Joint Involvement Can Predict Chikungunya in a Dengue Syndemic Setting in India.

Dengue and chikungunya have been endemic in India but have the tendency to cause periodic epidemics, often together, wherein they are termed 'syndemic'. Such a syndemic was observed in 2016 in India which resulted in a further scarcity of already resource-poor specific diagnostic infrastructure even in many urban conglomerates. A cross-sectional study was thus conducted, on 978 fever patients that consulted the ICMR-NIMR fever clinic, New Delhi, in September 2016, with an objective to identify symptom/s that could predict chikungunya with certainty. The overall aim was to rationally channelize the most clinically suitable patients for the required specific diagnosis of chikungunya. Based on their clinical profile, febrile patients attending NIMR's clinic, appropriate laboratory tests and their association analyses were performed. Bivariate analysis on 34 clinical parameters revealed that joint pain, joint swelling, rashes, red spots, weakness, itching, loss of taste, red eyes, and bleeding gums were found to be statistically significantly associated predictors of chikungunya as compared to dengue. While, in multivariate analysis, only four symptoms (joint pain in elbows, joint swelling, itching and bleeding gums) were found in statistically significant association with chikungunya. Hence, based on the results, a clinician may preferably channelize febrile patients with one or more of these four symptoms for chikungunya-specific diagnosis and divert the rest for dengue lab diagnosis in a dengue-chikungunya syndemic setting.

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.

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.

Evolutionary trilogy of malaria, angiotensin II and hypertension: deeper insights and the way forward.

Despite clinical and pathological distinctions between malaria and hypertension, accumulated epidemiological and evolutionary evidence indicate the need of deeper understanding how severe malaria contributes to elevated hypertension risk. Malaria is said to exert strong selection pressure on the host genome, thus selecting certain genetic polymorphisms. Few candidate polymorphisms have also been reported in the RAS (ACE I/D and ACE2 rs2106809) that are shown to increase angiotensin II (ang II) levels in a combinatorial manner. The raised ang II has some antiplasmodial actions in addition to protecting against severe/cerebral malaria. It is hypothesized that RAS polymorphisms may have been naturally selected over time in the malaria-endemic areas in such a way that hypertension, or the risk thereof, is higher in such areas as compared to non-malaria endemic areas. The purpose of this review is to gain deeper insights into various sparse evidence linking malaria and hypertension and suggesting a way forward.

Tirofiban: A Rare Cause of Thrombocytopenia in a Patient Undergoing Percutaneous Coronary Intervention.

Patients admitted to the hospital can develop thrombocytopenia due to multifactorial causes. It can be pseudo-thrombocytopenia or true thrombocytopenia. Among patients admitted for chest pain, coronary angiography (CAG) is a common diagnostic test to evaluate patients for coronary artery disease (CAD). Normally, patients undergoing angiogram receive antiplatelets and anticoagulants pre-catheterization, and platelet aggregation inhibitor agents are sometimes used during and after CAG like in patients with high thrombus burden. Glycoprotein IIb/IIIa receptor inhibitors are a type of platelet antiaggregant agents that can cause severe thrombocytopenia in few cases.  We present a case of a 68-year-old patient who came to the emergency department with inferior wall ST-segment elevation myocardial infarction and underwent angiography and had percutaneous coronary intervention (PCI) done. He was administered tirofiban during the angiogram that caused acute severe thrombocytopenia decreasing platelets count to 4000/microliter within one day. Patients' platelets gradually recovered after platelets transfusion.

"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.

Costing Analysis of a Pilot Community Health Worker Program in Rural Nepal.

Community health workers (CHWs) are essential to primary health care systems and are a cost-effective strategy to achieve the Sustainable Development Goals (SDGs). Nepal is strongly committed to universal health coverage and the SDGs. In 2017, the Nepal Ministry of Health and Population partnered with the nongovernmental organization Nyaya Health Nepal to pilot a program aligned with the 2018 World Health Organization guidelines for CHWs. The program includes CHWs who: (1) receive regular financial compensation; (2) meet a minimum education level; (3) are well supervised; (4) are continuously trained; (5) are integrated into local primary health care systems; (6) use mobile health tools; (7) have consistent supply chain; (8) live in the communities they serve; and (9) provide service without point-of-care user fees. The pilot model has previously demonstrated improved institutional birth rate, antenatal care completion, and postpartum contraception utilization. Here, we performed a retrospective costing analysis from July 16, 2017 to July 15, 2018, in a catchment area population of 60,000. The average per capita annual cost is US$3.05 (range: US$1.94 to US$4.70 across 24 villages) of which 74% is personnel cost. Service delivery and administrative costs and per beneficiary costs for all services are also described. To address the current discourse among Nepali policy makers at the local and federal levels, we also present 3 alternative implementation scenarios that policy makers may consider. Given the Government of Nepal's commitment to increase health care spending (US$51.00 per capita) to 7.0% of the 2030 gross domestic product, paired with recent health care systems decentralization leading to expanded fiscal space in municipalities, this CHW program provides a feasible opportunity to make progress toward achieving universal health coverage and the health-related SDGs. This costing analysis offers insights and practical considerations for policy makers and locally elected officials for deploying a CHW cadre as a mechanism to achieve the SDG targets.

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.

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.

Physiological and morphological changes during early and later stages of fruit growth in Capsicum annuum.

Fruit-set involves a series of physiological and morphological changes that are well described for tomato and Arabidopsis, but largely unknown for sweet pepper (Capsicum annuum). The aim of this paper is to investigate whether mechanisms of fruit-set observed in Arabidopsis and tomato are also applicable to C. annuum. To do this, we accurately timed the physiological and morphological changes in a post-pollinated and un-pollinated ovary. A vascular connection between ovule and replum was observed in fertilized ovaries that undergo fruit development, and this connection was absent in unfertilized ovaries that abort. This indicates that vascular connection between ovule and replum is an early indicator for successful fruit development after pollination and fertilization. Evaluation of histological changes in the carpel of a fertilized and unfertilized ovary indicated that increase in cell number and cell diameter both contribute to early fruit growth. Cell division contributes more during early fruit growth while cell expansion contributes more at later stages of fruit growth in C. annuum. The simultaneous occurrence of a peak in auxin concentration and a strong increase in cell diameter in the carpel of seeded fruits suggest that indole-3-acetic acid stimulates a major increase in cell diameter at later stages of fruit growth. The series of physiological and morphological events observed during fruit-set in C. annuum are similar to what has been reported for tomato and Arabidopsis. This indicates that tomato and Arabidopsis are suitable model plants to understand details of fruit-set mechanisms in C. annuum.

Parthenocarpic potential in Capsicum annuum L. is enhanced by carpelloid structures and controlled by a single recessive gene.

BACKGROUND: Parthenocarpy is a desirable trait in Capsicum annuum production because it improves fruit quality and results in a more regular fruit set. Previously, we identified several C. annuum genotypes that already show a certain level of parthenocarpy, and the seedless fruits obtained from these genotypes often contain carpel-like structures. In the Arabidopsis bel1 mutant ovule integuments are transformed into carpels, and we therefore carefully studied ovule development in C. annuum and correlated aberrant ovule development and carpelloid transformation with parthenocarpic fruit set. RESULTS: We identified several additional C. annuum genotypes with a certain level of parthenocarpy, and confirmed a positive correlation between parthenocarpic potential and the development of carpelloid structures. Investigations into the source of these carpel-like structures showed that while the majority of the ovules in C. annuum gynoecia are unitegmic and anatropous, several abnormal ovules were observed, abundant at the top and base of the placenta, with altered integument growth. Abnormal ovule primordia arose from the placenta and most likely transformed into carpelloid structures in analogy to the Arabidopsis bel1 mutant. When pollination was present fruit weight was positively correlated with seed number, but in the absence of seeds, fruit weight proportionally increased with the carpelloid mass and number. Capsicum genotypes with high parthenocarpic potential always showed stronger carpelloid development. The parthenocarpic potential appeared to be controlled by a single recessive gene, but no variation in coding sequence was observed in a candidate gene CaARF8. CONCLUSIONS: Our results suggest that in the absence of fertilization most C. annuum genotypes, have parthenocarpic potential and carpelloid growth, which can substitute developing seeds in promoting fruit development.

Mapping and characterization of novel parthenocarpy QTLs in tomato.

Parthenocarpy is the development of the fruit in absence of pollination and/or fertilization. In tomato, parthenocarpy is considered as an attractive trait to solve the problems of fruit setting under unfavorable conditions. We studied the genetics of parthenocarpy in two different lines, IL5-1 and IVT-line 1, both carrying Solanum habrochaites chromosome segments. Parthenocarpy in IL5-1 is under the control of two QTLs, one on chromosome 4 (pat4.1) and one on chromosome 5 (pat5.1). IVT-line 1 also contains two parthenocarpy QTLs, one on chromosome 4 (pat4.2) and one on chromosome 9 (pat9.1). In addition, we identified one stigma exsertion locus in IL5-1, located on the long arm of chromosome 5 (se5.1). It is likely that pat4.1, from IL5-1 and pat4.2, from IVT-line 1, both located near the centromere of chromosome 4 are allelic. By making use of the microsynteny between tomato and Arabidopsis in this genetic region, we identified ARF8 as a potential candidate gene for these two QTLs. ARF8 is known to act as an inhibitor for further carpel development in Arabidopsis, in absence of pollination/fertilization. Expression of an aberrant form of the Arabidopsis ARF8 gene, in tomato, has been found to cause parthenocarpy. This candidate gene approach may lead to the first isolation of a parthenocarpy gene in tomato and will allow further use in several crop species.