Tropical Cardiovascular Diseases: The Forgotten Orphans.

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Generating evidence from contextual clinical research in low- to middle income countries: A roadmap based on theory of change

Along with inadequate access to high-quality care, competing health priorities, fragile health systems, and conflicts, there is an associated delay in evidence generation and research from LMICs. Lack of basic epidemiologic understanding of the disease burden in these regions poses a significant knowledge gap as solutions can only be developed and sustained if the scope of the problem is accurately defined. Congenital heart disease (CHD), for example, is the most common birth defect in children. The prevalence of CHD from 1990 to 2017 has progressively increased by 18.7% and more than 90% of children with CHD are born in Low and Middle-Income Countries (LMICs). If diagnosed and managed in a timely manner, as in high-income countries (HICs), most children lead a healthy life and achieve adulthood. However, children with CHD in LMICs have limited care available with subsequent impact on survival. The large disparity in global health research focus on this complex disease makes it a solid paradigm to shape the debate. Despite many challenges, an essential aspect of improving research in LMICs is the realization and ownership of the problem around paucity of local evidence by patients, health care providers, academic centers, and governments in these countries. We have created a theory of change model to address these challenges at a micro- (individual patient or physician or institutions delivering health care) and a macro- (government and health ministries) level, presenting suggested solutions for these complex problems. All stakeholders in the society, from government bodies, health ministries, and systems, to frontline healthcare workers and patients, need to be invested in addressing the local health problems and significantly increase data to define and improve the gaps in care in LMICs. Moreover, interventions can be designed for a more collaborative and effective HIC-LMIC and LMIC-LMIC partnership to increase resources, capacity building, and representation for long-term productivity

Generating Evidence From Contextual Clinical Research in Low- to Middle Income Countries: A Roadmap Based on Theory of Change

Along with inadequate access to high-quality care, competing health priorities, fragile health systems, and conflicts, there is an associated delay in evidence generation and research from LMICs. Lack of basic epidemiologic understanding of the disease burden in these regions poses a significant knowledge gap as solutions can only be developed and sustained if the scope of the problem is accurately defined. Congenital heart disease (CHD), for example, is the most common birth defect in children. The prevalence of CHD from 1990 to 2017 has progressively increased by 18.7% and more than 90% of children with CHD are born in Low and Middle-Income Countries (LMICs). If diagnosed and managed in a timely manner, as in high-income countries (HICs), most children lead a healthy life and achieve adulthood. However, children with CHD in LMICs have limited care available with subsequent impact on survival. The large disparity in global health research focus on this complex disease makes it a solid paradigm to shape the debate. Despite many challenges, an essential aspect of improving research in LMICs is the realization and ownership of the problem around paucity of local evidence by patients, health care providers, academic centers, and governments in these countries. We have created a theory of change model to address these challenges at a micro- (individual patient or physician or institutions delivering health care) and a macro- (government and health ministries) level, presenting suggested solutions for these complex problems. All stakeholders in the society, from government bodies, health ministries, and systems, to frontline healthcare workers and patients, need to be invested in addressing the local health problems and significantly increase data to define and improve the gaps in care in LMICs. Moreover, interventions can be designed for a more collaborative and effective HIC-LMIC and LMIC-LMIC partnership to increase resources, capacity building, and representation for long-term productivity.publishedVersio

Simple and Effective Multi-Paragraph Reading Comprehension

We consider the problem of adapting neural paragraph-level question answering models to the case where entire documents are given as input. Our proposed solution trains models to produce well calibrated confidence scores for their results on individual paragraphs. We sample multiple paragraphs from the documents during training, and use a shared-normalization training objective that encourages the model to produce globally correct output. We combine this method with a state-of-the-art pipeline for training models on document QA data. Experiments demonstrate strong performance on several document QA datasets. Overall, we are able to achieve a score of 71.3 F1 on the web portion of TriviaQA, a large improvement from the 56.7 F1 of the previous best system.Comment: 11 pages, updated a referenc

Prevalence and determinants of asymptomatic Leishmania infection in HIV-infected individuals living within visceral leishmaniasis endemic areas of Bihar, India

People living with HIV (PLHIV) have an increased risk of developing visceral leishmaniasis (VL) and poor outcomes compared to HIV negative individuals. Here, we aim to establish the prevalence and determinants of asymptomatic Leishmania infection (ALI) in a cohort of PLHIV in Bihar, India. We hoped to evaluate optimal diagnostic algorithms to detect ALI in PLHIV. We conducted a cross-sectional survey of PLHIV ≥18 years of age with no history or current diagnosis of VL or post kala-azar dermal leishmaniasis (PKDL) at anti-retroviral therapy centres within VL endemic districts of Bihar. ALI was defined as a positive rK39 enzyme-linked immunosorbent assay (ELISA), rK39 rapid diagnostic test (RDT) and/or quantitative polymerase chain reaction (qPCR). Additionally, the urinary Leishmania antigen ELISA was evaluated. Determinants for ALI were established using logistic regression and agreement between diagnostic tests calculated using Cohen’s Kappa. A total of 1,296 PLHIV enrolled in HIV care, 694 (53.6%) of whom were female and a median age of 39 years (interquartile range 33–46), were included in the analysis. Baseline prevalence of ALI was 7.4% (n = 96). All 96 individuals were positive by rK39 ELISA, while 0.5% (n = 6) and 0.4% (n = 5) were positive by qPCR and rK39 RDT, respectively. Negligible or weak agreement was seen between assays. Independent risk factors for ALI were CD4 counts <100 (OR 3.1; 95% CI 1.2–7.6) and CD4 counts 100–199 (OR = 2.1;95% CI:1.1–4.0) compared to CD4 counts ≥300, and a household size ≥5 (OR = 1.9;95% CI:1.1–3.1). A total of 2.2% (n = 28) participants were positive by Leishmania antigen ELISA, detecting 20 additional participants to the asymptomatic cohort. Prevalence of ALI in PLHIV in VL endemic villages in Bihar was relatively high. Using the Leishmania antigen ELISA, prevalence increased to 9.0%. Patients with low CD4 counts and larger household size were found to have significantly higher risk of ALI

Visceral leishmaniasis and HIV co-infection in Bihar, India: long-term effectiveness and treatment outcomes with liposomal amphotericin B (AmBisome).

BACKGROUND: Visceral Leishmaniasis (VL; also known as kala-azar) is an ultimately fatal disease endemic in the Indian state of Bihar, while HIV/AIDS is an emerging disease in this region. A 2011 observational cohort study conducted in Bihar involving 55 VL/HIV co-infected patients treated with 20-25 mg/kg intravenous liposomal amphotericin B (AmBisome) estimated an 85.5% probability of survival and a 26.5% probability of VL relapse within 2 years. Here we report the long-term field outcomes of a larger cohort of co-infected patients treated with this regimen between 2007 and 2012. METHODS AND PRINCIPAL FINDINGS: Intravenous AmBisome (20-25 mg/kg) was administered to 159 VL/HIV co-infected patients (both primary infections and relapses) in four or five doses of 5 mg/kg over 4-10 days. Initial cure of VL at discharge was defined as improved symptoms, cessation of fever, improvement of appetite and recession of spleen enlargement. Test of cure was not routinely performed. Antiretroviral treatment (ART) was initiated in 23 (14.5%), 39 (24.5%) and 61 (38.4%) before, during and after admission respectively. Initial cure was achieved in all discharged patients. A total of 36 patients died during follow-up, including six who died shortly after admission. Death occurred at a median of 11 weeks (IQR 4-51) after starting VL treatment. Estimated mortality risk was 14.3% at six months, 22.4% at two years and 29.7% at four years after treatment. Among the 153 patients discharged from the hospital, 26 cases of VL relapse were diagnosed during follow-up, occurring at a median of 10 months (IQR 7-14) after discharge. After accounting for competing risks, the estimated risk of relapse was 16.1% at one year, 20.4% at two years and 25.9% at four years. Low hemoglobin level and concurrent infection with tuberculosis were independent risk factors for mortality, while ART initiated shortly after admission for VL treatment was associated with a 64-66% reduced risk of mortality and 75% reduced risk of relapse. SIGNIFICANCE: This is the largest cohort of HIV-VL co-infected patients reported from the Indian subcontinent. Even after initial cure following treatment with AmBisome, these patients appear to have much higher rates of VL relapse and mortality than patients not known to be HIV-positive, although relapse rates appear to stabilize after 2 years. These results extend the earlier findings that co-infected patients are at increased risk of death and require a multidisciplinary approach for long-term management

A NEW SPECTROPHOTOMETRIC METHOD FOR THE DETERMINATION OF TRACE AMOUNTS OF TITANIUM(IV)

Abstract. A new, rapid, simple, precise and extraction-free spectrophotometric method is proposed for the micro determination of titanium(IV) employing N&apos;-(2-hydroxybenzylidene)-3-oxobutanehydrazide as a reagent. Under the optimum conditions established, the absorbance was found to increase linearly with the concentration of titanium(IV) i

Combination Treatment for Visceral Leishmaniasis Patients Coinfected with Human Immunodeficiency Virus in India.

BACKGROUND: There are considerable numbers of patients coinfected with human immunodeficiency virus (HIV) and visceral leishmaniasis (VL) in the VL-endemic areas of Bihar, India. These patients are at higher risk of relapse and death, but there are still no evidence-based guidelines on how to treat them. In this study, we report on treatment outcomes of coinfected patients up to 18 months following treatment with a combination regimen. METHODS: This retrospective analysis included all patients with confirmed HIV-VL coinfection receiving combination treatment for VL at a Médecins Sans Frontières treatment center between July 2012 and September 2014. Patients were treated with 30 mg/kg body weight intravenous liposomal amphotericin B (AmBisome) divided as 6 equal dose infusions combined with 14 days of 100 mg/day oral miltefosine (Impavido). All patients were encouraged to start or continue on antiretroviral therapy (ART). RESULTS: 102 patients (76% males, 57% with known HIV infection, 54% with a prior episode of VL) were followed-up for a median of 11 months (interquartile range: 4-18). Cumulative incidence of all-cause mortality and VL relapse at 6, 12, and 18 months was 11.7%, 14.5%, 16.6% and 2.5%, 6.0%,13.9%, respectively. Cumulative incidence of poor outcome at 6, 12, and 18 months was 13.9%, 18.4%, and 27.2%, respectively. Not initiating ART and concurrent tuberculosis were independent risk factors for mortality, whereas no factors were associated with relapse. CONCLUSIONS: In this Bihar-based study, combination therapy appeared to be well tolerated, safe, and effective and may be considered as an option for treatment of VL in HIV coinfected patients

Linking world bank development indicators and outcomes of congenital heart surgery in low-income and middle-income countries: Retrospective analysis of quality improvement data

Objective Many low-income and middle-income countries (LMICs) struggle to provide the health services investment required for life-saving congenital heart disease (CHD) surgery. We explored associations between risk-adjusted CHD surgical mortality from 17 LMICs and global development indices to identify patterns that might inform investment strategies. Design Retrospective analysis: country-specific standardised mortality ratios were graphed against global development indices reflective of wealth and healthcare investment. Spearman correlation coefficients were calculated. Setting and participants The International Quality Improvement Collaborative (IQIC) keeps a volunteer registry of outcomes of CHD surgery programmes in low-resource settings. Inclusion in the IQIC is voluntary enrolment by hospital sites. Patients in the registry underwent congenital heart surgery. Sites that actively participated in IQIC in 2013, 2014 or 2015 and passed a 10% data audit were asked for permission to share data for this study. 31 sites in 17 countries are included. Outcome measures In-hospital mortality: standardised mortality ratios were calculated. Risk adjustment for in-hospital mortality uses the Risk Adjustment for Congenital Heart Surgery method, a model including surgical risk category, age group, prematurity, presence of a major non-cardiac structural anomaly and multiple congenital heart procedures during admission. Results The IQIC registry includes 24 917 congenital heart surgeries performed in children less than 18 years of age. The overall in-hospital mortality rate was 5.0%. Country-level congenital heart surgery standardised mortality ratios were negatively correlated with gross domestic product (GDP) per capita (r=-0.34, p=0.18), and health expenditure per capita (r=-0.23, p=0.37) and positively correlated with under-five mortality (r=0.60, p=0.01) and undernourishment (r=0.39, p=0.17). Countries with lower development had wider variation in mortality. GDP per capita is a driver of the association between some other measures and mortality. Conclusions Results display a moderate relationship among wealth, healthcare investment and malnutrition, with significant variation, including superior results in many countries with low GDP per capita. These findings provide context and optimism for investment in CHD procedures in low-resource settings. © 2019 BMJ Publishing Group Limited