Rajesh Kumar Yadav

Bio: Rajesh Kumar Yadav is an academic researcher from Pokhara University. The author has contributed to research in topics: Cancer & Reproductive health. The author has an hindex of 4, co-authored 8 publications receiving 47 citations. Previous affiliations of Rajesh Kumar Yadav include Manmohan Memorial Institute of Health Sciences & Hodges University.

Barriers in the access, diagnosis and treatment completion for tuberculosis patients in central and western Nepal: A qualitative study among patients, community members and health care workers

Abstract: Background Nepal has achieved a significant reduction of TB incidence over the past decades. Nevertheless, TB patients continue to experience barriers in access, diagnosis and completion of the treatment. The main objective of this study was to explore the factors affecting the access to the health services, diagnosis and the treatment completion for TB patients in central and western Nepal. Methods Data were collected using in-depth interviews (IDI) with the TB patients (n = 4); Focus Group Discussions (FGDs) with TB suspected patients (n = 16); Semi Strucutred Interviews (SSIs) with health workers (n = 24) and traditional healers (n = 2); and FGDs with community members (n = 8). All data were audio recorded, transcribed and translated to English. All transcriptions underwent thematic analysis using qualitative data analysis software: Atlas.ti. Results Barriers to access to the health centre were the long distance, poor road conditions, and costs associated with travelling. In addition, lack of awareness of TB and its consequences, and the belief, prompted many respondents to visit traditional healers. Early diagnosis of TB was hindered by lack of trained health personnel to use the equipment, lack of equipment and irregular presence of health workers. Additional barriers that impeded the adherence and treatment completion were the need to visit health centre daily for DOTS treatment and associated constraints, complex treatment regimen, and the stigma. Conclusions Barriers embedded in health services and care seekers’ characteristics can be dealt by strengthening the peripheral health services. A continuous availability of (trained) human resources and equipment for diagnosis is critical. As well as increasing the awareness and collaborating with the traditional healers, health services utilization can be enhanced by compensating the costs associated with it, including the modification in current DOTS strategy by providing medicine for a longer term under the supervision of a family member, peer or a community volunteer.

Anxiety and Depression Among Health Sciences Students in Home Quarantine During the COVID-19 Pandemic in Selected Provinces of Nepal.

Abstract: Aim: This study aimed to assess anxiety and depression among health sciences students at home quarantine during the COVID-19 pandemic in selected provinces of Nepal. Methods: A web-based cross-sectional study was conducted among 409 health science students enrolled at graduate and post-graduate levels in selected universities and their affiliated colleges. Students from selected colleges were asked to fill out a survey, that was made available through email and social media outlets such as Facebook and Viber. The data were downloaded in Excel and imported to SPSS version 16 for analysis. Results : The prevalence of anxiety and depression was 15.7 and 10.7%, respectively. The study showed significant associations between (i) place of province and anxiety; (ii) sleep per day and depression; (iii) hours spent on the internet per day for education and depression; (iv) postponement of final exams and depression. There were no significant associations with the socio-demographic variables. Conclusion: Anxiety and depression in health science students showed correlation with the province, internet use for education, and postponement of exams. These correlations could be common among students in other fields as well. A large-scale study covering a wider geographical area and various fields of education is necessary to further evaluate the impact of COVID-19 on (health sciences) students. The integration of mental health programs both as an intervention and a curriculum level among students is critical to ensure the health of the students.

Proportion and factors affecting for post-natal care utilization in developing countries: A systematic review

Abstract: Background: Majority of neonatal and maternal mortalities occur in developing countries. Moreover, around half of both mortalities occur in immediate postnatal period. Postnatal care utilization is aimed to reduce both mortalities and promote their health status. Methods: We searched PubMed, Google Scholar and HINARI between Jan 1, 2006 and Apr 31, 2014. Cross-sectional studies, surveys published in English language with finding of percentage of and factors affecting postnatal care utilization were included in the analysis. Weighted percentage with 95% CI was calculated to summarize the proportion. Odds ratio of minimum and maximum value was used to summarize associated factors. P-value <0.01 was taken as cut-off for significance of associated factors. Results: Of 45 accessed and reviewed full-text articles, nine included in the review. The studies were conducted in seven countries and total postnatal mothers in all samples were 49385. The weighted percentage of postnatal service utilization was 36.0 (95% CI, 22.5-49.5). Mother’s and husband’s higher educational level; higher wealth quintile of the family; occupation; mother's age at last delivery; number of ANC visit; and number of pregnancy were found associated with postnatal care utilization. Conclusion: The data that only around one in every three mothers utilizing post-natal care shows that scaling-up and improving the service is imperative. The education including literacy programs for both mother and husband; scaling-up of 4th ANC visit; creating earning opportunities for mothers and focusing the mothers of 20-30 years age group would be some intervening areas, however, further evaluation and reviews from interventional designs are suggested before reaching the firm conclusion. Journal of Manmohan Memorial Institute of Health Sciences Vol. 2 2016 p.14-19

Vaccine Therapy for Pancreatic Cancer: A Battle against Deadly Cancer

Abstract: Pancreatic cancer is one of the deadliest human malignancies and little progress has been achieved in its treatment over the past decades. Historically, chemotherapy or radiotherapy did not provide significant survival benefit in advanced pancreatic cancer. Thus, new therapeutic approaches are needed. As there is strong evidence that vaccine therapy against pancreatic cancer elicits antitumor immune responses, scientists have tried to stimulate the antitumor activities of the immune system to fight against pancreatic cancer, but has not reached to an expected result. Pancreatic cancer activates both antitumor immune responses and immunosuppressive mechanisms leading to tumor development and progression. This action is achieved through mobilization and activation of immune suppressive cells (CAFs), tolerogenic DCs, MDSCs, TAMs, Treg cells and cancer cells-derived soluble factors that promote the induction of tolerance through the generation of CD4+αchain of IL-2R (CD25)+forkhead box P3 (Foxp3) subset. In addition, pancreatic cancer cells modulate the immune system and avoid detection by effector immune by production of immune suppressive cytokines (e.g., TGF-β, IL-10, and IL-6), by expressing surface molecules that mediate immune suppression (e.g., vascular endothelial growth factors (VEGFs), Fas ligand (Fas-L), programmed death-1 ligand (PD-L1), indolamine-2, and 3-dioxygenase (IDO). Identification of pancreatic cancer-associated antigens has spurred the development of vaccination-based strategies for treatment. Vaccine therapy relies on the administration of biological preparations that include an antigen that is specifically expressed by malignant cells, boosting the natural ability of the immune system to react against neoplastic cells. Potent vaccines stimulate antigen presentation by dendritic cells, hence driving the expansion of antigen-specific effector and memory T cells. Further, immune modulation and immunosuppressive environment by pancreatic cancer can be overcome by enhancing vaccine efficacy by combinatorial therapy. In this paper, we analyze recent preclinical and clinical efforts towards vaccine therapy for pancreatic cancer designed to target pancreatic cancer-associated antigens and to elicit an antitumor response in vivo.

Local Phototherapy Synergizes with Immunoadjuvant for Treatment of Pancreatic Cancer through Induced Immunogenic Tumor Vaccine

Abstract: Purpose: To develop a synergistic combination therapy for advanced pancreatic cancer, using local phototherapy and immunotherapy, and to determine the efficacy and mechanism of the novel combination therapy using a highly metastatic pancreatic tumor model in mice.Experimental Design: Mice bearing Panc02-H7 pancreatic tumors (both subcutaneous and orthotopic) were treated with noninvasive or interventional photothermal therapy, followed by local application of an immunoadjuvant. Tumor growth and animal survival were assessed. Immune cell populations within spleen and tumors were evaluated by FACS and IHC, and cytokine levels were determined by ELISA.Results: Up to 75% of mice bearing subcutaneous tumors treated with combination therapy had complete tumor regression. Local photothermal therapy exposed/released damage-associated molecular patterns, which initiated an immunogenic tumor cell death, resulting in infiltration of antigen-presenting cells and Th1 immunity. Concomitant application of immunoadjuvant amplified Th1 immunity, especially the tumor-specific cytotoxic T lymphocyte response, with increased quantity and quality of T cells. Combination therapy also induced tumor-specific immune memory, as demonstrated by resistance to tumor rechallenge and production of memory T cells. For the treatment of orthotopic tumor, the combination therapy significantly reduced the primary tumors and metastases, and prolonged the animal survival time.Conclusions: This study indicated that combination of local phototherapy and immunotherapy induced a systemic immunity against established tumors and metastases in an aggressive, preclinical pancreatic tumor model, leading to a potential clinical method for patients with advanced pancreatic cancer. Clin Cancer Res; 24(21); 5335-46. ©2018 AACR.

Nanomaterial-Based Tumor Photothermal Immunotherapy.

Abstract: In recent years, photothermal therapy (PTT) particularly nanomaterial-based PTT is a promising therapeutic modality and technique for cancer tumor ablation. In addition to killing tumor cells directly through heat, PTT also can induce immunogenic cell death (ICD) to activate the whole-body anti-tumor immune response, including the redistribution and activation of immune effector cells, the expression and secretion of cytokines and the transformation of memory T lymphocytes. When used in combination with immunotherapy, the efficacy of nanomaterial-based PTT can be improved. This article summarized the mechanism of nanomaterial-based PTT against cancer and how nanomaterial-based PTT impacts the tumor microenvironment and induces an immune response. Moreover, we reviewed recent advances of nanomaterial-based photothermal immunotherapy and discussed challenges and future outlook.

Postnatal care service utilization and associated factors among women who gave birth in Debretabour town, North West Ethiopia: a community- based cross-sectional study.

Abstract: World health organization stated that postnatal care is defined as a care given to the mother and her newborn baby immediately after the birth of the placenta and for the first six weeks of life. Majority of maternal and neonatal deaths occur during childbirth and the postpartum period. Scaling up of maternal and newborn health through proper postnatal care services is the best way of reducing maternal and neonatal mortality. A community based cross sectional study was conducted among 588 mothers who gave birth in the last one year from March 1–21; 2017. Systematic random sampling technique was used to select study participants. A pre-tested and structured questionnaire was used to collect the data. Data was entered in EPI info version 7 and analyzed using SPSS version 21. Logistic regression was applied to identify association between explanatory variables and the outcome variable. An adjusted odds ratio with 95% confidence interval and p-value less than 0.05 was computed to determine the level of significance. A total of 588 participants were included in the analysis which was the response rate of 100%. The prevalence of postnatal care service utilization in this study was 57.5%. Maternal educational status of secondary school and above (AOR = 3.29, 95%CI: 1.94–5.57), family monthly income of above 1500 ETB (AOR = 2.85, 95%CI: 1.21–6.68), alive birth outcome of last pregnancy (AOR = 5.70, 95%CI: 1.53–21.216), planned and supported last pregnancy (AOR = 3.94, 95%CI: 1.72–9.01) and institutional delivery of last pregnancy (AOR = 3.08, 95%CI: 1.24–7.68) were positively associated with PNC service utilization. This study showed that the overall utilization of PNC service in Debretabour town is low. Mothers’ education, monthly income, last pregnancy birth outcome, wantedness of the pregnancy and place of delivery were significantly associated with postnatal care service utilization. To enhance PNC service utilization and reduce maternal and neonatal mortality women should obtain appropriate education. Furthermore all pregnant women should give birth in the health facilities.

Immune monitoring and TCR sequencing of CD4 T cells in a long term responsive patient with metastasized pancreatic ductal carcinoma treated with individualized, neoepitope-derived multipeptide vaccines: a case report

Abstract: Cancer vaccines can effectively establish clinically relevant tumor immunity. Novel sequencing approaches rapidly identify the mutational fingerprint of tumors, thus allowing to generate personalized tumor vaccines within a few weeks from diagnosis. Here, we report the case of a 62-year-old patient receiving a four-peptide-vaccine targeting the two sole mutations of his pancreatic tumor, identified via exome sequencing. Vaccination started during chemotherapy in second complete remission and continued monthly thereafter. We tracked IFN-γ+ T cell responses against vaccine peptides in peripheral blood after 12, 17 and 34 vaccinations by analyzing T-cell receptor (TCR) repertoire diversity and epitope-binding regions of peptide-reactive T-cell lines and clones. By restricting analysis to sorted IFN-γ-producing T cells we could assure epitope-specificity, functionality, and TH1 polarization. A peptide-specific T-cell response against three of the four vaccine peptides could be detected sequentially. Molecular TCR analysis revealed a broad vaccine-reactive TCR repertoire with clones of discernible specificity. Four identical or convergent TCR sequences could be identified at more than one time-point, indicating timely persistence of vaccine-reactive T cells. One dominant TCR expressing a dual TCRVα chain could be found in three T-cell clones. The observed T-cell responses possibly contributed to clinical outcome: The patient is alive 6 years after initial diagnosis and in complete remission for 4 years now. Therapeutic vaccination with a neoantigen-derived four-peptide vaccine resulted in a diverse and long-lasting immune response against these targets which was associated with prolonged clinical remission. These data warrant confirmation in a larger proof-of concept clinical trial.

Health system’s readiness to provide cardiovascular, diabetes and chronic respiratory disease related services in Nepal: analysis using 2015 health facility survey

Abstract: The burgeoning rise of non-communicable diseases (NCDs) is posing serious challenges in resource constrained health facilities of Nepal. The main objective of this study was to assess the readiness of health facilities for cardiovascular diseases (CVDs), diabetes and chronic respiratory diseases (CRDs) services in Nepal. This study utilized data from the Nepal Health Facility Survey 2015. General readiness of 940 health facilities along with disease specific readiness for CVDs, diabetes, and CRDs were assessed using the Service Availability and Readiness Assessment manual of the World Health Organization. Health facilities were categorized into public and private facilities. Out of a total of 940 health facilities assessed, private facilities showed higher availability of items of general service readiness except for standard precautions for infection prevention, compared to public facilities. The multivariable adjusted regression coefficients for CVDs (β = 2.87, 95%CI: 2.42–3.39), diabetes (β =3.02, 95%CI: 2.03–4.49), and CRDs (β = 15.95, 95%CI: 4.61–55.13) at private facilities were higher than the public facilities. Health facilities located in the hills had a higher readiness index for CVDs (β = 1.99, 95%CI: 1.02–1.39). Service readiness for CVDs (β = 1.13, 95%CI: 1.04–1.23) and diabetes (β = 1.78, 95%CI: 1.23–2.59) were higher in the urban municipalities than in rural municipalities. Finally, disease-related services readiness index was sub-optimal with some degree of variation at the province level in Nepal. Compared to province 1, province 2 (β = 0.83, 95%CI: 0.73–0.95) had lower, and province 4 (β =1.24, 95%CI: 1.07–1.43) and province 5 (β =1.17, 95%CI: 1.02–1.34) had higher readiness index for CVDs. This study found sub-optimal readiness of services related to three NCDs at the public facilities in Nepal. Compared to public facilities, private facilities showed higher readiness scores for CVDs, diabetes, and CRDs. There is an urgent need for policy reform to improve the health services for NCDs, particularly in public facilities.