Changing temporal trends in non-AIDS cancer mortality among people diagnosed with AIDS: San Francisco,California, 1996–2013

BackgroundAntiretroviral therapy (ART) has reduced AIDS-defining cancer (ADC) mortality, but its effect on non-AIDS-defining cancer (NADC) mortality is unclear. To help inform cancer prevention and screening, we evaluated trends in NADC mortality among people with AIDS (PWA) in the ART era.MethodsThis retrospective cohort study analyzed AIDS surveillance data, including causes of death from death certificates, for PWA in San Francisco who died in 1996–2013. Proportional mortality ratios (PMRs), and year, age, race, sex-adjusted standardized mortality ratios (SMRs) were calculated for 1996–1999, 2000–2005, and 2006–2013, corresponding to advances in ART.ResultsThe study included 5822 deceased PWA of whom 90% were male and 68% were aged 35–54 at time of death. Over time, the PMRs significantly decreased for ADCs (2.6%, 1.4%, 1.2%) and increased for NADCs (4.3%, 7.0%, 12.3%). For all years combined (1996–2013) and compared to the California population, significantly elevated SMRs were observed for these cancers: all NADCs combined (2.1), anal (58.4), Hodgkin lymphoma (10.5), liver (5.2), lung/larynx (3.0), rectal (5.2), and tongue (4.7). Over time, the SMRs for liver cancer (SMR 19.8, 11.2, 5.0) significantly decreased while the SMRs remained significantly elevated over population levels for anal (SMR 123, 48.2, 45.5), liver (SMR 19.8, 11.2, 5.0), and lung/larynx cancer (SMR 5.3, 4.7, 3.6).ConclusionA decline in ADC PMRs and increase in NADC PMRs represent a shift in the cancer burden, likely due to ART use. Moreover, given their elevated SMRs, anal, liver, and lung/larynx cancer remain targets for improved cancer prevention, screening, and treatment.     

Osteogenesis imperfecta: the audiological phenotype lacks correlation with the genotype

Background

Neurofibromatosis 1 (NF1), a common autosomal dominant disorder, was shown in one study to be associated with a 15-year decrease in life expectancy. However, data on mortality in NF1 are limited. Our aim was to evaluate mortality in a large retrospective cohort of NF1 patients seen in France between 1980 and 2006.

Methods

Consecutive NF1 patients referred to the National French Referral Center for Neurofibromatoses were included. The standardized mortality ratio (SMR) with its 95% confidence interval (CI) was calculated as the ratio of observed over expected numbers of deaths. We studied factors associated with death and causes of death.

Results

Between 1980 and 2006, 1895 NF1 patients were seen. Median follow-up was 6.8 years (range, 0.4-20.6). Vital status was available for 1226 (65%) patients, of whom 1159 (94.5%) survived and 67 (5.5%) died. Overall mortality was significantly increased in the NF1 cohort (SMR, 2.02; CI, 1.6-2.6; P < 10^-4). The excess mortality occurred among patients aged 10 to 20 years (SMR, 5.2; CI, 2.6-9.3; P < 10^-4) and 20 to 40 years (SMR, 4.1; 2.8-5.8; P < 10^-4). Significant excess mortality was found in both males and females. In the 10-20 year age group, females had a significant increase in mortality compared to males (SMR, 12.6; CI, 5.7-23.9; and SMR, 1.8; CI, 0.2-6.4; respectively). The cause of death was available for 58 (86.6%) patients; malignant nerve sheath tumor was the main cause of death (60%).

Conclusions

We found significantly increased SMRs indicating excess mortality in NF1 patients compared to the general population. The definitive diagnosis of NF1 in all patients is a strength of our study, and the high rate of death related to malignant transformation is consistent with previous work. The retrospective design and hospital-based recruitment are limitations of our study. Mortality was significantly increased in NF1 patients aged 10 to 40 years and tended to be higher in females than in males.     

Recent decline in the U.S. death rate from myeloproliferative neoplasms, 1999-2006

Background: Myeloproliferative neoplasms (MPNs) are classified as neoplasms of uncertain or unknown behavior in the International Classification of Diseases (ICD) Version 10 and can contribute to risk of death from complications (especially thrombosis). Methods: U.S age-standardized death rates using ICD-Version 10 codes relevant to classical MPN (i.e., polycythemia vera, essential thrombocythemia, and “chronic myeloproliferative disease”) were examined for 1999–2006. The underlying cause of death and also all causes (“multiple causes” or “mentions”) coded on death certificates were considered. Trends were assessed by using percentage change (PC) in rate between 1999 and 2006, and annual percentage change (APC) estimated from linear regression. Results: The decline in death rates was large for MPN, whether based only the underlying cause (PC = ?19.7%, APC = ?3.4%) or on the substantially higher rates based on any cause (PC = ?24.1%, APC = ?3.8%), and was consistent by gender and age group (<65 and 65+ years). For deaths with MPN coded as other than the underlying cause, cardiovascular diseases were the most common underlying cause and the ASR for these deaths declined substantially (PC = ?40.0%). Conclusions: Use of the underlying cause of death in surveillance will considerably underestimate MPN-related mortality rates in the population. Studies are needed on treatment in random samples of MPN patients from population-based cancer registries. Continued surveillance of MPN-related mortality rates in the population is needed in view of recent attempts (including the use of aspirin) to control cardiovascular complications of MPN.     

Relationship of income and childlessness

ABSTRACT

We investigated the impact of diabetes on US life expectancy by sex and race/ethnicity using a prospective cohort study design. Cohorts were drawn from 1997 to 2009 waves of the National Health Interview Survey and linked to death records through December 31, 2011. We combined data on the prevalence of diabetes among decedents with estimates of the hazard ratios of individuals diagnosed with diabetes to calculate population attributable fractions (PAFs) by age, sex, and race/ethnicity at ages 30 and above. These estimates were then applied to deaths in the official US life table for 2010 to estimate effects of diabetes on life expectancy.

Diabetes was responsible for a reduction of 0.83 years of life expectancy for men at age 30 and 0.89 years for 30-year-old women. The impact was greatest among Black women at 1.05 years. Estimates based on traditional demographic and actuarial methods using the frequency with which a disease appears as an underlying cause of death on death certificates produced a reduction in life expectancy at age 30 of only 0.33 years.

We conclude that diabetes is substantially reducing US longevity and that its effect is seriously underestimated when using data on underlying causes of death.     

Impact of using multiple causes of death codes to compute site-specific, death certificate-based cancer mortality statistics in the United States

Background: Cancer mortality statistics, an important indicator for monitoring cancer burden, are traditionally restricted to instances when cancer is determined to be the underlying cause of death (UCD) based on information recorded on standard certificates of death. This study's objective was to determine the impact of using multiple causes of death codes to compute site-specific cancer mortality statistics. Methods: The state cancer registries of California, Colorado and Idaho provided linked cancer registry and death certificate data for individuals who died between 2002 and 2004, had at least one cancer listed on their death certificate and were diagnosed with cancer between 1993 and 2004. These linked data were used to calculate the site-specific proportion of cancers not selected as the UCD (non-UCD) among all cancer-related deaths (any mention on the death certificate). In addition, the retrospective concordance between the death certificate and the population-based cancer registry, measured as confirmations rates, was calculated for deaths with cancer as the UCD, as a non-UCD, and for any mention. Results: Overall, non-UCD deaths comprised 9.5 percent of total deaths; 11 of the 79 cancer sites had proportions greater than 3 standard deviations from 9.5 percent. The confirmation rates for UCD and for any mention did not differ significantly for any of the cancer sites. Conclusion and impact: The site-specific variation in proportions and rates suggests that for a few cancer sites, death rates might be computed for both UCD and any mention of the cancer site on the death certificate. Nevertheless, this study provides evidence that, in general, restricting to UCD deaths will not under report cancer mortality statistics.     

Postmortem investigations and identification of multiple causes of child deaths: An analysis of findings from the Child Health and Mortality Prevention Surveillance (CHAMPS) network

BackgroundThe current burden of >5 million deaths yearly is the focus of the Sustainable Development Goal (SDG) to end preventable deaths of newborns and children under 5 years old by 2030. To accelerate progression toward this goal, data are needed that accurately quantify the leading causes of death, so that interventions can target the common causes. By adding postmortem pathology and microbiology studies to other available data, the Child Health and Mortality Prevention Surveillance (CHAMPS) network provides comprehensive evaluations of conditions leading to death, in contrast to standard methods that rely on data from medical records and verbal autopsy and report only a single underlying condition. We analyzed CHAMPS data to characterize the value of considering multiple causes of death.Methods and findingsWe examined deaths identified from December 2016 through November 2020 from 7 CHAMPS sites (in Bangladesh, Ethiopia, Kenya, Mali, Mozambique, Sierra Leone, and South Africa), including 741 neonatal, 278 infant, and 241 child <5 years deaths for which results from Determination of Cause of Death (DeCoDe) panels were complete. DeCoDe panelists included all conditions in the causal chain according to the ICD-10 guidelines and assessed if prevention or effective management of the condition would have prevented the death. We analyzed the distribution of all conditions listed as causal, including underlying, antecedent, and immediate causes of death. Among 1,232 deaths with an underlying condition determined, we found a range of 0 to 6 (mean 1.5, IQR 0 to 2) additional conditions in the causal chain leading to death. While pathology provides very helpful clues, we cannot always be certain that conditions identified led to death or occurred in an agonal stage of death. For neonates, preterm birth complications (most commonly respiratory distress syndrome) were the most common underlying condition (n = 282, 38%); among those with preterm birth complications, 256 (91%) had additional conditions in causal chains, including 184 (65%) with a different preterm birth complication, 128 (45%) with neonatal sepsis, 69 (24%) with lower respiratory infection (LRI), 60 (21%) with meningitis, and 25 (9%) with perinatal asphyxia/hypoxia. Of the 278 infant deaths, 212 (79%) had ≥1 additional cause of death (CoD) beyond the underlying cause. The 2 most common underlying conditions in infants were malnutrition and congenital birth defects; LRI and sepsis were the most common additional conditions in causal chains, each accounting for approximately half of deaths with either underlying condition. Of the 241 child deaths, 178 (75%) had ≥1 additional condition. Among 46 child deaths with malnutrition as the underlying condition, all had ≥1 other condition in the causal chain, most commonly sepsis, followed by LRI, malaria, and diarrheal disease. Including all positions in the causal chain for neonatal deaths resulted in 19-fold and 11-fold increases in attributable roles for meningitis and LRI, respectively. For infant deaths, the proportion caused by meningitis and sepsis increased by 16-fold and 11-fold, respectively; for child deaths, sepsis and LRI are increased 12-fold and 10-fold, respectively. While comprehensive CoD determinations were done for a substantial number of deaths, there is potential for bias regarding which deaths in surveillance areas underwent minimally invasive tissue sampling (MITS), potentially reducing representativeness of findings.ConclusionsIncluding conditions that appear anywhere in the causal chain, rather than considering underlying condition alone, markedly changed the proportion of deaths attributed to various diagnoses, especially LRI, sepsis, and meningitis. While CHAMPS methods cannot determine when 2 conditions cause death independently or may be synergistic, our findings suggest that considering the chain of events leading to death can better guide research and prevention priorities aimed at reducing child deaths.

In an analysis of data from the Child Health and Mortality Prevention Surveillance (CHAMPS) network, Robert Breiman, Dianna Blau, and colleagues investigate how considering all conditions in the causal chain leading to death informs the identification of deaths attributable to various diagnoses.     

The impact of highly active antiretroviral therapy on the survival of vertically HIV-infected children and adolescents in Belo Horizonte, Brazil

The use of highly active antiretroviral therapy (HAART) for human immunodeficiency virus (HIV)-infected patients has reduced the number of acquired immune deficiency syndrome-related deaths worldwide. This study assessed the impact of HAART on the survival and death rates of vertically HIV-infected children and adolescents in Belo Horizonte, Brazil. Data were obtained from a historic cohort of vertically HIV-infected children and adolescents aged zero-19 years old who were admitted from March 1989-December 2004 and were followed until June 2006. Patients who used HAART were included if they were treated for at least 12 weeks. Of 359 patients, 320 patients met the inclusion criteria. The overall mortality rate was 9.7% [31/320; 95% confidence interval (CI): 6.0-13%]. The median survival for the non-HAART and HAART groups was 31.5 and 55.9 months, respectively (log rank = 22.11, p < 0.0001). In the multivariate analysis, the statistically significant variables were HAART and the weight-for-age Z score < -2, with HAART constituting a protective factor [relative risk (RR): 0.13; CI 95%: 0.05-0.33] and malnutrition constituting a risk factor (RR: 3.44; CI 95%: 1.60-7.40) for death. The incidence of death was 5.1/100 person-years in the non-HAART group and 0.8/100 person-years in the HAART group (p < 0.0001).     

Trend (1999–2009) in U.S. death rates from myelodysplastic syndromes: Utility of multiple causes of death in surveillance

BackgroundFor myelodysplastic syndromes (MDS) (formerly known as preleukemia), a diverse group of myeloid neoplasms usually involving anemia in elderly persons, trends in U.S. death rates apparently have not been reported.MethodsTrends in annual age-standardized rates per 100,000 from 1999 to 2009 were examined for MDS using multiple causes vs. underlying cause alone, coded on death certificates for U.S. residents.ResultsThe death rate (all ages combined) for MDS increased from 1999 to 2009, from 1.62 to 1.84 using underlying cause alone and from 2.89 to 3.27 using multiple causes. Rates using multiple causes were about 80% higher than those based on underlying cause alone. From 2001 to 2004 the rate for MDS using underlying cause alone (but not using multiple causes) declined, accompanied by an increase in the rate for deaths from leukemia as underlying cause with mention of MDS; this trend coincided with the advent of the 2001 World Health Organization's reclassification of certain MDS as leukemia. The MDS rate for age 65+ years increased after 2005, whereas the rate for age 25–64 years was low but declined from 2001 to 2003 and then stabilized. For deaths with MDS coded as other than underlying cause, rates did not decline for deaths from each of the two most common causes (i.e., cardiovascular diseases and leukemia).ConclusionsEvidence for decreases in MDS-related mortality rates was limited; the increase at age 65+ years is consistent with increases in incidence rates reported from cancer registries. Using multiple causes of death vs. only the underlying cause results in substantially higher MDS-related death rates, shows the impact of changes in the classification of myeloid neoplasms and emphasizes the importance of reducing cardiovascular disease mortality in MDS patients.     

The validity of cancer information on death certificates in Norway and the impact of death certificate initiated cases on cancer incidence and survival

BackgroundDeath certificates are an important source of information for cancer registries. The aim of this study was to validate the cancer information on death certificates, and to investigate the effect of including death certificate initiated (DCI) cases in the Cancer Registry of Norway when estimating cancer incidence and survival.MethodsAll deaths in Norway in the period 2011–2015 with cancer mentioned on the death certificates were linked to the cancer registry. Notifications not registered from other sources were labelled death certificate notifications (DCNs), and considered as either cancer or not, based on available information in the registry or from trace-back to another source.ResultsFrom the total of 65 091 cancers mentioned on death certificates in the period 2011–2015, 58,425 (89.8%) were already in the registry. Of the remaining 6 666 notifications, 2 636 (2 129 with cancer as underlying cause) were not regarded to be new cancers, which constitutes 4.0% of all cancers mentioned on death certificates and 39.5% of the DCNs. Inclusion of the DCI cases increased the incidence of all cancers combined by 2.6%, with largest differences for cancers with poorer prognosis and for older age groups. Without validation, including the 2 129 disregarded death certificates would over-estimate the incidence by 1.3%. Including DCI cases decreased the five-year relative survival estimate for all cancer sites combined with 0.5% points.ConclusionIn this study, almost 40% of the DCNs were regarded not to be a new cancer case, indicating unreliability of death certificate information for cancers that are not already registered from other sources. The majority of the DCNs where, however, registered as new cases that would have been missed without death certificates. Both including and excluding the DCI cases will potentially bias the survival estimates, but in different directions. This biases were shown to be small in the Cancer Registry of Norway.     

Causes of Mortality for Indonesian Hajj Pilgrims: Comparison between Routine Death Certificate and Verbal Autopsy Findings

Background

Indonesia provides the largest single source of pilgrims for the Hajj (10%). In the last two decades, mortality rates for Indonesian pilgrims ranged between 200–380 deaths per 100,000 pilgrims over the 10-week Hajj period. Reasons for high mortality are not well understood. In 2008, verbal autopsy was introduced to complement routine death certificates to explore cause of death diagnoses. This study presents the patterns and causes of death for Indonesian pilgrims, and compares routine death certificates to verbal autopsy findings.

Methods

Public health surveillance was conducted by Indonesian public health authorities accompanying pilgrims to Saudi Arabia, with daily reporting of hospitalizations and deaths. Surveillance data from 2008 were analyzed for timing, geographic location and site of death. Percentages for each cause of death category from death certificates were compared to that from verbal autopsy.

Results

In 2008, 206,831 Indonesian undertook the Hajj. There were 446 deaths, equivalent to 1,968 deaths per 100,000 pilgrim years. Most pilgrims died in Mecca (68%) and Medinah (24%). There was no statistically discernible difference in the total mortality risk for the two pilgrimage routes (Mecca or Medinah first), but the number of deaths peaked earlier for those traveling to Mecca first (p=0.002). Most deaths were due to cardiovascular (66%) and respiratory (28%) diseases. A greater proportion of deaths were attributed to cardiovascular disease by death certificate compared to the verbal autopsy method (p<0.001). Significantly more deaths had ill-defined cause based on verbal autopsy method (p<0.001).

Conclusions

Despite pre-departure health screening and other medical services, Indonesian pilgrim mortality rates were very high. Correct classification of cause of death is critical for the development of risk mitigation strategies. Since verbal autopsy classified causes of death differently to death certificates, further studies are needed to assess the method’s utility in this setting.     

Relationship between Body Mass Index and Mortality in HIV-Infected HAART Users in the Women's Interagency HIV Study

Background

Early HIV studies suggested protective associations of overweight against mortality, yet data are lacking for the era of potent highly active antiretroviral therapy (HAART). We evaluated associations of pre-HAART initiation body mass index (BMI) with mortality among HAART-using women.

Methods

Prospective study of time to death after HAART initiation among continuous HAART users in the Women’s Interagency HIV Study. Unadjusted Kaplan–Meier and adjusted proportional hazards survival models assessed time to AIDS and non-AIDS death by last measured pre-HAART BMI.

Results

Of 1428 continuous HAART users 39 (2.7%) were underweight, 521 (36.5%) normal weight, 441 (30.9%) overweight, and 427 (29.9%) obese at time of HAART initiation. A total of 322 deaths occurred during median follow-up of 10.4 years (IQR 5.9–14.6). Censoring at non-AIDS death, the highest rate of AIDS death was observed among underweight women (p = 0.0003 for all 4 categories). In multivariate models, women underweight prior to HAART died from AIDS more than twice as rapidly vs. normal weight women (aHR 2.04, 95% CI 1.03, 4.04); but being overweight or obese (vs. normal weight) was not independently associated with AIDS death. Cumulative incidence of non-AIDS death was similar across all pre-HAART BMI categories.

Conclusions

Among continuous HAART-using women, being overweight prior to initiation was not associated with lower risk of AIDS or non-AIDS death. Being underweight prior to HAART was associated with over double the rate of AIDS death in adjusted analyses. Although overweight and obesity may be associated with many adverse health conditions, neither was predictive of mortality among the HAART-using women.     

Mortality and cancer incidence in males with Y polysomy in Britain: a cohort study

The mortality and cancer incidence risks among males with Y polysomy are unknown because there have been no large long-term cohort studies carried out of such men. We conducted a cohort study of 667 men diagnosed with the abnormality in Britain since 1959 to compare their mortality and cancer incidence rates with those of the general population. Sixty deaths occurred during follow-up to December 2005, twice the number expected from general population rates (standardised mortality ratio (SMR) = 2.0 (95% confidence interval (CI) 1.5–2.6)). Significantly raised mortality was observed for diseases of the nervous system (SMR = 7.0, 95% CI: 2.3–16.4), circulatory system (SMR = 2.1, 95% CI: 1.3–3.2), respiratory system (SMR = 4.0, 95% CI: 1.8–7.5), genitourinary system (SMR = 10.2, 95% CI: 1.2–36.9), and congenital anomalies (SMR = 11.9, 95% CI: 3.2–30.5). Four of the five nervous system deaths were from epilepsy, the risk of death from this condition being more than 20-fold raised. The rates of cancer incidence and mortality among these men was not significantly different from those in the general population. This study provides evidence that mortality rates from several specific causes are raised among men with Y polysomy. The use of these data in genetic counselling should be cautious particularly for cases of Y polysomy that are detected prenatally. Further investigations are required to confirm these findings and to elucidate the possible role of genes on the Y chromosome in the aetiology of these causes of death.     

Evaluation of cause of deaths' validity using outcome measures from a prospective, population based cohort study in Tehran, Iran

Objective

The aim of this study was to evaluate the validity of cause of death stated in death certificates in Tehran using outcome measures of the Tehran Lipid and Glucose Study (TLGS), an ongoing prospective cohort study.

Methods

The cohort was established in 1999 in a population of 15005 people, 3 years old and over, living in Tehran; 3551 individuals were added to this population three years later. As part of cohort''s outcome measures, deaths occurring in the cohort are investigated by a panel of medical specialists (Cohort Outcome Panel-COP) and underlying cause of death is determined for each death. The cause of death assigned in a deceased''s original death certificate was evaluated against the cause of death determined by COP and sensitivity and positive predictive values (PPV) were determined. In addition, determinants of assigning accurate underlying cause of death were determined using logistic regression model.

Result

A total of 231 death certificates were evaluated. The original death certificates over reported deaths due to neoplasms and underreported death due to circulatory system and transport accidents. Neoplasms with sensitivity of 0.91 and PPV of 0.71 were the most valid category. The disease of circulatory system showed moderate degree of validity with sensitivity of 0.67 and PPV of 0.78. The result of logistic regression indicated if the death certificate is issued by a general practitioner, there is 2.3 (95% CI 1.1, 5.1) times chance of being misclassified compared with when it is issued by a specialist. If the deceased is more than 60 years, the chance of misclassification would be 2.5 times (95% CI of 1.1, 5.9) compared with when the deceased is less than 60 years.     

Cancer mortality in Itapúa—A rural province of Paraguay 2003–2012

BackgroundItapúa is a rural department in Paraguay with a population of about 500,000 and a high degree of agro-mechanization for the production of soybean and other crops. So far, only basic health care is provided. Here we analyzed the cancer mortality in this region as a first step towards epidemiological data for cancer prevention.MethodsWe calculated the age-adjusted mortality rates according to world standard (AMRWs) for the major cancer sites in both males and females between 2003 and 2012, and estimated the differences between the capital and more central districts of Itapúa vs. remote districts.ResultsThere were about 2000 cancer deaths in the decade studied, with AMRWs for all malignancies of 90.9/100,000 in males from central vs. 49.1/100,000 in remote districts and 69.0/100,000 vs. 45.0/100,000 in women. Cancer was mentioned in 12.4% of all death certificates and outweighed mortality from certain infectious and parasitic diseases (3.6%). Cause of death was ill-defined in 19.6% of all death certificates, especially in remote regions and among the elderly. The part of cancer located in the uterus (47.8%) or cell type of neoplasm of the lymphatic or hematopoietic system (73.1%) were often not specified. The uterus (mainly the cervix) (C53–C55) was the leading cancer site in women with AMRWs of 17.2/100,000 in central and 14.0/100,000 in remote districts, followed by the breast. Lung and prostate were the leading cancer sites among men. The lung cancer mortality rate was 19.3/100,000 in the central region but 9.5/100,000 in remote districts. Although children comprised 36% of the population, only 24 death certificates listed cancer as cause of death in this decade.ConclusionsAnalysis of cancer mortality in this rural region of Paraguay, which lacks resources for diagnostics and care, revealed an already large number of cases, with higher rates in the central region than in remote districts. Lung and uterus (primarily the cervix) are common cancer sites and indicate the potential for prevention. However, the quality of the vital statistics needs to be improved. The true cancer burden is most likely underestimated, especially in remote regions and children.     

Reduction of Maternal Mortality with Highly Active Antiretroviral Therapy in a Large Cohort of HIV-Infected Pregnant Women in Malawi and Mozambique

Background

HIV infection is a major contributor to maternal mortality in resource-limited settings. The Drug Resource Enhancement Against AIDS and Malnutrition Programme has been promoting HAART use during pregnancy and postpartum for Prevention-of-mother-to-child-HIV transmission (PMTCT) irrespective of maternal CD4 cell counts since 2002.

Methods

Records for all HIV+ pregnancies followed in Mozambique and Malawi from 6/2002 to 6/2010 were reviewed. The cohort was comprised by pregnancies where women were referred for PMTCT and started HAART during prenatal care (n = 8172, group 1) and pregnancies where women were referred on established HAART (n = 1978, group 2).

Results

10,150 pregnancies were followed. Median (IQR) baseline values were age 26 years (IQR:23–30), CD4 count 392 cells/mm³ (IQR:258–563), Viral Load log₁₀ 3.9 (IQR:3.2–4.4), BMI 23.4 (IQR:21.5–25.7), Hemoglobin 10.0 (IQR: 9.0–11.0). 101 maternal deaths (0.99%) occurred during pregnancy to 6 weeks postpartum: 87 (1.1%) in group 1 and 14 (0.7%) in group 2. Mortality was 1.3% in women with <than 350 CD4 cells/mm³ and 0.7% in women with greater than 350 CD4s cells/mm³ [OR = 1.9 (CL 1.3–2.9) p = 0.001]. Mortality was higher in patients with shorter antenatal HAART: 22/991 (2.2%) if less than 30 days and 79/9159 (0.9%) if 31 days or greater [OR = 2.6 (CL 1.6–4.2) p<0.001]. By multivariate analysis, shorter antenatal HAART (p<0.001), baseline values for CD4 cell count (p = 0.012), hemoglobin (p = 0.02), and BMI (p<0.001) were associated with mortality. Four years later, survival was 92% for women with shorter antenatal HAART and 98% for women on established therapy prior to pregnancy, p = 0.001.

Conclusions

Antiretrovirals for PMTCT purposes have significant impact on maternal mortality as do CD4 counts and nutritional status. In resource-limited settings, PMTCT programs should provide universal HAART to all HIV+ pregnant women given its impact in prevention of maternal death.     

Individuals with higher metabolic rates have lower levels of reactive oxygen species in vivo

There is increasing interest in the effect of energy metabolism on oxidative stress, but much ambiguity over the relationship between the rate of oxygen consumption and the generation of reactive oxygen species (ROS). Production of ROS (such as hydrogen peroxide, H₂O₂) in the mitochondria is primarily inferred indirectly from measurements in vitro, which may not reflect actual ROS production in living animals. Here, we measured in vivo H₂O₂ content using the recently developed MitoB probe that becomes concentrated in the mitochondria of living organisms, where it is converted by H₂O₂ into an alternative form termed MitoP; the ratio of MitoP/MitoB indicates the level of mitochondrial H₂O₂ in vivo. Using the brown trout Salmo trutta, we tested whether this measurement of in vivo H₂O₂ content over a 24 h-period was related to interindividual variation in standard metabolic rate (SMR). We showed that the H₂O₂ content varied up to 26-fold among fish of the same age and under identical environmental conditions and nutritional states. Interindividual variation in H₂O₂ content was unrelated to mitochondrial density but was significantly associated with SMR: fish with a higher mass-independent SMR had a lower level of H₂O₂. The mechanism underlying this observed relationship between SMR and in vivo H₂O₂ content requires further investigation, but may implicate mitochondrial uncoupling which can simultaneously increase SMR but reduce ROS production. To our knowledge, this is the first study in living organisms to show that individuals with higher oxygen consumption rates can actually have lower levels of H₂O₂.     

Trauma-Related Mortality among Adults in Rural Western Kenya: Characterising Deaths Using Data from a Health and Demographic Surveillance System

Background

Information on trauma-related deaths in low and middle income countries is limited but needed to target public health interventions. Data from a health and demographic surveillance system (HDSS) were examined to characterise such deaths in rural western Kenya.

Methods And Findings

Verbal autopsy data were analysed. Of 11,147 adult deaths between 2003 and 2008, 447 (4%) were attributed to trauma; 71% of these were in males. Trauma contributed 17% of all deaths in males 15 to 24 years; on a population basis mortality rates were greatest in persons over 65 years. Intentional causes accounted for a higher proportion of male than female deaths (RR 2.04, 1.37-3.04) and a higher proportion of deaths of those aged 15 to 65 than older people. Main causes in males were assaults (n=79, 25%) and road traffic injuries (n=47, 15%); and falls for females (n=17, 13%). A significantly greater proportion of deaths from poisoning (RR 5.0, 2.7-9.4) and assault (RR 1.8, 1.2-2.6) occurred among regular consumers of alcohol than among non-regular drinkers. In multivariate analysis, males had a 4-fold higher risk of death from trauma than females (Adjusted Relative Risk; ARR 4.0; 95% CI 1.7-9.4); risk of a trauma death rose with age, with the elderly at 7-fold higher risk (ARR 7.3, 1.1-49.2). Absence of care was the strongest predictor of trauma death (ARR 12.2, 9.4-15.8). Trauma-related deaths were higher among regular alcohol drinkers (ARR 1.5, 1.1-1.9) compared with non-regular drinkers.

Conclusions

While trauma accounts for a small proportion of deaths in this rural area with a high prevalence of HIV, TB and malaria, preventive interventions such as improved road safety, home safety strategies for the elderly, and curbing harmful use of alcohol, are available and could help diminish this burden. Improvements in systems to record underlying causes of death from trauma are required.     

Hot-water spraying is a sensitive test for signs of life before dressing and scalding in pig abattoirs with carbon dioxide (CO2) stunning

This study investigated the benefits of hot-water spraying (HWS) as a diagnostic test to verify the absence of signs of life (SOL) before scalding in pigs slaughtered with carbon dioxide (CO₂) stunning. A total of 37 108 finishing pigs from five German abattoirs (A to E) operating at 55 to 571 pigs per hour were assessed. Suspended pigs were sprayed onto the muzzle, head and front legs (143 to 258 s post sticking for 4 to 10 s, 57°C to 72°C). Any active movements during HWS were rated as positive test outcomes. In comparison, SOL were considered to be absent if a subsequent manual examination was negative and no active movements were observed following HWS. The incidence of pigs with activity during hot-water spraying (PWA) was restricted to two abattoirs (B: 0.25%; D: 0.02%; A, C, E: 0.00%). PWA showed movements of facial muscles (88%), mouth opening (78%), righting reflex (63%), isolated leg movements (35%) and vocalization (4%). The manual examination was positive in 71% of PWA (corneal/dazzle reflex: 67%/53%, nasal septum pinch: 33%), whereas all inactive pigs tested negative (P<0.001). The sensitivity for HWS as a test for SOL was calculated as 100%, dropping to 75% when only obvious and strong movements were taken into account. The specificity was >99.9% in either case. Any positive manual findings as well as any respiratory activity were instantly terminated using a penetrating captive bolt. Active movements triggered by the shot were shown to be an indicator for SOL (P<0.001). Video analyses revealed that spontaneous movements (SM) following sticking were present in 100% of PWA as opposed to 3.1% in pigs without such activity (controls). Results for different categories of SM in PWA v. controls were as follows: 100% v. 2.6% for mouth opening, 16.0% v. 0.1% for righting reflex and 22.0% v. 0.9% for isolated leg movements (all P<0.001). First mouth opening after sticking was observed later in PWA (28±24 v. 10±7 s), but mouth openings were observed for a longer period of time (141±44 v. 27±25 s) (both P<0.001). PWA with shorter mouth-opening intervals showed higher movement intensities during HWS and more positive manual findings (P<0.05). We conclude that HWS is a promising test for SOL. SM and sustained mouth opening in particular are indicators for compromised animal welfare and affected pigs should be shot by captive bolt.