What influences family planning in rural Pakistan: Franchised service provider and community health worker perspective

Background: Pakistan has a low modern contraceptive prevalence rate, 26%, leading family planning (FP) programmes to explore partnerships with local private providers to improve access to quality FP services. This study aims to understand the socio-cultural and organizational factors that influence delivery of quality family planning services. Methods: This qualitative study was conducted with private service providers and community health workers (CHW) in Marie Stopes Society\u27s (MSS) social franchise network. A total of 31 providers and 28 CHWs from Sindh, Punjab, and Khyber Pakhtunkhwa provinces of Pakistan were purposively selected for in-depth interviews. The study used thematic content analysis to understand providers\u27 and health workers\u27 perspectives of family planning service provision. Results: This study found that normative environment, propagation of myths and misconceptions, and health concerns remain major barriers to service provision in rural communities. Findings showed that CHWs were instrumental in increasing awareness and positive attitudes towards family planning in the catchment areas. Moreover, social franchising was effective in increasing access to high-quality, subsidised family planning services amongst economically marginalised and low-awareness communities. Providers and health workers expressed satisfaction with the franchising approach, and revealed that being part of this network substantially increased their client volume and ability to serve poorer segments of the population. Conclusion: The study found that franchising private service providers in rural areas enhances their ability to serve clients, and when coupled with demand-generation elements, such as vouchers and community health workers, it substantially increases their client volume. Albeit effective, the franchising approach currently lacks the element of long-term service provision at the current scale, and may require further strategizing by the franchisor. Moreover, alternate strategies should be explored to ensure continued provision of FP services without vouchers and CHWs

Influence of Differential Calcification in the Descending Thoracic Aorta on Aortic Pulse Pressure

Purpose: Multiple studies have shown pulse pressure (PP) to be a strong predictor of aortic calcification. However, no studies are available that correlate PP with aortic calcification at the segmental level. Methods: We identified 37 patients with aortic PP measured during cardiac catheterization. Their noncontrast chest computed tomography scans were evaluated for the presence of calcium in different segments (ascending aorta, arch of aorta [arch], descending aorta) and quantified. Patients with calcification (Calcified Group A) were compared against patients without calcification (Noncalcified Group B) in terms of PP, calcification and compliance. Results: The mean of the total calcium score was higher in the descending aorta than the arch or ascending aorta (691 vs 571 vs 131, respectively, P < 0.0001). PP had the strongest correlation with calcification in the descending aorta (r = 0.47, P = 0.004). Calcified Group A had a much higher PP than Noncalcified Group B, with the greatest difference in the descending aorta (20 mmHg, P < 0.0001), lesser in the ascending aorta (10 mmHg, P = 0.12) and the least in the arch (5 mmHg, P = 0.38). Calcified Group A patients also had much lower compliance than Noncalcified Group B patients, with the greatest difference among groups seen in the descending aorta (0.7 mL/mmHg, P = 0.002), followed by the ascending aorta, then arch. Conclusions: These are the first data to evaluate the relative impact of aortic segments in PP. Finding the greatest amount of calcification along with greatest change in PP and compliance in the descending aorta makes a case that the descending aorta plays a major role in PP as compared to other segments of the thoracic aorta

Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN): an international, randomised, double-blind, placebo-controlled trial

Background Post-partum haemorrhage is the leading cause of maternal death worldwide. Early administration of tranexamic acid reduces deaths due to bleeding in trauma patients. We aimed to assess the effects of early administration of tranexamic acid on death, hysterectomy, and other relevant outcomes in women with post-partum haemorrhage. Methods In this randomised, double-blind, placebo-controlled trial, we recruited women aged 16 years and older with a clinical diagnosis of post-partum haemorrhage after a vaginal birth or caesarean section from 193 hospitals in 21 countries. We randomly assigned women to receive either 1 g intravenous tranexamic acid or matching placebo in addition to usual care. If bleeding continued after 30 min, or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Patients were assigned by selection of a numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Participants, care givers, and those assessing outcomes were masked to allocation. We originally planned to enrol 15 000 women with a composite primary endpoint of death from all-causes or hysterectomy within 42 days of giving birth. However, during the trial it became apparent that the decision to conduct a hysterectomy was often made at the same time as randomisation. Although tranexamic acid could influence the risk of death in these cases, it could not affect the risk of hysterectomy. We therefore increased the sample size from 15 000 to 20 000 women in order to estimate the effect of tranexamic acid on the risk of death from post-partum haemorrhage. All analyses were done on an intention-to-treat basis. This trial is registered with ISRCTN76912190 (Dec 8, 2008); ClinicalTrials.gov, number NCT00872469; and PACTR201007000192283. Findings Between March, 2010, and April, 2016, 20 060 women were enrolled and randomly assigned to receive tranexamic acid (n=10 051) or placebo (n=10 009), of whom 10 036 and 9985, respectively, were included in the analysis. Death due to bleeding was significantly reduced in women given tranexamic acid (155 [1·5%] of 10 036 patients vs 191 [1·9%] of 9985 in the placebo group, risk ratio [RR] 0·81, 95% CI 0·65–1·00; p=0·045), especially in women given treatment within 3 h of giving birth (89 [1·2%] in the tranexamic acid group vs 127 [1·7%] in the placebo group, RR 0·69, 95% CI 0·52–0·91; p=0·008). All other causes of death did not differ significantly by group. Hysterectomy was not reduced with tranexamic acid (358 [3·6%] patients in the tranexamic acid group vs 351 [3·5%] in the placebo group, RR 1·02, 95% CI 0·88–1·07; p=0·84). The composite primary endpoint of death from all causes or hysterectomy was not reduced with tranexamic acid (534 [5·3%] deaths or hysterectomies in the tranexamic acid group vs 546 [5·5%] in the placebo group, RR 0·97, 95% CI 0·87-1·09; p=0·65). Adverse events (including thromboembolic events) did not differ significantly in the tranexamic acid versus placebo group. Interpretation Tranexamic acid reduces death due to bleeding in women with post-partum haemorrhage with no adverse effects. When used as a treatment for postpartum haemorrhage, tranexamic acid should be given as soon as possible after bleeding onset. Funding London School of Hygiene & Tropical Medicine, Pfizer, UK Department of Health, Wellcome Trust, and Bill & Melinda Gates Foundation

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Gender and Violence in Urban Pakistan

The experience of violence is pervasive in Pakistan; while residents of Rawalpindi-Islamabad face violence mostly from people they know, in Karachi, residents are more likely to experience violence from strangers i.e. criminal and political. The findings overwhelmingly point towards access to services and vulnerability profiles of households as major drivers of violence. Evidence and analysis is presented through narratives at the intersection of violence and gender, including themes of vulnerability, illness, mobility, service provision and access to services. The state has a major role in perpetrating violence and as well, is a cause of social violence

Risk Factors for Enterotoxigenic Bacteroides fragilis Infection and Association with Environmental Enteric Dysfunction and Linear Growth in Children : Results from the MAL-ED Study

Despite reports of enterotoxigenic Bacteroides fragilis (ETBF) isolation from asymptomatic children, no reports exist regarding the possible association of ETBF with long-term complications such as development of environmental enteric dysfunction (EED) and subsequent linear growth faltering in childhood. We aimed to establish a potential association between the burden of asymptomatic ETBF infection and EED and linear growth at 24 months of age using the data collected from 1,715 children enrolled in the multi-country birth cohort study, known as the Etiology, Risk Factors, and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health study. Using Poisson regression models, we evaluated the site-specific incidence rate and, subsequently, identified the risk factors and assessed the association between the burden of ETBF infection and EED score and linear growth at 24 months of age. The overall incidence rate of ETBF infections per 100 child-months across all study sites was 10.6%, with the highest and lowest incidence of ETBF infections being reported in Tanzania (19.6%) and Peru (3.6%), respectively. Female gender, longer duration of breastfeeding, and improved water access, sanitation, and hygiene practices, such as improved drinking water source, improved sanitation, and improved floor material in households, along with enhanced maternal education and less crowding in the households were found to be protective against incidences of ETBF infection. The burden of ETBF infections was found to have significant associations with EED and linear growth faltering at 24 months of age across all the study sites. Our findings warrant regular clinical monitoring to reduce the burden of ETBF infections and diminish the burden of enteropathy and linear growth faltering in childhood.publishedVersionPeer reviewe

Normal diameter of the ascending aorta in adults: the impact of stricter criteria on selection of subjects free of disease

BACKGROUND: The American Society of Echocardiography 2015 guidelines for measurement of the aorta utilized studies, including one by Devereaux et al., that suffered from smaller sample sizes and lax criteria for selection of normal subjects, using absence of clinical etiologies of aortic aneurysm without consideration of echocardiographic normalcy. This study was carried out to determine the normal dimension of the ascending thoracic aorta in a large population using stricter selection criteria. METHODS: Echocardiographic studies of patients ≥15 years of age performed at a large tertiary care hospital over the last four years were retrospectively evaluated. Only those who did not fulfill any of the 28 causes of aortic dilatation, as defined by AHA 2010 guidelines, either in their clinical records or echocardiograms were included as “normal subjects.” The dimensions of the mid-ascending thoracic aorta were measured by standardized echocardiography in a plane perpendicular to that of the long axis of the aorta, at end-diastole, using leading edge–to–leading edge technique. RESULTS: Out of 3,201 normal subjects, 974 were men and 2,227 were women. The mean age was 37.91±14.94 years. The mean diameter of the ascending aorta (Asc Ao) in men was 2.91±0.40 cm, compared with 3.34±0.34 cm in prior studies. The mean diameter of Asc Ao in women was 2.70±0.36 cm, compared with 2.98±0.34 cm in prior studies. CONCLUSIONS: These data suggest that in a larger population with more stringent criteria for normalcy, the prevalence of dilated aorta will be higher than those suggested by the current guidelines, if the suggested cutoffs are applied

The increasing burden of amyloidosis from apex to base: new insights from technetium-99m pyrophosphate imaging

BACKGROUND: Two-dimensional speckle-tracking strain echocardiography (2D STE) in cardiac amyloidosis (CA) patients has shown relatively preserved left ventricle apical systolic function as measured by longitudinal strain (LS). Technetium-99m pyrophosphate ( 99mTc-PYP) myocardial imaging has gained favor in diagnosis of transthyretin amyloidosis. Since 99mTc-PYP binds amyloid fibrils, we hypothesized this technique can elucidate relative distribution of amyloid in the heart. METHODS: We identified 9 patients with CA diagnosis who had had 2D STE and 9mTc-PYP scans. Segmental LS was measured by 2D STE as a measure of systolic function. Segmental uptake of 99mTc-PYP was measured using a 17-segment model as a measure of CA burden in the specific segment. If uptake was 100% of maximum, it was categorized as 0% defect. Results: Mean LS was markedly decreased in CA patients (-8.3) and much lower in normal patients. Strain increased from base to apex on 2D STE (average basal strain [-3.3] vs. mid strain [-8.3] vs. apical strain [-14]); p\u3c0.01 for all comparisons. Percent defect increased gradually from base to mid to apex (10%, 38%, 60% defect, respectively) in CA patients; p\u3c0.0001 for all comparisons. Apical cap percent defect was not significant from apex (48.7 vs 59.5; p=0.7547). CONCLUSIONS: These data provide the first insight into relative distribution of amyloid in the ventricle and suggest the relative apical sparing of systolic strain may be a function of amyloid deposition of the ventricular base

Prevalence of dilated mid-ascending aorta in individuals 15 years and older: In search of optimal diagnostic criteria and their effect on the burden of disease

Background:Controversy regarding the definition of the upper limit of normal (ULN) for dilated mid-ascending aorta (mAA) stems from variation in criteria, based on several small-sized studies with small datasets of normal subjects (DONS). The present study was carried out to demonstrate this variation in the prevalence of mAA dilation and to identify the optimal definition by creating the largest DONS. Methods:Echocardiographic studies of patients ≥ 15 years of age performed at a large tertiary care center over 4 years ( n = 49,330) were retrospectively evaluated. The leading-edge-to-leading-edge technique was used to measure the mAA in diastole. The largest-to-date DONS ( n = 2334) was created, including those who were normal on medical record review, did not have any of the 28 causes of dilated aorta, and had normal echocardiograms. Because age had the strongest correlation with mAA (multivariate adjusted R2 = 0.26), as compared with sex, height, and weight, we created a new ULN based on the DONS with narrow age stratification (10-year intervals). Results:The prevalence of dilated mAA varied between 17% and 23% when absolute criteria were used with sex stratification, and it varied between 6% and 11% when relative criteria (relative to age, body surface area, and sex) were used. Based on new criteria from the DONS, it was 7.6%, with a ULN of 3.07-3.64 cm in women and 3.3-3.91 cm in men. Conclusions:These data demonstrate the undesirable variation in the prevalence of dilated mAA based on prior criteria and propose a new ULN for dilated mAA