The measurement of pneumonia incidence and mortality in Malawi in children under five

Background Globally, pneumonia is a leading cause of death in children under-five. Although pneumonia is responsible for nearly a million under-five deaths worldwide each year, there is limited information on community-level pneumonia incidence. To guide data-informed policies and resource allocation, policymakers require nationally representative, regularly available, sub-national estimates of disease incidence and mortality. We explore the use of available health sector data, including routine data captured in Malawi’s Health Information System (HIS) and survey data, to construct sub-national estimates of pneumonia incidence and mortality. As an initial step in this process, we explore the quality of routine HIS diagnosis data. Methods Our methods vary by research questions. In Chapter 2, we estimate district-level pneumonia mortality in children 1-59 months using the Lives Saved Tool (LiST). We estimate district-level coverage of preventive and curative health sector interventions to determine how change in intervention coverage has impacted pneumonia mortality over time and across districts. In Chapter 3, we use a mixed methods study to explore the quality and use of routine HIS data. Guided by the World Health Organization data quality metrics, we describe the quality of routine acute respiratory infection (ARI) data collected through the HIS. We use qualitative methods to understand how the data collection process contributes to quality and use of the ARI data. In Chapter 4, we use Bayesian estimation methods to estimate district-level pneumonia incidence. Bayesian estimation techniques allow us to use available health sector information—the ARI data that we explored in Chapter 3, the intervention coverage data that we used in Chapter 2, and census data on under-five population—to estimate community-level pneumonia incidence, an unknown quantity. Results Pneumonia mortality has declined from 2000 to 2014 across all districts in Malawi. The decline is attributed to preventive interventions (Haemophilus influenzae type B and pneumococcal vaccines), treatment of pneumonia with antibiotics, and reductions in stunting and wasting. Pneumonia mortality is <4 per 1,000 children under-five in all districts in Malawi in 2014. We estimate community-level under-five pneumonia incidence to be 66.5 per 1,000 (SD: 23.2 per 1,000) across Malawi’s 28 districts in June 2015. Pneumonia incidence increases slightly over time and demonstrates seasonal variation. Routine data on ARI diagnosis in children under five, used to estimate pneumonia incidence, is available, complete, and consistent over time. However, data in the HIS are an overestimate of number of cases recorded in the register as verified by our study team (mean difference in number of cases: 94.0). Conclusion We demonstrate that Malawi’s available health information includes information that can be used to create sub-national estimates of incidence and mortality. District-level variation and trends over time can be used for the directed allocation of resources and to identify and respond to areas of above-average disease burden

Comprehensive and integrated district health systems strengthening: the Rwanda Population Health Implementation and Training (PHIT) Partnership

Background: Nationally, health in Rwanda has been improving since 2000, with considerable improvement since 2005. Despite improvements, rural areas continue to lag behind urban sectors with regard to key health outcomes. Partners In Health (PIH) has been supporting the Rwanda Ministry of Health (MOH) in two rural districts in Rwanda since 2005. Since 2009, the MOH and PIH have spearheaded a health systems strengthening (HSS) intervention in these districts as part of the Rwanda Population Health Implementation and Training (PHIT) Partnership. The partnership is guided by the belief that HSS interventions should be comprehensive, integrated, responsive to local conditions, and address health care access, cost, and quality. The PHIT Partnership represents a collaboration between the MOH and PIH, with support from the National University of Rwanda School of Public Health, the National Institute of Statistics, Harvard Medical School, and Brigham and Women’s Hospital. Description of intervention The PHIT Partnership’s health systems support aligns with the World Health Organization’s six health systems building blocks. HSS activities focus across all levels of the health system — community, health center, hospital, and district leadership — to improve health care access, quality, delivery, and health outcomes. Interventions are concentrated on three main areas: targeted support for health facilities, quality improvement initiatives, and a strengthened network of community health workers. Evaluation design The impact of activities will be assessed using population-level outcomes data collected through oversampling of the demographic and health survey (DHS) in the intervention districts. The overall impact evaluation is complemented by an analysis of trends in facility health care utilization. A comprehensive costing project captures the total expenditures and financial inputs of the health care system to determine the cost of systems improvement. Targeted evaluations and operational research pieces focus on specific programmatic components, supported by partnership-supported work to build in-country research capacity. Discussion Building on early successes, the work of the Rwanda PHIT Partnership approach to HSS has already seen noticeable increases in facility capacity and quality of care. The rigorous planned evaluation of the Partnership’s HSS activities will contribute to global knowledge about intervention methodology, cost, and population health impact

A systematic review of the effectiveness and cost-effectiveness of peer education and peer support in prisons.

BACKGROUND: Prisoners experience significantly worse health than the general population. This review examines the effectiveness and cost-effectiveness of peer interventions in prison settings. METHODS: A mixed methods systematic review of effectiveness and cost-effectiveness studies, including qualitative and quantitative synthesis was conducted. In addition to grey literature identified and searches of websites, nineteen electronic databases were searched from 1985 to 2012. Study selection criteria were: Population: Prisoners resident in adult prisons and children resident in Young Offender Institutions (YOIs). INTERVENTION: Peer-based interventions Comparators: Review questions 3 and 4 compared peer and professionally led approaches. OUTCOMES: Prisoner health or determinants of health; organisational/ process outcomes; views of prison populations. STUDY DESIGNS: Quantitative, qualitative and mixed method evaluations. RESULTS: Fifty-seven studies were included in the effectiveness review and one study in the cost-effectiveness review; most were of poor methodological quality. Evidence suggested that peer education interventions are effective at reducing risky behaviours, and that peer support services are acceptable within the prison environment and have a positive effect on recipients, practically or emotionally. Consistent evidence from many, predominantly qualitative, studies, suggested that being a peer deliverer was associated with positive effects. There was little evidence on cost-effectiveness of peer-based interventions. CONCLUSIONS: There is consistent evidence from a large number of studies that being a peer worker is associated with positive health; peer support services are also an acceptable source of help within the prison environment and can have a positive effect on recipients. Research into cost-effectiveness is sparse. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ref: CRD42012002349

Phospho-ERK and AKT status, but not KRAS mutation status, are associated with outcomes in rectal cancer treated with chemoradiotherapy

<p>Abstract</p> <p>Background</p> <p><it>KRAS </it>mutations may predict poor response to radiotherapy. Downstream events from <it>KRAS</it>, such as activation of <it>BRAF</it>, AKT and ERK, may also confer prognostic information but have not been tested in rectal cancer (RC). Our objective was to explore the relationships of <it>KRAS </it>and <it>BRAF </it>mutation status with p-AKT and p-ERK and outcomes in RC.</p> <p>Methods</p> <p>Pre-radiotherapy RC tumor biopsies were evaluated. <it>KRAS </it>and <it>BRAF </it>mutations were assessed by pyrosequencing; p-AKT and p-ERK expression by immunohistochemistry.</p> <p>Results</p> <p>Of 70 patients, mean age was 58; 36% stage II, 56% stage III, and 9% stage IV. Responses to neoadjuvant chemoradiotherapy: 64% limited, 19% major, and 17% pathologic complete response. 64% were <it>KRAS </it>WT, 95% were <it>BRAF </it>WT. High p-ERK levels were associated with improved OS but not for p-AKT. High levels of p-AKT and p-ERK expression were associated with better responses. <it>KRAS </it>WT correlated with lower p-AKT expression but not p-ERK expression. No differences in OS, residual disease, or tumor downstaging were detected by <it>KRAS </it>status.</p> <p>Conclusions</p> <p><it>KRAS </it>mutation was not associated with lesser response to chemoradiotherapy or worse OS. High p-ERK expression was associated with better OS and response. Higher p-AKT expression was correlated with better response but not OS.</p

H I - MaNGA : H I follow-up for the MaNGA survey

We present the H I-MaNGA programme of H I follow-up for the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey. MaNGA, which is part of the Fourth phase of the Sloan Digital Sky Surveys, is in the process of obtaining integral field unit spectroscopy for a sample of ∼10 000 nearby galaxies. We give an overview of the H I 21cm radio follow-up observing plans and progress and present data for the first 331 galaxies observed in the 2016 observing season at the Robert C. Bryd Green Bank Telescope. We also provide a cross-match of the current MaNGA(DR15) sample with publicly available H I data from the Arecibo Legacy Fast Arecibo L-band Feed Array survey. The addition of H I data to the MaNGA data set will strengthen the survey's ability to address several of its key science goals that relate to the gas content of galaxies, while also increasing the legacy of this survey for all extragalactic science.Publisher PDFPeer reviewe

Applying a zero-corrected, gravity model estimator reduces bias due to heterogeneity in healthcare utilization in community-scale, passive surveillance datasets of endemic diseases

International audienceData on population health are vital to evidence-based decision making but are rarely adequately localized or updated in continuous time. They also suffer from low ascertainment rates, particularly in rural areas where barriers to healthcare can cause infrequent touch points with the health system. Here, we demonstrate a novel statistical method to estimate the incidence of endemic diseases at the community level from passive surveillance data collected at primary health centers. The zerocorrected, gravity-model (ZERO-G) estimator explicitly models sampling intensity as a function of health facility characteristics and statistically accounts for extremely low rates of ascertainment. The result is a standardized, real-time estimate of disease incidence at a spatial resolution nearly ten times finer than typically reported by facility-based passive surveillance systems. We assessed the robustness of this method by applying it to a case study of field-collected malaria incidence rates from a rural health district in southeastern Madagascar. The ZERO-G estimator decreased geographic and financial bias in the dataset by over 90% and doubled the agreement rate between spatial patterns in malaria incidence and incidence estimates derived from prevalence surveys. The ZERO-G estimator is a promising method for adjusting passive surveillance data of common, endemic diseases, increasing the availability of continuously updated, high quality surveillance datasets at the community scale. Health metrics are vital to public health efforts, allowing decision makers to better understand the state of population health and evaluate the impact of health interventions 1,2. Many of these metrics are based on routine passive disease surveillance from facility-based health management information systems (HMIS), which record the number of disease cases received at each facility at a regular frequency. Health records are then aggregated, digitized, and transferred to the district and, eventually, national health offices 3. While the exact structure differs by country, the scale of spatial aggregation of the data in an HMIS corresponds to the specific level of the health system and its corresponding health infrastructure. For example, national-level data are used by international organizations to monitor long-term, multi-country trends and inform policy; regional-and district-level surveillance data may be used by national public health offices to allocate resources within the country; and individual health facility information is used by district health offices for program management

A Conserved SREBP-1/Phosphatidylcholine Feedback Circuit Regulates Lipogenesis in Metazoans

Sterol regulatory element-binding proteins (SREBPs) activate genes involved in the synthesis and trafficking of cholesterol and other lipids and are critical for maintaining lipid homeostasis. Aberrant SREBP activity, however, can contribute to obesity, fatty liver disease, and insulin resistance, hallmarks of metabolic syndrome. Our studies identify a conserved regulatory circuit in which SREBP-1 controls genes in the one-carbon cycle, which produces the methyl donor S-adenosylmethionine (SAMe). Methylation is critical for the synthesis of phosphatidylcholine (PC), a major membrane component, and we find that blocking SAMe or PC synthesis in C. elegans, mouse liver, and human cells causes elevated SREBP-1-dependent transcription and lipid droplet accumulation. Distinct from negative regulation of SREBP-2 by cholesterol, our data suggest a feedback mechanism whereby maturation of nuclear, transcriptionally active SREBP-1 is controlled by levels of PC. Thus, nutritional or genetic conditions limiting SAMe or PC production may activate SREBP-1, contributing to human metabolic disorders. [Display omitted] ► SREBP-1 transcription factors regulate the one-carbon cycle in metazoans ► Low levels of SAMe and phosphatidylcholine (PC) activate SREBP-1 and lipogenesis ► Low PC production causes Golgi to ER relocalization of SREBP-activating proteases ► PC depletion preferentially affects SREBP-1, whereas cholesterol regulates SREBP-2 A membrane component, phosphatidylcholine, modulates lipid homeostasis via SREBP-1, suggesting a link between fatty liver disease and dietary intake of phosphatidylcholine precursors such as folates, methionine, and choline