Standardized Mortality Ratios Estimates Research Articles

Relationship between changes in the public health nurses’ workforce and the empirical Bayes estimates of standardized mortality ratio: a longitudinal ecological study of municipalities in Japan

BackgroundThe role of public health nurses (PHNs) in the community is expected to become increasingly important, along with the promotion of a comprehensive community care system. However, a comprehensive study of all municipalities is yet to be undertaken, and the relationship between the workforce of PHNs and health indicators is yet to be clarified. This study examined the effect of workforce change among PHNs, one of the structural indicators of PHNs’ activities regarding changes in the empirical Bayes estimate of standardized mortality ratios (EBSMRs).MethodsAn ecological study was conducted using municipality-level aggregate data. The data used were publicly available Japanese government statistics. The first-difference model of panel data analysis was used to examine the relationship between changes in EBSMR and changes in the number of PHNs per 100,000 population from 2010 to 2015, adjusting for the effects of population and other healthcare resources, including the number of physicians, medical clinics, general hospitals, and welfare facilities. The variation by the 47 prefectures was added to the linear model as a random effect. We also performed a sensitivity analysis using the full Bayesian inference using the Besag-York-Mollie model.ResultsFor males, EBSMRs for all causes and malignant neoplasms significantly decreased with an increase in the number of PHNs per population (coefficients: -1.00 and -0.89, p values: 0.008 and 0.043, respectively). For females, although all EBSMRs except malignant neoplasms showed decreased tendencies due to the increase in the number of PHNs per population, none of them were significant. The full Bayesian inference confirmed these associations.ConclusionsAn increase in the number of PHNs per population was significantly associated with a greater reduction in deaths from all causes and malignant neoplasms in males. The results of the full Bayesian inference also suggest that the workforce of PHNs may be related to changes in standardized mortality ratios for deaths from all causes in females.

Racial disparities of liver cancer mortality in Wisconsin.

To calculate tract-level estimates of liver cancer mortality in Wisconsin and identify relationships with racial and socioeconomic variables. County-level standardized mortality ratios (SMRs) of liver cancer in Wisconsin were calculated using traditional indirect adjustment methods for cases from 2003 to 2012. Tract-level SMRs were calculated using adaptive spatial filtering (ASF). The tract-level SMRs were checked for correlations to a socioeconomic advantage index (SEA) and percent racial composition. Non-spatial and spatial regression analyses with tract-level SMR as the outcome were conducted. County-level SMR estimates were shown to mask much of the variance within counties across their tracts. Liver cancer mortality was strongly correlated with the percent of Black residents in a census tract and moderately associated with SEA. In the multivariate spatially-adjusted regression analysis, only Percent Black composition remained significantly associated with an increased liver cancer SMR. Using ASF, we developed a high-resolution map of liver cancer mortality in Wisconsin. This map provided details on the distribution of liver cancer that were inaccessible in the county-level map. These tract-level estimates were associated with several racial and socioeconomic variables.

Conditional Survival in Patients with Multiple Myeloma Undergoing Upfront Autologous Stem Cell Transplantation

Background Conditional survival (CS) is defined as the probability of surviving an additional x years given a patient has already survived y years since diagnosis or a time-point of interest. Although there are readily available overall survival (OS) estimates in multiple myeloma (MM) from the time of diagnosis or autologous stem cell transplantation (ASCT), data on CS in those who had already survived a landmark time since ASCT are lacking. Our objective was to investigate 5-year CS rate and standardized mortality ratio (SMR) in 1-, 3- and 5-year survivors after front-line ASCT in MM. Method We reviewed the institutional transplant database at Cleveland Clinic to identify 340 patients who underwent frontline ASCT (≤18 months from diagnosis) for MM between 1996 and 2013. OS was estimated by the Kaplan-Meier method. Relapse mortality (RM) and non-relapse mortality (NRM) were estimated with cumulative incidence. SMR was defined as the ratio of number of deaths in the study patients to that in an age, sex and race-matched healthy population. Estimates of outcomes and SMR are presented with 95% confidence intervals (CI). Results We identified 309 survivors at 1 year, 246 at 3 years, and 178 at 5 years from ASCT. The median age at ASCT was 56 years (range, 22-76) in all 3 cohorts. The median time from diagnosis to ASCT was 7.9 months in 1- and 3-year and 8.2 months in 5-year survivors. Approximately 40%, 35%, and 25% of patients had ISS stage I, II and III disease respectively at diagnosis in all cohorts. Median follow-up from ASCT in surviving patients was 88 months, 90 months and 100 months in 1-, 3- and 5-year survivors respectively. Estimated 5-year CS was 59% (53-64) in 1-year survivors, 60% (53-67) in 3-year survivors and 62% (53-70) in 5-year survivors. The respective cumulative incidence of 5-year conditional RM was 34% (28-39), 29% (23-35) and 25% (18-33) and that of NRM was 7% (5-11), 11% (7-16) and 13% (8-19). The SMR of 1-year, 3-year and 5-year survivors was 6.9 (5.8-8.2), 6.1 (5.0-7.5) and 5.6 (4.3-7.3) respectively, indicating significantly worse survival compared to demographically-matched healthy population irrespective of the duration of survival after ASCT. Survival curves for the 3 cohorts are shown in Figure I. Conclusion The probability of surviving an additional 5 years in patients with MM undergoing front-line ASCT does not improve with time, as shown in 1-, 3- and 5-year survivors, with estimated 5-year CS staying constant at around 60%. However, a decrease in the magnitude of SMR was observed with increase in the number of years already survived after ASCT. Information on CS and SMR is a pragmatic resource for long-term survivorship and beneficial at an individual level for counselling patients.

Impact of Post-Hematopoietic Cell Transplant (HCT) Survival on Cost-Effectiveness of CPX-351 Versus 7+3 in the Treatment of Therapy-Related AML or AML-MRC in the United States

Background: A central goal of treatment for high-risk AML is enabling patients to receive HCT. CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin at a synergistic ratio. A large randomized, open-label, multicenter, phase 3 trial demonstrated superior outcomes, including significantly longer overall survival and a larger fraction of patients reaching HCT, for CPX-351 versus conventional cytarabine/daunorubicin (7+3 regimen) in patients aged 60 to 75 years with newly diagnosed therapy-related AML (tAML) or AML with myelodysplasia-related changes (AML-MRC; Lancet JE, et al. J Clin Oncol. 2018). In order to estimate the cost-effectiveness of treatments for AML, and for CPX-351 in particular, it is necessary to extrapolate survival of patients undergoing HCT to the long-term. The objective of this analysis was to assess the impact of different estimates of post-HCT mortality on cost-effectiveness of CPX-351.Methods: An existing economic model of CPX-351 versus 7+3 for the treatment of tAML or AML-MRC was used to project lifetime health and cost outcomes. The modeled population included 30% patients <60 years of age and 70% between 60 and 75 years of age. The model uses a survival-partition approach, with distinct survival curves for cohorts defined by treatment pathways (response and transplantation). Projected life expectancy for each cohort was estimated based on trial data (for those 60-75 years of age), US population life-tables, and published data. For patients younger than age 60, response rates were adjusted based on published literature. Standardized mortality ratio (SMR) values following HCT were selected individually for the younger and older cohorts. SMR values were calibrated in the model to match the literature finding that post-HCT mortality results in a loss of approximately 30% of life expectancy. This yielded an SMR of 2.25 for older patients and 4.0 for younger patients. Values ranged from 1.0 to 4.0 in sensitivity analyses based on recent appraisals by the United Kingdom's National Institute for Health and Care Excellence (NICE). Model outputs included survival, quality-adjusted life-years (QALYs), costs, and incremental cost-effectiveness ratio (ICER).Results: In the base case with different SMR values by age, the model yielded a predicted ICER value of $111,841/QALY in the overall cohort, which compares favorably to the typical $150,000/QALY threshold (Bae 2014) for good value care in the United States. Using the same estimates of SMR in all patients yielded ICER values of $125,280/QALY and $151,793/QALY for SMR values of 2.25 and 4.0, respectively. Assuming no excess mortality post-HCT relative to the general population, using an SMR of 1.0, resulted in modest improvements in cost-effectiveness (ICER = $102,298/QALY).Conclusions: CPX-351 is a cost-effective option for the treatment of patients with tAML or AML-MRC when accounting for potentially increased mortality following HCT. DisclosuresKansal:Jazz Pharmaceuticals: Consultancy. Reifsnider:Jazz Pharmaceuticals: Consultancy. Todorova:Jazz Pharmaceuticals: Employment, Equity Ownership. Coughlan:Jazz Pharmaceuticals: Consultancy. Villa:Jazz Pharmaceuticals: Employment, Equity Ownership, Other: Stock and stock options.

Spatial epidemiology of premature mortality in Ontario, Canada

IntroductionGeographic disparities in health indicators, such as premature mortality, may reveal area-level weaknesses in health system performance. Monitoring geographic trends can therefore have powerful implications for system evaluation and planning. However, attempts to understand patterns of population health can be complicated by underlying regional differences in demographics and behaviours.&#x0D; Objectives and ApproachThis study aimed to identify regional disparities in premature mortality (defined as death before age 75), and to investigate how fully these disparities can be explained by population-level characteristics. Ontario’s 76 administrative Local Health Integration Network (LHIN) sub-regions, which vary in geographic and population size, were analyzed using linked population-level data from the Institute for Clinical Evaluative Sciences and Cancer Care Ontario.&#x0D; Spatially structured, sex-stratified Bayesian hierarchical models were used to estimate standardized mortality ratios (SMRs) for each LHIN sub-region in the 2011-2015 period. Models were adjusted for key population-level demographic and behavioural risk factors.&#x0D; ResultsLarge disparities in premature mortality presented at the sub-region level in males and females. Low premature mortality clustered around large, urban population centers in Ottawa and Toronto. Premature mortality was comparatively higher throughout the rest of the province, particularly in northern and southeast Ontario.&#x0D; Higher prevalence of material deprivation, overweight and obesity, sedentary behaviour, and smoking were all significantly (α=0.05) associated with elevated premature mortality risk, while increased alcohol consumption and immigrant population were associated with decreased risk.&#x0D; Adjusting for model covariates reduced variance of sub-region SMR estimates by 87% in males and 89% in females. Population-level characteristics thus explain a large proportion of geographic inequality in premature mortality. However, residual spatial variation suggests that systematic regional differences in premature mortality extend beyond population-level traits.&#x0D; Conclusion/Implications&#x0D; This study represents a novel application of small-area analytic techniques to Ontario mortality data, made possible by comprehensive linkage of vital statistics. The findings highlight the importance of population composition to geographic disparities in health. Future work should investigate the influence of system-level factors in areas with elevated premature mortality.

Survival and prognosis factors in systemic sclerosis: Data of a French multicenter cohort of incident patients, systematic review and meta-analysis of the literature

Introduction Several studies have assessed prognosis factors in systemic sclerosis (SSc), but only few have investigated extensive clinical and laboratory factors in a large, incident and well phenotyped population. The aim of the present study was to describe survival, standardized mortality ratio (SMR) and prognostic factors in a well-phenotyped and multicenter French cohort of incident SSc patients. A systematic review and meta-analysis of cohort studies to assess SMR and prognostic factors in SSc was then performed. Patients and methods Survival, SMR and prognosis factors were assessed in a cohort of SSc patients followed in five referral centers in France. A systematic review of the literature was carried out in Pubmed up to July 2017. Cohort studies of unselected SSc patients reporting SMR and prognostic factors were included in the analysis. We calculated the pooled summary estimates of SMR and hazard ratios (HR) of prognosis factors. Results Out of the 42 referral centers included in the French SSc registry, the present analysis was restricted to 5 centers to ensure the lowest rate of missing data. 625 SSc patients [28.6% of diffuse SSc (dcSSc)] with recent diagnosis were followed from January 2000 to December 2013. Mean age at disease onset was 50.6 ± 14.5 years and mean follow-up was 5.2 ± 3.6 years. In total, 104 deaths were recorded. Overall survival rates at 1, 3, 5 and 10 years from diagnosis were 98.0%, 92.5%, 85.9% and 71.7% respectively. Overall SMR was 5.73 [95% confidence interval (CI) 4.68–6.94]. Age at diagnosis > 60 years, dcSSc, scleroderma renal crisis, severe dyspnoea, FVC 8 mg/L were associated with a poorer survival. Eighteen articles were included in the SMR meta-analysis, representing a total population of 11,329 patients and 33 studies were included in the prognosis factors meta-analysis, representing a total of 23,520 patients. Pooled SMR was 3.45 [IC95% 3.03–3.94]. Age at disease onset, age at diagnosis, male sex, black race, dcSSc subtype, anti-Scl70 autoantibodies, cardiac and renal involvements, interstitial lung disease, PH and malignancy were significantly associated with a worse prognosis. Presence of ACA autoantibodies was associated with a better survival. Conclusion Our study confirms a high mortality rate in SSc and previously described prognosis factors related to skin extension, autoantibody status and organ involvement while reporting new association such as telangiectases and valvular disease.

Reliability of using Standardized Mortality Ratio in Estimation of Relative Risk of Under-Five Mortality in Uganda; an Empirical Analysis

In Uganda, using survey data, estimates of under-five mortality have only been available at national and regional levels. However, estimation of under-five mortality can be made for districts using small area estimation techniques. The simpler way is to use the Standardized Mortality Ratio (SMR). Literature has shown that use of SMR is subject to unreliable results but no empirical study has verified that this is so. The author used Uganda Demographic and Health Survey data of 1995, 2001 and 2006 in the investigations to explore empirically how reliable is the use of SMR in estimation of relative risk of under-5 mortality. The author applied the coefficient of variation to measure reliability of the SMR estimates. Utilization of the traditional SMR could potentially be associated with very high coefficient of variations. The author recommends that before utilization of SMR, there is need to explore reliability of the results using coefficient of variation.

Reliability of using Standardized Mortality Ratio in Estimation of Relative Risk of Under-Five Mortality in Uganda; an Empirical Analysis

In Uganda, using survey data, estimates of under-five mortality have only been available at national and regional levels. However, estimation of under-five mortality can be made for districts using small area estimation techniques. The simpler way is to use the Standardized Mortality Ratio (SMR). Literature has shown that use of SMR is subject to unreliable results but no empirical study has verified that this is so. The author used Uganda Demographic and Health Survey data of 1995, 2001 and 2006 in the investigations to explore empirically how reliable is the use of SMR in estimation of relative risk of under-5 mortality. The author applied the coefficient of variation to measure reliability of the SMR estimates. Utilization of the traditional SMR could potentially be associated with very high coefficient of variations. The author recommends that before utilization of SMR, there is need to explore reliability of the results using coefficient of variation.

Mortality and Incidence of Malignancy in Korean Patients with Rheumatoid Arthritis

To determine the standardized mortality ratio (SMR) and standardized incidence ratio (SIR) for malignancy in Korean patients with rheumatoid arthritis (RA). We enrolled 1534 patients with RA who fulfilled the American College of Rheumatology criteria, from October 2001 to December 2007. Baseline assessment included sociodemographic variables, laboratory findings including rheumatoid factor, anticitrullinated protein antibody, functional class, radiological stage, medication, and the Korean version of the Health Assessment Questionnaire. We used the national mortality rate from 2001 to 2007 from the Korean National Statistical Office (KNSO) and the incidence rate from the Korean Central Cancer Registry (KCCR) from 2001 to 2007 as comparison data for estimates of SMR and SIR. Confidence intervals were calculated based on the Poisson distribution. There were 57 deaths in 6683 person-years of followup. The number of expected deaths (derived from the KNSO) was 42.33 and the SMR for patients with RA was 1.35 (95% CI 1.02-1.74). The main causes of death were malignancy, cardiovascular disease, and respiratory disease. In the cause-specific SMR, deaths from respiratory disease, especially from interstitial lung disease (ILD) and pneumonia, were significantly higher than expected: 4.66 (95% CI 2.13-8.85) for all respiratory disease, 18.18 (95% CI 2.20-65.64) for ILD, and 10.26 (95% CI 2.79-26.26) for pneumonia. Thirty malignancies had occurred in 1501 patients. The number of expected malignancies derived from the KCCR was 34.91, yielding a SIR for cancer of 0.86 (95% CI 0.58-1.23). Our study demonstrates that the SMR was slightly higher in patients with RA, but the incidence rates of malignancies were not significantly different from the general population. But deaths from respiratory diseases were significantly higher.

A Novel Postoperative Seizure Classification for Long-term Mortality of Patients With Intractable Epilepsy: Comparison With the Engel System

To explore the association of clinical seizure pattern with the long-term prognosis after epilepsy surgery is important for patient counseling and risk management. To study the long-term mortality after surgery of intractable epilepsy patients with a novel classification of clinical patterns by long-term frequency and duration of seizure compared with the Engel classification. We conducted a longitudinal cohort study by enrolling 280 patients with epilepsy who underwent anterior temporal lobectomy between 1987 and 2002. In addition to the Engel classification, we proposed a novel classification of clinical patterns pertaining to at least 1 year of follow-up of the frequency and duration of seizures after surgery (inactive, delayed, intermittent, and intensive groups). We followed the vital status of these members until 2007 to obtain a 15-year survival rate for each classification. The standardized mortality ratio and hazard ratios with proportional hazards regression model by the extent of severity were estimated. The overall 15-year survival rate for patients who underwent anterior temporal lobectomy was 95.1%. The standardized mortality ratio estimates (95% confidence interval) for our classification showed a gradient relationship from 0.6 (0.1-2.3), 2.5 (0.7-6.3), 7.6 (0.8-27.3), and 8.9 (3.2-19.3) for inactive, delayed, intermittent, and intensive groups, respectively (Trend test, P = .04), whereas the corresponding estimates were 0.8 (0.2-2.2), 5.9 (1.2-17.2), 6.7 (2.5-14.7), and 7.2 (0.8-25.9) for Engel I to IV, respectively, which showed a less increasing trend (Trend test, P = .82). Similar findings were noted for hazard ratios for the 2 classifications. The proposed novel classification with long-term observed frequency and duration of seizures after surgery is more informative for predicting long-term mortality than the Engel classification.

Non-cancer mortality in poultry slaughtering/processing plant workers belonging to a union pension fund

Background The role of the biological environment in the occurrence of many chronic human diseases has been little studied. Humans are commonly exposed to transmissible agents that infect and cause a wide variety of subacute and chronic diseases in chickens and turkeys. The objective of this study is to investigate whether these agents cause similar diseases in humans, by studying workers in poultry slaughtering and processing plants who have one of the highest human exposures to these agents. Methods Mortality in poultry workers was compared with that in the United States general population through the estimation of standardized mortality ratios. Results Excess mortality from infectious and parasitic diseases was observed in the poultry workers. In addition, excess occurrences of deaths involving several sites of the cardiovascular, neurological, endocrine, gastrointestinal and reproductive systems, were observed, although the numbers involved were few in some instances. Conclusion The results indicate that poultry workers are at increased risk of dying from certain causes of death, including infections. This is consistent with other reports. Although it is possible that occupational exposure to transmissible agents present in poultry may be one of the causes of the excess occurrence of some of these diseases, other factors that were not considered because of the nature of the study design, could be equally important. Also, the small number of deaths involved in some instances calls for caution in interpreting the results. However, the study is important, as it has succeeded in newly identified areas that need further research, and which may have implications not only for workers, but also for the general population.

Cancer mortality in poultry slaughtering/processing plant workers belonging to a union pension fund

Background The role of zoonotic biological agents in human cancer occurrence has been little studied. Humans are commonly exposed to viruses that naturally infect and cause cancer in food animals such as poultry that constitute part of the biological environment. It is not known if these viruses cause cancer in humans. Objective To study cancer mortality in the largest cohort to date, of 20,132 workers in poultry slaughtering and processing plants, a group with the highest human exposures to these viruses. Methods Mortality in poultry workers was compared with that in the US general population through the estimation of standardized mortality ratios. Results Significantly increased risks were observed in the cohort as a whole or in subgroups, for several cancer sites, viz: cancers of the buccal cavity and pharynx; pancreas; trachea/bronchus/lung; brain; cervix; lymphoid leukemia; monocytic leukemia; and tumors of the hemopoietic and lymphatic systems. Elevated SMRs that were not statistically significant were observed for cancers of the liver, nasopharynx, myelofibrosis, and myeloma. New sites observed to be significantly in excess in this study were cancers of the cervix and penis. Conclusion This large study provides evidence that a human group with high exposure to poultry oncogenic viruses has increased risk of dying from several cancers. Other occupational carcinogenic exposures could be of importance in explaining some of the findings, such as fumes from wrapping machines. These findings may have implications for public health amongst persons in the general population who may also be exposed to these viruses. What is needed now are epidemiologic studies that can demonstrate whether the excess of specific cancers can be attributed to specific occupational exposures while adequately controlling for other potential occupational and non-occupational carcinogenic exposures.

Long‐term mortality and renal outcome in a cohort of 100 patients with Lupus Nephritis

To evaluate the long-term mortality and renal outcome in a cohort of Danish patients with lupus nephritis (LN) and to identify outcome predictors among findings registered at the time of the first renal biopsy. The cohort consisted of 100 patients diagnosed with LN (World Health Organization classes I-VI) between 1971 and 1995 and followed for a median duration of 14.7 years (range 0.01-36.9 years). Standardized mortality ratios (SMRs) were calculated on the basis of national age-, sex-, and calendar-year period-specific death rates. Thirty-seven deaths occurred in the cohort, corresponding to an overall SMR of 6.8 (95% confidence interval [95% CI] 4.9-9.4). Excess mortality was observed throughout followup. The SMR estimates were 9.0 (95% CI 4.7-17.1), 6.2 (95% CI 4.0-9.5), and 6.6 (95% CI 3.1-13.8) for patients diagnosed during the calendar-year periods 1971-1979, 1980-1989, and 1990-1995, respectively. The cumulative renal survival after 5, 10, and 20 years of followup was 87%, 83%, and 73%, respectively. The risk of end-stage renal disease (ESRD) did not decrease significantly across calendar-year periods. Systolic blood pressure >or=180 mm Hg, focal segmental nephritis, and advanced sclerosing nephritis were identified as baseline predictors of death in multivariate regression analyses, while systolic blood pressure >or=180 mm Hg, serum creatinine level >or=140 mumoles/liter, and diagnostic delay predicted progression to ESRD. LN is associated with excess long-term mortality, and patients may progress to ESRD even after prolonged followup. Our analyses indicate that focal segmental histopathology at disease onset constitutes an important risk factor for death among LN patients. Moreover, our data underscore the importance of early intervention, blood pressure control, and long-term followup in LN.

Three‐year mortality and predictors after release: a longitudinal study of the first‐time drug offenders in Taiwan

To assess the possible increase in mortality rate and associated socio-demographic and judiciary determinants among first-time drug offenders during the first 3 years after release from correctional facilities. A total of 22 224 male and 4444 female adults who had served a sentence of at least 1 day in correctional facilities for illegal drug-related offences were identified from the judiciary records of the Ministry of Justice, Taiwan. The underlying causes of death were defined by the International Classification of Diseases, ninth revision. Findings All-cause standardized mortality ratios (SMR) were 7 for schedule I (e.g. heroin) and 3 for schedule II (e.g. methamphetamine) drug offenders, respectively; accidents, suicide and circulatory diseases were three leading causes of death. After release, the risk of death among those drug offenders without subsequent incarceration increased gradually until the 9th month. Those who were aged 30 years or older, had an engagement with a higher-ranked schedule substance or who received severe sentences were two to three times more likely to die. Substantial reduction in the risk of death was linked with re-imprisonment. The SMR estimates for external causes were greater than those for disease-related causes in drug offenders, and schedule I drugs-related mortality rate was twice as high as that with schedule II drugs. In transitioning from the correctional setting to the community, the health needs of drug offenders should be addressed by the provision of continuous, adequate medical care tailored to individual background, medical history and drug experience.

The safety profile of tadalafil as prescribed in general practice in England: results from a prescription‐event monitoring study involving 16 129 patients

To examine the safety of tadalafil as used in general practice in England, and to compare the mortality rate due to ischaemic heart disease (IHD) in tadalafil users with that in the male population in England. Patients in this observational cohort study were identified from dispensed prescriptions for tadalafil issued by general practitioners (GPs) from February 2003 to November 2004. Demographic and outcome data (clinical events) were requested from patients' GPs using a postal questionnaire. A standardized mortality ratio (SMR) was calculated using indirect standardization for deaths from IHD in the cohort (where age was known) over a 1-year observation period compared to that in the English male population (2003). A sensitivity analysis was carried out to investigate the effects of missing data for age and cause of death. Clinical information was obtained for 16 129 patients (median age 60 years, interquartile range 52-67); the age was not specified for 3212 (19.9%) patients. At least a third of the patients had diabetes mellitus and 29% had hypertension. Comparison of the mortality rate due to IHD for the patients of known age with that in the English male population provided an SMR of 0.57 (95% confidence interval 0.38-0.83) indicating fewer observed deaths in the cohort than expected. The results of the sensitivity analyses investigating the effect of missing data for age and cause of death produced similar SMR estimates. One confirmed case of non-arteritic anterior ischaemic optic neuropathy (NAION) was reported during tadalafil therapy in a patient with other risk factors for this condition. The results from this prescription-event monitoring study suggest that tadalafil is generally well tolerated when used in general practice in England. The most frequently reported adverse clinical events were in keeping with clinical trial data and include headache, dyspepsia and back pain. There was no evidence of a greater mortality rate due to IHD in the tadalafil cohort than in the general male population. However, these results are limited by the use of an external comparator group and might be explained by a 'healthy cohort effect'. One event of NAION was reported, and although a causal relationship was not established it indicates that NAION occurs rarely in patients prescribed tadalafil.

Mortality Among Workers Exposed to Acrylonitrile in Fiber Production: An Update

The investigation updates the mortality experience through 2002 for a cohort of workers exposed to acrylonitrile (AN). Standardized mortality ratios (SMR) were estimated based on two reference populations: the US population and a regional employee population. Exposure-response analyses were conducted using Cox regression models for cumulative and mean intensity exposure measures. In the cohort of 2548 workers, 839 deaths have occurred with 91 deaths due to respiratory system cancer. Most standardized mortality ratio estimates are at or near no-effects levels. Hazard ratio (HR) estimates indicate no increased mortality risk for respiratory system cancer (adjusted HR = 0.96, 95% confidence interval: 0.74, 1.25). In summary, no mortality outcome of a priori interest, principally respiratory system cancer, is associated with increased AN exposure among fiber production workers over five decades of follow-up.

Analysis of the spatial distribution of infant mortality by cause of death in Austria in 1984 to 2006

BackgroundIn Austria, over the last 20 years infant mortality declined from 11.2 per 1,000 life births (1985) to 4.7 per 1,000 in1997 but remained rather constant since then. In addition to this time trend we already reported a non-random spatial distribution of infant mortality rates in a recent study covering the time period 1984 to 2002.This present study includes four additional years and now covers about 1.9 million individual birth certificates. It aimes to elucidate the observed non-random spatial distribution in more detail. We split up infant mortality into six groups according to the underlying cause of death. The underlying spatial distribution of standardized mortality ratios (SMR) is estimated by univariate models as well as by two models incorporating all six groups simultaneously.ResultsWe observe strong correlations between the individual spatial patterns of SMR's except for "Sudden Infant Death Syndrome" and to some extent for "Peripartal Problems". The spatial distribution of SMR's is non-random with an area of decreased risk in the South-East of Austria. The group "Sudden Infant Death Syndrome" clearly and the group "Peripartal Problems" slightly show deviations from the common pattern. When comparing univariate and multivariate SMR estimates we observe that the resulting spatial distributions are very similar.ConclusionWe observe different non-random spatial distributions of infant mortality rates when grouped by cause of death. The models applied were based on individual data thereby avoiding ecological regression bias. The estimated spatial distributions do not substantially depend on the employed estimation method. The observed non-random spatial patterns of Austrian infant mortality remain to appear ambiguous.

Retrospective Cohort Mortality Study of Workers in a Polymer Production Plant Including a Reference Population of Regional Workers

Based on previous reports of increased serum lipid levels in workers at a U.S. polymer manufacturing facility, the study objective was to investigate ischemic heart disease (IHD) mortality as well as a broad range of mortality causes for an occupational cohort at the facility. The cohort comprised 6,027 men and women who had worked at the facility between 1948 and 2002; these years delimit the mortality follow-up period. Standardized mortality ratios (SMR) were estimated to compare observed numbers of deaths to expected numbers derived from mortality rates for 3 reference populations: the U.S. population, the West Virginia state population, and an 8-state regional employee population from the same company. Most SMR estimates based on U.S. and state populations were below 100. Comparison to the employee population also resulted in many SMR estimates at or near a no-effect level. Relative to the regional worker population, a nonsignificant elevation for IHD mortality was observed (SMR = 109, 95% confidence interval [CI]: 96, 124). Mortality associated with diabetes was significantly increased compared to the regional worker population (SMR = 197, 95% CI: 123, 298). A corresponding increase in the SMR for IHD and diabetes mortality was not detected for comparisons with the two general populations. The results reported herein show little evidence of increased cause-specific mortality risks for workers at the plant. This study demonstrates the utility of comparing occupational cohorts with a similar worker reference population in order to reduce bias associated with the healthy worker effect.

Sequential Comparison of the Proportionate Mortality Ratio for an Ongoing Study of Mortality in an Occupational Cohort

Potential adverse health effects associated with occupational exposure to acrylonitrile have been studied since a report of increased lung cancer incidence among DuPont fiber production workers in 1980. Six investigations have been conducted for the cohort through 2002. At each iteration, standardized mortality ratios (SMR) taking into account age and period characteristics have been reported. The objective of this study is to apply the proportionate mortality ratio (PMR) and the proportionate cancer mortality ratio (PCMR) to compare serial estimates of respiratory and all malignant cancer mortality risks in a closed cohort. The cohort includes 2,548 male employees from two fiber production facilities operating from 1947 through 1991. Sequential mortality risks have been assessed through the years 1976, 1981, 1991, 1997, and 2002. We calculated the PMR and PCMR from estimates of the SMR for respiratory cancer, malignant cancer, and overall mortality based on two referent populations, the U.S. general population and a regional population of workers from the same company. Compared to the company reference rates, respiratory cancer, malignant cancer, and overall SMR were increased in early analyses (SMR > 1.1 for each mortality category) but decreased over time (SMR < 1.0 for each). PMR and PCMR estimates for cancer mortality were consistent (PMR = 0.98 to 1.05) indicating a non-varying mortality pattern over time. Bias in the overall SMR due to the healthy worker effect resulted in notable upward bias for PMR calculated from SMR based on the U.S. population. We find the PMR to be a useful indicator of temporal variation in mortality patterns for ongoing occupational cohort studies. As the number of deaths increases for an aging cohort, the magnitude and direction of the PMR may be used to compare serial estimates of cause-specific relative mortality risks. SMR estimates can vary within a closed cohort over time and may not be a suitable longitudinal risk indicator. The PMR can be applied to evaluate internal consistency of results as well as the strength of association for sequential investigations of closed cohorts.

Mortality in heroin-assisted treatment in Switzerland 1994–2000

Background: A major goal of heroin-assisted treatment in Switzerland has been to reduce the drug-related mortality of heroin users. Therefore, a continuous monitoring of deaths under treatment is essential. Aims: To assess mortality of participants in heroin-assisted treatment in Switzerland over a 7-year period from 1994 to 2000, and to compare this mortality to the general population and to other populations of opioid users, as reported in the literature. Method: Estimation of person years under heroin-assisted treatment from the complete case registry of heroin-assisted treatment in Switzerland. Estimation of standardized mortality ratios comparing the population in treatment to the Swiss population (standardized to the year 2000). Results: Over the 7-year period, the crude death rate of patients in heroin-assisted treatment, and including one month after discharge from treatment, was 1% per year. The standardized mortality ratio for the entire observation period was 9.7 (95% C.I. 7.3–12.8), with females having higher standardized mortality ratios (SMR 17.2) than males (SMR 8.4). There was no clear time trend. Conclusion: Mortality in heroin-assisted treatment was low compared to the mortality rate of Swiss opioid users 1990s (estimated to be between 2.5 and 3%). It was also low compared to mortality rates of opioid users in other maintenance treatments in other countries as reported in the literature. The SMR was also lower than that reported in the only meta-analysis in the literature: 13.2 (95% C.I. 12.3–14.1). The low mortality rate is all the more noteworthy as heroin-assisted treatment in Switzerland included only refractory opioid addicts with existing severe somatic and/or mental problems. Declaration of interest: No conflicts of interest declared