Factors associated with physician agreement and coding choices of cause of death using verbal autopsies for 1130 maternal deaths in India

Background

The Indian Sample Registration System (SRS) with verbal autopsy methods provides estimations of cause specific mortality for maternal deaths, where the majority of deaths occur at home, unregistered. We aim to examine factors that influence physician agreement and coding choices in assigning causes of death from verbal autopsies.

Methodology/Principal Findings

Among adult deaths identified in the SRS, pregnancy-related deaths recorded in 2001–2003 were assigned ICD-10 codes by two independent physicians. Inter-rater reliability was estimated using Landis Koch Kappa classification – poor to fair agreement; > – moderate agreement; > – substantial agreement; >– high agreement. We identified factors associated with physician agreement using multivariate logistic regression. A central consensus panel reviewed cases for errors and reclassified as needed based on 2011 ICD-10 coding guidelines. Of 1130 pregnancy-related deaths, 1040 were assigned ICD-10 codes by two physicians. We found substantial agreement regardless of the woman''s residence, whether the death was registered, religion, respondent''s or deceased''s education, age, hospital admission or gestational age. Physician agreement was not influenced by the above variables, with the exception of greater agreement in cases where the respondent did not live with the deceased, or early gestational age at the time of death. A central consensus panel reviewed all cases and recoded 10% of cases due to insufficient use of information in the verbal autopsy by the coding physicians and rationale for this reclassification are discussed.

Conclusion

In the absence of complete vital registration and universal healthcare services, physician coded verbal autopsies continues to be heavily relied upon to ascertain pregnancy-related death. From this study, two independent physicians had good inter-rater reliability for assigning pregnancy-related causes of death in a nationally-represented sample, and physician coding does not appear to be heavily influenced by case characteristics or demographics.     

Excess risk of maternal death from sickle cell disease in Jamaica: 1998-2007

Background

Decreases in direct maternal deaths in Jamaica have been negated by growing indirect deaths. With sickle cell disease (SCD) a consistent underlying cause, we describe the epidemiology of maternal deaths in this population.

Methods

Demographic, service delivery and cause specific mortality rates were compared among women with (n = 42) and without SCD (n = 376), and between SCD women who died in 1998–2002 and 2003–7.

Results

Women with SCD had fewer viable pregnancies (p: 0.02) despite greater access to high risk antenatal care (p: 0.001), and more often died in an intensive care unit (p: 0.002). In the most recent period (2003–7) SCD women achieved more pregnancies (median 2 vs. 3; p: 0.009), made more antenatal visits (mean 3.3 vs. 7.3; p: 0.01) and were more often admitted antenatally (p:<0.0001). The maternal mortality ratio for SCD decedents was 7–11 times higher than the general population, with 41% of deaths attributable to their disorder. Cause specific mortality was higher for cardiovascular complications, gestational hypertension and haemorrhage. Respiratory failure was the leading immediate cause of death.

Conclusions

Women with SCD experience a significant excess risk of dying in pregnancy and childbirth [MMR: (SCD) 719/100,000, (non SCD) 78/100,000]. MDG5 cannot be realised without improving care for women with SCD. Tertiary services (e.g. ventilator support) are needed at regional centres to improve outcomes in this and other high risk populations. Universal SCD screening in pregnancy in populations of African and Mediterranean descent is needed as are guidelines for managing SCD pregnancies and educating families with SCD.     

Applying the risk of bias tool in a systematic review of combination long-acting beta-agonists and inhaled corticosteroids for persistent asthma

Background

The Risk of Bias (RoB) tool is used to assess internal validity of randomized controlled trials (RCTs). Our objectives were to: 1) evaluate inter-rater agreement of the RoB tool; 2) determine the time to access supplemental study information; 3) compare the RoB tool with the Jadad scale and Schulz allocation concealment (AC); and 4) examine the relationship between RoB and effect estimates.

Methods

We conducted a systematic review of long-acting beta agonists (LABA) combined with inhaled corticosteroids (ICS) for adults with persistent asthma. Two reviewers independently assessed 107 trials using RoB, Jadad, and AC. One reviewer searched for study protocols. We assessed inter-rater agreement using weighted Kappa (κ) and the correlation between tools using Kendall''s Tau (τ). Mean differences in effect sizes for RCTs with different RoB were calculated using inverse variance method and random effects model.

Results

Trials had good Jadad scores (median 4, IQR 3-4); however, 85% had unclear AC and 87% high RoB. The factor that most influenced RoB was the potential inappropriate influence of study sponsors (95% industry funded). Agreement on RoB domains was fair (κ = 0.40) to almost perfect (κ = 0.86), and moderate for overall RoB (κ = 0.41). Median time to complete RoB assessments was 21 minutes (IQR 14-27) and 12 minutes (IQR 9-16) to search for protocols. Protocols were identified for 5/42 studies (12%); in 3 cases the assessment of selective outcome reporting changed. There was low correlation between overall RoB vs. Jadad (τ = 0.04, p = 0.3) and AC (τ = −0.02, p = 0.7). Analyses comparing effect estimates and risk showed no important patterns.

Conclusions

Inter-rater agreement on RoB assessments was better than previously reported suggesting that review-specific guidelines are important. The correlation between RoB and Jadad was low suggesting measurement of different constructs (risk of bias vs. quality of reporting). The extensive involvement of the pharmaceutical industry in this LABA/ICS research should raise concerns about potential overestimates of treatment effects.     

The OSCAR-IB consensus criteria for retinal OCT quality assessment

Background

Retinal optical coherence tomography (OCT) is an imaging biomarker for neurodegeneration in multiple sclerosis (MS). In order to become validated as an outcome measure in multicenter studies, reliable quality control (QC) criteria with high inter-rater agreement are required.

Methods/Principal Findings

A prospective multicentre study on developing consensus QC criteria for retinal OCT in MS: (1) a literature review on OCT QC criteria; (2) application of these QC criteria to a training set of 101 retinal OCT scans from patients with MS; (3) kappa statistics for inter-rater agreement; (4) identification reasons for inter-rater disagreement; (5) development of new consensus QC criteria; (6) testing of the new QC criteria on the training set and (7) prospective validation on a new set of 159 OCT scans from patients with MS. The inter-rater agreement for acceptable scans among OCT readers (n = 3) was moderate (kappa 0·45) based on the non-validated QC criteria which were entirely based on the ophthalmological literature. A new set of QC criteria was developed based on recognition of: (O) obvious problems, (S) poor signal strength, (C) centration of scan, (A) algorithm failure, (R) retinal pathology other than MS related, (I) illumination and (B) beam placement. Adhering to these OSCAR-IB QC criteria increased the inter-rater agreement to kappa from moderate to substantial (0.61 training set and 0.61 prospective validation).

Conclusions

This study presents the first validated consensus QC criteria for retinal OCT reading in MS. The high inter-rater agreement suggests the OSCAR-IB QC criteria to be considered in the context of multicentre studies and trials in MS.     

Correlates of in-hospital deaths among hospitalizations with pulmonary embolism: findings from the 2001-2008 National Hospital Discharge Survey

Background

Deep vein thrombosis and pulmonary embolism (PE) are responsible for substantial mortality, morbidity, and impaired health-related quality of life. The aim of this study was to evaluate the correlates of in-hospital deaths among hospitalizations with a diagnosis of PE in the United States.

Methods

By using data from the 2001−2008 National Hospital Discharge Survey, we assessed the correlates of in-hospital deaths among 14,721 hospitalizations with a diagnosis of PE and among subgroups stratified by age, sex, race, days of hospital stay, type of admission, cancer, pneumonia, and fractures. We produced adjusted rate ratios (aRR) and 95% confidence intervals using log-linear multivariate regression models.

Results

Regardless of the listing position of diagnostic codes, we observed an increased likelihood of in-hospital death in subgroups of hospitalizations with ages 50 years and older (aRR = 1.82−8.48), less than 7 days of hospital stay (aRR = 1.43−1.57), cancer (aRR = 2.10−2.28), pneumonia (aRR = 1.79−2.20), or fractures (aRR = 2.18) (except for first-listed PE), when compared to the reference groups with ages 1−49 years, 7 days or more of hospital stay, without cancer, pneumonia, or fractures while adjusting for covariates. In addition, we observed an increased likelihood of in-hospital death for first-listed PE in hospitalizations of women, when compared to those of men (aRR = 1.45).

Conclusions

The results of this study provide support for identifying, developing, and implementing effective, evidence-based clinical assessment and management strategies to reduce PE-related morbidity and mortality among hospitalized PE patients who may have concurrent health conditions including cancer, pneumonia, and fractures.     

Declines in the lethality of suicide attempts explain the decline in suicide deaths in australia

Background

To investigate the epidemiology of a steep decrease in the incidence of suicide deaths in Australia.

Methods

National data on suicide deaths and deliberate self-harm for the period 1994–2007 were obtained from the Australian Institute of Health and Welfare. We calculated attempt and death rates for five major methods and the lethality of these methods. Negative binomial regression was used to estimate the size and significance of method-specific time-trends in attempts and lethality.

Results

Hanging, motor vehicle exhaust and firearms were the most lethal methods, and together accounted for 72% of all deaths. The lethality of motor vehicle exhaust attempts decreased sharply (RR = 0.94 per year, 95% CI 0.93–0.95) while the motor vehicle exhaust attempt rate changed little; this combination of motor vehicle exhaust trends explained nearly half of the overall decline in suicide deaths. Hanging lethality also decreased sharply (RR = 0.96 per year, 95% CI 0.956–0.965) but large increases in hanging attempts negated the effect on death rates. Firearm lethality changed little while attempts decreased.

Conclusion

Declines in the lethality of suicide attempts–especially attempts by motor vehicle exhaust and hanging–explain the remarkable decline in deaths by suicide in Australia since 1997.     

The WHO Maternal Near-Miss Approach and the Maternal Severity Index Model (MSI): Tools for Assessing the Management of Severe Maternal Morbidity

Objectives

To validate the WHO maternal near-miss criteria and develop a benchmark tool for severe maternal morbidity assessments.

Methods

In a multicenter cross-sectional study implemented in 27 referral maternity hospitals in Brazil, a one-year prospective surveillance on severe maternal morbidity and data collection was carried out. Diagnostic accuracy tests were used to assess the validity of the WHO maternal near-miss criteria. Binary logistic regression was used to model the death probability among women with severe maternal complications and benchmark the management of severe maternal morbidity.

Results

Of the 82,388 women having deliveries in the participating health facilities, 9,555 women presented pregnancy-related complications, including 140 maternal deaths and 770 maternal near misses. The WHO maternal near-miss criteria were found to be accurate and highly associated with maternal deaths (Positive likelihood ratio 106.8 (95% CI 99.56–114.6)). The maternal severity index (MSI) model was developed and found to able to describe the relationship between life-threatening conditions and mortality (Area under the ROC curve: 0.951 (95% CI 0.909–0.993)).

Conclusion

The identification of maternal near-miss cases using the WHO list of pregnancy-related life-threatening conditions was validated. The MSI model can be used as a tool for benchmarking the performance of health services managing women with severe maternal complications and provide case-mix adjustment.     

Lessons learned developing a diagnostic tool for HIV-associated dementia feasible to implement in resource-limited settings: pilot testing in Kenya

Objective

To conduct a preliminary evaluation of the utility and reliability of a diagnostic tool for HIV-associated dementia (HAD) for use by primary health care workers (HCW) which would be feasible to implement in resource-limited settings.

Background

In resource-limited settings, HAD is an indication for anti-retroviral therapy regardless of CD4 T-cell count. Anti-retroviral therapy, the treatment for HAD, is now increasingly available in resource-limited settings. Nonetheless, HAD remains under-diagnosed likely because of limited clinical expertise and availability of diagnostic tests. Thus, a simple diagnostic tool which is practical to implement in resource-limited settings is an urgent need.

Methods

A convenience sample of 30 HIV-infected outpatients was enrolled in Western Kenya. We assessed the sensitivity and specificity of a diagnostic tool for HAD as administered by a primary HCW. This was compared to an expert clinical assessment which included examination by a physician, neuropsychological testing, and in selected cases, brain imaging. Agreement between HCW and an expert examiner on certain tool components was measured using Kappa statistic.

Results

The sample was 57% male, mean age was 38.6 years, mean CD4 T-cell count was 323 cells/µL, and 54% had less than a secondary school education. Six (20%) of the subjects were diagnosed with HAD by expert clinical assessment. The diagnostic tool was 63% sensitive and 67% specific for HAD. Agreement between HCW and expert examiners was poor for many individual items of the diagnostic tool (K = .03–.65). This diagnostic tool had moderate sensitivity and specificity for HAD. However, reliability was poor, suggesting that substantial training and formal evaluations of training adequacy will be critical to enable HCW to reliably administer a brief diagnostic tool for HAD.     

Early second trimester maternal plasma choline and betaine are related to measures of early cognitive development in term infants

Background

The importance of maternal dietary choline for fetal neural development and later cognitive function has been well-documented in experimental studies. Although choline is an essential dietary nutrient for humans, evidence that low maternal choline in pregnancy impacts neurodevelopment in human infants is lacking. We determined potential associations between maternal plasma free choline and its metabolites betaine and dimethylglycine in pregnancy and infant neurodevelopment at 18 months of age.

Methodology

This was a prospective study of healthy pregnant women and their full-term, single birth infants. Maternal blood was collected at 16 and 36 weeks of gestation and infant neurodevelopment was assessed at 18 months of age for 154 mother-infant pairs. Maternal plasma choline, betaine, dimethylglycine, methionine, homocysteine, cysteine, total B12, holotranscobalamin and folate were quantified. Infant neurodevelopment was evaluated using the Bayley Scales of Infant Development–III. Multivariate regression, adjusting for covariates that impact development, was used to determine the associations between maternal plasma choline, betaine and dimethylglycine and infant neurodevelopment.

Results

The maternal plasma free choline at 16 and 36 weeks gestation was median (interquartile range) 6.70 (5.78–8.03) and 9.40 (8.10–11.3) µmol/L, respectively. Estimated choline intakes were (mean ±SD) 383±98.6 mg/day, and lower than the recommended 450 mg/day. Betaine intakes were 142±70.2 mg/day. Significant positive associations were found between infant cognitive test scores and maternal plasma free choline (B = 6.054, SE = 2.283, p = 0.009) and betaine (B = 7.350, SE = 1.933, p = 0.0002) at 16 weeks of gestation. Maternal folate, total B12, or holotranscobalamin were not related to infant development.

Conclusion

We show that choline status in the first half of pregnancy is associated with cognitive development among healthy term gestation infants. More work is needed on the potential limitation of choline or betaine in the diets of pregnant women.     

An appraisal of the maternal mortality decline in Nepal

Background

A decline in the national maternal mortality ratio in Nepal has been observed from surveys conducted between 1996 and 2008. This paper aims to assess the plausibility of the decline and to identify drivers of change.

Methods

National and sub-national trends in mortality data were investigated using existing demographic and health surveys and maternal mortality and morbidity surveys. Potential drivers of the variation in maternal mortality between districts were identified by regressing district-level indicators from the Nepal demographic health surveys against maternal mortality estimates.

Results

A statistically significant decline of the maternal mortality ratio from 539 maternal deaths to 281 per 100,000 (95% CI 91,507) live births between 1993 and 2003 was demonstrated. The sub-national changes are of similar magnitude and direction to those observed nationally, and in the terai region (plains) the differences are statistically significant with a reduction of 361 per 100,000 live births (95% CI 36,686) during the same time period.The reduction in fertility, changes in education and wealth, improvements in components of the human development index, gender empowerment and anaemia each explained more than 10% of the district variation in maternal mortality. A number of limitations in each of the data sources used were identified. Of these, the most important relate to the underestimation of numbers of deaths.

Conclusion

It is likely that there has been a decline in Nepal''s maternal mortality since 1993. This is good news for the country''s sustained commitments in this area. Conclusions on the magnitude, pattern of the change and drivers of the decline are constrained by lack of data. We recommend close tracking of maternal mortality and its determinants in Nepal, attention to the communication of future estimates, and various options for bridging data gaps.     

Risk factors for progression from severe maternal morbidity to death: a national cohort study

Background

Women continue to die unnecessarily during or after pregnancy in the developed world. The aim of this analysis was to compare women with severe maternal morbidities who survived with those who died, to quantify the risk associated with identified factors to inform policy and practice to improve survival.

Methods and Findings

We conducted a national cohort analysis using data from two sources obtained between 2003 and 2009: the Centre for Maternal and Child Enquiries maternal deaths database and the United Kingdom Obstetric Surveillance System database. Included women had eclampsia, antenatal pulmonary embolism, amniotic fluid embolism, acute fatty liver of pregnancy or antenatal stroke. These conditions were chosen as major causes of maternal mortality and morbidity about which data were available through both sources, and include 42% of direct maternal deaths over the study period. Rates, risk ratios, crude and adjusted odd ratios were used to investigate risks factors for maternal death. Multiple imputation and sensitivity analysis were used to handle missing data.We identified 476 women who survived and 100 women who died. Maternal death was associated with older age (35+ years aOR 2.36, 95%CI 1.22–4.56), black ethnicity (aOR 2.38, 95%CI 1.15–4.92), and unemployed, routine or manual occupation (aOR 2.19, 95%CI 1.03–4.68). An association was also observed with obesity (BMI≥30 kg/m² aOR 2.73, 95%CI 1.15–6.46).

Conclusions

Ongoing high quality national surveillance programmes have an important place in addressing challenges in maternal health and care. There is a place for action to reverse the rising trends in maternal age at childbirth, and to reduce the burden of obesity in pregnancy, as well as ongoing recognition of the impact of older maternal age on the risks of pregnancy. Development and evaluation of services to mitigate the risk of dying associated with black ethnicity and lower socioeconomic status is also essential.     

Effect of early detection and treatment on malaria related maternal mortality on the north-western border of Thailand 1986-2010

Introduction

Maternal mortality is high in developing countries, but there are few data in high-risk groups such as migrants and refugees in malaria-endemic areas. Trends in maternal mortality were followed over 25 years in antenatal clinics prospectively established in an area with low seasonal transmission on the north-western border of Thailand.

Methods and Findings

All medical records from women who attended the Shoklo Malaria Research Unit antenatal clinics from 12^th May 1986 to 31^st December 2010 were reviewed, and maternal death records were analyzed for causality. There were 71 pregnancy-related deaths recorded amongst 50,981 women who attended antenatal care at least once. Three were suicide and excluded from the analysis as incidental deaths. The estimated maternal mortality ratio (MMR) overall was 184 (95%CI 150–230) per 100,000 live births. In camps for displaced persons there has been a six-fold decline in the MMR from 499 (95%CI 200–780) in 1986–90 to 79 (40–170) in 2006–10, p<0.05. In migrants from adjacent Myanmar the decline in MMR was less significant: 588 (100–3260) to 252 (150–430) from 1996–2000 to 2006–2010. Mortality from P.falciparum malaria in pregnancy dropped sharply with the introduction of systematic screening and treatment and continued to decline with the reduction in the incidence of malaria in the communities. P.vivax was not a cause of maternal death in this population. Infection (non-puerperal sepsis and P.falciparum malaria) accounted for 39.7 (27/68) % of all deaths.

Conclusions

Frequent antenatal clinic screening allows early detection and treatment of falciparum malaria and substantially reduces maternal mortality from P.falciparum malaria. No significant decline has been observed in deaths from sepsis or other causes in refugee and migrant women on the Thai–Myanmar border.     

Transplacentally acquired maternal antibody against hepatitis B surface antigen in infants and its influence on the response to hepatitis B vaccine

Background

Passively acquired maternal antibodies in infants may inhibit active immune responses to vaccines. Whether maternal antibody against hepatitis B surface antigen (anti-HBs) in infants may influence the long-term immunogenicity of hepatitis B vaccine remains unknown.

Methodology/Principal Findings

Totally 338 pairs of mothers and children were enrolled. All infants were routinely vaccinated against hepatitis B based on 0-, 1- and 6-month schedule. We characterized the transplacental transfer of maternal anti-HBs, and compared anti-HBs response in children of mothers with or without anti-HBs. In a prospective observation, all 63 anti-HBs positive mothers transferred anti-HBs to their infants; 84.1% of the infants had higher anti-HBs concentrations than their mothers. One and half years after vaccination with three doses of hepatitis B vaccine, the positive rate and geometric mean concentration (GMC) of anti-HBs in 32 infants with maternal anti-HBs were comparable with those in 32 infants without maternal antibody (90.6% vs 87.5%, P = 0.688, and 74.5 vs 73.5 mIU/ml, P = 0.742, respectively). In a retrospective analysis, five and half years after vaccination with three doses vaccine, the positive rates of anti-HBs in 88 children of mothers with anti-HBs ≥1000 mIU/ml, 94 children of mothers with anti-HBs 10–999 mIU/ml, and 61 children of mothers with anti-HBs <10 mIU/ml were 72.7%, 69.2%, and 63.9% (P = 0.521), respectively; anti-HBs GMC in these three groups were 38.9, 43.9, and 31.7 mIU/ml (P = 0.726), respectively.

Conclusions/Significance

The data demonstrate that maternal anti-HBs in infants, even at high concentrations, does not inhibit the long-term immunogenicity of hepatitis B vaccine. Thus, current hepatitis B vaccination schedule for infants will be still effective in the future when most infants are positive for maternal anti-HBs due to the massive vaccination against hepatitis B.     

Novel meta-analysis-derived type 2 diabetes risk loci do not determine prediabetic phenotypes

Background

Genome-wide association (GWA) studies identified a series of novel type 2 diabetes risk loci. Most of them were subsequently demonstrated to affect insulin secretion of pancreatic β-cells. Very recently, a meta-analysis of GWA data revealed nine additional risk loci with still undefined roles in the pathogenesis of type 2 diabetes. Using our thoroughly phenotyped cohort of subjects at an increased risk for type 2 diabetes, we assessed the association of the nine latest genetic variants with the predominant prediabetes traits, i.e., obesity, impaired insulin secretion, and insulin resistance.

Methodology/Principal Findings

One thousand five hundred and seventy-eight metabolically characterized non-diabetic German subjects were genotyped for the reported candidate single nucleotide polymorphisms (SNPs) JAZF1 rs864745, CDC123/CAMK1D rs12779790, TSPAN8/LGR5 rs7961581, THADA rs7578597, ADAMTS9 rs4607103, NOTCH2 rs10923931, DCD rs1153188, VEGFA rs9472138, and BCL11A rs10490072. Insulin sensitivity was derived from fasting glucose and insulin concentrations, oral glucose tolerance test (OGTT), and hyperinsulinemic-euglycemic clamp. Insulin secretion was estimated from OGTT data. After appropriate adjustment for confounding variables and Bonferroni correction for multiple comparisons (corrected α-level: p = 0.0014), none of the SNPs was reliably associated with adiposity, insulin sensitivity, or insulin secretion (all p≥0.0117, dominant inheritance model). The risk alleles of ADAMTS9 SNP rs4607103 and VEGFA SNP rs9472138 tended to associate with more than one measure of insulin sensitivity and insulin secretion, respectively, but did not reach formal statistical significance. The study was sufficiently powered (1-β = 0.8) to detect effect sizes of 0.19≤d≤0.25 (α = 0.0014) and 0.13≤d≤0.16 (α = 0.05).

Conclusions/Significance

In contrast to the first series of GWA-derived type 2 diabetes candidate SNPs, we could not detect reliable associations of the novel risk loci with prediabetic phenotypes. Possible weak effects of ADAMTS9 SNP rs4607103 and VEGFA SNP rs9472138 on insulin sensitivity and insulin secretion, respectively, await further confirmation by larger studies.     

Clinical features and serum biomarkers in HIV immune reconstitution inflammatory syndrome after cryptococcal meningitis: a prospective cohort study

Background

Although antiretroviral therapy (ART) improves survival in persons with cryptococcal meningitis (CM) and AIDS, ART frequently elicits HIV immune reconstitution inflammatory syndrome (IRIS), an exaggerated and frequently deadly inflammatory reaction that complicates recovery from immunodeficiency. The pathogenesis of IRIS is poorly understood and prediction of IRIS is not possible.

Methods and Findings

We prospectively followed 101 ART-naïve Ugandans with AIDS and recent CM for one year after initiating ART, and used Luminex multiplex assays to compare serum cytokine levels in participants who did or did not develop IRIS. IRIS occurred in 45% of participants with recent CM on ART, including 30% with central nervous system (CNS) manifestations. The median time to CM-IRIS was 8.8 wk on ART. Overall mortality on ART was 36% with IRIS and 21% without IRIS. CM-IRIS was independently associated with death (HR = 2.3, 95% CI 1.1–5.1, p = 0.04). Patients experiencing subsequent CM-IRIS had 4-fold higher median serum cryptococcal antigen (CRAG) levels pre-ART (p = 0.006). Higher pre-ART levels of interleukin (IL)-4 and IL-17 as well as lower tumor necrosis factor (TNF)-α, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), and vascular endothelial growth factor (VEGF) predicted future IRIS in multivariate analyses (area under the curve [AUC] = 0.82). An algorithm based on seven pre-ART serum biomarkers was a robust tool for stratifying high (83%), moderate (48%), and low risk (23%) for IRIS in the cohort. After ART was initiated, increasing levels of C-reactive protein (CRP), D-dimer, IL-6, IL-7, IL-13, G-CSF, or IL-1RA were associated with increasing hazard of IRIS by time-to-event analysis (each p≤0.001). At the time of IRIS onset, multiple proinflammatory cytokine responses were present, including CRP and IL-6. Mortality was predicted by pre-ART increasing IL-17, decreasing GM-CSF, and CRP level >32 mg/l (highest quartile). Pre-ART CRP level >32 mg/l alone was associated with future death (OR = 8.3, 95% CI 2.7–25.6, p<0.001).

Conclusions

Pre-ART increases in Th₁₇ and Th₂ responses (e.g., IL-17, IL-4) and lack of proinflammatory cytokine responses (e.g., TNF-α, G-CSF, GM-CSF, VEGF) predispose individuals to subsequent IRIS, perhaps as biomarkers of immune dysfunction and poor initial clearance of CRAG. Although requiring validation, these biomarkers might be an objective tool to stratify the risk of CM-IRIS and death, and could be used clinically to guide when to start ART or use prophylactic interventions. Please see later in the article for the Editors'' Summary     

Productivity cost due to maternal ill health in sri lanka

Background

The global impact of maternal ill health on economic productivity is estimated to be over 15 billion USD per year. Global data on productivity cost associated with maternal ill health are limited to estimations based on secondary data. Purpose of our study was to determine the productivity cost due to maternal ill health during pregnancy in Sri Lanka.

Methods and Findings

We studied 466 pregnant women, aged 24 to 36 weeks, residing in Anuradhapura, Sri Lanka. A two stage cluster sampling procedure was used in a cross sectional design and all pregnant women were interviewed at clinic centers, using the culturally adapted Immpact tool kit for productivity cost assessment. Of the 466 pregnant women studied, 421 (90.3%) reported at least one ill health condition during the pregnancy period, and 353 (83.8%) of them had conditions affecting their daily life. Total incapacitation requiring another person to carry out all their routine activities was reported by 122 (26.1%) of the women. In this study sample, during the last episode of ill health, total number of days lost due to absenteeism was 3,356 (32.9% of total loss) and the days lost due to presenteeism was 6,832.8 (67.1% of the total loss). Of the 353 women with ill health conditions affecting their daily life, 280 (60%) had coping strategies to recover loss of productivity. Of the coping strategies used to recover productivity loss during maternal ill health, 76.8% (n = 215) was an intra-household adaptation, and 22.8% (n = 64) was through social networks. Loss of productivity was 28.9 days per episode of maternal ill health. The mean productivity cost due to last episode of ill health in this sample was Rs.8,444.26 (95% CI-Rs.6888.74-Rs.9999.78).

Conclusions

Maternal ill health has a major impact on household productivity and economy. The major impact is due to, generally ignored minor ailments during pregnancy.     

Chronic maternal depression is associated with reduced weight gain in latino infants from birth to 2 years of age

Background

Latino children are at increased risk for mirconutrient deficiencies and problems of overweight and obesity. Exposures in pregnancy and early postpartum may impact future growth trajectories.

Objectives

To evaluate the relationship between prenatal and postnatal maternal depressive symptoms experienced in pregnancy and infant growth from birth to 2 years of age in a cohort of Latino infants.

Methods

We recruited pregnant Latina mothers at two San Francisco hospitals and followed their healthy infants to 24 months of age. At 6, 12 and 24 months of age, infants were weighed and measured. Maternal depressive symptoms were assessed prenatally and at 4-6 weeks postpartum. Women who had high depressive symptoms at both time periods were defined as having chronic depression. Logistic mixed models were applied to compare growth curves and risk for overweight and underweight based on exposure to maternal depression.

Results

We followed 181 infants to 24 months. At 12 and 24 months, respectively, 27.4% and 40.5% were overweight, and 5.6% and 2.2% were underweight. Exposure to chronic maternal depression was associated with underweight (OR = 12.12, 95%CI 1.86-78.78) and with reduced weight gain in the first 2 years of life (Coef = -0.48, 95% CI -0.94—0.01) compared with unexposed infants or infants exposed to episodic depression (depression at one time point). Exposure to chronic depression was also associated with reduced risk for overweight in the first 2 years of life (OR 0.28, 95%CI 0.03-0.92).

Conclusions

Exposure to chronic maternal depression in the pre- and postnatal period was associated with reduced weight gain in the first two years of life and greater risk for failure to thrive, in comparison with unexposed infants or those exposed episodically. The infants of mothers with chronic depression may need additional nutritional monitoring and intervention.     

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.