Investigating Financial Incentives for Maternal Health: An Introduction

Projection of current trends in maternal and neonatal mortality reduction shows that many countries will fall short of the UN Millennium Development Goal 4 and 5. Underutilization of maternal health services contributes to this poor progress toward reducing maternal and neonatal morbidity and mortality. Moreover, the quality of services continues to lag in many countries, with a negative effect on the health of women and their babies, including deterring women from seeking care. To enhance the use and provision of quality maternal care, countries and donors are increasingly using financial incentives. This paper introduces the JHPN Supplement, in which each paper reviews the evidence of the effectiveness of a specific financial incentive instrument with the aim of improving the use and quality of maternal healthcare and impact. The US Agency for International Development and the US National Institutes of Health convened a US Government Evidence Summit on Enhancing Provision and Use of Maternal Health Services through Financial Incentives on 24-25 April 2012 in Washington, DC. The Summit brought together leading global experts in finance, maternal health, and health systems from governments, academia, development organizations, and foundations to assess the evidence on whether financial incentives significantly and substantially increase provision, use and quality of maternal health services, and the contextual factors that impact the effectiveness of these incentives. Evidence review teams evaluated the multidisciplinary evidence of various financial mechanisms, including supply-side incentives (e.g. performance-based financing, user fees, and various insurance mechanisms) and demand-side incentives (e.g. conditional cash transfers, vouchers, user fee exemptions, and subsidies for care-seeking). At the Summit, the teams presented a synthesis of evidence and initial recommendations on practice, policy, and research for discussion. The Summit enabled structured feedback on recommendations which the teams included in their final papers appearing in this Supplement. Papers in this Supplement review the evidence for a specific financial incentive mechanism (e.g. pay for performance, conditional cash transfer) to improve the use and quality of maternal healthcare and makes recommendations for programmes and future research. While data on programmes using financial incentives for improved use and indications of the quality of maternal health services support specific conclusions and recommendations, including those for future research, data linking the use of financial incentives with improved health outcomes are minimal

Financial Incentives and Maternal Health: Where Do We Go from Here?

Health financing strategies that incorporate financial incentives are being applied in many low- and middle-income countries, and improving maternal and neonatal health is often a central goal. As yet, there have been few reviews of such programmes and their impact on maternal health. The US Government Evidence Summit on Enhancing Provision and use of Maternal Health Services through Financial Incentives was convened on 24-25 April 2012 to address this gap. This article, the final in a series assessing the effects of financial incentives\u2014performance-based incentives (PBIs), insurance, user fee exemption programmes, conditional cash transfers, and vouchers\u2014summarizes the evidence and discusses issues of context, programme design and implementation, cost-effectiveness, and sustainability. We suggest key areas to consider when designing and implementing financial incentive programmes for enhancing maternal health and highlight gaps in evidence that could benefit from additional research. Although the methodological rigor of studies varies, the evidence, overall, suggests that financial incentives can enhance demand for and improve the supply of maternal health services. Definitive evidence demonstrating a link between incentives and improved health outcomes is lacking; however, the evidence suggests that financial incentives can increase the quantity and quality of maternal health services and address health systems and financial barriers that prevent women from accessing and providers from delivering quality, lifesaving maternal healthcare

Active management of the third stage of labour with and without controlled cord traction: a randomised, controlled, non-inferiority trial.

BACKGROUND: Active management of the third stage of labour reduces the risk of post-partum haemorrhage. We aimed to assess whether controlled cord traction can be omitted from active management of this stage without increasing the risk of severe haemorrhage. METHODS: We did a multicentre, non-inferiority, randomised controlled trial in 16 hospitals and two primary health-care centres in Argentina, Egypt, India, Kenya, the Philippines, South Africa, Thailand, and Uganda. Women expecting to deliver singleton babies vaginally (ie, not planned caesarean section) were randomly assigned (in a 1:1 ratio) with a centrally generated allocation sequence, stratified by country, to placental delivery with gravity and maternal effort (simplified package) or controlled cord traction applied immediately after uterine contraction and cord clamping (full package). After randomisation, allocation could not be concealed from investigators, participants, or assessors. Oxytocin 10 IU was administered immediately after birth with cord clamping after 1-3 min. Uterine massage was done after placental delivery according to local policy. The primary (non-inferiority) outcome was blood loss of 1000 mL or more (severe haemorrhage). The non-inferiority margin for the risk ratio was 1·3. Analysis was by modified intention-to-treat, excluding women who had emergency caesarean sections. This trial is registered with the Australian and New Zealand Clinical Trials Registry, ACTRN 12608000434392. FINDINGS: Between June 1, 2009, and Oct 30, 2010, 12,227 women were randomly assigned to the simplified package group and 12,163 to the full package group. After exclusion of women who had emergency caesarean sections, 11,861 were in the simplified package group and 11,820 were in the full package group. The primary outcome of blood loss of 1000 mL or more had a risk ratio of 1·09 (95% CI 0·91-1·31) and the upper 95% CI limit crossed the pre-stated non-inferiority margin. One case of uterine inversion occurred in the full package group. Other adverse events were haemorrhage-related. INTERPRETATION: Although the hypothesis of non-inferiority was not met, omission of controlled cord traction has very little effect on the risk of severe haemorrhage. Scaling up of haemorrhage prevention programmes for non-hospital settings can safely focus on use of oxytocin. FUNDING: United States Agency for International Development and UN Development Programme/UN Population Fund/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, Department of Reproductive Health and Research

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Progression of the first stage of spontaneous labour: A prospective cohort study in two sub-Saharan African countries.

BACKGROUND: Escalation in the global rates of labour interventions, particularly cesarean section and oxytocin augmentation, has renewed interest in a better understanding of natural labour progression. Methodological advancements in statistical and computational techniques addressing the limitations of pioneer studies have led to novel findings and triggered a re-evaluation of current labour practices. As part of the World Health Organization's Better Outcomes in Labour Difficulty (BOLD) project, which aimed to develop a new labour monitoring-to-action tool, we examined the patterns of labour progression as depicted by cervical dilatation over time in a cohort of women in Nigeria and Uganda who gave birth vaginally following a spontaneous labour onset. METHODS AND FINDINGS: This was a prospective, multicentre, cohort study of 5,606 women with singleton, vertex, term gestation who presented at ≤ 6 cm of cervical dilatation following a spontaneous labour onset that resulted in a vaginal birth with no adverse birth outcomes in 13 hospitals across Nigeria and Uganda. We independently applied survival analysis and multistate Markov models to estimate the duration of labour centimetre by centimetre until 10 cm and the cumulative duration of labour from the cervical dilatation at admission through 10 cm. Multistate Markov and nonlinear mixed models were separately used to construct average labour curves. All analyses were conducted according to three parity groups: parity = 0 (n = 2,166), parity = 1 (n = 1,488), and parity = 2+ (n = 1,952). We performed sensitivity analyses to assess the impact of oxytocin augmentation on labour progression by re-examining the progression patterns after excluding women with augmented labours. Labour was augmented with oxytocin in 40% of nulliparous and 28% of multiparous women. The median time to advance by 1 cm exceeded 1 hour until 5 cm was reached in both nulliparous and multiparous women. Based on a 95th percentile threshold, nulliparous women may take up to 7 hours to progress from 4 to 5 cm and over 3 hours to progress from 5 to 6 cm. Median cumulative duration of labour indicates that nulliparous women admitted at 4 cm, 5 cm, and 6 cm reached 10 cm within an expected time frame if the dilatation rate was ≥ 1 cm/hour, but their corresponding 95th percentiles show that labour could last up to 14, 11, and 9 hours, respectively. Substantial differences exist between actual plots of labour progression of individual women and the 'average labour curves' derived from study population-level data. Exclusion of women with augmented labours from the study population resulted in slightly faster labour progression patterns. CONCLUSIONS: Cervical dilatation during labour in the slowest-yet-normal women can progress more slowly than the widely accepted benchmark of 1 cm/hour, irrespective of parity. Interventions to expedite labour to conform to a cervical dilatation threshold of 1 cm/hour may be inappropriate, especially when applied before 5 cm in nulliparous and multiparous women. Averaged labour curves may not truly reflect the variability associated with labour progression, and their use for decision-making in labour management should be de-emphasized

Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics

In December 2016, a panel of experts in microbiology, nutrition and clinical research was convened by the International Scientific Association for Probiotics and Prebiotics to review the definition and scope of prebiotics. Consistent with the original embodiment of prebiotics, but aware of the latest scientific and clinical developments, the panel updated the definition of a prebiotic: a substrate that is selectively utilized by host microorganisms conferring a health benefit. This definition expands the concept of prebiotics to possibly include non-carbohydrate substances, applications to body sites other than the gastrointestinal tract, and diverse categories other than food. The requirement for selective microbiota-mediated mechanisms was retained. Beneficial health effects must be documented for a substance to be considered a prebiotic. The consensus definition applies also to prebiotics for use by animals, in which microbiota-focused strategies to maintain health and prevent disease is as relevant as for humans. Ultimately, the goal of this Consensus Statement is to engender appropriate use of the term ‘prebiotic’ by relevant stakeholders so that consistency and clarity can be achieved in research reports, product marketing and regulatory oversight of the category. To this end, we have reviewed several aspects of prebiotic science including its development, health benefits and legislation