An Online Pediatric Palliative Care Education and Mentoring (Project ECHO) in Nepal: A Program Implementation Case Study and Assessment of Changes in Healthcare Providers' Knowledge, Confidence, and Attitudes.

OBJECTIVES: The goal of this implementation study was to describe the implementation and evaluation of the impact of an online pediatric palliative care training program in Nepal, using the Project ECHO model. METHODS: The study used mixed methods, including a program case study describing the online learning program and before-and-after surveys of program participants, assessing learning through changes in knowledge, comfort, and attitudes. An end-of-program survey was used to evaluate participants' overall experiences with the learning program and use of the learning resources. RESULTS: A literature review, stakeholder surveys, and expert input informed the design of the intervention. The course used the Project ECHO model of online education, with modifications based on the leadership team's previous ECHO experiences and local stakeholder input. The intervention occurred over 9 months, with 22 online teaching sessions. Each session consisted of a didactic lecture, case presentation, and interactive discussion with expert clinical teachers. Fifty-five clinicians in Nepal participated, including physicians (47%), nurses (44%), and psychotherapists (5%). Clinicians reported improvements in knowledge, skills, and attitudes after program participation. Program acceptability scores were high, with 93% of participants reporting that the course provided effective learning. CONCLUSIONS: Project ECHO can be successfully implemented to deliver continuing professional development in Nepal. Delivering palliative care education online using the Project ECHO model, leads to improved knowledge, skills, and attitudes for clinicians. Project ECHO suggests an innovative solution which can provide training and support to clinicians in settings where educational opportunities in palliative care are limited.

Outcome of Epidermal Growth Factor Receptor Mutated and Non Mutated Adenocarcinoma Lung to Standard Therapy.

BACKGROUND: Asian patients with adenocarcinoma of lung have higher incidence of epidermal growth factor receptor mutations which predict increased response and survival in patients to oral tyrosine kinase inhibitors. This study was conducted to study the frequency of epidermal growth factor receptor mutation in patients in Nepal and compare the outcome in epidermal growth factor receptor mutated versus non-mutated patients receiving standard therapy. METHODS: This is an observational study conducted among newly diagnosed patients with stage IV adenocarcinoma of lung in Bir Hospital from April 2017 to June 2018. Demographic and clinical data collection along with epidermal growth factor receptor mutation testing was done. Patients with epidermal growth factor receptor mutations received Gefitinib while non-mutated patients received systemic chemotherapy. Response evaluation, progression free survival at 1 year, objective response rate and quality of life were compared. Follow up period was for 1 year. RESULTS: Eighty three (33%, n=253) patients were diagnosed with adenocarcinoma of the lung with mean age at diagnosis being 59.4 years. epidermal growth factor receptor mutations were found in 29% patients. Complete response was achieved in 9.1% vs 3.0 % (p=0.46), objective response rate was 27.3% versus 15.2% (p=0.23), progression free survival at 1 year was 39% vs 27%, (p = 0.29) and mean score of global health status was 68.1 versus 61.6 in epidermal growth factor receptor mutated versus non-mutated (p = 0.036). CONCLUSIONS: The frequency of epidermal growth factor receptor mutation in patients with adenocarcinoma of the lung was lower than in Eastern Asian studies, but higher than in western populations. epidermal growth factor receptor mutated patients had improved survival, better treatment response and quality of life in comparison with non-mutated.

Building a 'Virtual Library': continuing a global collaboration to strengthen research capacity within Nepal and other low- and middle-income countries.

To fill the gap in health research capacity-building efforts, we created the 'Virtual Library' (VL) - a web-based repository of context-relevant resources for health researchers in low- and middle-income countries (LMICs). This paper describes the participatory process used to systematically develop the VL, and describes how our interprofessional team - representing both an LMIC (Nepal) and a high-income country (HIC) (USA, US) - engaged in shared meaning-making. A team of researchers and clinicians representing a range of subdisciplines from Nepal and the US created a replicable search strategy and standardized Resource Screening Guide (RSG) to systematically assess resources to be included within the VL. Descriptive methods were used to summarize findings from the RSG and lessons learned from the collaborative process. Collectively, 14 team members reviewed 564 potential resources (mean = 40, SD = 22.7). Mean RSG score was 7.02/10 (SD = 2). More than 76% of resources met each of the four quality criteria (relevant; reputable, accessible; understandable). Within the published VL, 298 resources were included, organized by 15 topics and 45 sub-topics. Of these, 223 resources were evaluated by the RSG; 75 were identified by team member expertise. The collaborative process involved regular meetings, iterative document revisions, and peer review. Resource quality was better than expected, perhaps because best practices/principles related to health research are universally relevant, regardless of context. While the RSG was essential to systematize our search and ensure reproducibility, team member expertise was valuable. Pairing team members during peer-review led to bi-directional knowledge sharing and was particularly successful. This work reflects a highly collaborative global partnership and offers a model for future health research capacity-building efforts. We invite engagement with the Virtual Library as one supportive pillar of infrastructure to develop individual and institutional research capacity.

Cancer Prevention Strategies for Nepal.

In Nepal, the commonest major malignancies and causes of cancer death are lung, cervix, stomach, breast, head and neck (lip, mouth, pharynx, larynx), gallbladder, ovary and liver. There are seven cancer-causative exposures which should be the focus of attention such as; tobacco smoking in 29% of men, and 6% of women, solid fuel burning in 69% of homes (multiple cancers), betel-nut chewing in 40 % of men and 3% of women (head and neck cancers), alcohol abuse (liver and other cancers), Human Papilloma Virus (cervical cancer), Helicobacter pylori (stomach cancer) and Hepatitis B virus (liver cancer). To better address these reducible exposures, we suggest greater targeted strategies in three areas: Public health messaging for tobacco, solid-fuel burning, betel-nut, and alcohol; national policies for Hepatitis B virus vaccination; and analytic epidemiological and interventional research for Human Papilloma Virus and helicobacter.

Illness Representations of Hypertension among Nepali Patients at a Tertiary Care Hospital Clinic: An exploratory survey.

BACKGROUND: The prevalence of stage 2 hypertension approaches one-third in adult Nepalis and despite inexpensive effective treatment, long-term compliance is poor. World-wide, a major impediment is the incongruity between hypertension and patients' symptom-based illness representations. The Common-Sense Model of Self-regulation was used to investigate Nepali illness representations through open-ended interviews of patients with hypertension. METHODS: In a tertiary hospital setting, 50 self-identified hypertensive patients were interviewed about their representations of health, hypertension, and hypertensive treatment. Responses were analyzed with a modified Interpretative Phenomenological Analysis. RESULTS: An Ayurvedic-influenced health model appeared in illness identity and coping responses. Hypertension was identified as a serious disease having observable, wide-ranging symptoms with chronic and intermittent timelines. Concerns included side-effects and barriers to treatment. CONCLUSIONS: Further confirmation and investigation of Nepali common-sense hypertension models in a sample size sufficient for factor analysis is warranted for effective adherence interventions.

Reorganizing Hospital Cancer Care In Nepal.

While mortality rates for major common cancers- of the lung, breast, stomach, ovary, and lymphomas-- have declined significantly in high-income countries over the last decade, comparable rates for these malignancies have not fallen in Nepal. The explanations for the high-income country mortality trends are multiple and certainly include incidence reductions, but better treatments are also contributory. How to bring to Nepal the global lessons in achieving better cancer care is uncertain. We need to create an environment of ideas and a powerful vision to meet the needs for better major cancer management for Nepalis. Broadly, the Nepalese challenges are in creating more accessible and affordable care of sufficiently high-quality to make a difference. Hospitals are the major places where these issues have to be considered. To address these challenges, we offer a vision and suggest here strategies of major organizational changes in: Innovative staffing models, emphasizing teamwork, with increases in responsibilities, activities and work force percentages of non-physician health professionals; Increased outpatient care and tele-health; 3.Creating and following evidence-based diagnostic pathway and treatment clinical practice guidelines and checklists; 4. Increased application of information technology tools, particularly electronic medical records; and 5. Service implementation research evaluating quality based on structure, process and outcomes of care. Developing such effective changes requires strong community linkages, local institutional-specific coalition initiatives and experimentation, and national and international collaborations and financial support to effect practical and data-based plans and budgets. Keywords: Guidelines; improving treatment; information technology tools; outpatient services; staffing models; tele-health.

KRAS Oncogene Mutations in Colorectal Cancer Patients in a Nepalese Tertiary Care Hospital.

BACKGROUND: Colorectal cancer is one of the most common cancers in the world and ranks among top ten cancer in Nepal. Limited data have been reported in the literature regarding the prevalence of Kristen Rat Sarcoma viral oncogene mutation in Nepalese patients with colorectal cancer. In a low income country such as Nepal where majority of cancer patient pay for treatment out-of-pocket, it is important to ascertain Kristen Rat Sarcoma viral oncogene mutation status before starting treatment with these agents. METHODS: We analysed 22 colorectal cancer specimens diagnosed histopathologically. Real Time Polymerase Chain Reaction was performed on extracted DNA using RoterGene from Qiagen. US Food and Drug Administration approved kit was used for detection of Kristen Rat Sarcoma viral oncogene mutation i.e. TheraScreen: K-RAS Mutation Kit: The K-RAS Kit detects seven Kristen Rat Sarcoma viral oncogene mutations in codons 12 and 13 of the Kristen Rat Sarcoma viral oncogene. RESULTS: Kristen Rat Sarcoma viral oncogene mutation was observed in 13 (59%) of the samples studied. All samples had point mutation on codons 12 while 5 samples (38%) also had a point mutation on codons 13. No association was found between the presence of Kristen Rat Sarcoma viral oncogene mutation and gender or age or sidedness of the cancer. CONCLUSIONS: Kristen Rat Sarcoma viral oncogene was commonly present in colorectal cancer specimens. Further efforts towards establishment of diagnostic test, generation of new database, development and scale up of laboratory services are needed throughout the nation.

Distress Screening among Patients with Hematological Malignancies: A Descriptive Cross-sectional Study.

INTRODUCTION: Distress is a major concern during diagnosis and treatment of hematological malignancies. The Distress Thermometer is a commonly used screening tool to detect distress. The objectives of this study was to know the prevalence and identify distress score among patients with hematological malignancies in Nepal. METHODS: A descriptive cross sectional study was carried out at the Hematology Unit of Civil Service Hospital after obtaining an ethical approval from the Institutional Review Committee (reference number 931/076/077). A convenient sampling technique was used for this study. Statistical Package for the Social Sciences version 20.0 was used. All patients within one week of diagnosis and before the start of definitive treatment of hematological malignancies were included in the study. National Comprehensive Cancer Network Psychosocial Distress Screening Tool was used to measure the seriousness of distress. RESULTS: A total of 100 patients were enrolled in the study, among them 56 (56%) were male and 44 (44%) were female. The mean distress score in our study was found to be 5.68±1.75. Mean distress score among male and female patients were 5.84±1.65 and 5.48±1.86 respectively. Thirty three percentage (n=33) of patient had mild distress whereas, sixty six percentage (n=67) of patients experienced moderate to severe distress. CONCLUSIONS: There was a significant level of distress among the patients with hematological malignancies in Nepal. Therefore, distress screening should be done to all the patients when initial diagnosis is made.

Reliance on Self-Medication Increase Delays in Diagnosis and Management of GI Cancers: Results From Nepal.

PURPOSE: Patients with GI cancers in Nepal often present with advanced disease and poor outcomes. The purpose of the study was to determine the time to presentation, diagnosis, and treatment of GI cancer and the baseline factors that may be associated with delays. PATIENTS AND METHODS: An institutional review board-approved study was performed in Kathmandu, Nepal, from July 2018 to June 2019. Patients with newly diagnosed GI cancers were asked to fill out a standardized questionnaire. Baseline factors such as residence, literacy, and use of self-medication were recorded. Patients were asked to report the time from first symptom to presentation, time from primary care visit to pathologic diagnosis, and time from diagnosis to surgery and/or treatment. Baseline factors were analyzed using 2-tailed t tests (Prism 8.0; GraphPad, La Jolla, CA) to determine whether any factors were associated with longer time delays in these 3 intervals. RESULTS: The cohort comprised of 104 patients with a median age of 53.5 years (range, 22-77 years); 61.5% were men, 46.2% had upper GI cancers, and 83.7% presented with stage III or IV disease. The median time to presentation was 150 days, time to diagnosis was 220 days, and time to treatment was 50 days. There was no statistically significant difference in time intervals between upper and lower GI cancers. Use of self-medication (88.5%) was the only factor associated with longer time intervals to presentation, diagnosis, and treatment. CONCLUSION: Patients in Nepal have long time intervals to presentation, diagnosis, and treatment of GI cancer. Self-medication led to longer delays. Reasons for self-medication and other potential barriers will be explored in future studies in the hopes of improving outcomes.

Procalcitonin and C-Reactive Protein As Markers of Bacteremia in Patients With Febrile Neutropenia Who Receive Chemotherapy for Acute Leukemia: A Prospective Study From Nepal.

PURPOSE: The purpose of this study was to evaluate the clinical significance of the biomarkers procalcitonin (PCT) and C-reactive protein (CRP) in patients with febrile neutropenia (FN) undergoing chemotherapy for acute leukemia. METHODS: We conducted a prospective, observational study in patients who developed FN while undergoing chemotherapy for acute leukemia. PCT and CRP were obtained in patients who presented with FN. Blood cultures also were obtained. The primary goals were to evaluate the ability of PCT and CRP to predict bacteremia in patients with FN. The secondary goals were to assess the prognostic role of PCT and CRP and to assess the microbiologic profile and culture sensitivity patterns in the study population. RESULTS: A total of 124 episodes of FN that involved 67 patients with acute leukemia occurred in the study. PCT was superior to CRP in the prediction of bacteremia. The median PCT level in the bacteremia group was 3.25 ng/mL compared with 0.51 ng/mL in the group without bacteremia (P < .01). The median values of CRP in the bacteremia and without-bacteremia groups were 119.3 mg/L and 94.5 mg/L, respectively (P = .07). There were no differences in median PCT and CRP in patients who died and those who improved. Of the 42 positive cultures, Gram-negative bacteremia was common (86%), and Escherichia coli was the most frequent organism isolated. Carbapenem resistance was seen in 39% of positive cultures. CONCLUSION: PCT is an effective biomarker to predict bacteremia in patients with FN undergoing chemotherapy for acute leukemia.

Microalbuminuria and Its Risk Factors in Type 2 Diabetic Patients.

BACKGROUND: Diabetic nephropathy is one of the dreaded complications of diabetes leading to chronic kidney disease and end stage renal failure globally. Microalbuminuria is the most sensitive marker of early recognition of the diabetic nephropathy. This study was carried out to find out the prevalence and potential risk factors of microalbuminuria which is the marker of diabetic nephropathy among diabetes patients in Nepal. METHODS: A cross-sectional study was conducted on a random sample of 227 in T2DM patients in private diabetic clinics and Bir hospital in Kathmandu. Data were collected using standard questionnaire format to collect demography, anthropometry, and laboratory assessment of, HbA1c, post prandial, fasting glucose and micro albumin in urine. Micro albuminuria was measured using early morning urine specimen. Micro albuminuria was considered positive when urinary albumin to creatinine ratio was found to be 30-300 mg/g creatinine in preferably an early morning or a spot urine sample. The entire lab test will be done by applying the internationally accepted standards of tools and techniques.Those that were reported >30mg/mL of micro albumin were considered as positive. RESULTS:   Out of total 217 diabetic patients, 56.2% (122/217) were male and 43.8% (95/217) were female. Among all age groups, maximum patients enrolled were between the age group 41 to 80 (95%).Of the total, 20% (44/217)) patientswereMA positive. A statistical significant association was seen between MA and BMI (p=0.029), duration of DM (p=<0.001, hypertension (p=<0.001, smoking (p=<0.001) and physical activity (p=<0.001). CONCLUSIONS: Diabetic patients in Nepal have prevalence of 20.3% microalbuminurea. Hypertension, obesity, sedentary lifestyles, duration more than 5 years of illness are found the most important risk factors for the development of microalbuminurea in diabetes.     Keywords:  Mellitus; microalbuminuria; type 2 diabetes.

Randomized Phase II Trial to Compare the Efficacy of Haloperidol and Olanzapine in the Control of Chemotherapy-Induced Nausea and Vomiting in Nepal.

PURPOSE: The purpose of the study was to compare efficacy and toxicity of olanzapine (OLN; a higher-cost drug) and haloperidol (HAL; a lower-cost drug) in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients who receive highly emetogenic chemotherapy (HEC). PATIENTS AND METHODS: In a randomized, phase II trial, patients were randomly assigned to receive either OLN 10 mg orally on days 1 to 4 or HAL 1 mg orally on day 1 and 0.5 mg twice daily on days 2 to 4. Both groups received ondansetron 16 mg and dexamethasone 12 mg intravenously on day 1. Patients recorded their nausea using the Edmonton Symptom Assessment Scale (ESAS) and recorded daily episodes of vomiting from day 1 to day 5. The primary end point was complete nausea prevention (CNP; ie, ESAS of 0). Secondary end point was complete emesis prevention (CEP). RESULTS: Sixty-five patients were randomly assigned, and 64 received their allocated treatment (n = 32 in each arm). There was no difference in CNP during the overall period (days 1 to 5) between OLN and HAL (68.7% v 71.8%; P = .78). In the acute period (day 1) and the delayed period (days 2 to 5), CNP was similar between OLN and HAL (acute: 84.3% v 81.2%; delayed: 68.7% v 75%). No difference was identified in the rate of CEP during the overall period (81.2% with OLN v 78.1% with HAL; P = .75), during the acute period (93.7% with OLN v 90.6% with HAL), or during the delayed period (84.3% with OLN v 84.3% with HAL). No difference in toxicities was noted between treatment arms. CONCLUSION: In this study, HAL had comparable efficacy to OLN in the management of CINV, which suggests that it is the higher-value option in patients who receive HEC in resource-scarce countries.

Access to pain relief and essential opioids in the WHO South-East Asia Region: challenges in implementing drug reforms.

It is a justifiable assumption that more than 15 million people in the World Health Organization South-East Asia Region are experiencing serious health-related suffering, much of it caused by persistent, severe pain. Despite this burden of suffering, overall access to pain relief and palliative care services is abysmal. The lack of access to controlled drugs for pain management is striking: the average morphine equivalence in the region in 2015 was just 1.7 mg per capita, while the global average was 61.5 mg per capita. Until recently, implementation of national legislation to facilitate medical and scientific use of opioids has proven to be very complex and difficult to achieve. The effects on the region of the exploitative British opium trade in previous centuries prompted countries to adopt draconian legislation on opioids, focused on restricting illicit use. In India, the Narcotic Drugs and Psychotropic Substances Act of 1985, for example, stipulated harsh custodial sentences for even minor clerical errors in hospitals stocking opioids. Decades of persistent efforts by civil society resulted in the landmark amendment of the Act in 2014 to improve medical access, but implementation remains highly protracted. Although some progress has been made in recent years in Bangladesh, India, Nepal, Sri Lanka and Thailand, pain is a symptom that is grossly undertreated in most parts of the region. On both human rights and public health grounds, there is an urgent need for well-formulated drug policies to increase access to opioid medications, coupled with capacity-building and comprehensive public health systems incorporating palliative care.

Opioid availability and palliative care in Nepal: influence of an international pain policy fellowship.

Globally, cancer incidence and mortality are increasing, and most of the burden is shifting to low- and middle-income countries (LMICs), where patients often present with late-stage disease and severe pain. Unfortunately, LMICs also face a disproportionate lack of access to pain-relieving medicines such as morphine, despite the medical and scientific literature that shows morphine to be effective to treat moderate and severe cancer pain. In 2008, an oncologist from Nepal, one of the poorest countries in the world, was selected to participate in the International Pain Policy Fellowship, a program to assist LMICs, to improve patient access to pain medicines. Following the World Health Organization public health model for development of pain relief and palliative care, the Fellow, working with colleagues and mentors, has achieved initial successes: three forms of oral morphine (syrup, immediate-release tablets, and sustained-release tablets) are now manufactured in the country; health-care practitioners are receiving training in the use of opioids for pain relief; and a new national palliative care association has developed a palliative care training curriculum. However, long-term implementation efforts, funding, and technical assistance by governments, philanthropic organizations, and international partners are necessary to ensure that pain relief and palliative care become accessible by all in need in Nepal and other LMICs.