatment effects from clinical trials, but this is not true of the semiparametric Proportional Hazards model for survival data when there is underlying risk heterogeneity. Here, a new formula is proposed for estimation of this bias, improving on a previous formula through ease of use and clarity regarding the role of the mid-study cumulative hazard rate, shown to be an important factor for the bias magnitude. Informative censoring (IC) is recognised as a source of bias. Here, work on selection effects among survivors due to risk heterogeneity is extended to include IC. A new formula shows that bias in causal effect estimation under IC has two sources: one consequent on heterogeneity and one from the additional impact of IC. The formula provides new insights not previously shown: there may less bias under IC than when there is no IC and even, in principle, zero bias. When tested against simulated data, the new formulae are shown to be very accurate for prediction of bias in Proportional Hazards and accelerated failure time analyses which ignore heterogeneity. These data are also used to investigate the performance of accelerated failure time models which explicitly model risk heterogeneity ('frailty models') and G estimation. These methods remove bias when there is simple censoring but not with informative censoring when they may lead to overestimation of treatment effects. The new formulae may be used to help researchers judge the possible extent of bias in past studies. Copyright © 2017 John Wiley & Sons, Ltd.

Accounting for reporting fatigue is required to accurately estimate incidence in voluntary reporting health schemes.

OBJECTIVE: Accurate estimation of the true incidence of ill-health is a goal of many surveillance systems. In surveillance schemes including zero reporting to remove ambiguity with nonresponse, reporter fatigue might increase the likelihood of a false zero case report in turn underestimating the true incidence rate and creating a biased downward trend over time. STUDY DESIGN AND SETTING: Multilevel zero-inflated negative binomial models were fitted to incidence case reports of three surveillance schemes running between 1996 and 2012 in the United Kingdom. Estimates of the true annual incidence rates were produced by weighting the reported number of cases by the predicted excess zero rate in addition to the within-scheme standard adjustment for response rate and the participation rate. RESULTS: Time since joining the scheme was associated with the odds of excess zero case reports for most schemes, resulting in weaker calendar trends. Estimated incidence rates (95% confidence interval) per 100,000 person years, were approximately doubled to 30 (21-39), 137 (116-157), 33 (27-39), when excess zero-rate adjustment was applied. CONCLUSION: If we accept that excess zeros are in reality nonresponse by busy reporters, then usual estimates of incidence are likely to be significantly underestimated and previously thought strong downward trends overestimated.

Changes in selected metabolic parameters in patients over 65 receiving hydrochlorothiazide plus amiloride, atenolol or placebo in the MRC elderly trial.

BACKGROUND: Treatment of hypertension reduces incidence of stroke, myocardial infarction and heart failure perhaps partly by controlling different metabolic parameters. There is limited information regarding the changes in potassium, sodium, weight, cholesterol and glucose levels in patients using anti-hypertensives. This study aimed to determine changes in potassium, sodium, glucose, cholesterol, weight, urea and urate levels in patients using anti-hypertensives. Furthermore, to describe these changes and differences between the atenolol, hydrochlorothiazide plus amiloride and placebo arms of the Medical Research Council (MRC) elderly randomised controlled trial. METHODS: Patients were randomly allocated to one of the three treatment arms. Measurements were taken at baseline, end of year one and end of year two in 4396 subjects. Linear Mixed Models (LMM) were used to determine the longitudinal profiles of sodium, potassium, weight, cholesterol, glucose, urea and urate. Estimates of changes within groups and difference between groups were obtained. RESULTS: Patients randomised to receive hydrochlorothiazide + amiloride experienced a significantly greater mean reduction in potassium, sodium and weight compared to placebo at end of year one - mean differences in change -0.18 mmol/L, (95 % CI: -0.21, -0.15); -1.45 mmol/L, (95 % CI: -1.62, -1.29) and -0.46 kgs (95 % CI: -0.73, -0.20) respectively, and greater increases in cholesterol, urea and urate - mean differences in change 0.16 mmol/L, (95 % CI: 0.10,0.22); 0.77 mmol/L, (95 % CI: 0.68, 0.87) and 53.10 µmol/L, (95 % CI: 49.35, 56.85) respectively. Changes were in the same direction but smaller in the atenololarm except for potassium and weight (increases). No group differences in glucose were found. CONCLUSION: Results were in line with expectation except for lack of change in glucose in the hydrochlorothiazide + amiloride arms.

Gestational Age and Birth Weight and the Risk of Childhood Type 1 Diabetes: A Population-Based Cohort and Sibling Design Study.

OBJECTIVE: We investigated the effects of gestational age, birth weight, small for gestational age (SGA), and large for gestational age (LGA) on risk of childhood type 1 diabetes. RESEARCH DESIGN AND METHODS: We conducted a population-based cohort study of all singleton live births in Sweden between 1973 and 2009 and a sibling control study. Perinatal data were extracted from the Swedish Medical Birth Register. Children with type 1 diabetes diagnosis were identified from the Swedish National Patient Register. Log-linear Poisson regression and conditional logistic regression were used for data analysis. RESULTS: The study cohort consisted of 3,624,675 singleton live births (42,411,054 person-years). There were 13,944 type 1 diabetes cases during the study period. The sibling control study consisted of 11,403 children with type 1 diabetes and 17,920 siblings. Gestational age between 33 and 36 weeks (relative risk [RR] 1.18 [95% CI 1.09, 1.28) and 37 and 38 weeks (RR 1.12 [95% CI 1.07, 1.17]) was associated with type 1 diabetes in the cohort study and remained significant in the sibling control study. SGA (RR 0.83 [95% CI 0.75, 0.93]) and LGA (RR 1.14 [95% CI 1.04, 1.24]) were associated with type 1 diabetes in the cohort study. The SGA association remained unchanged in the sibling study, while the LGA association disappeared. Very low birth weight was associated with a reduced risk of type 1 diabetes. CONCLUSIONS: The findings suggest a small association between gestational age and type 1 diabetes that is not likely due to familial confounding factors. Gestational age and type 1 diabetes may be related to insulin resistance due to early life growth restriction or altered gut microbiota in preterm babies.

Trends in incidence of occupational asthma, contact dermatitis, noise-induced hearing loss, carpal tunnel syndrome and upper limb musculoskeletal disorders in European countries from 2000 to 2012.

OBJECTIVES: The European Union (EU) strategy for health and safety at work underlines the need to reduce the incidence of occupational diseases (OD), but European statistics to evaluate this common goal are scarce. We aim to estimate and compare changes in incidence over time for occupational asthma, contact dermatitis, noise-induced hearing loss (NIHL), carpal tunnel syndrome (CTS) and upper limb musculoskeletal disorders across 10 European countries. METHODS: OD surveillance systems that potentially reflected nationally representative trends in incidence within Belgium, the Czech Republic, Finland, France, Italy, the Netherlands, Norway, Spain, Switzerland and the UK provided data. Case counts were analysed using a negative binomial regression model with year as the main covariate. Many systems collected data from networks of 'centres', requiring the use of a multilevel negative binomial model. Some models made allowance for changes in compensation or reporting rules. RESULTS: Reports of contact dermatitis and asthma, conditions with shorter time between exposure to causal substances and OD, were consistently declining with only a few exceptions. For OD with physical causal exposures there was more variation between countries. Reported NIHL was increasing in Belgium, Spain, Switzerland and the Netherlands and decreasing elsewhere. Trends in CTS and upper limb musculoskeletal disorders varied widely within and between countries. CONCLUSIONS: This is the first direct comparison of trends in OD within Europe and is consistent with a positive impact of European initiatives addressing exposures relevant to asthma and contact dermatitis. Taking a more flexible approach allowed comparisons of surveillance data between and within countries without harmonisation of data collection methods.

Pesticide exposure and screen-positive neuropsychiatric disease in British sheep farmers.

BACKGROUND: Epidemiological evidence linking low dose pesticide exposure and chronic ill-health in UK sheep farmers is limited. Our aim was to examine whether neuropsychiatric disorders were associated with low dose chronic and/or more acute pesticide exposure in sheep farmers. METHODS: A cohort of British farmers working in the 1970s was sent a screening questionnaire which asked about their health and work history. The prevalence of screen-positive depression, dementia, Parkinsonism and neuropathy was determined using a priori algorithms. Self-reported pesticide exposure was assessed by whether the participant had ever handled the pesticide concentrate (for low dose chronic exposure) or sought advice for pesticide poisoning (acute exposure) and participants categorised into those with only acute or chronic exposure, those with both acute and chronic exposure and those with neither acute nor chronic exposure. Associations between acute and chronic pesticide exposure, and screen-positive ill-health were determined after adjustment for demographic, lifestyle, occupation and somatic severity scores and other variables. RESULTS: In those participants, who had never sought advice for pesticide poisoning, handling the pesticide concentrate for treating sheep was associated with elevated ORs for screen-positive neuropathy (ORadi 1.57 95%CI 0.97-2.54) and Parkinsonism (ORadj 1.56 95%CI 0.95-2.56) but not depression or dementia. In those participants who had handled the pesticide concentrate, seeking advice for pesticide poisoning was associated with screen-positive depression (Odds ratio, ORadj=9.97 95%CI 4.76-20.8 ), dementia (OR=6.94 95%CI 3.44-14.0), Parkinsonism (ORadj=4.77 95% 2.39-9.52), and neuropathy (ORadj=4.77 95%CI 2.39-9.52). Adjustment for somatic severity score modified little the associations with pesticide handling in those not acutely exposed but reduced the ORs for seeking advice for pesticide poisoning in those exposed chronically. Furthermore, stratification of results based upon somatic severity score indicated that the highest ORs for handling the pesticide concentrate associated with neuropathy and Parkinsonism were found in those participants whose somatic score was minimal. CONCLUSIONS: Results are consistent with low-dose exposure to pesticides being associated with screen-positive neuropathy and Parkinsonism but the stronger associations between seeking advice for pesticide poisoning and screen-positive ill-health suggest that acute pesticide exposure remains an important determinant of ill-health. Further work is required to better delineate to what extent low dose exposures may contribute to ill-health in populations without acute exposures. Somatising tendency does not appear to play an important role in this population.

Occupation exposures and sperm morphology: a case-referent analysis of a multi-centre study.

OBJECTIVE: We examined occupational exposures and sperm morphology to establish whether exposures implicated differed from those affecting motile sperm concentration. METHODS: Computer aided sperm morphometric assessment was undertaken on morphology slides obtained as part of a multi-centre study in 1999-2002 of occupational factors in male infertility. Men attending 14 fertility clinics across the UK were recruited and gave a semen sample. Before results of the semen analysis were known, the men completed detailed questionnaires about their employment and lifestyle. Occupational exposures were assessed by occupational hygienists. Data were analysed using an unmatched case-referent design, allowing for clustering and for confounders. Three case definitions were used: poor morphology (normal morphology <4%), low motile sperm count (MSC) (<4.8×10(6)) and either condition. RESULTS: Morphology results were available for 1861/2011 men employed at the time of recruitment. Of these 1861, 296 (15.9%) had poor morphology; of the 2011with sperm count, 453 (22.5%) had low MSC; 654/1981 (33.0%) had either condition. Poor morphology, adjusted for confounding, was related to self-reported lifetime exposure to lead (OR=1.33; 95% CI 1.00 to 1.75). Low MSC was also related to self-reported lead and to hygienist-assessed glycol ether exposure. Self-reported use of paint stripper (OR=1.47; 95% CI 1.07 to 2.03) and lead, but not glycol ether, were significantly related to the combined case definition. CONCLUSIONS: While this study did not identify any occupational exposure uniquely related to sperm morphology, the capacity of the study to detect risk was increased by including morphology with sperm concentration and motility.

Air pollution exposure and adverse pregnancy outcomes in a large UK birth cohort: use of a novel spatio-temporal modelling technique.

OBJECTIVES: Previous work suggests an association between air pollution exposure and adverse pregnancy outcomes, even at relatively low concentrations. Our aim was to quantify the effect of air pollution having an adverse effect on preterm birth (PTB) and fetal growth in a large UK cohort using a novel exposure estimation technique [spatio-temporal (S-T) model] alongside a traditional nearest stationary monitor technique (NSTAT). METHODS: All available postcodes from a Northwest England birth outcome dataset during 2004-2008 were geocoded (N=203 562 deliveries). Pollution estimates were linked to corresponding pregnancy periods using temporally adjusted background modelled concentrations as well as NSTAT. Associations with PTB, small for gestational age (SGA), and birth weight were investigated using regression models adjusting for maternal age, ethnicity, parity, birth season, socioeconomic status (SES), body mass index (BMI), and smoking. RESULTS: Based on the novel S-T model, a small statistically significant association was observed for particulate matter (PM10) and SGA, particularly with exposure in the first and third trimesters. Similar effects on SGA were also found for nitrogen dioxide (NO 2), particulate matter (PM 2,5), and carbon monoxide (CO) in later pregnancy, but no overall increased risk was observed. No associations were found with NO xor the outcomes PTB and reduction in birth weight. CONCLUSION: Our findings suggest an association between air pollution exposure and birth of a SGA infant, particularly in the later stages of pregnancy but not with PTB or mean birth weight change.

Has the short-term effect of black smoke exposure on pneumonia mortality been underestimated because hospitalisation is ignored: findings from a case-crossover study.

BACKGROUND: Short-term associations have been demonstrated between air pollution and respiratory mortality including pneumonia. Studies typically estimate exposure based only on place of residence, yet many are in hospital prior to death. This study investigates lag length and tests the hypothesis that the effect of 'black smoke' is greater when restricted to pneumonia deaths in the community - Community Deaths from Pneumonia. METHODS: A time-stratified case-crossover design using conditional logistic regression estimated the daily percentage increase in risk of pneumonia mortality in relation to 'black smoke' in the preceding 30 days. Cases were pneumonia deaths in Edinburgh 1981-1996. Multiple 'control' periods, were defined using the same weekdays for the same month as the case death. Lag structure was investigated by a stratified lag model with five 6-day periods and by distributed lag models. Hospital admissions data, defined a community death as someone who had not been in hospital in any of the 30 days before death. RESULTS: Of 14,346 subjects who died from pneumonia, 7,536 were community deaths. Larger estimated increases in risks were seen in the community for all lag periods. Both stratified and distributed lag methods suggested positive effect estimates for 18 days after exposure and negative thereafter; the average percent increase per day across the 18 days was 0.70% (95% C.I. 0.29-1.14) for community subjects and 0.30% (95% C.I. 0.03-0.59) for all subjects. CONCLUSIONS: Studies which fail to account for hospitalisation may underestimate exposure effects as stronger pollution effects on mortality were evident in community based subjects.

Maternal residential proximity to major roads in north west England and adverse pregnancy outcomes.

OBJECTIVE: To investigate the effects of maternal residential proximity to major roads on adverse pregnancy outcomes. METHODS: Major road networks in North West England were linked to the maternal residence of 190,909 births (2004 to 2008). Distance between the residence and the nearest major road was calculated and dichotomized at 200 m. Logistic regression analyses were performed to investigate the association between distance to the major road with small for gestational age, low birth weight, and preterm birth. Analyses were adjusted for maternal age, ethnicity, socioeconomic status, parity, birth season, smoking, and body mass index. RESULTS: No significant associations were observed between preterm birth (odds ratio [OR] = 1.04; 95% confidence interval [CI] = 0.98 to 1.11), low birth weight (OR = 0.99; 95% CI = 0.93 to 1.05) and small for gestational age (OR = 1.00; 95% CI = 0.95 to 1.06) and living less than 200 m from a major road. CONCLUSIONS: These results, from a study with high statistical power, suggest that living less than 200 m from a major road per se does not pose any great risk of an adverse perinatal outcome. Nevertheless, it may be limited to this geographic location. Further work is needed to quantify individual pollutant effects in pregnancy.

A comparison of population air pollution exposure estimation techniques with personal exposure estimates in a pregnant cohort.

There is increasing evidence of the harmful effects for mother and fetus of maternal exposure to air pollutants. Most studies use large retrospective birth outcome datasets and make a best estimate of personal exposure (PE) during pregnancy periods. We compared estimates of personal NOx and NO2 exposure of pregnant women in the North West of England with exposure estimates derived using different modelling techniques. A cohort of 85 pregnant women was recruited from Manchester and Blackpool. Participants completed a time-activity log and questionnaire at 13-22 weeks gestation and were provided with personal Ogawa samplers to measure their NOx/NO2 exposure. PE was compared to monthly averages, the nearest stationary monitor to the participants' home, weighted average of the closest monitor to home and work location, proximity to major roads, as well as to background modelled concentrations (DEFRA), inverse distance weighting (IDW), ordinary kriging (OK), and a land use regression model with and without temporal adjustment. PE was most strongly correlated with monthly adjusted DEFRA (NO2r = 0.61, NOxr = 0.60), OK and IDW (NO2r = 0.60; NOxr = 0.62) concentrations. Correlations were stronger in Blackpool than in Manchester. Where there is evidence for high temporal variability in exposure, methods of exposure estimation which focus solely on spatial methods should be adjusted temporally, with an improvement in estimation expected to be better with increased temporal variability.

Advanced maternal age and adverse pregnancy outcome: evidence from a large contemporary cohort.

BACKGROUND: Recent decades have witnessed an increase in mean maternal age at childbirth in most high-resourced countries. Advanced maternal age has been associated with several adverse maternal and perinatal outcomes. Although there are many studies on this topic, data from large contemporary population-based cohorts that controls for demographic variables known to influence perinatal outcomes is limited. METHODS: We performed a population-based cohort study using data on all singleton births in 2004-2008 from the North Western Perinatal Survey based at The University of Manchester, UK. We compared pregnancy outcomes in women aged 30-34, 35-39 and ≥40 years with women aged 20-29 years using log-linear binomial regression. Models were adjusted for parity, ethnicity, social deprivation score and body mass index. RESULTS: The final study cohort consisted of 215,344 births; 122,307 mothers (54.19%) were aged 20-29 years, 62,371(27.63%) were aged 30-34 years, 33,966(15.05%) were aged 35-39 years and 7,066(3.13%) were aged ≥40 years. Women aged 40+ at delivery were at increased risk of stillbirth (RR = 1.83, [95% CI 1.37-2.43]), pre-term (RR = 1.25, [95% CI: 1.14-1.36]) and very pre-term birth (RR = 1.29, [95% CI:1.08-1.55]), Macrosomia (RR = 1.31, [95% CI: 1.12-1.54]), extremely large for gestational age (RR = 1.40, [95% CI: 1.25-1.58]) and Caesarean delivery (RR = 1.83, [95% CI: 1.77-1.90]). CONCLUSIONS: Advanced maternal age is associated with a range of adverse pregnancy outcomes. These risks are independent of parity and remain after adjusting for the ameliorating effects of higher socioeconomic status. The data from this large contemporary cohort will be of interest to healthcare providers and women and will facilitate evidence based counselling of older expectant mothers.

Time trends in the incidence of work-related mental ill-health and musculoskeletal disorders in the UK.

OBJECTIVES: To determine UK trends (from 1996 to 2009) in incidence of work-related mental ill-health and musculoskeletal disorders, for all industry as well as for health and social care employees. Second, to investigate whether there may have been a recent shift from a physical to psychological perspective in how patients present their illness by comparing reporting trends for back pain and 'other work stress'. METHODS: Multilevel models were used to investigate changes in incidence of work-related illness, as diagnosed by specialist physicians. The dependent variable comprised case reports to The Health and Occupation Research network. Comparisons were made between medical specialties, industry (health and social care vs all other employees), gender and diagnosis. RESULTS: Trends for Occupational Physicians' (OP) reporting mental ill-health (average annual increase +3.7% (95% CI +2.2% to +5.2%)) differed significantly (p<0.001) from psychiatrists' reporting over the same time period (-5.9% (95% CI -7.6% to -4.2%)). For OPs' reporting, the rate of increase was greater for females and for health and social care employees. A fall in incidence of musculoskeletal disorders for OPs of -5.8% (95% CI -7.3% to -4.3%) and rheumatologists' reporting -6.6% (95% CI -8.3% to -4.8%) was found, with little variation by gender or industry. Within health and social care, an increase in incidence of 'other work stress' was accompanied by a similar decrease in 'spine/back pain'. CONCLUSIONS: The evidence presented is consistent with a shift in the presentation of ill-health from a physical to psychological perspective, although changes in hazards, prevention measures and physician awareness should also be considered as explanations.

Applying optimal model selection in principal stratification for causal inference.

Noncompliance to treatment allocation is a key source of complication for causal inference. Efficacy estimation is likely to be compounded by the presence of noncompliance in both treatment arms of clinical trials where the intention-to-treat estimate provides a biased estimator for the true causal estimate even under homogeneous treatment effects assumption. Principal stratification method has been developed to address such posttreatment complications. The present work extends a principal stratification method that adjusts for noncompliance in two-treatment arms trials by developing model selection for covariates predicting compliance to treatment in each arm. We apply the method to analyse data from the Esprit study, which was conducted to ascertain whether unopposed oestrogen (hormone replacement therapy) reduced the risk of further cardiac events in postmenopausal women who survive a first myocardial infarction. We adjust for noncompliance in both treatment arms under a Bayesian framework to produce causal risk ratio estimates for each principal stratum. For mild values of a sensitivity parameter and using separate predictors of compliance in each arm, principal stratification results suggested that compliance with hormone replacement therapy only would reduce the risk for death and myocardial reinfarction by about 47% and 25%, respectively, whereas compliance with either treatment would reduce the risk for death by 13% and reinfarction by 60% among the most compliant. However, the results were sensitive to the user-defined sensitivity parameter.

Evaluating interventions aimed at reducing occupational exposure to latex and rubber glove allergens.

OBJECTIVE: Concerns over occupational exposures to blood-borne viruses resulted in increased protective glove use; consequentially latex allergy became a hazard for some occupational groups. Interventions aimed at managing this problem included substitution measures (eg, non-powdered/non-latex gloves), but such changes may not occur simultaneously across occupational sectors. This study evaluated whether the incidence of occupational dermatoses fell after interventions aiming to reduce exposure to 'latex and rubber glove allergens' ('latex') were introduced, and whether these interventions were more effective for healthcare workers (HCWs), compared with non-HCWs. METHODS: Incidence rate ratios (IRRs) comparing cases reported to EPIDERM (a UK-wide surveillance scheme) during post versus pre-intervention periods were calculated, both where 'latex' was cited and for cases associated with other exposures ('controls'). RESULTS: Among HCWs, cases of contact urticaria and allergic contact dermatitis (ACD) where 'latex' was cited showed significant downward trends post-intervention, with IRRs of 0.72, 95% CI; 0.52 to 1.00 and 0.47, 95% CI; 0.35 to 0.64 respectively. For HCWs, this fall in 'latex' associated ACD was significantly greater (p=0.02) than for other exposures ('controls') IRR=0.85, 95% CI; 0.57 to 1.28, and greater than that among non-HCWs (IRR 0.75, 95% CI; 0.61 to 0.93). Increases over time were seen for irritant contact dermatitis (ICD) reporting for HCWs, both for cases associated with 'latex' (IRR 1.47, 95% CI: 1.02 to 2.13) and for other exposures ('controls') IRR 1.36, 95% CI 1.06 to 1.76, but not for non-HCWs. CONCLUSIONS: A reduction in overall ACD, particularly in HCWs, coincided with interventions aimed at managing workplace contact dermatoses associated with 'latex' exposure. A coincidental rise in ICD reporting is also important, both for hand care and for infection control strategies.

The predictive ability of blood pressure in elderly trial patients.

OBJECTIVES: To assess the impact of the blood pressure (BP) profile on cardiovascular risk in the Medical Research Council (UK) elderly trial; investigate whether the effects of hypertensive drugs in reducing event rates are solely a product of systolic pressure reduction. METHODS: Using longitudinal BP data from 4396 hypertensive patients, the general trend over time was estimated using a first-stage multilevel model. We then investigated how BP acted alongside other BP-related covariates in a second-stage 'time-to-event' statistical model, assessing risk for stroke events and coronary heart disease (CHD). Differences in outcome prediction between diuretic, ß-blocker and placebo treatment arms were investigated. RESULTS: The ß-blocker arm experienced comparatively poor control of current SBP, episodic peaks and variability in BP levels. After adjusting for the mean level, variability in SBP over time was significant: risk ratio was 1.15 [95% confidence interval (CI): 1.01-1.31] across all patients for stroke events. The risk ratio for current SBP was 1.36 (95% CI: 1.16-1.58). Current DBP and variability in DBP also predicted stroke independently: risk ratios was 1.43 and 1.18, respectively. The risk factors exhibited weaker associations with CHD risk; only the highest measured value and variability in SBP showed a statistically significant association: risk ratios were 1.26 and 1.16, respectively. CONCLUSION: Individual risk characterization could be augmented with additional prognostic information, besides current SBP, including current diastolic pressure, temporal variability over and above general trends and historical measurements.