Prevention of Rheumatic Fever and Heart Disease: Nepalese Experience

Rheumatic heart disease (RHD) is a major public health problem in Nepal that affects young children and adolescents. Historically, many young people suffered severe valvular disease and died awaiting heart valve replacement. For some years, the Nepal Heart Foundation (NHF) advocated for a more comprehensive program to reduce the burden of RHD. In 2007, the government of Nepal announced funding for an RHD control program to be implemented by the NHF. The core focus of the program was to deliver antibiotics for the secondary prophylaxis of RHD. The NHF has developed a program of community awareness, free medication, RHD register development, health worker training, guideline development, and clinical audit. These services are being implemented with expanding geographic scope. This paper provides a narrative overview of the Nepalese experience designing, implementing, and beginning to evaluate this program. Challenges and successes relevant to register-based programs are highlighted.     

Heart Failure with Preserved Ejection Fraction and 30-Day Readmission

Objective:Several studies identify heart failure (HF) as a potential risk for hospital readmission; however, studies on predictability of heart failure readmission is limited. The objective of this work was to investigate whether a specific type of heart failure (HFpEF or HFrEF) has a higher association to the rate of 30-day hospital readmission and compare their predictability with the two risk scores: HOSPITAL score and LACE index.Design:Retrospective study from single academic center.Methods:Sample size included adult patients from an academic hospital in a two-year period (2015 - 2017). Exclusion criteria included death, transfer to another hospital, and unadvised leave from hospital. Baseline characteristics, diagnosis-related group, and ICD diagnosis codes were obtained. Variables affecting HOSPITAL score and LACE index and types of heart failure present were also extracted. Qualitative variables were compared using Pearson chi² or Fisher’s exact test (reported as frequency) and quantitative variables using non-parametric Mann–Whitney U test (reported as mean ± standard deviation). Variables from univariate analysis with P values of 0.05 or less were further analyzed using multivariate logistic regression. Odds ratio was used to measure potential risk.Results:The sample size of adult patients in the study period was 1,916. All eligible cohort of patients who were readmitted were analyzed. Cumulative score indicators of HOSPITAL Score, LACE index (including the Charlson Comorbidity Index) predicted 30-day readmissions with P values of <0.001. The P value of HFpEF was found to be significant in the readmitted group (P < 0.001) compared to HFrEF (P = 0.141). Multivariate logistic regression further demonstrated the association of HFpEF with higher risk of readmission with odds ratio of 1.77 (95% CI: 1.25 – 2.50) and P value of 0.001.Conclusions:Our data from an academic tertiary care center supports HFpEF as an independent risk factor for readmission. Multidisciplinary management of HFpEF may be an important target for interventions to reduce hospital readmissions.     

A comparative study of the effectiveness of diagnostic tests for visceral leishmaniasis

We compared the validity of pancytopenia, the formol-gel test (FGT), the indirect fluorescence antibody test (IFAT), the direct agglutination test (DAT), and the rK39 dipstick test as diagnostic criteria for visceral leishmaniasis (VL) in Nepal. Between September 2000 and January 2002, 310 clinical suspects had a bone marrow aspirate, and if negative, a spleen aspirate smear examined for Leishmania donovani. Sensitivity and specificity of all tests were determined compared with parasitology and by latent class analysis (LCA). Compared with parasitology, the sensitivities of the other tests were as follows: pancytopenia = 16.3% (95% confidence interval [CI] = 11.3-22.5%), FGT = 39.9% (95% CI = 32.7-47.4%), IFAT = 28.4% (95% CI = 22.0-35.5%), DAT = 95.1% (95% CI = 90.8-97.7%), and the rK39 dipstick test = 87.4% (95% CI = 81.7-91.9%). Sensitivity estimates obtained by LCA were similar, but specificity estimates were substantially higher (DAT = 93.7% versus 77.8%; rK39 dipstick test = 93.1% versus 77.0%). The DAT or the rK39 dipstick test can replace parasitology as the basis of a decision to treat VL in Nepalese peripheral health services.     

Evaluation of a urinary antigen-based latex agglutination test in the diagnosis of kala-azar in eastern Nepal

BACKGROUND: We evaluated the diagnostic accuracy as well as the reproducibility of the urine latex agglutination test 'KAtex' in the diagnosis of kala-azar in patients recruited at a tertiary care centre in Dharan, Nepal, between November 2000 and January 2002. METHODS: All patients presenting with fever of 2 weeks or more and splenomegaly were consecutively enrolled. Bone marrow and--if negative--spleen aspirates were examined for Leishmania donovani. Serum and urine samples were taken in duplicate for the Direct Agglutination Test (DAT) and KAtex. The reference laboratory determined sensitivity and specificity of KAtex. Reproducibility between both laboratories was assessed. RESULTS: KAtex was performed on urine from 155 parasitologically confirmed kala-azar and 77 non-kala-azar cases (parasitology and DAT-negative). KAtex showed a sensitivity of 47.7% (74/155, 95% CI: 39.7-55.9) and a specificity of 98.7% (76/77, 95% CI: 93.0-100.0). Reproducibility of KAtex showed a kappa of 0.684 (P < 0.001, n = 232). CONCLUSION: KAtex evaluation showed high specificity, low sensitivity and moderate reproducibility. A urine test for kala-azar could become a real breakthrough in kala-azar management if its reproducibility and sensitivity could be further improved.     

Regulation of corticotropin-releasing factor-binding protein expression in amygdalar neuronal cultures

Corticotropin-releasing factor-binding protein (CRF-BP) is known to regulate the bioavailability of CRF and may also play a role in stress behaviours. CRF-BP has been localized in the pituitary as well as central nervous system (CNS) limbic and cortical areas, including the amygdala. The signal transduction pathways which regulate amygdalar CRF-BP are not well understood. In this report, we have examined the effect of protein kinase A and C activators, CRF, dexamethasone and interleukin-6 (IL6) on CRF-BP mRNA and protein expression in dissociated fetal amygdalar cultures. CRF-BP mRNA levels were determined by Northern analysis following 12 h treatment with the following agents: forskolin (1-30 microM), CRF (1-1000 nM), phorbol-12-myristate-13-acetate (TPA; 1-50 nM), dexamethasone (1-100 nM) and IL6 (10-500 pM). Significant increases in CRF-BP mRNA were observed in response to forskolin (30 mM), CRF (100, 1000 nM), IL6 (100, 500 pM), TPA (50 nM) and dexamethasone (100 nM; P<0.05 for all; n=3-6 for all). We extended our observations of CRF-BP expression to the protein level by performing semiquantitative Western analysis of total cellular protein after treatment with the same agents. Twenty-four hour treatment with 30 microM forskolin, 1000 nM CRF, 50 nM TPA, 100 pM IL6 or 100 nM dexamethasone significantly increased CRF-BP expression (P<0.05, n=3 for each treatment). The primary cultures were then transfected with a rat CRF-BP-reporter construct containing 3500 base pairs of CRF-BP 5' flanking DNA. Treatment with all five agents produced statistically significant increases above control (P<0.05; n=3 for each). The results suggest that CRF-BP in the amygdala is stimulated by numerous pathways which may play a significant role in promoting behavioural changes.     

HIV/AIDS prevention in the Nepalese context

With their numbers now approaching almost 30 million, Nepalese feature importantly in the South Asian demography. Yet, it has been only 60 years since Nepal gained international recognition as a nation-state. Nepal at present is one of the world's poorest countries and is in dire need of development, especially in the area of health. Given the current civil instability coupled with rapid modernization, the health and well-being of the Nepalese people have been increasingly affected by newer threats, such as HIV/AIDS. The present study discusses the uniqueness of the Nepalese context in relation to HIV/AIDS prevention. The authors suggest that HIV/AIDS prevention programs in Nepal should now focus more on adolescents from rural regions. The authors also suggest the ways one may approach the task of developing a prevention program targeting rural youths.     

Barriers to sexual health services for young people in Nepal

Although sexual and reproductive health education and services are provided to young people, current rates of HIV infection and pregnancy are increasing in Nepal, indicating that young people do not always use sexual health services. Health facilities have apparently failed to provide young people with specialized sexual health education and services. This study explored the barriers to using sexual health services, including condom-use among young people in Nepal. Participants from 10 focus groups and 31 in-depth interviews, carried out by a same-sex researcher, reported many socioeconomic, cultural and physical norms that impose barriers to accessing information on sexual health and relevant services. It is concluded that the establishment of youth-friendly service centres in convenient places might help encourage young people to use sexual health services.     

Characterization of thymic masses using 18F-FDG PET-CT

Background  The resectability and survival may be improved in thymoma and thymic carcinoma with multimodality therapy. Various diagnostic imaging modalities are required for accurate diagnosis and preoperative staging of thymic masses. The present prospective study was planned to evaluate if Fluorodeoxyglucose (FDG) PET-CT can help differentiate various thymic lesions noted on conventional imaging modalities. Methods  A prospective study was undertaken in 23 patients who had shown either an anterior mediastinal mass consistent with thymic origin or suspicious for a thymic mass on contrast-enhanced computed tomography scan. All patients underwent whole body FDG PET-CT after intravenous injection of 370 MBq of FDG. The interpretation of PET-CT images was based on the following criteria: FDG uptake (present or absent), SUVmax, pattern of uptake, invasion to surrounding structures, presence of metastasis and necrosis. The results of PET-CT were correlated with the final histopathology following surgery. Statistical analysis was performed with SPSS 11.5 for Windows software. The mean SUVmax of the 3 groups of pathology was compared using the Kruskal–Wallis Test. Results  Thymic hyperplasia had an enlarged thymus with mean SUVmax of 1.1. Low risk thymoma had large tumors and their mean SUVmax was 3. High risk thymoma had small tumors with mean SUVmax of 2.1. As a group, thymoma had mean SUVmax value of 2.3. All thymic carcinomas were large, and their mean SUVmax was 7. The difference between the mean SUVmax for thymic hyperplasia, thymoma and thymic carcinoma was statistically significant. The difference between the SUVmax of high risk and low risk thymoma was not significant. Conclusion   ¹⁸F-FDG PET-CT can help characterize various thymic lesions noted on conventional imaging modalities. However, larger prospective studies are further required to substantiate these findings.