Challenges of implementing an individual randomized controlled trial (women first: Preconception maternal nutrition study) in a rural study site: A case study from Pakistan

Persistent global disparities in maternal and neonatal outcomes associated with poor maternal nutrition provided the genesis of the Women First (WF) study, an individually randomized controlled trial on preconceptional maternal nutrition. This article describes the challenges that arose in implementing this trial related to nutrition or diet of the mother, in District Thatta-Pakistan. During different phases of the study, we encountered problems in identifying the eligible participants, taking consent from couples, randomizing participants in different arms, conducting biweekly follow-up visits on time, ensuring compliance to the intervention, and measuring the primary outcome within the 24 hours of birth. Each challenge was itself an opportunity for the research team to address the same through effective coordination and teamwork. Moreover, with adequate resources and dedicated staff with diverse backgrounds, it was possible to implement the WF study across the widely scattered geographic clusters of District Thatta. In addition, there are some broad strategies that could be applied to other studies such as very close contact either in person or at least by talking to mothers via phones and rapport with the study participants, the study leadership of country coordinator and the field supervisors to build trust between those on front lines and the study leadership. Moreover, continuous monitoring and supervision with frequent training and refreshers were also found to be more important to assure the data quality and to meet the study targets. Community meetings were also found to be very helpful and effective to follow the participants for a long time. Researchers conducting a similar type of studies particularly in rural areas can learn many lessons from such experiences. Thus, the process of implementing the study in one of the rural areas of Pakistan provides an insight into where and how similar individual randomized trials might be deployed

Use of smokeless tobacco before conception and its relationship with maternal and fetal outcomes of pregnancy in Thatta, Pakistan: Findings from women first study

Introduction: Smokeless tobacco (SLT) consumption during pregnancy has adverse consequences for the mother and fetus. We aimed to investigate the effects of maternal pre-pregnancy SLT consumption on maternal and fetal outcomes in the district of Thatta, Pakistan.Methods: We conducted a secondary data analysis of an individual randomized controlled trial of preconception maternal nutrition. Study participants were women of reproductive age residing in the district of Thatta, Pakistan. Participants were asked questions regarding the usage of commonly consumed SLT known as gutka (exposure variable). Study outcomes included maternal anemia, miscarriage, preterm births, stillbirths, and low birth weight. We performed a cox-regression analysis by controlling for confounders such as maternal age, education, parity, working status, body mass index, and geographic clusters.Results: The study revealed that 71.5% of the women reported using gutka, with a higher proportion residing in rural areas as compared to urban areas in the district of Thatta, Pakistan. In the multivariable analysis, we did not find a statistically significant association between gutka usage and anemia [(RR: 1.04, 95% CI (0.92-1.16)]; miscarriage [(RR: 1.08, 95% CI (0.75-1.54)]; preterm birth [(RR: 1.37, 95% CI (0.64-2.93)]; stillbirth [(RR: 1.02, 95% CI (0.39-2.61)] and low birth weight [(RR: 0.96, 95% CI (0.72-1.28)].Conclusion: The study did not find an association between gutka usage before pregnancy and adverse maternal and fetal outcomes. In the future, robust epidemiological studies are required to detect true differences with a dose-response relationship between gutka usage both before and during pregnancy and adverse feto-maternal outcomes.Implications: While most epidemiological studies conducted in Pakistan have focused on smoking and its adverse outcomes among males, none of the studies have measured the burden of SLT among women of reproductive age (WRA) and its associated adverse outcomes. In addition, previously conducted studies have primarily assessed the effect of SLT usage during pregnancy rather than before pregnancy on adverse fetal and maternal outcomes. The current study is unique because it provides an insight into the usage of SLT among WRA before pregnancy and investigated the association between pre-pregnancy SLT usage and its adverse feto-maternal outcomes in rural Pakistan

Pregnant women in four low-middle income countries have a high prevalence of inadequate dietary intakes that are improved by dietary diversity

Background: Up-to-date dietary data are required to understand the diverse nutritional challenges of pregnant women living in low-middle income countries (LMIC). To that end, dietary data were collected from 1st trimester pregnant women in rural areas of Guatemala, India, Pakistan, and Democratic Republic of the Congo (DRC) participating in a maternal lipid-based nutrient supplement (LNS) Randomized Controlled Trial to examine dietary diversity (DD), usual group energy and nutrient intakes, and prevalence of inadequate dietary intakes.Methods: Two 24-h dietary recalls were conducted in ~240 pregnant women/site (total n = 966) prior to 12-week gestation. Adequate DD was assessed, i.e., ≥5 major food groups consumed within the past 24 h. Median, Q1, Q3 intakes (without LNS) of energy, macronutrients, 12 micronutrients, and phytate were examined. The at risk prevalence of inadequate intakes were based on international guidelines for pregnant women.Results: Dietary patterns varied widely among sites, with adequate DD reported: 20% (Pakistan), 25% (DRC), 50% (Guatemala), and 70% (India). Significantly higher intakes of most key nutrients were observed in participants with adequate DD. More than 80% of women in all sites had inadequate intakes of folate, vitamin B12, and choline, and \u3e80% of women in India and DRC also had inadequate intakes of calcium, thiamine, riboflavin, and vitamin B6.Conclusions: Our data highlight the likely need for micronutrient supplementation in pregnancy, specifically multi-micronutrient interventions, and support the value of increasing DD as part of sustainable long-term nutrition programs for women of reproductive age in these poor rural settings in LMIC

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

An open toolkit for tracking open science partnership implementation and impact.

Serious concerns about the way research is organized collectively are increasingly being raised. They include the escalating costs of research and lower research productivity, low public trust in researchers to report the truth, lack of diversity, poor community engagement, ethical concerns over research practices, and irreproducibility. Open science (OS) collaborations comprise of a set of practices including open access publication, open data sharing and the absence of restrictive intellectual property rights with which institutions, firms, governments and communities are experimenting in order to overcome these concerns. We gathered two groups of international representatives from a large variety of stakeholders to construct a toolkit to guide and facilitate data collection about OS and non-OS collaborations. Ultimately, the toolkit will be used to assess and study the impact of OS collaborations on research and innovation. The toolkit contains the following four elements: 1) an annual report form of quantitative data to be completed by OS partnership administrators; 2) a series of semi-structured interview guides of stakeholders; 3) a survey form of participants in OS collaborations; and 4) a set of other quantitative measures best collected by other organizations, such as research foundations and governmental or intergovernmental agencies. We opened our toolkit to community comment and input. We present the resulting toolkit for use by government and philanthropic grantors, institutions, researchers and community organizations with the aim of measuring the implementation and impact of OS partnership across these organizations. We invite these and other stakeholders to not only measure, but to share the resulting data so that social scientists and policy makers can analyse the data across projects

Mutations in REEP6 Cause Autosomal-Recessive Retinitis Pigmentosa

Retinitis pigmentosa (RP) is the most frequent form of inherited retinal dystrophy. RP is genetically heterogeneous and the genes identified to date encode proteins involved in a wide range of functional pathways, including photoreceptor development, phototransduction, the retinoid cycle, cilia, and outer segment development. Here we report the identification of biallelic mutations in Receptor Expression Enhancer Protein 6 (REEP6) in seven individuals with autosomal-recessive RP from five unrelated families. REEP6 is a member of the REEP/Yop1 family of proteins that influence the structure of the endoplasmic reticulum but is relatively unstudied. The six variants identified include three frameshift variants, two missense variants, and a genomic rearrangement that disrupts exon 1. Human 3D organoid optic cups were used to investigate REEP6 expression and confirmed the expression of a retina-specific isoform REEP6.1, which is specifically affected by one of the frameshift mutations. Expression of the two missense variants (c.383C>T [p.Pro128Leu] and c.404T>C [p.Leu135Pro]) and the REEP6.1 frameshift mutant in cultured cells suggest that these changes destabilize the protein. Furthermore, CRISPR-Cas9-mediated gene editing was used to produce Reep6 knock-in mice with the p.Leu135Pro RP-associated variant identified in one RP-affected individual. The homozygous knock-in mice mimic the clinical phenotypes of RP, including progressive photoreceptor degeneration and dysfunction of the rod photoreceptors. Therefore, our study implicates REEP6 in retinal homeostasis and highlights a pathway previously uncharacterized in retinal dystrophy

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Admixture mapping: from paradigms of race and ethnicity to population history

Admixture mapping is a whole genome association strategy that takes advantage of population history—or genetic ancestry—to map genes for complex diseases. However, because it uses racial/ethnic groupings to examine differential disease risk, admixture mapping raises ethical and social concerns. While there has been much theoretical commentary regarding the ethical and social implications of population-based genetic research, empirical data from stakeholders most closely involved with these studies is limited. One of the first admixture mapping studies carried out was a scan for Multiple Sclerosis (MS) risk factors in an African-American population. Applying qualitative research methods, we used this example to explore developing views, experiences and perceptions of the ethical and social implications of admixture mapping and other population-based research—their value, risks and benefits, and the future prospects of the field. Additionally, we sought to understand how social and ethical risks might be mitigated, and the benefits of this research optimized. We draw on in-depth, one-on-one interviews with leading population geneticists, genome scientists, bioethicists, and African-Americans with MS. Here we present our findings from this unique group of key informants and stakeholders

Chemical characterisation and the anti-inflammatory, anti-angiogenic and antibacterial properties of date fruit (Phoenix dactylifera L.)

Ethnopharmacological relevance: Date fruit, Phoenix dactylifera L. has traditionally been used as a medicine in many cultures for the treatment of a range of ailments such as stomach and intestinal disorders, fever, oedema, bronchitis and wound healing. Aim of the review: The present review aims to summarise the traditional use and application of Phoenix dactylifera date fruit in different ethnomedical systems, additionally the botany and phytochemistry are identified. Critical evaluation of in vitro and in vitro studies examining date fruit in relation to anti-inflammatory, anti-angiogenic and antimicrobial activities are outlined. Key Findings: The ethnomedical use of Phoenix dactylifera in the treatment of inflammatory disease has been previously identified and reported. Furthermore, date fruit and date fruit co-products such as date syrup are rich sources of polyphenols, anthocyanins, sterols and carotenoids. In vitro studies have demonstrated that date fruit exhibits antibacterial, anti-inflammatory and anti-angiogenic activity. The recent interest in the identification of the numerous health benefits of dates using in vitro and in vivo studies have confirmed that date fruit and date syrup have beneficial health effects that can be attributed to the presence of natural bioactive compounds. Conclusions: Date fruit and date syrup have therapeutic properties, which have the potential to be beneficial to health. However, more investigations are needed to quantify and validate these effects

Addressing disparities in maternal health care in Pakistan: gender, class and exclusion

Background: After more than two decades of the Safe Motherhood Initiative and Millennium Development Goals aimed at reducing maternal mortality, women continue to die in childbirth at unacceptably high rates in Pakistan. While an extensive literature describes various programmatic strategies, it neglects the rigorous analysis of the reasons these strategies have been unsuccessful, especially for women living at the economic and social margins of society. A critical gap in current knowledge is a detailed understanding of the root causes of disparities in maternal health care, and in particular, how gender and class influence policy formulation and the design and delivery of maternal health care services. Taking Pakistan as a case study, this research builds upon two distinct yet interlinked conceptual approaches to understanding the phenomenon of inequity in access to maternal health care: social exclusion and health systems as social institutions. Methods/Design: This four year project consists of two interrelated modules that focus on two distinct groups of participants: (1) poor, disadvantaged women and men and (2) policy makers, program managers and health service providers. Module one will employ critical ethnography to understand the key axes of social exclusion as related to gender, class and zaat and how they affect women’s experiences of using maternal health care. Through health care setting observations, interviews and document review, Module two will assess policy design and delivery of maternal health services. Discussion: This research will provide theoretical advances to enhance understanding of the power dynamics of gender and class that may underlie poor women’s marginalization from health care systems in Pakistan. It will also provide empirical evidence to support formulation of maternal health care policies and health care system practices aimed at reducing disparities in maternal health care in Pakistan. Lastly, it will enhance inter-disciplinary research capacity in the emerging field of social exclusion and maternal health and help reduce social inequities and achieve the Millennium Development Goal No. 5