A Type II hybrid effectiveness-implementation study of an integrated CHW intervention to address maternal healthcare in rural Nepal.

Skilled care during pregnancy, childbirth, and postpartum is essential to prevent adverse maternal health outcomes, yet utilization of care remains low in many resource-limited countries, including Nepal. Community health workers (CHWs) can mitigate health system challenges and geographical barriers to achieving universal health coverage. Gaps remain, however, in understanding whether evidence-based interventions delivered by CHWs, closely aligned with WHO recommendations, are effective in Nepal's context. We conducted a type II hybrid effectiveness-implementation, mixed-methods study in two rural districts in Nepal to evaluate the effectiveness and the implementation of an evidence-based integrated maternal and child health intervention delivered by CHWs, using a mobile application. The intervention was implemented stepwise over four years (2014-2018), with 65 CHWs enrolling 30,785 families. We performed a mixed-effects Poisson regression to assess institutional birth rate (IBR) pre-and post-intervention. We used the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework to evaluate the implementation during and after the study completion. There was an average 30% increase in IBR post-intervention, adjusting for confounding variables (p<0.0001). Study enrollment showed 35% of families identified as dalit, janjati, or other castes. About 78-89% of postpartum women received at least one CHW-counseled home visit within 60 days of childbirth. Ten (53% of planned) municipalities adopted the intervention during the study period. Implementation fidelity, measured by median counseled home visits, improved with intervention time. The intervention was institutionalized beyond the study period and expanded to four additional hubs, albeit with adjustments in management and supervision. Mechanisms of intervention impact include increased knowledge, timely referrals, and longitudinal CHW interaction. Full-time, supervised, and trained CHWs delivering evidence-based integrated care appears to be effective in improving maternal healthcare in rural Nepal. This study contributes to the growing body of evidence on the role of community health workers in achieving universal health coverage.

Benefits and risks of low molecular weight heparin use on reproductive outcomes: A retrospective cohort study.

OBJECTIVE: Low molecular weight heparin (LMWH) has been given to reproductive-age women with various indications. This study aims to assess the benefits and risks of such use. MATERIALS AND METHODS: We retrospectively reviewed data (n = 204) between Jan 2016 and May 2019. Logistic regression analysis was conducted to evaluate the correlation between indications and reproductive outcomes. RESULTS: LMWH use had higher odds of live birth in women less than 30 years of age (OR: 4.98; 95% CI = 1.13-21.98; p = 0.034) and with protein S deficiency (OR: 3.90; 95% CI = 1.77-8.59; p = 0.001). For the subgroup of recurrent pregnant loss, LMWH use was only advantageous to women with protein S deficiency (OR: 2.45; 95%:1.01-5.97; p = 0.048). Risks such as preterm delivery, small-for-gestational-age, placental abruption, antepartum/postpartum hemorrhage were not significantly increased among subgroups. Women treated with LMWH and who had successful live births (n = 171) had a slightly increased risk of postpartum hemorrhage compared to controls (n = 8058) during this period in our institution (2.9% vs 1.2%, p < 0.001). CONCLUSION: LMWH administration produces a higher chance of live-birth to women younger than 30 years of age or with protein S deficiency. However, risk of postpartum hemorrhage is increased.

Proposal for Practical Approach in Prenatal Diagnosis of Beckwith-Wiedemann Syndrome and Review of the Literature.

BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is a phenotypically and genetically heterogeneous disorder associated with epigenetic/genetic aberrations on chromosome 11p15.4p15.5. There is no consensus criterion for prenatal diagnosis of BWS. METHODS: Three BWS patients with their clinical histories, prenatal ultrasonographic features, and results of molecular diagnosis were presented. Likewise, by incorporating the findings of our cases and literature review, the phenotypic spectrum and genotype-phenotype correlations of fetal BWS were summarized, and a practical approach in prenatal diagnosis of BWS was proposed. RESULTS: A total of 166 BWS cases with prenatal features were included for analysis. Common fetal features include abdominal wall defects (42.8%), polyhydramnios (33.1%), and macrosomia (32.5%). Molecular pathologies include methylation changes in imprinting control region 1 and 2 (ICR1 and ICR2), paternal uniparental disomy of chromosome 11p15.5, copy number change involving 11p15, etc. Some genotype-phenotype correlations were observed. However, the broad phenotypic spectrum but limited features manifested by affected fetuses rendering ultrasonographic diagnosis not easy. CONCLUSIONS: Molecular tests are used for prenatal diagnosis of BWS suspected by ultrasonography. Methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) is recommended as the first-line molecular tool because it simultaneously detects ICR1/ICR2 methylation statuses and copy numbers that solve the majority of clinical cases in the prenatal scenario.

Comparing two data collection methods to track vital events in maternal and child health via community health workers in rural Nepal.

BACKGROUND: Timely tracking of health outcomes is difficult in low- and middle-income countries without comprehensive vital registration systems. Community health workers (CHWs) are increasingly collecting vital events data while delivering routine care in low-resource settings. It is necessary, however, to assess whether routine programmatic data collected by CHWs are sufficiently reliable for timely monitoring and evaluation of health interventions. To study this, we assessed the consistency of vital events data recorded by CHWs using two methodologies-routine data collected while delivering an integrated maternal and child health intervention, and data from a birth history census approach at the same site in rural Nepal. METHODS: We linked individual records from routine programmatic data from June 2017 to May 2018 with those from census data, both collected by CHWs at the same site using a mobile platform. We categorized each vital event over a one-year period as 'recorded by both methods,' 'census alone,' or 'programmatic alone.' We further assessed whether vital events data recorded by both methods were classified consistently. RESULTS: From June 2017 to May 2018, we identified a total of 713 unique births collectively from the census (birth history) and programmatic maternal 'post-delivery' data. Three-fourths of these births (n = 526) were identified by both. There was high consistency in birth location classification among the 526 births identified by both methods. Upon including additional programmatic 'child registry' data, we identified 746 total births, of which 572 births were identified by both census and programmatic methods. Programmatic data (maternal 'post-delivery' and 'child registry' combined) captured more births than census data (723 vs. 595). Both methods consistently classified most infants as 'living,' while infant deaths and stillbirths were largely classified inconsistently or recorded by only one method. Programmatic data identified five infant deaths and five stillbirths not recorded in census data. CONCLUSIONS: Our findings suggest that data collected by CHWs from routinely tracking pregnancies, births, and deaths are promising for timely program monitoring and evaluation. Despite some limitations, programmatic data may be more sensitive in detecting vital events than cross-sectional census surveys asking women to recall these events.

Polyhydramnios as a sole ultrasonographic finding for detecting fetal hemolytic anemia caused by anti-c alloimmunization.

OBJECTIVE: The prenatal course of a rare case with fetal anemia caused by maternal anti-c alloimmunization was reported. CASE REPORT: A 39-year-old female with anti-c and anti-E antibodies against red cells had previously experienced a stillbirth. At her present pregnancy, titers of maternal antibodies and fetal middle cerebral artery peak systolic velocity (MCA-PSV) were frequently monitored to investigate the severity of fetal hemolytic anemia. Rather than manifesting as an increase in MCA-PSV, the anemic fetus was delivered at 32 weeks and one day of gestation with a sole presentation: polyhydramnios. Neonatal hospitalization course were compatible with hemolytic anemia. The baby was discharged at 48 days of age. CONCLUSION: This case illustrated the complexities of dealing with maternal red cell alloimmunization during pregnancy and the limitations of noninvasive diagnostic modalities for detecting fetal anemia, and highlighted that obstetricians should refer all available clinical parameters in order to offer appropriate perinatal care.

Human amniotic fluid mesenchymal stem cells attenuate pancreatic cancer cell proliferation and tumor growth in an orthotopic xenograft mouse model.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a malignant cancer and chemotherapy ineffectively treats PDAC, leading to the requirement for alternative tumor-targeted treatment. Human amniotic fluid mesenchymal stem cells (hAFMSCs) have been revealed to suppress tumor growth in various cancers and they are a strong candidate for treating PDAC. METHODS: To evaluate the effects of hAFMSCs on human pancreatic carcinoma cells (PANC1, AsPC1 and BxPC3 cell lines) and the possible mechanism involved, an in vitro cell coculture system was used. A PANC1 orthotopic xenograft mouse model was established and hAFMSCs were injected intravenously at 4 weeks post-xenograft. RESULTS: An in vitro coculture assay showed that hAFMSCs inhibited PANC1 cell proliferation by inducing S phase cell cycle arrest and increased cell apoptosis in a time-dependent manner. In PANC1 cells, hAFMSCs caused the downregulation of Cyclin A and Cyclin B1 as well as the upregulation of p21 (CDKN1A) at 24 h post coculture. The upregulation of pro-apoptotic factors Caspase-3/-8 and Bax at 24 h post coculture reduced the migration and invasion ability of PANC1 cells through inhibiting the epithelial-mesenchymal transition (EMT) process. In a PANC1 orthotopic xenograft mouse model, a single injection of hAFMSCs showed significant tumor growth inhibition with evidence of the modulation of cell cycle and pro-apoptotic regulatory genes and various genes involved in matrix metallopeptidase 7 (MMP7) signaling-triggered EMT process. Histopathological staining showed lower Ki67 levels in tumors from hAFMSCs-treated mice. CONCLUSIONS: Our data demonstrated that hAFMSCs strongly inhibit PDAC cell proliferation, tumor growth and invasion, possibly by altering cell cycle arrest and MMP7 signaling-triggered EMT.

Comparison of One-Stage and Two-Stage Intraoperative Uterine Artery Embolization during Cesarean Delivery for Placenta Accreta: Report of Two Clinical Cases at a Tertiary Referral Medical Center.

Placenta accreta spectrum (PAS) described the anchoring placental villi attached or penetrating into/through the myometrium. PAS is clinically important because of the unpredictable bleeding amount when manually removing the defective decidualization at the endometrial-myometrial interface. Therefore, a multidisciplinary strategy for cesarean delivery with PAS is crucial. Postoperative embolization after cesarean hysterectomy in a hybrid suite was studied by many scientists. In this study, we demonstrated two cases of intraoperative embolization without hysterectomy in a hybrid operating room for cesarean delivery with placenta accreta. Our results show that intraoperative uterine artery embolization with a hybrid suite is a time-preserving and safe method for cesarean delivery with PAS owing to avoiding the risk of morbidity and mortality during patient transfer.

Pap Smear and Mammogram Screening Rates in a Refugee and General OB/GYN Clinic: A Retrospective Review.

Although multiple studies have shown that resettled refugee women are less likely to receive preventative cancer screenings like pap smears and mammograms, a small number have demonstrated the opposite. This retrospective chart review, conducted between January 2017 and October 2018, compares pap smear and mammogram rates of patients seen in a refugee-specific OB/GYN clinic with patients from the general OB/GYN clinic at the same institution. Data from 298 patients (149 refugee and 149 general clinic patients matched by age and date-of-visit) were analyzed. Pap smear screening rates were 90.60% in the refugee group and 73.83% in the general group [p < 0.009, aOR 3.46 (1.36-8.81)], while mammogram screening rates were 36.84% and 38.60%, respectively (p = 0.46). The provision of holistic services meeting refugee women's unique needs can effectively increase pap smear screening rates.

IL-4 and IL-13 Promote Proliferation of Mammary Epithelial Cells through STAT6 and IRS-1.

T helper (Th)2 cytokines such as interleukin (IL)-4 and IL-13 control immune function by acting on leukocytes. They also regulate multiple responses in non-hematopoietic cells. During pregnancy, IL-4 and IL-13 facilitate alveologenesis of mammary glands. This particular morphogenesis generates alveoli from existing ducts and requires substantial cell proliferation. Using 3D cultures of primary mouse mammary epithelial cells, we demonstrate that IL-4 and IL-13 promote cell proliferation, leading to enlargement of mammary acini with partially filled lumens. The mitogenic effects of IL-4 and IL-13 are mediated by STAT6 as inhibition of STAT6 suppresses cell proliferation and improves lumen formation. In addition, IL-4 and IL-13 stimulate tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1). Prolonged treatment with these cytokines leads to increased IRS-1 abundance, which, in turn, amplifies IL-4- and IL-13-stimulated IRS-1 tyrosine phosphorylation. Through signaling crosstalk between IL-4/IL-13 and insulin, a hormone routinely included in mammary cultures, IRS-1 tyrosine phosphorylation is further enhanced. Lowering IRS-1 expression reduces cell proliferation, suggesting that IRS-1 is involved in IL-4- and IL-13-stimulated cell proliferation. Thus, a Th2-dominant cytokine milieu during pregnancy confers mammary gland development by promoting cell proliferation.

Prenatal Diagnosis of True Fetal Mosaicism with Small Supernumerary Marker Chromosome Derived from Chromosome 16 by Funipuncture and Molecular Cytogenetics Including Chromosome Microarray.

This study examined the molecular characterization of a prenatal case with true fetal mosaicism of small supernumerary marker chromosome 16 (sSMC(16)). A 41-year-old female underwent amniocentesis at 19 weeks of gestation due to advanced maternal age. Chromosomal analysis for cultured amniocytes revealed a karyotype of 47,XY,+mar[4]/46,XY[16]. Spectral karyotyping and metaphase fluorescence in situ hybridization (FISH) demonstrated that the sSMC was derived from chromosome 16 (47,XY,+mar.ish der(16)(D16Z1+)[13/20]). Confined placental mosaicism was initially suspected because the prenatal ultrasound revealed a normal structure and the pregnancy was uneventful. However, interphase FISH of cord blood performed at 28 weeks of gestation showed 20% mosaicism of trisomy chromosome 16 (nuc ish(D16Z2×3)[40/200]). Chromosome microarray analysis further demonstrated 55% mosaicism of an 8.02 Mb segmental duplication at the subcentromeric region of 16p12.1p11.1 (arr[GRCh37] 16p12.1p11.1(27021975_35045499)×3[0.55]). The results demonstrated a true fetal mosaicism of sSMC(16) involving chromosome16p12.1p11.1 that is associated with chromosome 16p11.2 duplication syndrome (OMIM #614671). After non-directive genetic counseling, the couple opted for late termination of pregnancy. This case illustrated the use of multiple molecular cytogenetic tools to elucidate the origin and structure of sSMC, which is crucial for prenatal counseling, decision making, and clinical management.

"Our mothers do not tell us": a qualitative study of adolescent girls' perspectives on sexual and reproductive health in rural Nepal.

Adolescent girls in low- and middle-income countries continue to face poor sexual and reproductive health (SRH). In Nepal, early marriage and motherhood, gender-based violence, and unmet need for contraception remain pervasive. Adolescent girls in rural areas bear a disproportionate burden of poor reproductive health outcomes, but there are limited context-specific data. This is a qualitative study to identify factors that impact adolescent girls' utilisation of and access to SRH services in a rural district of Nepal. We conducted 21 individual interviews with adolescent girls aged 15-19 years, and three focus group discussions with community health workers. We used an inductive analytic approach to identify emergent and recurrent themes and present the themes using the social ecological model. Individual-level factors that contribute to low uptake of services among adolescent girls include lack of knowledge, self-perceived lack of need, low decision-making autonomy, and shyness. Interpersonal factors that impact access include unsupportive family norms, absence of open communication, and need for permission from family members to access care. At the community level, disparate gender norms, son preference, and judgment by community members affect adolescent SRH. Inadequate sex education, far travel distance to facilities, lack of female healthcare providers and teachers, and inability to access abortion services were identified as organisational and systems barriers. Stigma was a factor cross-cutting several levels. Our findings suggest the need for multi-level strategies to address these factors to improve adolescent girls' SRH.

Relevance of Copy Number Variation at Chromosome X in Male Fetuses Inherited from the Mother May Be Ascertained by Including Male Relatives from the Maternal Lineage in Addition to Trio Analyses.

Chromosome microarray analysis has been used for prenatal detection of copy number variations (CNVs) and genetic counseling of CNVs has been greatly improved after the accumulation of knowledge from postnatal outcomes in terms of the genotype-phenotype correlation. However, a significant number of CNVs are still regarded as variants of unknown significance (VUS). CNVs at the chromosome X (X-CNVs) represent a unique group of genetic changes in genetic counseling; X-CNVs are similar to X-linked recessive monogenic disorders in that the prognosis in males is expected to be poor. Trio analysis is typically advised to patients with X-CNVs but such an approach may be inadequate in prenatal settings since the clinical relevance is sometimes uninformative, particularly for the maternally inherited X-CNVs in male fetuses. Here, we reported four healthy women whose male fetuses were found to have X-CNVs inherited from the mothers. The X-CNVs were initially recognized as VUS or likely pathogenic in males according to the publicly available information. After extending genetic analyses to male relatives of the maternal lineages, however, the relevance of the X-CNVs was reconsidered to be likely benign. The results highlight that an extended analysis to include more relatives, in addition to the parents, provides further information for genetic counseling when X-CNVs are encountered in prenatal settings.

Community-based postpartum contraceptive counselling in rural Nepal: a mixed-methods evaluation.

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 postpartum women in the pre-intervention group and 508 in the post-intervention group. Modern contraceptive use increased from 29% pre-intervention to 46% post-intervention (p < 0.0001). Adjusting for age, caste, and household expenditure, time since delivery and sex of child in the index pregnancy, postpartum women one-year post-intervention had twice the odds (OR 2.3; CI 1.7, 3.1; p < 0.0001) of using a modern contraceptive method as compared to pre-intervention. Factors at the individual, family, and systems level influenced women's contraceptive decisions. The intervention contributed to increasing contraceptive use through knowledge transfer, demand generation, referrals to healthcare facilities, and follow-up. A community-based, patient-centred contraceptive counselling intervention supported by mobile technology and integrated into longitudinal care delivered by community health workers appears to be an effective strategy for improving uptake of modern contraception among postpartum women in rural Nepal.

Whole Exome Sequencing with Comprehensive Gene Set Analysis Identified a Biparental-Origin Homozygous c.509G>A Mutation in PPIB Gene Clustered in Two Taiwanese Families Exhibiting Fetal Skeletal Dysplasia during Prenatal Ultrasound.

Skeletal dysplasia (SD) is a complex group of bone and cartilage disorders often detectable by fetal ultrasound, but the definitive diagnosis remains challenging because the phenotypes are highly variable and often overlap among different disorders. The molecular mechanisms underlying this condition are also diverse. Hundreds of genes are involved in the pathogenesis of SD, but most of them are yet to be elucidated, rendering genotyping almost infeasible except those most common such as fibroblast growth factor receptor 3 (FGFR3), collagen type I alpha 1 chain (COL1A1), collagen type I alpha 2 chain (COL1A2), diastrophic dysplasia sulfate transporter (DTDST), and SRY-box 9 (SOX9). Here, we report the use of trio-based whole exome sequencing (trio-WES) with comprehensive gene set analysis in two Taiwanese non-consanguineous families with fetal SD at autopsy. A biparental-origin homozygous c.509G>A(p.G170D) mutation in peptidylprolyl isomerase B (PPIB) gene was identified. The results support a diagnosis of a rare form of autosomal recessive SD, osteogenesis imperfecta type IX (OI IX), and confirm that the use of a trio-WES study is helpful to uncover a genetic explanation for observed fetal anomalies (e.g., SD), especially in cases suggesting autosomal recessive inheritance. Moreover, the finding of an identical PPIB mutation in two non-consanguineous families highlights the possibility of the founder effect, which deserves future investigations in the Taiwanese population.

Prenatal diagnosis of partial monosomy 21q (21q22.1→qter) associated with intrauterine growth restriction and corpus callosum dysgenesis.

OBJECTIVE: A prenatal diagnosis of partial monosomy 21q(21q22.1→ qter) in fetus with intrauterine growth restriction and corpus callosum dysgenesis but escaped from the detection by cell free DNA testing was reported. CASE REPORT: A 31-year-old, primigravida women, presented with intrauterine growth restriction and corpus callosum dysgenesis at 23 weeks of gestational age by anatomic ultrasound screening. The interphase fluorescence in situ hybridization (FISH) analysis on amniocytes revealed monosomy 21, while the cytogenetic analysis and array comparative genomic hybridization (CGH) with CytoScan gene chip ascertained a 12.35 Mb deletion at 21q22.1q22.3. CONCLUSION: Although noninvasive prenatal testing is used extensively and can be applied to certain microdeletion diseases, the application for uncommon deletion disorders such as the present case remains limited. Prenatal examination with detailed ultra-sonography combined with different modalities of invasive prenatal testing can provide a more comprehensive information.

Rides for Refugees: A Transportation Assistance Pilot for Women's Health.

Transportation barriers can limit access to healthcare for refugee and asylum seeking women. This study assesses the efficacy of a healthcare-directed rideshare application for overcoming these barriers at an urban health clinic. A pilot study was conducted at Boston Medical Center's Refugee Women's Health Clinic from June 2018 to February 2019. Women with gynecologic visits reporting transportation difficulties were offered rides. The primary outcome was no-show rates. Secondary outcomes included cost, and patient/provider experiences. Of 102 eligible visits, 31 reported transportation insecurity and received rides. Those women had a 6% no-show rate, compared to 30% in women denying transportation barriers, and 50% amongst unreachable women (p < 0.0001). The intervention cost $2033 and generated $30,337 in charges. Minimal adverse experiences were reported. Healthcare-directed rideshare applications are an effective and cost-efficient strategy for refugee and asylum seeking women to access essential health services.

Prenatal Diagnosis of Autosomal Recessive Renal Tubular Dysgenesis with Anhydramnios Caused by a Mutation in the AGT Gene.

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.

Transition to active learning in rural Nepal: an adaptable and scalable curriculum development model.

BACKGROUND: Traditional medical education in much of the world has historically relied on passive learning. Although active learning has been in the medical education literature for decades, its incorporation into practice has been inconsistent. We describe and analyze the implementation of a multidisciplinary continuing medical education curriculum in a rural Nepali district hospital, for which a core objective was an organizational shift towards active learning. METHODS: The intervention occurred in a district hospital in remote Nepal, staffed primarily by mid-level providers. Before the intervention, education sessions included traditional didactics. We conducted a mixed-methods needs assessment to determine the content and educational strategies for a revised curriculum. Our goal was to develop an effective, relevant, and acceptable curriculum, which could facilitate active learning. As part of the intervention, physicians acted as both learners and teachers by creating and delivering lectures. Presenters used lecture templates to prioritize clarity, relevance, and audience engagement, including discussion questions and clinical cases. Two 6-month curricular cycles were completed during the study period. Daily lecture evaluations assessed ease of understanding, relevance, clinical practice change, and participation. Periodic lecture audits recorded learner talk-time, the proportion of lecture time during which learners were talking, as a surrogate for active learning. Feedback from evaluation and audit results was provided to presenters, and pre- and post-curriculum knowledge assessment exams were conducted. RESULTS: Lecture audits showed a significant increase in learner talk-time, from 14% at baseline to 30% between months 3-6, maintained at 31% through months 6-12. Lecture evaluations demonstrated satisfaction with the curriculum. Pre- and post-curriculum knowledge assessment scores improved from 50 to 64% (difference 13.3% ± 4.5%, p = 0.006). As an outcome for the measure of organizational change, the curriculum was replicated at an additional clinical site. CONCLUSION: We demonstrate that active learning can be facilitated by implementing a new educational strategy. Lecture audits proved useful for internal program improvement. The components of the intervention which are transferable to other rural settings include the use of learners as teachers, lecture templates, and provision of immediate feedback. This curricular model could be adapted to similar settings in Nepal, and globally.

A Silicon-based Coral-like Nanostructured Microfluidics to Isolate Rare Cells in Human Circulation: Validation by SK-BR-3 Cancer Cell Line and Its Utility in Circulating Fetal Nucleated Red Blood Cells.

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.

Developing and deploying a community healthcare worker-driven, digitally- enabled integrated care system for municipalities in rural Nepal.

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.