Misoprostol for the prevention of post-partum haemorrhage in Mozambique: an analysis of the interface between human rights, maternal health and development.

BACKGROUND:Mozambique has high maternal mortality which is compounded by limited human resources for health, weak access to health services, and poor development indicators. In 2011, the Mozambique Ministry of Health (MoH) approved the distribution of misoprostol for the prevention of post-partum haemorrhage (PPH) at home births where oxytocin is not available. Misoprostol can be administered by a traditional birth attendant or self-administered. The objective of this paper is to examine, through applying a human rights lens, the broader contextual, policy and institutional issues that have influenced and impacted the early implementation of misoprostol for the prevention of PPH. We explore the utility of rights-based framework to inform this particular program, with implications for sexual and reproductive health programs more broadly. METHODS:A human rights, health and development framework was used to analyse the early expansion phase of the scale-up of Mozambique's misoprostol program in two provinces. A policy document review was undertaken to contextualize the human rights, health and development setting in Mozambique. Qualitative primary data from a program evaluation of misoprostol for the prevention of PPH was then analysed using a human rights lens; these results are presented alongside three examples where rights are constrained. RESULTS:Structural and institutional challenges exacerbated gaps in the misoprostol program, and sexual and reproductive health more generally. While enshrined in the constitution and within health policy documents, human rights were not fully met and many individuals in the study were unaware of their rights. Lack of information about the purpose of misoprostol and how to access the medication contributed to power imbalances between the state, health care workers and beneficiaries. The accessibility of misoprostol was further limited due to dynamics of power and control. CONCLUSIONS:Applying a rights-based approach to the Mozambican misoprostol program is helpful in contextualising and informing the practical changes needed to improve access to misoprostol as an essential medicine, and in turn, preventing PPH. This study adds to the evidence of the interconnection between human rights, health and development and the importance of integrating the concepts to ensure women's rights are prioritized within health service delivery

Intersectionality: Social Marginalisation and Self-Reported Health Status in Young People.

BACKGROUND:The aim of this study was to measure young people's health status and explore associations between health status and belonging to one or more socio-culturally marginalised group. METHODS:part of the Access 3 project, this cross-sectional survey of young people aged 12-24 years living in New South Wales, Australia, oversampled young people from one or more of the following groups: Aboriginal and or Torres Strait Islander; living in rural and remote areas; homeless; refugee; and/or, sexuality and/or gender diverse. This paper reports on findings pertaining to health status, presence of chronic health conditions, psychological distress, and wellbeing measures. RESULTS:1416 participants completed the survey; 897 (63.3%) belonged to at least one marginalised group; 574 (40.5%) to one, 281 (19.8%) to two and 42 (3.0%) to three or four groups. Belonging to more marginalised groups was significantly associated with having more chronic health conditions (p = 0.001), a greater likelihood of high psychological distress (p = 0.001) and of illness or injury related absence from school or work (p < 0.05). CONCLUSIONS:increasing marginalisation is associated with decreasing health status. Using an intersectional lens can to be a useful way to understand disadvantage for young people belonging to multiple marginalised groups

A hierarchical Bayesian model for estimating age-specific COVID-19 infection fatality rates in developing countries

The COVID-19 infection fatality rate (IFR) is the proportion of individuals infected with SARS-CoV-2 who subsequently die. As COVID-19 disproportionately affects older individuals, age-specific IFR estimates are imperative to facilitate comparisons of the impact of COVID-19 between locations and prioritize distribution of scare resources. However, there lacks a coherent method to synthesize available data to create estimates of IFR and seroprevalence that vary continuously with age and adequately reflect uncertainties inherent in the underlying data. In this paper we introduce a novel Bayesian hierarchical model to estimate IFR as a continuous function of age that acknowledges heterogeneity in population age structure across locations and accounts for uncertainty in the estimates due to seroprevalence sampling variability and the imperfect serology test assays. Our approach simultaneously models test assay characteristic, serology, and death data, where the serology and death data are often available only for binned age groups. Information is shared across locations through hierarchical modeling to improve estimation of the parameters with limited data. Modeling data from 26 developing country locations during the first year of the COVID-19 pandemic, we found seroprevalence did not change dramatically with age, and the IFR at age 60 was above the high-income country benchmark for most locations

A Comprehensive Framework for Human Resources for Health System Development in Fragile and Post-Conflict States

Noriko Fujita and colleagues offer a comprehensive framework for human resource system development, based upon experiences in three fragile and post-conflict health systems: Afghanistan, the Democratic Republic of Congo, and Cambodia

Private Sector Participation and Health System Performance in Sub-Saharan Africa

BACKGROUND: The role of the private health sector in developing countries remains a much-debated and contentious issue. Critics argue that the high prices charged in the private sector limits the use of health care among the poorest, consequently reducing access and equity in the use of health care. Supporters argue that increased private sector participation might improve access and equity by bringing in much needed resources for health care and by allowing governments to increase focus on underserved populations. However, little empirical exists for or against either side of this debate. METHODOLOGY/PRINCIPAL FINDINGS: We examine the association between private sector participation and self-reported measures of utilization and equity in deliveries and treatment of childhood respiratory disease using regression analysis, across a sample of nationally-representative Demographic and Health Surveys from 34 SSA economies. We also examine the correlation between private sector participation and key background factors (socioeconomic development, business environment and governance) and use multivariate regression to control for potential confounders. Private sector participation is positively associated with greater overall access and reduced disparities between rich and poor as well as urban and rural populations. The positive association between private sector participation and improved health system performance is robust to controlling for confounders including per capita income and maternal education. Private sector participation is positively correlated with measures of socio-economic development and favorable business environment. CONCLUSIONS/SIGNIFICANCE: Greater participation is associated with favorable intermediate outcomes in terms of access and equity. While these results do not establish a causal link between private sector participation and health system performance, they suggest that there is no deleterious link between private sector participation and health system performance in SSA

Methylphenidate for attention-deficit/hyperactivity disorder in children and adolescents: Cochrane systematic review with meta-analyses and trial sequential analyses of randomised clinical trials

Study question: Is methylphenidate beneficial or harmful for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents? / Methods: Electronic databases were searched up to February 2015 for parallel and crossover randomised clinical trials comparing methylphenidate with placebo or no intervention in children and adolescents with ADHD. Meta-analyses and trial sequential analyses (TSA) were conducted. Quality was assessed using GRADE. Teachers, parents, and observers rated ADHD symptoms and general behaviour. / Study answer and limitations: The analyses included 38 parallel group trials (n=5111, median treatment duration 49 days) and 147 crossover trials (n=7134, 14 days). The average age across all studies was 9.7 years. The analysis suggested a beneficial effect of methylphenidate on teacher rated symptoms in 19 parallel group trials (standardised mean difference (SMD) −0.77, n=1698), corresponding to a mean difference of −9.6 points on the ADHD rating scale. There was no evidence that methylphenidate was associated with an increase in serious adverse events (risk ratio 0.98, nine trials, n=1532; TSA adjusted intervention effect RR 0.91). Methylphenidate was associated with an increased risk of non-serious adverse events (1.29, 21 trials, n=3132; TSA adjusted RR 1.29). Teacher rated general behaviour seemed to improve with methylphenidate (SMD −0.87, five trials, n=668) A change of 7 points on the child health questionnaire (CHQ) has been deemed a minimal clinically relevant difference. The change reported in a meta-analysis of three trials corresponds to a mean difference of 8.0 points on the CHQ (range 0-100 points), which suggests that methylphenidate may improve parent reported quality of life (SMD 0.61, three trials, n=514). 96.8% of trials were considered high risk of bias trials according to the Cochrane guidelines. All outcomes were assessed very low quality according to GRADE. / What this study adds: The results suggest that among children and adolescents with a diagnosis of ADHD, methylphenidate may improve teacher reported symptoms of ADHD and general behaviour and parent reported quality of life. However, given the risk of bias in the included studies, and the very low quality of outcomes, the magnitude of the effects is uncertain. Methylphenidate is associated with an increased risk of non-serious but not serious adverse events. / Funding, competing interests, data sharing: Region Zealand Research Foundation and Copenhagen Trial Unit. Competing interests are given in the full paper on bmj.com. Full data are available in the version of this review published in The Cochrane Library

A novel combretastatin A-4 derivative, AC7700, strongly stanches tumour blood flow and inhibits growth of tumours developing in various tissues and organs

In a previous study, we used subcutaneous LY80 tumours (a subline of Yoshida sarcoma), Sato lung carcinoma, and methylcholanthrene-induced primary tumours, to demonstrate that a novel water-soluble combretastatin A-4 derivative, AC7700, abruptly and irreversibly stopped tumour blood flow. As a result of this interrupted supply of nutrients, extensive necrosis was induced within the tumour. In the present study, we investigated whether AC7700 acts in the same way against solid tumours growing in the liver, stomach, kidney, muscle, and lymph nodes. Tumour blood flow and the change in tumour blood flow induced by AC7700 were measured by the hydrogen clearance method. In a model of cancer chemotherapy against metastases, LY80 cells (2×106) were injected into the lateral tail vein, and AC7700 at 10 mg kg−1 was injected i.v. five times at intervals of 2 days, starting on day 7 after tumour cell injection. The number and size of tumours were compared with those in the control group. The change in tumour blood flow and the therapeutic effect of AC7700 on microtumours were observed directly by using Sato lung carcinoma implanted in a rat transparent chamber. AC7700 caused a marked decrease in the tumour blood flow of all LY80 tumours developing in various tissues and organs and growth of all tumours including lymph node metastases and microtumours was inhibited. In every tumour, tumour blood flow began to decrease immediately after AC7700 administration and reached a minimum at approximately 30 min after injection. In many tumour capillaries, blood flow completely stopped within 3 min after AC7700 administration. These results demonstrate that AC7700 is effective for tumours growing in various tissues and organs and for metastases. We conclude that tumour blood flow stanching induced by AC7700 may become an effective therapeutic strategy for all cancers, including refractory cancers because the therapeutic effect is independent of tumour site and specific type of cancer

Calcium Handling in Human Induced Pluripotent Stem Cell Derived Cardiomyocytes

BACKGROUND: The ability to establish human induced pluripotent stem cells (hiPSCs) by reprogramming of adult fibroblasts and to coax their differentiation into cardiomyocytes opens unique opportunities for cardiovascular regenerative and personalized medicine. In the current study, we investigated the Ca(2+)-handling properties of hiPSCs derived-cardiomyocytes (hiPSC-CMs). METHODOLOGY/PRINCIPAL FINDINGS: RT-PCR and immunocytochemistry experiments identified the expression of key Ca(2+)-handling proteins. Detailed laser confocal Ca(2+) imaging demonstrated spontaneous whole-cell [Ca(2+)](i) transients. These transients required Ca(2+) influx via L-type Ca(2+) channels, as demonstrated by their elimination in the absence of extracellular Ca(2+) or by administration of the L-type Ca(2+) channel blocker nifedipine. The presence of a functional ryanodine receptor (RyR)-mediated sarcoplasmic reticulum (SR) Ca(2+) store, contributing to [Ca(2+)](i) transients, was established by application of caffeine (triggering a rapid increase in cytosolic Ca(2+)) and ryanodine (decreasing [Ca(2+)](i)). Similarly, the importance of Ca(2+) reuptake into the SR via the SR Ca(2+) ATPase (SERCA) pump was demonstrated by the inhibiting effect of its blocker (thapsigargin), which led to [Ca(2+)](i) transients elimination. Finally, the presence of an IP3-releasable Ca(2+) pool in hiPSC-CMs and its contribution to whole-cell [Ca(2+)](i) transients was demonstrated by the inhibitory effects induced by the IP3-receptor blocker 2-Aminoethoxydiphenyl borate (2-APB) and the phospholipase C inhibitor U73122. CONCLUSIONS/SIGNIFICANCE: Our study establishes the presence of a functional, SERCA-sequestering, RyR-mediated SR Ca(2+) store in hiPSC-CMs. Furthermore, it demonstrates the dependency of whole-cell [Ca(2+)](i) transients in hiPSC-CMs on both sarcolemmal Ca(2+) entry via L-type Ca(2+) channels and intracellular store Ca(2+) release