Unnatural Deaths in South African Platinum Miners, 1992-2008

Background: The mortality rate from unnatural deaths for South Africa is nearly double the world average. Reliable data are limited by inaccurate and incomplete ascertainment of specific causes of unnatural death. This study describes trends in causes of unnatural death between 1992 and 2008 in a cohort of South African miners.Methodology/Principal Findings: The study used routinely-collected retrospective data with cause of death determined from multiple sources including the mine's human resources database, medical records, death registration, and autopsy. Cause-specific mortality rates and Poisson regression coefficients were calculated by calendar year and age group. The cohort included 40,043 men. One quarter of all 2937 deaths were from unnatural causes (n = 805). Causes of unnatural deaths were road traffic accidents 38% (109/100,000 py), homicides 30% (88/100,000 py), occupational injuries 17% (50/100,000 py), suicides 8% (24/100,000 py), and other accidents 6% (19/100,000 py). Rates of unnatural deaths declined by 2% (95% CI -4%,-1%) per year over the study period, driven by declining rates of road traffic and other accidents. The rate of occupational injury mortality did not change significantly over time (-2% per year, 95% CI -5%,+ 2%). Unnatural deaths were less frequent in this cohort of workers than in the South African population (IRR 0.89, 95% CI 0.82-0.95), particularly homicides (IRR 0.48, 95% CI 0.42-0.55).Conclusions/Significance: Unnatural deaths were a common cause of preventable and premature death in this cohort of miners. While unnatural death rates declined between 1992 and 2008, occupational fatalities remained at a high level. Evidence-based prevention strategies to address these avoidable deaths are urgently needed

Sources of brand benefits in manufacturer-reseller B2B relationships

Purpose – The aim of the paper is to develop a conceptual framework that explores the sources of manufacturer brand benefits for resellers. Design/methodology/approach – The paper reports a qualitative investigation where packaged goods resellers were interviewed about the benefits of manufacturer brands for their businesses. The qualitative data is analysed to develop several research propositions about the role of brands in reseller B2B relationships. Findings – A conceptual framework is developed that shows that manufacturers’ brands provide financial, customer and managerial benefits for resellers. These benefits have an impact on reseller relationship outcomes with the manufacturer’s brand, which include satisfaction, dependence, cooperation, commitment and trust. Practical implications – The conceptual framework provides a model that manufacturers of both major and minor brands can use to understand and manage these brand benefits in order to enhance the relationship outcomes with resellers. Originality/value – The paper responds to a need for empirical research to understand the role that brands play in channel relationships. It presents a conceptual framework that links manufacturer brand benefits to reseller relationship outcomes. The framework also includes major and minor brands as moderating variables and thus provides a basis for further quantitative research

Population-level effect of HSV-2 therapy on the incidence of HIV in sub-Saharan Africa.

BACKGROUND: Herpes simplex virus type 2 (HSV-2) infection increases acquisition and transmission of HIV, but the results of trials measuring the impact of HSV-2 therapy on HIV genital shedding and HIV acquisition are mixed, and the potential impact of HSV-2 therapy on the incidence of HIV at the population level is unknown. METHODS: The effects of episodic and suppressive HSV-2 therapy were simulated using the individual-level model STDSIM fitted to data from Cotonou, Benin (relatively low HIV prevalence) and Kisumu, Kenya (high HIV prevalence). Clinician- and patient-initiated episodic therapy, started when symptomatic, were assumed to reduce ulcer duration. Suppressive therapy, given regardless of symptoms, was also assumed to reduce ulcer frequency and HSV-2 infectiousness. RESULTS: Clinician-initiated episodic therapy in the general population had almost no effect on the incidence of HIV. The impact of patient-initiated therapy was higher because of earlier treatment initiation, but still low (20% in the long term. Impact was increased in both cities by also treating a proportion of their clients. Long-term suppressive therapy with high coverage in the general population could reduce HIV incidence by more than 30%. CONCLUSIONS: These results show that HSV-2 therapy could potentially have a population-level impact on the incidence of HIV, especially in more concentrated epidemics. However, a substantial impact requires high coverage and long duration therapy, or very high symptom recognition and treatment-seeking behaviour

Incident venous thromboembolic events in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER)

<p>Background: Venous thromboembolic events (VTE), including deep venous thrombosis and pulmonary embolism, are common in older age. It has been suggested that statins might reduce the risk of VTE however positive results from studies of middle aged subjects may not be generalisable to elderly people. We aimed to determine the effect of pravastatin on incident VTE in older people; we also studied the impact of clinical and plasma risk variables.</p> <p>Methods: This study was an analysis of incident VTE using data from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), a randomized, double-blind, placebo-controlled trial of pravastatin in men and women aged 70-82. Mean follow-up was 3.2 years. Risk for VTE was examined in non-warfarin treated pravastatin (n = 2834) and placebo (n = 2865) patients using a Cox's proportional hazard model, and the impact of other risk factors assessed in a multivariate forward stepwise regression analysis. Baseline clinical characteristics, blood biochemistry and hematology variables, plasma levels of lipids and lipoproteins, and plasma markers of inflammation and adiposity were compared. Plasma markers of thrombosis and hemostasis were assessed in a nested case (n = 48) control (n = 93) study where the cohort was those participants, not on warfarin, for whom data were available.</p> <p>Results: There were 28 definite cases (1.0%) of incident VTE in the pravastatin group recipients and 20 cases (0.70%) in placebo recipients. Pravastatin did not reduce VTE in PROSPER compared to placebo [unadjusted hazard ratio (95% confidence interval) 1.42 (0.80, 2.52) p = 0.23]. Higher body mass index (BMI) [1.09 (1.02, 1.15) p = 0.0075], country [Scotland vs Netherlands 4.26 (1.00, 18.21) p = 0.050 and Ireland vs Netherlands 6.16 (1.46, 26.00) p = 0.013], lower systolic blood pressure [1.35 (1.03, 1.75) p = 0.027] and lower baseline Mini Mental State Examination (MMSE) score [1.19 (1.01, 1.41) p = 0.034] were associated with an increased risk of VTE, however only BMI, country and systolic blood pressure remained significant on multivariate analysis. In a nested case control study of definite VTE, plasma Factor VIII levels were associated with VTE [1.52 (1.01, 2.28), p = 0.044]. However no other measure of thrombosis and haemostasis was associated with increased risk of VTE.</p> <p>Conclusions: Pravastatin does not prevent VTE in elderly people at risk of vascular disease. Blood markers of haemostasis and inflammation are not strongly predictive of VTE in older age however BMI, country and lower systolic blood pressure are independently associated with VTE risk.</p&gt

Analysis of neonatal clinical trials with twin births

<p>Abstract</p> <p>Background</p> <p>In neonatal trials of pre-term or low-birth-weight infants, twins may represent 10–20% of the study sample. Mixed-effects models and generalized estimating equations are common approaches for handling correlated continuous or binary data. However, the operating characteristics of these methods for mixes of correlated and independent data are not well established.</p> <p>Methods</p> <p>Simulation studies were conducted to compare mixed-effects models and generalized estimating equations to linear regression for continuous outcomes. Similarly, mixed-effects models and generalized estimating equations were compared to ordinary logistic regression for binary outcomes. The parameter of interest is the treatment effect in two-armed clinical trials. Data from the National Institute of Child Health & Human Development Neonatal Research Network are used for illustration.</p> <p>Results</p> <p>For continuous outcomes, while the coverage never fell below 0.93, and the type I error rate never exceeded 0.07 for any method, overall linear mixed-effects models performed well with respect to median bias, mean squared error, coverage, and median width. For binary outcomes, the coverage never fell below 0.90, and the type I error rate never exceeded 0.07 for any method. In these analyses, when randomization of twins was to the same treatment group or done independently, ordinary logistic regression performed best. When randomization of twins was to opposite treatment arms, a rare method of randomization in this setting, ordinary logistic regression still performed adequately. Overall, generalized linear mixed models showed the poorest coverage values.</p> <p>Conclusion</p> <p>For continuous outcomes, using linear mixed-effects models for analysis is preferred. For binary outcomes, in this setting where the amount of related data is small, but non-negligible, ordinary logistic regression is recommended.</p

Siamese Survival Analysis with Competing Risks

Survival analysis in the presence of multiple possible adverse events, i.e., competing risks, is a pervasive problem in many industries (healthcare, finance, etc.). Since only one event is typically observed, the incidence of an event of interest is often obscured by other related competing events. This nonidentifiability, or inability to estimate true cause-specific survival curves from empirical data, further complicates competing risk survival analysis. We introduce Siamese Survival Prognosis Network (SSPN), a novel deep learning architecture for estimating personalized risk scores in the presence of competing risks. SSPN circumvents the nonidentifiability problem by avoiding the estimation of cause-specific survival curves and instead determines pairwise concordant time-dependent risks, where longer event times are assigned lower risks. Furthermore, SSPN is able to directly optimize an approximation to the C-discrimination index, rather than relying on well-known metrics which are unable to capture the unique requirements of survival analysis with competing risks

Decreased endothelin receptor B expression in large primary uveal melanomas is associated with early clinical metastasis and short survival

The most devastating aspect of cancer is the metastasis of tumour cells to organs distant from the original tumour site. The major problem facing oncologists treating uveal melanoma, the most common cancer of the eye, is metastatic disease. To lower mortality, it is necessary to increase our understanding of the molecular genetic alterations involved in this process. Using suppression subtractive hybridisation, we have analysed differential gene expression between four primary tumours from patients who have developed clinical metastasis and four primary tumours from patients with no evidence of metastasis to date. We have identified endothelin receptor type B as differentially expressed between these tumours and confirmed this observation using comparative multiplex RT–PCR. In a further 33 tumours, reduced endothelin receptor type B expression correlated with death from metastatic disease. Reduced expression also correlated with other known prognostic indicators, including the presence of epithelioid cells, chromosome 3 allelic imbalance and chromosome 8q allelic imbalance. Endothelin receptor type B expression was also reduced in four out of four primary small cell lung carcinomas compared to normal bronchial epithelium. We also show that the observed down-regulation of endothelin receptor type B in uveal melanoma was not due to gene deletion. Our findings suggest a role for endothelin receptor type B in the metastasis of uveal melanoma and, potentially, in the metastasis of other neural crest tumours

The prevalence, incidence and risk factors of herpes simplex virus type 2 infection among pregnant Zimbabwean women followed up nine months after childbirth

Background Herpes simplex virus type 2 (HSV-2) is the leading cause of genital ulcer disease worldwide. The virus can be transmitted to neonates and there are scarce data regarding incidence of HSV-2 among women in pregnancy and after childbirth. The aim of this study is to measure the incidence and risk factors for HSV-2 infection in women followed for 9 months after childbirth. Methods Pregnant women were consecutively enrolled late in pregnancy and followed at six weeks, four and nine months after childbirth. Stored samples were tested for HSV-2 at baseline and again at nine months after childbirth and HSV-2 seropositive samples at nine months after childbirth (seroconverters) were tested retrospectively to identify the seroconversion point. Results One hundred and seventy-three (50.9%) of the 340 consecutively enrolled pregnant women were HSV-2 seronegative at baseline. HSV-2 incidence rate during the 10 months follow up was 9.7 (95% CI 5.4-14.4)/100 and 18.8 (95% CI 13.9-26.1)/100 person years at risk (PYAR) at four months and nine months after childbirth respectively. Analysis restricted to women reporting sexual activity yielded higher incidence rates. The prevalence of HSV-2 amongst the HIV-1 seropositive was 89.3%. Risk factors associated with HSV-2 seropositivity were having other sexual partners in past 12 months (Prevalence Risk Ratio (PRR) 1.8 (95% CI 1.4-2.4) and presence of Trichomonas vaginalis (PRR 1.7 95% CI 1.4-2.1). Polygamy (Incidence Rate Ratio (IRR) 4.4, 95% CI 1.9-10.6) and young age at sexual debut (IRR 3.6, 95% CI 1.6-8.3) were associated with primary HSV-2 infection during the 10 months follow up. Conclusions Incidence of HSV-2 after childbirth is high and the period between late pregnancy and six weeks after childbirth needs to be targeted for prevention of primary HSV-2 infection to avert possible neonatal infections

The association between parity, infant gender, higher level of paternal education and preterm birth in Pakistan: a cohort study

<p>Abstract</p> <p>Background</p> <p>High rates of antenatal depression and preterm birth have been reported in Pakistan. Self reported maternal stress and depression have been associated with preterm birth; however findings are inconsistent. Cortisol is a biological marker of stress and depression, and its measurement may assist in understanding the influence of self reported maternal stress and depression on preterm birth.</p> <p>Methods</p> <p>In a prospective cohort study pregnant women between 28 to 30 weeks of gestation from the Aga Khan Hospital for Women and Children completed the A-Z Stress Scale and the Centre for Epidemiology Studies Depression Scale to assess stress and depression respectively, and had a blood cortisol level drawn. Women were followed up after delivery to determine birth outcomes. Correlation coefficients and Wilcoxon rank sum test was used to assess relationship between preterm birth, stress, depression and cortisol. Logistic regression analysis was used to determine the key factors predictive of preterm birth.</p> <p>Results</p> <p>132 pregnant women participated of whom 125 pregnant women had both questionnaire and cortisol level data and an additional seven had questionnaire data only. Almost 20% of pregnant women (19·7%, 95% CI 13·3-27·5) experienced a high level of stress and nearly twice as many (40·9%, 95% CI 32·4-49·8%) experienced depressive symptoms. The median of cortisol level was 27·40 ug/dl (IQR 22·5-34·2). The preterm birth rate was 11·4% (95% CI 6·5-18). There was no relationship between cortisol values and stress scale or depression. There was a significant positive relationship between maternal depression and stress. Preterm birth was associated with higher parity, past delivery of a male infant, and higher levels of paternal education. Insufficient numbers of preterm births were available to warrant the development of a multivariable logistic regression model.</p> <p>Conclusions</p> <p>Preterm birth was associated with higher parity, past delivery of a male infant, and higher levels of paternal education. There was no relationship between stress, and depression, cortisol and preterm birth. There were high rates of stress and depression among this sample suggesting that there are missed opportunities to address mental health needs in the prenatal period. Improved methods of measurement are required to better understand the psychobiological basis of preterm birth.</p

Impact Factor: outdated artefact or stepping-stone to journal certification?

A review of Garfield's journal impact factor and its specific implementation as the Thomson Reuters Impact Factor reveals several weaknesses in this commonly-used indicator of journal standing. Key limitations include the mismatch between citing and cited documents, the deceptive display of three decimals that belies the real precision, and the absence of confidence intervals. These are minor issues that are easily amended and should be corrected, but more substantive improvements are needed. There are indications that the scientific community seeks and needs better certification of journal procedures to improve the quality of published science. Comprehensive certification of editorial and review procedures could help ensure adequate procedures to detect duplicate and fraudulent submissions.Comment: 25 pages, 12 figures, 6 table