Vulnerable newborn types: analysis of subnational, population-based birth cohorts for 541 285 live births in 23 countries, 2000-2021.

OBJECTIVE: To examine prevalence of novel newborn types among 541 285 live births in 23 countries from 2000 to 2021. DESIGN: Descriptive multi-country secondary data analysis. SETTING: Subnational, population-based birth cohort studies (n = 45) in 23 low- and middle-income countries (LMICs) spanning 2000-2021. POPULATION: Liveborn infants. METHODS: Subnational, population-based studies with high-quality birth outcome data from LMICs were invited to join the Vulnerable Newborn Measurement Collaboration. We defined distinct newborn types using gestational age (preterm [PT], term [T]), birthweight for gestational age using INTERGROWTH-21st standards (small for gestational age [SGA], appropriate for gestational age [AGA] or large for gestational age [LGA]), and birthweight (low birthweight, LBW [<2500 g], nonLBW) as ten types (using all three outcomes), six types (by excluding the birthweight categorisation), and four types (by collapsing the AGA and LGA categories). We defined small types as those with at least one classification of LBW, PT or SGA. We presented study characteristics, participant characteristics, data missingness, and prevalence of newborn types by region and study. RESULTS: Among 541 285 live births, 476 939 (88.1%) had non-missing and plausible values for gestational age, birthweight and sex required to construct the newborn types. The median prevalences of ten types across studies were T+AGA+nonLBW (58.0%), T+LGA+nonLBW (3.3%), T+AGA+LBW (0.5%), T+SGA+nonLBW (14.2%), T+SGA+LBW (7.1%), PT+LGA+nonLBW (1.6%), PT+LGA+LBW (0.2%), PT+AGA+nonLBW (3.7%), PT+AGA+LBW (3.6%) and PT+SGA+LBW (1.0%). The median prevalence of small types (six types, 37.6%) varied across studies and within regions and was higher in Southern Asia (52.4%) than in Sub-Saharan Africa (34.9%). CONCLUSIONS: Further investigation is needed to describe the mortality risks associated with newborn types and understand the implications of this framework for local targeting of interventions to prevent adverse pregnancy outcomes in LMICs.

Thermodynamic Analysis of a Flat Plate Solar Collector with Different Hybrid Nanofluids as Working Medium-A Thermal Modelling Approach.

In this study, the performance of hybrid nanofluids in a flat plate solar collector was analysed based on various parameters such as entropy generation, exergy efficiency, heat transfer enhancement, pumping power, and pressure drop. Five different base fluids were used, including water, ethylene glycol, methanol, radiator coolant, and engine oil, to make five types of hybrids nanofluids containing suspended CuO and MWCNT nanoparticles. The nanofluids were evaluated at nanoparticle volume fractions ranging from 1% to 3% and flow rates of 1 to 3.5 L/min. The analytical results revealed that the CuO-MWCNT/water nanofluid performed the best in reducing entropy generation at both volume fractions and volume flow rate when compared to the other nanofluids studied. Although CuO-MWCNT/methanol showed better heat transfer coefficients than CuO-MWCNT/water, it generated more entropy and had lower exergy efficiency. The CuO-MWCNT/water nanofluid not only had higher exergy efficiency and thermal performance but also showed promising results in reducing entropy generation.

Health care in pregnancy during the COVID-19 pandemic and pregnancy outcomes in six low- and-middle-income countries: Evidence from a prospective, observational registry of the Global Network for Women's and Children's Health

Objective: To assess, on a population basis, the medical care for pregnant women in specific geographic regions of six countries before and during the first year of the coronavirus disease 2019 (COVID-19) pandemic in relationship to pregnancy outcom. Results: Across all sites, a small but statistically significant increase in home births occurred between the pre-COVID-19 and COVID-19 periods (18.9% versus 20.3%, adjusted relative risk [aRR] 1.12, 95% CI 1.05­1.19). A small but significant decrease in the mean number of antenatal care visits (from 4.1 to 4.0, p = <0.0001) was seen during the COVID-19 period. Of outcomes evaluated, overall, a small but significant decrease in low-birthweight infants in the COVID-19 period occurred (15.7% versus 14.6%, aRR 0.94, 95% CI 0.89­0.99), but we did not observe any significant differences in other outcomes. There was no change observed in maternal mortality or antenatal haemorrhage overall or at any of the sites. Conclusions: Small but significant increases in home births and decreases in the antenatal care services were observed during the initial COVID-19 period; however, there was not an increase in the stillbirth, neonatal mortality, maternal mortality, low birthweight, or preterm birth rates during the COVID-19 period compared with the previous year. Further research should help to elucidate the relationship between access to and use of pregnancy-related medical services and birth outcomes over an extended period

Combinatorial topology and geometry of fracture networks.

A map is proposed from the space of planar surface fracture networks to a four-parameter mathematical space, summarizing the average topological connectivity and geometrical properties of a network idealized as a convex polygonal mesh. The four parameters are identified as the average number of nodes and edges, the angular defect with respect to regular polygons, and the isoperimetric ratio. The map serves as a low-dimensional signature of the fracture network and is visually presented as a pair of three-dimensional graphs. A systematic study is made of a wide collection of real crack networks for various materials, collected from different sources. To identify the characteristics of the real materials, several well-known mathematical models of convex polygonal networks are presented and worked out. These geometric models may correspond to different physical fracturing processes. The proposed map is shown to be discriminative, and the points corresponding to materials of similar properties are found to form closely spaced groups in the parameter space. Results for the real and simulated systems are compared in an attempt to identify crack networks of unknown materials.

Knowledge, attitude and practices of pregnant women related to COVID-19 infection: A cross-sectional survey in seven countries from the Global Network for Women's and Children's Health

Objective. We sought to understand knowledge, attitudes and practices (KAP) regarding COVID-19 in pregnant women in seven low and middle-income countries (LMIC). Results. In all, 25 260 women completed the survey. Overall, 56.8% of women named ≥3 COVID-19 symptoms, 34.3% knew ≥2 transmission modes, 51.3% knew ≥3 preventive measures and 79.7% named at least one high-risk condition. Due to COVID-19 exposure concerns, 23.8% had avoided prenatal care and 7.5% planned to avoid hospital delivery. Over half the women in the Guatemalan site and 40% in the Pakistan site reduced care seeking due to COVID-19 exposure concerns. Of the women, 24.0% were afraid of getting COVID-19 from healthcare providers. Overall, 63.3% reported wearing a mask and 29.1% planned to stay at home to reduce COVID-19 exposure risk

Knowledge of Stroke and its Risk Factors among Stroke Survivors: A Hospital Based Study.

Significant variations observed in stroke incidence, risk factors and sufferings between high & resource poor countries. Considering lack of study in our country perspective, the study was designed to assess the knowledge of stroke and its risk factors among stroke survivors in Bangladeshi population. This hospital based cross-sectional study was conducted at the Department of Medicine and Department of Neurology in Uttara Adhunik Medical College & Hospital (UAMCH), Dhaka, Bangladesh. Patients aged >18 years who were admitted with stroke (Ischemic and hemorrhagic) were included in the study. Before enrollment informed consent was ensured. Total 50 patients were interviewed and assessed. Separate case record form was used during data collection. Final analysis was done by SPSS 22.00 version software. A 'good' knowledge of stroke was defined by correct answer to ≥4 out of 7 questions about location, cause, risk factor, warning sign, treatment, complication and prevention of stroke. Among 50 stroke survivors, mean age was 58.34±12.90 (SD) years. Male-female ratio was 1.08:1. Overall 78% patients had good knowledge of stroke. Brain was correctly identified as center of stroke by 52% stroke survivors and disturbance of blood supply to brain as a cause of stroke was recognized by 12%. Stress was the most common risk factor identified (50%). At least one warning sign was identified by 76% stroke survivors. Seventy-four percent stroke survivors knew that they have to be taken to nearest health facility and if possible, in hospital where neurological care is available. Only 4% knew about the golden hour of taking the stroke patient. On average knowledge about treatment, complication and prevention of stroke was good. Stroke knowledge was not significantly associated with demographic and socio-economic profile of stroke survivors. More than two thirds of the patients had knowledge regarding stroke and its risk factors but no uniform pattern of knowledge is noticed.

Altered distributions in circulating follicular helper and follicular regulatory T cells accountable for imbalanced cytokine production in multiple sclerosis.

Follicular T helper (Tfh) and regulatory (Tfr) cells are distinct subsets of CD4+ T lymphocytes, regulating humoral immune responses in the germinal center. It is widely accepted that dysregulated Tfh and Tfr cells are associated with autoimmunity. In this study, we evaluated the frequencies of circulating chemokine receptor (CXCR)5+ programmed cell death 1 (PD-1+ ) Tfh (cTfh) and CXCR5+ PD-1+ forkhead box protein 3 (FoxP3+ ) CD25+ Tfr (cTfr) cells, and their corresponding cytokines from the peripheral blood mononuclear cells of 28 patients with relapsing-remitting multiple sclerosis (MS) and 16 age- and sex-matched healthy controls (HC). Subsets of cTfh cells by Th1- and Th17-related surface markers (CXCR3 and CCR6) were also evaluated. We found that the frequency of cTfh cells was significantly higher in MS patients compared to that of HC. Conversely, the frequency of cTfr cells was lower in MS patients than that of HC. Interleukin (IL)-21-producing cTfh cells were significantly increased in MS patients, while IL-10-secreting cTfr cells were lower in MS patients compared to levels in HC. Among cTfh cells, cTfh17.1 cells were the major subtypes that were significantly increased in MS patients compared to HC, with the frequency of IL-21-secreting cells being the highest. These results suggest that an imbalanced distribution of cTfh and cTfr exist in MS patients, which contributes to the reciprocally altered IL-21 and IL-10 production.

Rehabilitation Approach of a Patient with Myositis Ossificans: Non-surgical Management, Hazard of being Unguided Over Exercised.

Myositis ossificans (MO) is a condition where calcification occurs in the soft tissue as well as around the bone following fracture, vigorous exercise or trauma. Although it is a radiological diagnosis, it often leads physician to an incorrect or missed diagnosis as recurrent fracture. Frequently, it follows haemorrhage into the muscle in the tissue space. We report a 45 years old house-wife presented with the complaints of weakness of right side of body and pain with restricted range of motion (ROM) in right lower limb. She was a diagnosed case of recurrent stroke with rheumatic valvular heart disease. After discharge, vigorous physical exercise was done at home by local physiotherapist without appropriate guidance from physiatrist. Gradually pain was so severe that she didn't allow moving her right lower limb. Over the course of time, she became incapacite and bed bound. She denied any positive family history. With the hip and lower limb problems she consulted with orthopedic surgeon and was referred to Physical Medicine and Rehabilitation department of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh for further management & rehabilitation. This case is presented to focus on hazard of being unguided, over-exercised and non-surgical management approach of this rare condition.

Design and microfabrication strategies for thin-film, flexible optical neural implant.

Advanced polymer science and design technologies are constantly evolving to meet ever-growing expectations for flexible optical MEMS. In this work, we present design and microfabrication considerations for designed flexible Polymeric Opto-Electro-Mechanical Systems (POEMS). The presented methods integrate waveguide fabrication and laser diode (LD) chip assembly with Lawrence Livermore National Laboratory's (LLNL's) flexible thin-film technology to enable LLNL's first neural optoelectrode that can deliver guided light for neural activation. We support our findings with electrical and optical bench verification tests, present thermal simulation models to analyze heat dissipation of laser light sources on polymer substrates and discuss potential modifications for next generation prototypes. This fully integrated approach will allow spatial precision, scalability and more particularly, longer lifetime, needed to enable chronic studies of brain activities.

Haloferax volcanii for biotechnology applications: challenges, current state and perspectives.

Haloferax volcanii is an obligate halophilic archaeon with its origin in the Dead Sea. Simple laboratory culture conditions and a wide range of genetic tools have made it a model organism for studying haloarchaeal cell biology. Halophilic enzymes of potential interest to biotechnology have opened up the application of this organism in biocatalysis, bioremediation, nanobiotechnology, bioplastics and the biofuel industry. Functionally active halophilic proteins can be easily expressed in a halophilic environment, and an extensive genetic toolkit with options for regulated protein overexpression has allowed the purification of biotechnologically important enzymes from different halophiles in H. volcanii. However, corrosion mediated damage caused to stainless-steel bioreactors by high salt concentrations and a tendency to form biofilms when cultured in high volume are some of the challenges of applying H. volcanii in biotechnology. The ability to employ expressed active proteins in immobilized cells within a porous biocompatible matrix offers new avenues for exploiting H. volcanii in biotechnology. This review critically evaluates the various application potentials, challenges and toolkits available for using this extreme halophilic organism in biotechnology.

Haloferax volcanii as immobilised whole cell biocatalyst: new applications for halophilic systems.

Enzyme-mediated synthesis of pharmaceutical compounds is a 'green' alternative to traditional synthetic chemistry, and microbial engineering opens up the possibility of using whole cells as mini-factories. Whole-cell biocatalysis reduces cost by eliminating expensive enzyme purification and cofactor addition steps, as well as resulting in increased enzyme stability. Haloferax volcanii is a model halophilic archaeon encoding highly salt and organic solvent tolerant enzymes such as alcohol dehydrogenase (HvADH2), which catalyses the reduction of aldehydes and ketone in the presence of NADPH/NADH cofactor. A H. volcanii strain for constitutive HvADH2 expression was generated using a strong synthetic promoter (p.syn). The strain was immobilised in calcium alginate beads and repeatedly used as a whole-cell biocatalyst. The reduction of acetophenone, used as test substrate, was very successful and high yields were detected from immobilised whole cells over repeated biotransformation cycles. The immobilised H. volcanii retained stability and high product yields after 1 month of storage at room temperature. This newly developed system offers halophilic enzyme expression in its native environment, high product yield, stability and reusability without the addition of any expensive NADPH/NADH cofactor. This is the first report of whole cell-mediated biocatalysis by the halophilic archaeon H. volcanii.

Seasonality and within-subject clustering of rotavirus infections in an eight-site birth cohort study.

Improving understanding of the pathogen-specific seasonality of enteric infections is critical to informing policy on the timing of preventive measures and to forecast trends in the burden of diarrhoeal disease. Data obtained from active surveillance of cohorts can capture the underlying infection status as transmission occurs in the community. The purpose of this study was to characterise rotavirus seasonality in eight different locations while adjusting for age, calendar time and within-subject clustering of episodes by applying an adapted Serfling model approach to data from a multi-site cohort study. In the Bangladesh and Peru sites, within-subject clustering was high, with more than half of infants who experienced one rotavirus infection going on to experience a second and more than 20% experiencing a third. In the five sites that are in countries that had not introduced the rotavirus vaccine, the model predicted a primary peak in prevalence during the dry season and, in three of these, a secondary peak during the rainy season. The patterns predicted by this approach are broadly congruent with several emerging hypotheses about rotavirus transmission and are consistent for both symptomatic and asymptomatic rotavirus episodes. These findings have practical implications for programme design, but caution should be exercised in deriving inferences about the underlying pathways driving these trends, particularly when extending the approach to other pathogens.

Impact of a structured ICU training programme in resource-limited settings in Asia.

OBJECTIVE: To assess the impact on ICU performance of a modular training program in three resource-limited general adult ICUs in India, Bangladesh, and Nepal. METHOD: A modular ICU training programme was evaluated using performance indicators from June 2009 to June 2012 using an interrupted time series design with an 8 to 15 month pre-intervention and 18 to 24 month post-intervention period. ICU physicians and nurses trained in Europe and the USA provided training for ICU doctors and nurses. The training program consisted of six modules on basic intensive care practices of 2-3 weeks each over 20 months. The performance indicators consisting of ICU mortality, time to ICU discharge, rate at which patients were discharged alive from the ICU, discontinuation of mechanical ventilation or vasoactive drugs and duration of antibiotic use were extracted. Stepwise changes and changes in trends associated with the intervention were analysed. RESULTS: Pre-Training ICU mortality in Rourkela (India), and Patan (Nepal) Chittagong (Bangladesh), was 28%, 41% and 62%, respectively, compared to 30%, 18% and 51% post-intervention. The intervention was associated with a stepwise reduction in cumulative incidence of in-ICU mortality in Chittagong (adjusted subdistribution hazard ratio [aSHR] (95% CI): 0.62 (0.40, 0.97), p = 0.03) and Patan (aSHR 0.16 (0.06, 0.41), p<0.001), but not in Rourkela (aSHR: 1.17 (0.75, 1.82), p = 0.49). The intervention was associated with earlier discontinuation of vasoactive drugs at Rourkela (adjusted hazard ratio for weekly change [aHR] 1.08 (1.03, 1.14), earlier discontinuation of mechanical ventilation in Chittagong (aHR 2.97 (1.24, 7.14), p = 0.02), and earlier ICU discharge in Patan (aHR 1.87 (1.02, 3.43), p = 0.04). CONCLUSION: This structured training program was associated with a decrease in ICU mortality in two of three sites and improvement of other performance indicators. A larger cluster randomised study assessing process outcomes and longer-term indicators is warranted.

Association between serum vitamin D, retinol and zinc status, and acute respiratory infections in underweight and normal-weight children aged 6-24 months living in an urban slum in Bangladesh.

We conducted a longitudinal assessment in 466 underweight and 446 normal-weight children aged 6-24 months living in the urban slum of Dhaka, Bangladesh to determine the association between vitamin D and other micronutrient status with upper respiratory tract infection (URI) and acute lower respiratory infection (ALRI). Incidence rate ratios of URI and ALRI were estimated using multivariable generalized estimating equations. Our results indicate that underweight children with insufficient and deficient vitamin D status were associated with 20% and 23-25% reduced risk of URI, respectively, compared to children with sufficient status. Underweight children, those with serum retinol deficiency were at 1·8 [95% confidence interval (CI) 1·4-2·4] times higher risk of ALRI than those with retinol sufficiency. In normal-weight children there were no significant differences between different vitamin D status and the incidence of URI and ALRI. However, normal-weight children with zinc insufficiency and those that were serum retinol deficient had 1·2 (95% CI 1·0-1·5) times higher risk of URI and 1·9 (95% CI 1·4-2·6) times higher risk of ALRI, respectively. Thus, our results should encourage efforts to increase the intake of retinol-enriched food or supplementation in this population. However, the mechanisms through which vitamin D exerts beneficial effects on the incidence of childhood respiratory tract infection still needs further research.

Association of vitamin D status with incidence of enterotoxigenic, enteropathogenic and enteroaggregative Escherichia coli diarrhoea in children of urban Bangladesh.

OBJECTIVE: To evaluate the association between vitamin D status and diarrhoeal episodes by enterotoxigenic (ETEC), enteropathogenic (EPEC) and enteroaggregative (EAEC) E. coli in underweight and normal-weight children aged 6-24 months in urban Bangladesh. METHODS: Cohorts of 446 normal-weight and 466 underweight children were tested separately for ETEC, EPEC and EAEC from diarrhoeal stool samples collected during 5 months of follow-up while considering vitamin D status at enrolment as the exposure. Cox proportional hazards models with unordered failure events of the same type were used to determine diarrhoeal risk factors after adjusting for sociodemographic and concurrent micronutrient status. RESULTS: Vitamin D status was not independently associated with the risk of incidence of ETEC, EPEC and EAEC diarrhoea in underweight children, but moderate-to-severe retinol deficiency was associated with reduced risk for EPEC diarrhoea upon adjustment. Among normal-weight children, insufficient vitamin D status and moderate-to-severe retinol deficiency were independently associated with 44% and 38% reduced risk of incidence of EAEC diarrhoea, respectively. These children were at higher risk of ETEC diarrhoea with vitamin D deficiency status when adjusted for micronutrient status only. CONCLUSION: This study demonstrates for the first time that normal-weight children with insufficient vitamin D status have a reduced risk of EAEC diarrhoea than children with sufficient status. Moderate-to-severe deficiency of serum retinol is associated with reduced risk of EPEC and EAEC diarrhoea in underweight and normal-weight children.

Study on the safety and efficacy of miltefosine for the treatment of children and adolescents with post-kala-azar dermal leishmaniasis in Bangladesh, and an association of serum vitamin E and exposure to arsenic with post-kala-azar dermal leishmaniasis: an open clinical trial and case-control study protocol.

INTRODUCTION: Post-kala-azar dermal leishmaniasis (PKDL) is a dermatological complication that occurs primarily among treated visceral leishmaniasis (VL) patients, and sporadically in a few without a history of VL. It mostly affects children and adolescents but is also common in adults. The conventional treatment with 120 intramuscular injections of sodium stibogluconate (SSG) is phasing out. Miltefosine (MF) is the only eventual alternative to SSG; however, its efficacy and safety profiles for treatment of children and adolescents with PKDL are lacking. In addition, risk factors for PKDL are poorly investigated. Host genetic, nutritional and environmental factors could be potential risk factors. As such, here we propose to evaluate the efficacy and safety of MF for 12 weeks at an allometric dose for children and adolescents with PKDL, and also to explore potential risk factors for PKDL. METHODS AND ANALYSIS: A cross-sectional survey will look for suspected participants with PKDL among treated VL children and adolescents, a subsequent open clinical trial with MF at allometric dose, with a follow-up at 12 months. A case-control study will be carried out for PKDL risk factors. Assuming 95% cure rate, 95% CI and α=0.05, a sample size of 73 children with PKDL is needed. Considering an attrition rate of 10%, the final sample size is 80 children in each group. Descriptive and analytical analyses will be performed. Primary outcome is safety and cure rate of 12 weeks of treatment with MF. ETHICS AND DISSEMINATION: International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B) Ethical Review Committee (ERC) approved the protocol (PR#013045). Written informed consent will be taken from all participants and their guardians (in case of minor). A Data and Safety Monitoring Board (DSMB) of ICDDR,B ERC will monitor all study activities to ensure the safety of the participants. TRIAL REGISTRATION NUMBER: NCT02193022; Pre-results.

Vitamin-D status is not a confounder of the relationship between zinc and diarrhoea: a study in 6-24-month-old underweight and normal-weight children of urban Bangladesh.

BACKGROUND/OBJECTIVE: The role of micronutrients particularly zinc in childhood diarrhoea is well established. Immunomodulatory functions of vitamin-D in diarrhoea and its role in the effect of other micronutrients are not well understood. This study aimed to investigate whether vitamin-D directly associated or confounded the association between other micronutrient status and diarrhoeal incidence and severity in 6-24-month underweight and normal-weight children in urban Bangladesh. SUBJECTS/METHODS: Multivariable generalised estimating equations were used to estimate incidence rate ratios for incidence (Poisson) and severity (binomial) of diarrhoea on cohorts of 446 normal-weight and 466 underweight children. Outcomes of interest included incidence and severity of diarrhoea, measured daily during a follow-up period of 5 months. The exposure of interest was vitamin-D status at enrolment. RESULTS: Normal-weight and underweight children contributed 62 117 and 62 967 day observation, with 14.2 and 12.8 days/child/year of diarrhoea, respectively. None of the models showed significant associations of vitamin-D status with diarrhoeal morbidity. In the final model, zinc-insufficient normal-weight children had 1.3 times more days of diarrhoea than sufficient children (P<0.05). Again zinc insufficiency and mother's education (1-5 and >5 years) had 1.8 and 2.3 times more risk of severe diarrhoea. In underweight children, older age and female had 24-63 and 17% fewer days of diarrhoea and 52-54 and 31% fewer chances of severe diarrhoea. CONCLUSION: Vitamin-D status was not associated with incidence and severity of diarrhoea in study children. Role of zinc in diarrhoea was only evident in normal-weight children. Our findings demonstrate that vitamin-D is not a confounder of the relationship between zinc and diarrhoea.

Continuous Combined Estrogen Plus Progestin and Endometrial Cancer: The Women's Health Initiative Randomized Trial.

BACKGROUND: While progestin addition to estrogen mitigates endometrial cancer risk, the magnitude of the effect on incidence, specific endometrial cancer histologies, and endometrial cancer mortality remains unsettled. These issues were assessed by analyses after extended follow-up of the Women's Health Initiative (WHI) randomized clinical trial evaluating continuous combined estrogen plus progestin use. METHODS: The WHI enrolled 16 608 postmenopausal women into a randomly assigned, double-blind, placebo-controlled trial. Women age 50 to 79 years with intact uteri with normal endometrial biopsy at entry were randomly assigned to once-daily 0.625 mg conjugated equine estrogen plus 2.5mg medroxyprogesterone acetate (n = 8506) as a single pill or matching placebo (n = 8102). Follow-up beyond the original trial completion date required reconsent, obtained from 12 788 (83%) of surviving participants. Analyses were by intent-to-treat. All statistical tests were two-sided. RESULTS: After 5.6 years' median intervention and 13 years' median cumulative follow-up, there were fewer endometrial cancers in the combined hormone therapy compared with the placebo group (66 vs 95 case patients, yearly incidence, 0.06% vs 0.10%; hazard ratio [HR] = 0.65, 95% confidence interval [CI] = 0.48 to 0.89, P = .007). While there were somewhat fewer endometrial cancers during intervention (25 vs 30, respectively; HR = 0.77, 95% CI = 0.45 to 1.31), the difference became statistically significant postintervention (41 vs 65, respectively; HR = 0.59, 95% CI = 0.40 to 0.88, P = .008), but hazard ratios did not differ between phases (P difference = .46). There was a statistically nonsignificant reduction in deaths from endometrial cancer in the estrogen plus progestin group (5 vs 11 deaths, HR = 0.42, 95% CI = 0.15 to 1.22). CONCLUSION: In postmenopausal women, continuous combined estrogen plus progestin decreases endometrial cancer incidence.

Benefit/risk for adjuvant breast cancer therapy with tamoxifen or aromatase inhibitor use by age, and race/ethnicity.

In early adjuvant breast cancer trial reports, aromatase inhibitors more effectively reduced breast recurrence with lower risk of thromboembolic events and endometrial cancer than tamoxifen, while aromatase inhibitors had higher fracture and cardiovascular disease risk. We used data from updated patient-level meta-analyses of adjuvant trials in analyses to summarize the benefits and risks of these agents in various clinical circumstances. Baseline incidence rates for health outcomes by age and race/ethnicity, absent aromatase inhibitor, or tamoxifen use were estimated from the Women's Health Initiative. Aromatase inhibitor and tamoxifen effects on distant recurrence were obtained from a meta-analysis of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) and Breast International Group (Big-1-98) clinical trials. Impact on other health outcomes were obtained from meta-analyses of randomized trials comparing aromatase inhibitor to tamoxifen use and from placebo-controlled chemoprevention trials. All health outcomes were given equal weight when modeling net benefit/risk for aromatase inhibitor compared to tamoxifen use by breast cancer recurrence risk, age (decade), race/ethnicity, hysterectomy (yes/no), and by prior myocardial infarction. Over a 10-year period, the benefit/risk index was more favorable for aromatase inhibitor than for tamoxifen as adjuvant breast cancer therapy in almost all circumstances regardless of patient age, race/ethnicity, breast cancer recurrence risk, or presence or absence of a uterus. Only in older women with prior myocardial infarction and low recurrence risk was an advantage for tamoxifen seen. Using a benefit/risk index for endocrine adjuvant breast cancer therapy in postmenopausal women, benefit was higher for aromatase inhibitor use in almost all circumstances.

Impact of neighborhood biomass cooking patterns on episodic high indoor particulate matter concentrations in clean fuel homes in Dhaka, Bangladesh.

Exposure to particulate matter (PM2.5 ) from the burning of biomass is associated with increased risk of respiratory disease. In Dhaka, Bangladesh, households that do not burn biomass often still experience high concentrations of PM2.5 , but the sources remain unexplained. We characterized the diurnal variation in the concentrations of PM2.5 in 257 households and compared the risk of experiencing high PM2.5 concentrations in biomass and non-biomass users. Indoor PM2.5 concentrations were estimated every minute over 24 h once a month from April 2009 through April 2010. We found that households that used gas or electricity experienced PM2.5 concentrations exceeding 1000 µg/m(3) for a mean of 35 min within a 24-h period compared with 66 min in biomass-burning households. In both households that used biomass and those that had no obvious source of particulate matter, the probability of PM2.5 exceeding 1000 µg/m(3) were highest during distinct morning, afternoon, and evening periods. In such densely populated settings, indoor pollution in clean fuel households may be determined by biomass used by neighbors, with the highest risk of exposure occurring during cooking periods. Community interventions to reduce biomass use may reduce exposure to high concentrations of PM2.5 in both biomass and non-biomass using households.