Availability and Affordability of Essential Palliative Care Medicines in Nepal: A Cross-Sectional Study.

CONTEXT: The government of Nepal adopted the 2017 Nepalese National Strategy for Palliative Care (NSPC), which proposed that Essential Palliative Care Medicines (EPCMs) listed by the International Association for Hospice and Palliative Care (IAHPC) should be available at each healthcare institution. In 2017 after the issuing of NSPC, the Lancet Commission developed an EPCM list. OBJECTIVES: To evaluate the inclusion of EPCMs recommended by both IAHPC and Lancet in national medicinal programmes, their availability, and affordability in Nepal. METHODS: A cross-sectional descriptive study of the availability of EPCMs in Nepal, and their inclusion in the national essential medicines list, government health insurance medicines list, government fixed rate medicines list, and free medicines list. Affordability was assessed using the World Health Organization Daily-Define-Dose and the Nepal Government-defined minimum daily wage. RESULTS: A total of 27 of 33 (82%) of the IAHPC-EPCMs and 41 of 60 (68%) of the recommended formulations were available in Nepal. All the Lancet Commission recommended EPCMs were available in Nepal. Morphine was available in all formulations used in palliative care. 22%, 18%, and 10% of IAHPC-EPCMs were available cost-free via district hospitals, primary healthcare centers, and health posts, respectively. The government had not included opioids on both free and fixed price lists. A total of 24 of 33 (73%) IAHPC-EPCMs were available on the Government Health Insurance Medicines List. A total of 19 of 41 (46%) available EPCMs were affordable. CONCLUSION: Many EPCM formulations included in NSPC of Nepal are not available, and most available EPCMs are unaffordable if purchased out-of-pocket. While the availability is better with the government health insurance scheme, many people are not registered for this. Further improvements should follow the development of a Nepalese palliative care formulary.

The use of Imatinib resistance mutation analysis to direct therapy in Philadelphia chromosome/BCR-ABL1 positive chronic myeloid leukaemia patients failing Imatinib treatment, in Patan Hospital, Nepal.

Philadelphia chromosome/BCR-ABL1 positive chronic myeloid leukaemia (CML) can be successfully treated with Glivec (Imatinib), which is available free of cost through the Glivec International Patient Assistance programme (GIPAP) to patients with proven CML without means to pay for the drug. We review the acquired mutations in the tyrosine kinase encoded by the BCR-ABL1 gene underlying Glivec failure or resistance in a cohort of 388 imatinib-treated CML patients (149 Female and 239 male) registered between February 2003 and June 2016 in Nepal. Forty-five patients (11 female 34 male) were studied; 18 different BCR-ABL1 mutations were seen in 33 patients. P-loop mutation, Kinase domain and A-loop mutations were seen in 9, 16 and 4 patients respectively. Other mutations were seen in five patients. A T315I mutation was the most common mutation, followed by F359V and M244V. Sixteen mutations showed intermediate activity to complete resistance to Glivec. Among the 45 patients evaluated for BCR-ABL1 mutations, 4 were lost to follow-up, 14 died and 27 are still alive. Among the surviving patients, 16 are receiving Nilotinib, 5 Dasatinib and 3 Ponatinib, while 3 patients were referred to India, one of who received allogenic bone marrow transplantation. Understanding the spectrum of further acquired mutations in BCR-ABL1 may help to choose more specific targeted tyrosine kinase inhibitors that can be provided by GIPAP.

Treating Philadelphia chromosome/BCR-ABL1 positive patients with Glivec (Imatinib mesylate): 10 years' experience at Patan Hospital, Nepal.

The Glivec International Patient Assistance Programme makes Glivec (Imatinib mesylate) available to Philadelphia chromosome/BCR-ABL1 positive patients with chronic myeloid leukaemia (CML) in Lower and Middle Income Countries (LMIC). We have established a large cohort of 211 CML patients who are eligible for Imatinib, in Kathmandu, Nepal. Thirty-one patients were lost to follow-up. We report on 180 CML patients with a median age of 38 years (range 9-81). Of these 180 patients, 162 underwent cytogenetic testing and 110 were investigated by reverse transcription polymerase chain reaction. One hundred and thirty-nine of the 180 patients (77·2%) had at least one optimal response. Taken together, our cohort has a 95% overall survival rate and 78% of the patients were still taking Glivec at a median time of 48·8 months (range 3-140 months). The number of patients who actually failed therapy, as defined by the LeukaemiaNet 2013 criteria, was 39 (21·7%). While our cohort has some differences with those in North America or Europe, we have shown Glivec is effective in inducing an optimal response in our patients in Nepal and that it is possible to deliver a clinical service for CML patients using tyrosine kinase inhibitors in resource-poor settings.

A staff support programme for rural hospitals in Nepal.

PROBLEM: District hospitals in Nepal struggle to provide essential services such as caesarean sections. APPROACH: Retention of health workers is critical to the delivery of long-term, quality health-care services. To promote retention and enhance performance in rural public hospitals, the Government of Nepal and the Nick Simons Institute progressively implemented a rural staff support programme in remote hospitals. After competitive selection for a compulsory-service scholarship and training, family practice doctors who could do basic surgery, orthopaedics and obstetrics were hired under a binding three-year contract in each participating hospital. Comfortable living quarters and an Internet connection were provided for the resident doctors; in-service training for all staff and capacity development for each hospital's management committee were provided. LOCAL SETTING: Nepal's mountainous landscape, poverty and inequitable rural/urban distribution of health workers pose barriers to adequate health care. RELEVANT CHANGES: Between 2011 and 2015 family practice doctors were maintained in all seven programme hospitals. All hospitals became providers of comprehensive emergency obstetric care and served more patients. Compared with hospitals not within the programme, deliveries increased significantly (203% versus 71% increase, respectively; P = 0.002). The programme recently expanded to 14 hospitals. LESSONS LEARNT: A package of human resource supports can improve the retention of doctors and the use of remote hospitals. Factors contributing to the success of this programme were compulsory-service scholarship, central personnel management, performance-based incentives and the provision of comfortable living quarters.

Career choices and what influences Nepali medical students and young doctors: a cross-sectional study.

BACKGROUND: Nepal, as a nation with limited resources and a large number of poor people, needs far more well-trained, committed general practitioners. The aim of this study was to understand medical career choices and the factors that influence medical students' and young doctors' career choices in Nepal and to understand what would encourage them to work in rural areas as generalists. METHODS: This was a cross-sectional study of 1137 medical students (first and final year) and young doctors (interns and residents) from six medical colleges in Nepal who completed a voluntary questionnaire, with some also participating in structured focus groups - 170 first years, 77 final years and 80 graduates - with an additional 28, 44 and 49 written responses respectively. RESULTS: Without selective admissions policies, 41.7% (464/1112) of respondents had a rural background - most significant in Year 1 students, males and in colleges outside of Kathmandu. Of the respondents, 569 (50.9%) had a specialty choice starting medical school - the greatest proportion in Year 1. Medicine (especially cardiology) and surgery (particularly among males) were most significant choices at all stages. Only five participants initially and four during their course chose general practice. There appears no interest in, recognition of, significant exposure to, or role models in general practice.Serving the sick, personal interest and social prestige were the most significant influencing factors - consistent across all groups. Course availability was also a factor. To attract doctors to work in rural areas most respondents affirmed the need for a good salary, infrastructure and facilities, scholarships and career development opportunities. CONCLUSIONS: Challenges include raising generalists' profiles within the medical community, government and patient community; changing undergraduate curricula to include greater exposure to good models of rural generalist practice; and providing incentives and attractions for post-graduate training and service.

Mobile phone support for rural health workers in Nepal through 'celemedicine'.

Globally, there is a shortage of health workers in rural areas. Effective health systems depend on having sufficient, accessible health workers with the right skills. In countries like Nepal, highly skilled health workers often prefer to work overseas or in urban centres, and therefore, in the short term, it may be pragmatic to focus on ensuring support and skills development of mid level or paramedical health workers. Information technology has the potential to support these health workers. We describe a pilot intervention undertaken in Gulmi District, whereby all mid level health workers in the district have been provided with a free phone number to call three General Practitioner Doctors (GPs) in the District Hospital. The intervention aims to increase appropriate referral, and increase connectivity between the District centre and peripheral health facilities. We hope that our intervention will provide support to rural health workers, and, if implemented as part of a package of interventions, may increase retention. We present some initial findings from discussions with health workers and analysis of call-log data, and describe our next phase evaluation and possible scale-up.

Patan hospital experience in treating philadelphia chromosome/BCR-ABL1 positive chronic myeloid leukemia patients with gleevec (imatinib mesylate); the first generation specific tyrosine kinase inhibitor.

BACKGROUND: Chronic Myeloid Leukemia (CML) is caused by the abnormal fusion protein BCR-ABL1, a constitutively active tyrosine kinase and product of the Philadelphia chromosome. Gleevec (Imatinib mesylate) is a selective inhibitor of this kinase. Treatment with this agent is known to result in hematologic, cytogenetic, and molecular responses. Patan hospital (Patan, Nepal) is one of the Gleevec International Patient Assistance Program (GIPAP) centers for patients with CML. METHODS: A total of 106 Philadelphia positive CML patients were enrolled in our center between Feb 2003 and Jun 2008, and 103 of them were eligible for cytogenetic and/or hematologic response analyses. RESULTS: Out of 103 patients, 27% patients underwent cytogenetic analysis. Imatinib induced major cytogenetic responses in 89% and complete hematologic responses in almost 100% of the patients with confirmed CML. After a mean follow up of 27 months, an estimated 90% of the patients on imatinib remained in hematologic remission and more than 90% of the patients are still alive. About 30% of patients developed some form of manageable myelosuppression. A few patients developed non-hematologic toxic side effects such as edema and hepatotoxicity. CONCLUSIONS: Our study demonstrates that imatinib is safe to use in a developing country. Furthermore, we demonstrate that imatinib is very effective and induced long lasting responses in a high proportion of patients with Ph chromosome/BCR-ABL1 positive CML. Imatinib is well tolerated by our patients. The lack of cytogenetic analysis in the majority of our patients hindered our ability to detect inadequate responses to imatinib and adjust therapy appropriately.

Retention of general practitioners in rural Nepal: a qualitative study.

OBJECTIVES: To explore the key issues that influence GP retention in rural areas of Nepal. DESIGN: A qualitative study using triangulation of data from one postal questionnaire, one hand-delivered questionnaire with semistructured interview and focus group discussions. Data from a small community survey from 13 rural districts also included. PARTICIPANTS: Sixty-two Nepali GPs, 25 doctors in General Practice training programs, 11 individuals involved in policy development and rural health care. RESULTS: The key issues identified by this study as critical to the retention of Nepali GPs in rural areas were: * Career/promotion prospects * Status/recognition * Financial incentives * Working conditions * Education for children * Continuing medical education * Political stability and security. CONCLUSIONS: The strongest theme was that of career development. This must be addressed by the Government of Nepal if there is to be any hope of improving retention of GPs in rural areas. GPs need to have a clear career ladder, with recognition of the value of service in rural areas. There is, however, no one single answer to the complex interacting factors that impact on GP retention in rural Nepal. A multifaceted, holistic response is necessary. From the level of community awareness, a career structure and financial remuneration to adequately set up hospitals, functional teams, family support, continuing professional development and a secure working environment - each area must be addressed for the whole to function.

Medical errors - a hospital in Nepal searches for answers.

Medical errors are recognized as a significant issue in medical practice. Ethical and professional guide-lines emphasize the responsibility of physicians to disclose errors to patients. However, in practice, even in the developed world this often does not happen. This study which involved 12 focus groups formed from 127 members of staff within Patan Hospital in the Kathmandu Valley sought to understand Nepali staff attitudes to medical errors and suggest how they could be handled. Most agreed, for good reasons of honesty and patient autonomy, that admission of errors is important, but the doctors struggled to decide how it should be done. For most of the staff the educational level was a key decider as to what would be disclosed. Most agreed that the socio-legal climate in Nepal, and the possible financial implications, made it difficult to be completely honest. Other strong fears included patient harm, violence from the patient, damage to the hospital's reputation and to the reputation of the doctors and possible loss of jobs for nurses. We recommend that the hospital initiate a clear hospital policy on dealing with errors and that they should: implement the development of incident reporting forms; set up an error investigation team; provide specific training in communicating about errors for the appropriate staff.

Rules vs. analogy in English past tenses: a computational/experimental study.

Are morphological patterns learned in the form of rules? Some models deny this, attributing all morphology to analogical mechanisms. The dual mechanism model (Pinker, S., & Prince, A. (1998). On language and connectionism: analysis of a parallel distributed processing model of language acquisition. Cognition, 28, 73-193) posits that speakers do internalize rules, but that these rules are few and cover only regular processes; the remaining patterns are attributed to analogy. This article advocates a third approach, which uses multiple stochastic rules and no analogy. We propose a model that employs inductive learning to discover multiple rules, and assigns them confidence scores based on their performance in the lexicon. Our model is supported over the two alternatives by new "wug test" data on English past tenses, which show that participant ratings of novel pasts depend on the phonological shape of the stem, both for irregulars and, surprisingly, also for regulars. The latter observation cannot be explained under the dual mechanism approach, which derives all regulars with a single rule. To evaluate the alternative hypothesis that all morphology is analogical, we implemented a purely analogical model, which evaluates novel pasts based solely on their similarity to existing verbs. Tested against experimental data, this analogical model also failed in key respects: it could not locate patterns that require abstract structural characterizations, and it favored implausible responses based on single, highly similar exemplars. We conclude that speakers extend morphological patterns based on abstract structural properties, of a kind appropriately described with rules.