Increased all-cause mortality following occupational injury: a comparison of two states.

OBJECTIVES: To measure the impact of lost-time occupational injuries on all-cause mortality in Washington State and, using the same data elements and study design, to determine whether the estimated impact was similar to previous estimates for New Mexico. METHODS: We linked injuries in the Washington workers' compensation system with Social Security Administration data on earnings and mortality. We estimated Cox survival models of mortality for women and men with lost-time compared with medical-only injuries, adjusting for age, pre-injury earnings and industry. We used quantitative bias analysis to account for confounding by pre-injury smoking and obesity. RESULTS: The estimated mortality HR was 1.24 for women (95% CI 1.21 to 1.28) and 1.22 for men (95% CI 1.20 to 1.24). After adjusting for unmeasured pre-injury smoking and obesity, the estimated HR for women was 1.10, 95% simulation interval (SI) 1.00 to 1.21; for men, it was 1.15, 95% SI 1.04 to 1.27. CONCLUSIONS: All-cause mortality for Washington workers with lost-time injuries was higher than for those with medical-only injuries. Estimated HRs for Washington were consistent with those previously estimated for New Mexico, a less populous state with lower median wages and a different workers' compensation insurance mechanism. This suggests that the relationship between workplace injury and long-term mortality may be generalisable to other US states. These findings support greater efforts to enhance safety and to investigate factors that improve postinjury employment opportunities and long-term health. This association should be examined in additional locations, with different study conditions, or using additional data on pre-injury risk factors.

End-stage renal disease and metalworking fluid exposure.

OBJECTIVE: Despite increasing prevalence of end-stage renal disease (ESRD), little attention has been directed to how occupational exposures may contribute to risk. Our objective was to investigate the relationship between metalworking fluids (MWF) and ESRD in a cohort of 36 703 male autoworkers. METHODS: We accounted for competing risk of death, using the subdistribution hazard approach to estimate subhazard ratios (sHRs) and 95% CIs in models with cubic splines for cumulative exposure to MWF (straight, soluble or synthetic). RESULTS: Based on 501 ESRD cases and 13 434 deaths, we did not observe an association between MWF and ESRD overall. We observed modest associations between MWF and ESRD classification of glomerulonephritis and diabetic nephropathy. For glomerulonephritis, the 60th percentile of straight MWF was associated with an 18% increased subhazard (sHR=1.18, 95% CI: 0.99 to 1.41). For diabetic nephropathy, the subhazard increased 28% at the 60th percentile of soluble MWF (sHR=1.28, 95% CI: 1.00 to 1.64). Differences by race suggest that black males may have higher disease rates following MWF exposure. CONCLUSIONS: Exposure to straight and soluble MWF may be related to ESRD classification, though this relationship should be further examined.

Mortality following workplace injury: Quantitative bias analysis.

PURPOSE: Recent studies have shown increased all-cause mortality among workers following disabling workplace injury. These studies did not account for 2 potentially important confounders, smoking and obesity. We estimated injury-related mortality accounting for these factors. METHODS: We followed workers receiving New Mexico workers' compensation benefits (1994-2000) through 2013. Using data from the Panel Study of Income Dynamics, we derived the joint distribution of smoking status and obesity for workers with and without lost-time injuries. We conducted a quantitative bias analysis (QBA) to determine the adjusted relationship of injury and mortality. RESULTS: We observed hazard ratios after adjusting for smoking and obesity of 1.13 for women (95% simulation interval (SI) 0.97 to 1.31) and 1.12 for men (95% SI 1.00 to 1.27). The estimated fully adjusted excess hazard was about half the estimates not adjusted for these factors. CONCLUSIONS: Using QBA to adjust for smoking and obesity reduced the estimated mortality hazard from lost-time injuries and widened the simulation interval. The adjusted estimate still showed more than a 10 percent increase for both women and men. The change in estimates reveals the importance of accounting for these confounders. Of course, the results depend on the methods and assumptions used.

Dysuria, heat stress, and muscle injury among Nicaraguan sugarcane workers at risk for Mesoamerican nephropathy.

OBJECTIVES: Nicaraguan sugarcane workers, particularly cane cutters, have an elevated prevalence of chronic kidney disease of unknown origin, also referred to as Mesoamerican nephropathy (MeN). The pathogenesis of MeN may include recurrent heat stress, crystalluria, and muscle injury with subsequent kidney injury. Yet, studies examining the frequency of such events in long-term, longitudinal studies are limited. METHODS: Using employment and medical data for male workers at a Nicaraguan sugarcane company, we classified months of active work as either work as a cane cutter or other sugarcane job and determined occurrence of dysuria, heat events and muscle events. Work months and events occurred January 1997 to June 2010. Associations between cane cutting and each outcome were analyzed using logistic regression based on generalized estimating equations for repeated events, controlling for age. RESULTS: Among 242 workers with 7257 active work months, 19.5% of person-months were as a cane cutter. There were 160, 21, and 16 episodes of dysuria, heat events, and muscle events, respectively. Compared with work months in other jobs, cane cutting was associated with an elevated odds of dysuria [odds ratio 2.40 (95% confidence interval 1.56-3.68)]. The number of heat and muscle events by cane cutter and other job were limited. CONCLUSIONS: Working as a cane cutter compared with other jobs in the sugarcane industry was associated with increased dysuria, supporting the hypothesis that cane cutters are at increased risk of events suspected of inducing or presaging clinically evident kidney injury.

Persistent organic pollutants and maternal glycemic outcomes in a diverse pregnancy cohort of overweight women.

BACKGROUND: Animal and human studies suggest certain persistent organic pollutants (POPs) may impact glucose metabolism; however, few epidemiologic studies have examined environmental determinants of glycemic outcomes during pregnancy. Our objective is to evaluate associations between exposures to individual and mixture of POPs and measures of prenatal fasting glucose, insulin, and insulin resistance during pregnancy in overweight women. METHODS: A cohort of overweight and obese pregnant women (N = 95) was recruited from California. Blood samples were collected during late first or second trimester (median = 16 weeks' gestation; range = 10-24 weeks). Exposures included serum concentrations of polybrominated diphenyl ethers (PBDEs) and hydroxylated metabolites (OH-PBDEs), polychlorinated biphenyls (PCBs), and poly- and perfluoroalkyl substances (PFASs). Outcomes included serum concentrations of fasting plasma glucose, fasting plasma insulin, and calculated homeostatic model assessment of insulin resistance (HOMA-IR). Generalized linear models were used to evaluate cross-sectional associations between individual and aggregate POPs and mean percent difference in fasting glucose, fasting insulin, and HOMA-IR. Bayesian kernel machine regression (BKMR) was used to assess the relative importance of each exposure to the association with our outcomes, using conditional and group posterior inclusion probabilities (PIPs). RESULTS: Study participants were racially/ethnically diverse and nearly half were below the federal poverty level. Across PBDEs and OH-PBDEs, the direction of associations with fasting glucose, fasting insulin and HOMA-IR were varied. A doubling of PCB-138, PCB-153, PCB-180, and ∑PCBs concentrations was associated with a 2.10% mmol/L (95%CI: 0.49%, 3.74%), 2.10% mmol/L (95%CI: -0.14%, 4.39%), 2.10% mmol/L (95%CI: 0.12%, 4.12%), and 2.81% mmol/L (95%CI: 0.38%, 5.31%) increase in fasting glucose, respectively. Exposure to individual PCBs was positively associated with both fasting insulin and HOMA-IR. All PFAS were inversely associated with fasting glucose, fasting insulin, and HOMA-IR. In BKMR models of fasting glucose, all four chemical classes were important contributors to the overall mixture, with PFASs identified as the most important contributor. DISCUSSION: Prenatal PCB exposure was positively associated while certain PBDE and PFAS analytes were inversely associated with fasting glucose concentrations in overweight women. Further examination of the relationship between POPs exposure and glycemic functioning in a larger study population of women during pregnancy is warranted.

Associations between sociodemographic characteristics and exposures to PBDEs, OH-PBDEs, PCBs, and PFASs in a diverse, overweight population of pregnant women.

Exposures to persistent organohalogen chemicals during pregnancy are associated with adverse health effects. Low-income, minority women with pre-existing co-morbidities may be particularly vulnerable to these exposures, but have historically been understudied. We aimed to characterize exposures to multiple chemical classes among a sample of ethnically diverse, lower income, overweight or obese pregnant women. Serum concentrations of polybrominated diphenyl ethers (PBDEs) and their hydroxylated metabolites (OH-PBDEs), polychlorinated biphenyls (PCBs), and poly- and perfluoroalkyl substances (PFASs) were measured in 98 pregnant women (California; 2011-2013). Aggregate exposures were evaluated using correlational clustering, a "chemical burden" score, and PCA. Associations between sociodemographic characteristics and individual and aggregate exposures were evaluated using multivariable linear regression. Clustering and PCA both produced four groupings: (PC1) PBDEs/OH-PBDEs, (PC2) PCBs, (PC3) PFNA/PFOA/PFDeA, (PC4) PFHxS/PFOS. Race/ethnicity and prepregnancy BMI were associated with PBDEs, OH-PBDEs and PC1. Maternal age was associated with PCBs and PC2. Parity was associated with PBDEs, OH-PBDEs and PC2. Poverty was negatively associated with PCBs, whereas food insecurity was positively associated with PFOS. We observed variations in sociodemographic profiles of exposures by chemical class and weak across-class correlations. These findings have implications for epidemiologic studies of chemical mixtures and for exposure reduction strategies.

Suicide and drug-related mortality following occupational injury.

BACKGROUND: Drug overdoses and suicides have been rising since 2000 and are major contributors to a 3-year decline in US life expectancy. Studies suggest that injured workers have elevated rates of depression and opioid use, but no studies have measured excess mortality related to these risks. MATERIALS AND METHODS: We linked New Mexico workers' compensation data for 100 806 workers injured in 1994 through 2000 with Social Security Administration earnings and mortality data through 2013 and National Death Index cause of death data. We then estimated the association between receiving lost-time workers' compensation benefits and mortality hazard ratios (HRs) and 95% confidence intervals (CIs) based on Fine and Gray cause-specific subdistribution hazards for common causes of death and for drug-related, suicide, and alcohol-related mortality. RESULTS: There was almost a 3-fold increase in combined drug-related and suicide mortality hazard among women (HR = 2.63, 95% CI = 1.91-3.64) and a substantial increase among men (HR = 1.42, 95% CI = 1.13-1.79). Circulatory disease mortality hazard was elevated for men (HR = 1.25, 95% CI = 1.05-1.50). CONCLUSION: Workplace injuries severe enough to require more than a week off work may impair workers' long-term health and well-being. Drug-related deaths and suicides may be important contributors to the long-term excess mortality of injured workers. Improved workplace conditions, improved pain treatment, better treatment of substance use disorders, and treatment of postinjury depression may substantially reduce mortality consequent to workplace injuries.

Medical Conditions and Modifiable Risk Factors for Myelodysplastic Syndrome: A Systematic Review.

BACKGROUND: The aim of this systematic review was to evaluate medical conditions and modifiable risk factors for myelodysplastic syndromes (MDS) using the 2001 or 2008 World Health Organization (WHO) diagnostic criteria. METHODS: PubMed, MEDLINE, and Scopus databases were searched for studies published between January 2001 and August 2017. Study characteristics and findings were abstracted for each article. RESULTS: Thirteen articles (4 cohort, 9 case-control) met the inclusion criteria. Smoking and alcohol use were each evaluated as potential MDS risk factors in four studies. Body mass index and anemia were each evaluated in two studies. Other potential risk factors evaluated in single studies included physical activity, dietary intake (tea, isoflavones, meat, fruit, or vegetables), history of allergies, autoimmune disorders and community-acquired infections, and use of antituberculosis drugs, traditional Chinese medicines, or hair dyes. CONCLUSIONS: Higher BMI, smoking, a history of autoimmune disorders, community-acquired infections, history of anemia, and use of antituberculosis drugs were associated with higher risk of MDS. Vigorous physical activity and tea and dietary isoflavone intake were associated with lower MDS risk. These findings suggest no association between the other factors and risk of MDS. IMPACT: Research on risk factors for MDS is limited, and further research in larger studies is needed.

Caregiving Intensity and Mortality in Older Women, Accounting for Time-Varying and Lagged Caregiver Status: The Caregiver-Study of Osteoporotic Fractures Study.

BACKGROUND AND OBJECTIVES: Caregiving is associated with reduced mortality in recent studies. Investigations of caregiving intensity may reveal an underlying mechanism. However, studies of caregiving intensity and mortality have mixed results, perhaps due to imprecise measurement of caregiving intensity, not accounting for healthier persons likely having greater caregiving involvement, or temporal changes in intensity. We examined the relationship between caregiving intensity (based on tasks performed) and mortality, treating intensity and health status as time-varying, and lagging exposure. RESEARCH DESIGN AND METHODS: Caregiving tasks among 1,069 women in the Caregiver-Study of Osteoporotic Fractures study (35% caregivers) were assessed at 5 interviews conducted between 1999 and 2009. Caregivers were categorized as high intensity if they assisted a person with dressing, transferring, bathing, or toileting; or as low intensity if they assisted with other instrumental or basic activities of daily living (I/ADLs). Alternatively, high intensity was defined as assisting with more than the median number of I/ADL tasks (median-based measure). Mortality was assessed through 2011. Cox proportional hazards models estimated adjusted hazard ratios (aHR) and 95% confidence intervals based on concurrent intensity, and lagging exposure 2 years. RESULTS: High-intensity caregivers had significantly lower mortality using the median-based measure after lagging exposure (aHR = 0.55, 0.34-0.89). Similar, but not statistically significant associations were observed in non-lagged analyses (aHR = 0.54, 0.29-1.04) and task-specific intensity (aHRs were 0.61 and 0.51). Low-intensity caregivers had similar mortality rates to noncaregivers in all analyses. DISCUSSION AND IMPLICATIONS: Among older women, high-intensity caregivers had lower mortality rates than noncaregivers. Whether this association extends to other populations merits investigation.

Influence of Competing Risks on Estimating the Expected Benefit of Warfarin in Individuals with Atrial Fibrillation Not Currently Taking Anticoagulants: The Anticoagulation and Risk Factors in Atrial Fibrillation Study.

OBJECTIVES: To provide greater understanding of the "real world" effect of anticoagulation on stroke risk over several years. DESIGN: Cohort study. SETTING: Anticoagulation and Risk Factors in Atrial Fibrillation Study community-based cohort. PARTICIPANTS: Adults with nonvalvular atrial fibrillation (AF) between 1996 and 2003 (13,559). MEASUREMENTS: All events were clinician adjudicated. Extended Cox regression with longitudinal warfarin exposure was used to estimate cause-specific hazard ratios (HRs) for thromboembolism and the competing risk event (all cause death). The Fine and Gray subdistribution regression approach was used to estimate this association while accounting for competing death events. As a secondary analysis, follow-up was limited to 1, 3, and 5 years. RESULTS: The rate of death was much higher in the group not taking warfarin (8.1 deaths/100 person-years (PY)) than in the group taking warfarin (5.5 deaths/100 PY). The cause-specific HR indicated a large reduction in thromboembolism with warfarin use (adjusted HR = 0.57, 95% confidence interval (CI) = 0.50-0.65), although this association was substantially attenuated after accounting for competing death events (adjusted HR = 0.87, 95% CI = 0.77-0.99). In analyses limited to 1 year of follow-up, with fewer competing death events, the results for models that did and did not account for competing risks were similar. CONCLUSION: Analyses accounting for competing death events may provide a more-realistic estimate of the longer-term stroke prevention benefits of anticoagulants than traditional noncompeting risk analyses for individuals with AF, particularly those who are not currently treated with anticoagulants.

Risk of renal cell carcinoma following exposure to metalworking fluids among autoworkers.

OBJECTIVES: Metalworking fluids (MWF), used to cool and lubricate metal in occupational settings, are linked to several cancers but data on kidney cancer are limited. We examine how MWF influence the rate of renal cell carcinoma (RCC) in a large prospective study. METHODS: A cohort of Michigan autoworkers consisting of 33 421 individuals was followed from 1985 to 2009. The cohort was linked to the Michigan Cancer Registry to identify new cases of RCC. We analysed RCC in relation to cumulative exposure to each specific type of MWF (straight, soluble and synthetic) and all 3 types pooled into a single MWF variable, with a 15-year lag. Cox proportional hazards regression with splines were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), controlling for age, gender, race, calendar year, year hired, time since hire, plant and other MWF types. RESULTS: There were 135 incident cases. A linear increase in the log-HR was observed for RCC with increasing cumulative exposure to each MWF type and total MWF exposure. At the mean of total MWF exposure (18.80 mg/m(3)-year), the estimated HR was 1.11 (95% CI 1.04 to 1.19). CONCLUSIONS: Our results provide evidence for a dose-dependent association between MWF exposure and RCC. The influence of components of oil-based and water-based MWF needs further examination.

The impact of non-fatal workplace injuries and illnesses on mortality.

BACKGROUND: Little research has examined the relationship between non-fatal workplace injuries and illnesses, and long-term mortality. METHODS: We linked non-fatal injury cases reported to the New Mexico workers' compensation system for 1994-2000 with Social Security Administration data on individual earnings and mortality through 2014. We then derived sex-specific Kaplan-Meier curves to show time to death for workers with lost-time injuries (n = 36,377) and comparison workers (n = 70,951). We fit multivariable Cox survival models to estimate the hazard ratio separately for male and female workers with lost-time injuries. RESULTS: The estimated hazard ratio for lost-time injuries is 1.24 for women and 1.21 for men. Ninety-five percent confidence intervals were 1.15, 1.35 and 1.15, 1.27, respectively. CONCLUSION: Lost-time occupational injuries are associated with a substantially elevated mortality hazard. This implies an important formerly unmeasured cost of these injuries and a further reason to focus on preventing them. Am. J. Ind. Med. 59:1061-1069, 2016. © 2016 Wiley Periodicals, Inc.

An Overview of Occupational Risks From Climate Change.

Changes in atmosphere and temperature are affecting multiple environmental indicators from extreme heat events to global air quality. Workers will be uniquely affected by climate change, and the occupational impacts of major shifts in atmospheric and weather conditions need greater attention. Climate change-related exposures most likely to differentially affect workers in the USA and globally include heat, ozone, polycyclic aromatic hydrocarbons, other chemicals, pathogenic microorganisms, vector-borne diseases, violence, and wildfires. Epidemiologic evidence documents a U-, J-, or V-shaped relationship between temperature and mortality. Whereas heat-related morbidity and mortality risks are most evident in agriculture, many other outdoor occupational sectors are also at risk, including construction, transportation, landscaping, firefighting, and other emergency response operations. The toxicity of chemicals change under hyperthermic conditions, particularly for pesticides and ozone. Combined with climate-related changes in chemical transport and distribution, these interactions represent unique health risks specifically to workers. Links between heat and interpersonal conflict including violence require attention because they pose threats to the safety of emergency medicine, peacekeeping and humanitarian relief, and public safety professionals. Recommendations for anticipating how US workers will be most susceptible to climate change include formal monitoring systems for agricultural workers; modeling scenarios focusing on occupational impacts of extreme climate events including floods, wildfires, and chemical spills; and national research agenda setting focusing on control and mitigation of occupational susceptibility to climate change.

Effect of Diabetes and Glycemic Control on Ischemic Stroke Risk in AF Patients: ATRIA Study.

BACKGROUND: Diagnosed diabetes mellitus (DM) is a consistently documented risk factor for ischemic stroke in patients with atrial fibrillation (AF). OBJECTIVES: The purpose of this study was to assess the association between duration of diabetes and elevated hemoglobin A1c (HbA1c) with risk of stroke among diabetic patients with AF. METHODS: We assessed this association in the ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) California community-based cohort of AF patients (study years 1996 to 2003) where all events were clinician adjudicated. We used Cox proportional hazards regression to estimate the rate of ischemic stroke in diabetic patients according to time-varying measures of estimated duration of diabetes (≥3 years compared with <3 years) and HbA1c values (≥9.0% and 7.0% to 8.9% compared with <7.0%), focusing on periods where patients were not anticoagulated. RESULTS: There were 2,101 diabetic patients included in the duration analysis: 40% with duration <3 years and 60% with duration ≥3 years at baseline. Among 1,933 diabetic patients included in the HbA1c analysis, 46% had HbA1c <7.0%, 36% between 7.0% and 8.9%, and 19% ≥9.0% at baseline. Duration of diabetes ≥3 years was associated with an increased rate of ischemic stroke compared with duration <3 years (adjusted hazard ratio [HR]: 1.74, 95% confidence interval [CI]: 1.10 to 2.76). The increased stroke rate was observed in older (age ≥75 years) and younger (age <75 years) individuals. Neither poor glycemic control (HbA1c ≥9.0%, adjusted HR: 1.04, 95% CI: 0.57 to 1.92) nor moderately increased HbA1c (7.0% to 8.9%, adjusted HR: 1.21, 95% CI: 0.77 to 1.91) were significantly associated with an increased rate of ischemic stroke compared with patients who had HbA1c <7.0%. CONCLUSIONS: Duration of diabetes is a more important predictor of ischemic stroke than glycemic control in patients who have diabetes and AF.

Occupational exposures and chronic kidney disease: Possible associations with endotoxin and ultrafine particles.

BACKGROUND: Chronic kidney disease (CKD) carries a high public health burden yet there is limited research on occupational factors, which are examined in this retrospective case-control study. METHODS: Newly diagnosed cases of CKD (n = 547) and controls (n = 508) from North Carolina provided detailed work histories in telephone interviews. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: There was heterogeneity in the association of CKD and agricultural work, with crop production associated with increased risk and work with livestock associated with decreased risk. Work with cutting/cooling/lubricating oils was associated with a reduced risk. CKD risk was increased for working in dusty conditions. CONCLUSIONS: CKD risk was reduced in subjects with occupational exposures previously reported to involve endotoxin exposure. Further, exposure to dusty conditions was consistently associated with increased risk of glomerulonephritis across industry, suggesting that research on CKD and ultrafine particulates is needed.

The Relationship Between Caregiving and Mortality After Accounting for Time-Varying Caregiver Status and Addressing the Healthy Caregiver Hypothesis.

BACKGROUND: Previous studies have shown inconsistent associations between caregiving and mortality. This may be due to analyzing caregiver status at baseline only, and that better health is probably related to taking on caregiving responsibilities and continuing in that role. The latter is termed The Healthy Caregiver Hypothesis, similar to the Healthy Worker Effect in occupational epidemiology. We applied common approaches from occupational epidemiology to evaluate the association between caregiving and mortality, including treating caregiving as time-varying and lagging exposure up to 5 years. METHODS: Caregiving status among 1,068 women (baseline mean age = 81.0 years; 35% caregivers) participating in the Caregiver-Study of Osteoporotic Fractures study was assessed at five interviews conducted between 1999 and 2009. Mortality was determined through January 2012. Cox proportional hazards models were used to estimate adjusted hazard ratios and 95% confidence intervals adjusted for sociodemographics, perceived stress, and functional limitations. RESULTS: A total of 483 participants died during follow-up (38.8% and 48.7% of baseline caregivers and noncaregivers, respectively). Using baseline caregiving status, the association with mortality was 0.77, 0.62-0.95. Models of time-varying caregiving status showed a more pronounced reduction in mortality in current caregivers (hazard ratios = 0.54, 0.38-0.75), which diminished with longer lag periods (3-year lag hazard ratio = 0.68, 0.52-0.88, 5-year lag hazard ratios = 0.76, 0.60-0.95). CONCLUSIONS: Overall, caregivers had lower mortality rates than noncaregivers in all analyses. These associations were sensitive to the lagged period, indicating that the timing of leaving caregiving does influence this relationship and should be considered in future investigations.

Comparison of frequency and outcome of major gastrointestinal hemorrhage in patients with atrial fibrillation on versus not receiving warfarin therapy (from the ATRIA and ATRIA-CVRN cohorts).

To date, there have been few studies evaluating outcomes of patients with atrial fibrillation (AF) who have experienced gastrointestinal (GI) hemorrhages. We examined short- and long-term mortality of major GI hemorrhage in patients with AF on and off warfarin in recent clinical care. We evaluated this association in the large Anticoagulation and Risk Factors in Atrial fibrillation (ATRIA) and ATRIA-Cardiovascular Research Network (CVRN) California community-based cohorts of patients with AF (study years 1996 to 2003 and 2006 to 2009, respectively), where all events were clinician adjudicated. We used proportional hazards regression with propensity score adjustment to estimate the short- (30 days) and long-term (>30 days for 1 year) mortality rate ratio for patients using warfarin compared with those who were not using warfarin at the time of GI hemorrhage. In the 414 ATRIA participants with major GI hemorrhage, 54% were taking warfarin at the time of the hemorrhage; in the 361 ATRIA-CVRN participants with major GI hemorrhage, 58% were taking warfarin. Warfarin use at the time of GI hemorrhage was not associated with 30-day mortality in the ATRIA cohort but was associated with significantly reduced 30-day mortality in the ATRIA-CVRN cohort (adjusted mortality rate ratio [95% confidence interval], ATRIA 0.97 [0.54 to 1.74]; ATRIA-CVRN 0.38 [0.17 to 0.83]). There was a modest suggestion of lower mortality on warfarin after 30 days in both cohorts. In conclusion, our study demonstrates that GI hemorrhages on warfarin are certainly no worse and may be less life threatening than those occurring off warfarin. These findings are in stark contrast to the deleterious effect of warfarin on mortality from intracranial hemorrhage and add another factor favoring anticoagulation in clinical decision making for patients with AF.

The influence of prevalent cohort bias in the association between periodontal disease progression and incident coronary heart disease.

PURPOSE: In longitudinal studies, the onset of the index condition (e.g. exposure) does not always coincide with the start of a study's observation period, leading to the possibility of bias in estimation that derives from studying prevalent exposure rather than new exposure. We investigate the possible role of this bias in the relationship between periodontitis progression and coronary heart disease (CHD) among a cohort of men participating in the Veterans Administration Dental Longitudinal Study. METHODS: At baseline, there were 298 men with existing (i.e., prevalent) periodontitis. During follow-up, routine dental inspection identified 163 new (i.e., incident) cases of periodontitis. Change in mean alveolar bone loss score (MBLS) served as the measure of disease progression. Tabular analyses were performed to obtain crude, stratified, and adjusted measures of the association for periodontitis cases overall and separately for prevalent and incident cases. Potential bias was evaluated by comparing estimates across these subcohorts. RESULTS: Among all periodontitis cases, increasing MBLS was associated with increasing risk of CHD event. Subdividing periodontal cases into new and prevalent cases revealed that the relationship was most pronounced among incident periodontitis cases (incident rate ratio for MBLS change >0.5 = 5.4), compared with prevalent cases (incident rate ratio for MBLS change >0.5 = 2.5). CONCLUSIONS: Studying prevalent cases of periodontitis underestimates the association between incidence periodontitis and CHD.

Occupational asbestos exposure is associated with pharyngeal squamous cell carcinoma in men from the greater Boston area.

OBJECTIVES: Asbestos is the name given to a group of naturally occurring silicate mineral fibres that were widely used in industry during the 20th century due to their desirable physical properties. Although use in the USA has fallen over the last three decades, significant exposure in the developing world continues and the burden of disease is considerable. Asbestos is a known risk factor for several malignant diseases, including lung cancer and mesothelioma, and has more recently been implicated in pharyngeal and laryngeal cancer. However, studies of asbestos and cancers of the larynx or pharynx with adequate sample size that control for major head and neck squamous cell carcinoma (HNSCC) risk factors remain relatively sparse. METHODS: We report findings from a case-control study of 674 incident male HNSCC cases from the greater Boston region and 857 population-based male controls, matched on age (±3 years), sex, and town or neighbourhood of residence. Multivariable logistic regression was used to assess the association between occupational asbestos exposure and HNSCC by primary tumour site. RESULTS: 190 cases (28.2%) and 203 controls (23.7%) reported occupational exposure to asbestos. Occupational asbestos exposure was associated with elevated risk of pharyngeal carcinoma in men (OR 1.41, 95% CI 1.01 to 1.97), adjusted for age, race, smoking, alcohol consumption, education, income and HPV16 serology, with borderline increasing risk for each decade in the exposed occupation (OR 1.10, 95% CI 0.99 to 1.23). CONCLUSIONS: These observations are consistent with mounting evidence that asbestos is a risk factor for pharyngeal cancer.

Evidence of a paradoxical relationship between endotoxin and lung cancer after accounting for left truncation in a study of Chinese female textile workers.

INTRODUCTION: Occupational exposure to endotoxin, found in Gram-negative bacteria in organic material, has been associated predominantly with a reduced risk of lung cancer among workers. An inverse exposure-response gradient among women textile workers in Shanghai, China, has been reported previously. In this case-cohort study, we investigated the influence of left truncation, which can itself induce a downward trend, on the observed association. METHODS: Subjects were enrolled between 1989 and 1991 and followed until 1998. The data were left-truncated as all subjects were hired before baseline. An analysis was performed with 3038 subcohort members and 602 cases of incident lung cancer. To evaluate left truncation, we compared lung cancer rates in those hired longer ago with those hired more recently among unexposed subjects. Cox proportional hazards modelling was used to estimate incident rate ratios (IRRs) and 95% CIs. RESULTS: Among those who were never exposed to workplace endotoxin, we compared lung cancer rates in those hired >35 years before enrolment with workers hired ≤35 years before enrolment and observed a reduced risk in the former group, IRR=0.74, 95% CI (0.51 to 1.07). After accounting for this downward bias from left truncation, the reduced risk associated with endotoxin remained among those hired ≤50 years before enrolment. In contrast, there was suggestion of an increased risk of lung cancer among those hired >50 years ago. CONCLUSIONS: After examination of left truncation bias, an inverse dose-response between endotoxin and lung cancer remained for all subjects except those hired longest ago.