BackgroundEvidence-based medicines, technologies, and protocols exist to prevent many of the annual 300,000 maternal, 2.7 million neonatal, and 9 million child deaths, but they are not being effectively implemented and utilized in rural areas. Nepal, one of South Asia’s poorest countries with over 80% of its population living in rural areas, exemplifies this challenge. Community health workers are an important cadre in low-income countries where human resources for health and health care infrastructure are limited. As local women, they are uniquely positioned to understand and successfully navigate barriers to health care access. Recent case studies of large community health worker programs have highlighted the importance of training, both initial and ongoing, and accountability through structured management, salaries, and ongoing monitoring and evaluation. A gap in the evidence regarding whether such community health worker systems can change health outcomes, as well as be sustainably adopted at scale, remains. In this study, we plan to evaluate a community health worker system delivering an evidence-based integrated reproductive, maternal, newborn, and child health intervention as it is scaled up in rural Nepal.MethodsWe will conduct a type 2 hybrid effectiveness-implementation study to test both the effect of an integrated reproductive, maternal, newborn, and child health intervention and the implementation process via a professional community health worker system. The intervention integrates five evidence-based approaches: (1) home-based antenatal care and post-natal care counseling and care coordination; (2) continuous surveillance of all reproductive age women, pregnancies, and children under age 2 years via a mobile application; (3) Community-Based Integrated Management of Newborn and Childhood Illness; (4) group antenatal and postnatal care; and 5) the Balanced Counseling Strategy to post-partum contraception. We will evaluate effectiveness using a pre-post quasi-experimental design with stepped implementation and implementation using the RE-AIM framework.DiscussionThis is the first hybrid effectiveness-implementation study of an integrated reproductive, maternal, newborn, and child health intervention in rural Nepal that we are aware of. As Nepal takes steps towards achieving the Sustainable Development Goals, the data from this three-year study will be useful in the detailed planning of a professionalized community health worker cadre delivering evidence-based reproductive, maternal, newborn, and child health interventions to the country’s rural population.Trial registrationClinicalTrials.gov Identifier: NCT03371186, registered 04 December 2017, retrospectively registered.Electronic supplementary materialThe online version of this article (10.1186/s13012-018-0741-x) contains supplementary material, which is available to authorized users.

Little is known about the importance of dose timing to successful antiretroviral therapy (ART). In a cohort comprised of Chinese HIV/AIDS patients, we measured adherence among subjects for six months using three methods in parallel: self-report using a visual analog scale (SR-VAS), pill count, and electronic drug monitors (EDM). We calculated two adherence metrics using the EDM data. The first metric used the proportion of doses taken; the second metric credited doses as adherent only if taken within a 1-hour window of a pre-specified dose time (EDM ‘proportion taken within dose time’). Of the adherence measures, EDM had the strongest associations with viral suppression. Of the two EDM metrics, incorporating dose timing had a stronger association with viral suppression. We conclude that dose timing is also an important determinant of successful ART, and should be considered as an additional dimension to overall adherence.

Integrating care at the home and facility level is a critical yet neglected function of healthcare delivery systems. There are few examples in practice or in the academic literature of affordable, digitally-enabled integrated care approaches embedded within healthcare delivery systems in low- and middle-income countries. Simultaneous advances in affordable digital technologies and community healthcare workers offer an opportunity to address this challenge. We describe the development of an integrated care system involving community healthcare worker networks that utilize a home-to-facility electronic health record platform for rural municipalities in Nepal. Key aspects of our approach of relevance to a global audience include: community healthcare workers continuously engaging with populations through household visits every three months; community healthcare workers using digital tools during the routine course of clinical care; individual and population-level data generated routinely being utilized for program improvement; and being responsive to privacy, security, and human rights concerns. We discuss implementation, lessons learned, challenges, and opportunities for future directions in integrated care delivery systems.

Circulating fetal cells (CFCs) in maternal blood are rare but have a strong potential to be the target for noninvasive prenatal diagnosis (NIPD). “Cell RevealTM system” is a silicon-based microfluidic platform capable to capture rare cell populations in human circulation. The platform is recently optimized to enhance the capture efficiency and system automation. In this study, spiking tests of SK-BR-3 breast cancer cells were used for the evaluation of capture efficiency. Then, peripheral bloods from 14 pregnant women whose fetuses have evidenced non-maternal genomic markers (e.g., de novo pathogenic copy number changes) were tested for the capture of circulating fetal nucleated red blood cells (fnRBCs). Captured cells were subjected to fluorescent in situ hybridization (FISH) on chip or recovered by an automated cell picker for molecular genetic analyses. The capture rate for the spiking tests is estimated as 88.1%. For the prenatal study, 2–71 fnRBCs were successfully captured from 2 mL of maternal blood in all pregnant women. The captured fnRBCs were verified to be from fetal origin. Our results demonstrated that the Cell RevealTM system has a high capture efficiency and can be used for fnRBC capture that is feasible for the genetic diagnosis of fetuses without invasive procedures.

In patients with endometrial cancer, a preoperative MRI contributes to accurate staging, allowing planning for the scale of surgery and preoperative counseling. In our study, the pretreatment identification of myometrium invasion provided the opportunity for small-scale surgery in the premenopausal women with early endometrial cancer. However, for the postmenopausal patients, the standard surgical procedure is indicated even if the degree of myometrium invasion is low.

Unmet need for postpartum contraception in rural Nepal remains high and expanding access to sexual and reproductive healthcare is essential to achieving universal healthcare. We evaluated the impact of an integrated intervention that employed community health workers aided by mobile technology to deliver patient-centred, home-based antenatal and postnatal counselling on postpartum modern contraceptive use. This was a pre-post-intervention study in seven village wards in a single municipality in rural Nepal. The primary outcome was modern contraceptive use among recently postpartum women. We performed a multivariable logistic regression to examine contraceptive use among postpartum women pre-and one-year post-intervention. We conducted qualitative interviews to explore the implementation process. There were 445

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Autosomal recessive renal tubular dysgenesis (ARRTD) is a rare and lethal disorder that causes stillbirth or early neonatal death. Most of the reported cases are diagnosed postnatally by a histopathological hallmark of the absence or paucity of differentiated proximal tubules in kidneys. Prenatal diagnosis of ARRTD is challenging because only a few fetal features (e.g., oligohydramnios/anhydramnios, anuria) are associated with this condition. In this study, we report a fetus with ARRTD, which showed anhydramnios and invisible urinary bladder since the second trimester, followed by growth restriction and reversed end diastolic flow in the middle cerebral artery (MCA-REDF). No morphological anomaly was detected on the fetal kidneys during an ultrasound scan. The baby died of refractory hypotension the day after their birth. Genetic analysis of genes that are involved in the renin-angiotensin-aldosterone system (RAAS), which are the known genetic causes of ARRTD, identified a novel, biparental-origin homozygous c.857-619_1269+243delinsTTGCCTTGC mutation in the AGT gene. The mutation is considered as pathogenic because it is cosegregated with ARRTD and detected in other unrelated ARRTD families. Our findings link the fetal ultrasound manifestations to the ARRTD, highlighting clues that are useful for prenatal diagnosis, which warrants confirmatory genotyping of the RAAS genes including oligohydramnios/anhydramnios, anuria (absent filling of a fetal urinary bladder), MCA-REDF, and a morphologically normal kidney.