Showing papers by "Bishal Gyawali published in 2016"

Low skeletal muscle density is associated with poor survival in patients who receive chemotherapy for metastatic gastric cancer.

Abstract: Low skeletal muscle density (SMD) and low skeletal muscle index (SMI) are associated with poor overall survival (OS) in patients with various types of cancer. We retrospectively studied SMD and SMI using computed tomographic (CT) scans in patients with gastric cancer receiving chemotherapy to evaluate its prognostic significance. SMD and SMI were obtained from CT-based analysis using Slice-O-Matic® medical imaging software in patients who received S-1 plus cisplatin chemotherapy for metastatic gastric cancer. The CT images taken within 1 month before starting chemotherapy were used. The cut-off values for determining low SMD [<33 Hounsfield units (HU) in obese and <41 HU in non-obese patients] and low SMI (<41 cm2/m2 in females, <43 cm2/m2 in non-obese males and <53 cm2/m2 in obese males) were referenced from a large population based study. The CT images of 53 patients were reviewed. The median SMD was 36.8 HU (range, 19.5-59.3 HU), and the median SMI was 39.8 cm2/m2 (range, 23.7-60.0 cm2/m2). Patients with low SMD had significantly shorter OS compared with patients having normal SMD (8.9 vs. 12.8 months, P=0.03). However, OS did not differ significantly between patients with low and normal SMI (11.1 and 14.3 months, P=0.18). Multivariate analyses confirmed that low SMD was an independent predictor of poor outcomes (P<0.01). SMD is an important prognosticator of survival in patients with metastatic gastric cancer receiving chemotherapy.

Challenges in diabetes mellitus type 2 management in Nepal: a literature review

Abstract: Background and objectives : Diabetes has become an increasingly prevalent and severe public health problem in Nepal. The Nepalese health system is struggling to deliver comprehensive, quality treatment and services for diabetes at all levels of health care. This study aims to review evidence on the prevalence, cost and treatment of diabetes mellitus type 2 and its complications in Nepal and to critically assess the challenges to be addressed to contain the epidemic and its negative economic impact. Design : A comprehensive review of available evidence and data sources on prevalence, risk factors, cost, complications, treatment, and management of diabetes mellitus type 2 in Nepal was conducted through an online database search for articles published in English between January 2000 and November 2015. Additionally, we performed a manual search of articles and reference lists of published articles for additional references. Results : Diabetes mellitus type 2 is emerging as a major health care problem in Nepal, with rising prevalence and its complications especially in urban populations. Several challenges in diabetes management were identified, including high cost of treatment, limited health care facilities, and lack of disease awareness among patients. No specific guideline was identified for the prevention and treatment of diabetes in Nepal. Conclusions : We conclude that a comprehensive national effort is needed to stem the tide of the growing burden of diabetes mellitus type 2 and its complications in Nepal. The government should develop a comprehensive plan to tackle diabetes and other non-communicable diseases supported by appropriate health infrastructure and funding. Keywords: diabetes mellitus type 2; diabetes complications; costs; low-income country; health care; Nepal (Published: 18 October 2016) Citation: Glob Health Action 2016, 9 : 31704 - http://dx.doi.org/10.3402/gha.v9.31704

Muscle wasting associated with the long-term use of mTOR inhibitors.

Abstract: Some targeted therapies alter muscle mass due to interference with pathways of muscle metabolism. The effects of mammalian target of ra pamycin (mTOR) inhibitors on muscle mass have yet to be fully elucidated. In the present study, the computerized tomography (CT) scans of patients receiving mTOR inhibitors for at least 6 months taken at baseline and post-therapy were retrospectively retrieved, and body composition analyses were performed using the software, sliceOmatic version 5.0 (TomoVision, Inc., Magog, QC, Canada). The difference in body composition parameters was evaluated for significance. The time to treatment (TTF) failure was also compared between the sarcopenic and non-sarcopenic patients at the baseline. Of the 75 patients studied, 20 matched the inclusion criteria (including 16 males). The mean duration between the CT scans was 14.4±2.0 months. A total of 12 (60%) patients were sarcopenic at the baseline, whereas three more (75% in total) became sarcopenic following treatment. The use of mTOR inhibitors significantly decreased the skeletal muscle area (P=0.011) and lean body mass (P=0.007), although it had no effect on adipose tissue (P=0.163) or body weight (P=0.262). The rate of skeletal muscle wasting was 2.6 cm2/m2, or 2.3 kg in 6 months. The TTF did not differ between sarcopenic and non-sarcopenic patients, and was not significantly associated with any other parameter. To the best of our knowledge, this is the first study to demonstrate that the long-term use of mTOR inhibitors induces a marked loss of muscle mass. Due to the predictive and prognostic role of sarcopenia in cancer patients, these findings may have important clinical implications.

Prevalence and correlates of psychological distress symptoms among patients with substance use disorders in drug rehabilitation centers in urban Nepal: a cross-sectional study

Abstract: The burden of substance misuse in developing countries is large and increasing, with negative consequences for physical and psychological health. Substance use disorders and psychological distress commonly co-exist, however few studies have examined this relationship in developing countries, including Nepal. Our aim was to investigate the prevalence of psychological distress symptoms and associated factors among patients with substance use disorders attending drug rehabilitation centers in Nepal. We conducted a cross-sectional study including 180 patients attending drug rehabilitation centers in the Kathmandu Valley region of Nepal. We used the 6-item Kessler scale (K6) to measure symptoms of psychological distress, and data on socio-demographics, behavioral and psychosocial factors. Multivariable analyses were used to identify factors associated with distress. The prevalence of high psychological distress symptoms among patients with substance use disorder was 51.1 %. The mean score found on the K6 was 12.22 (SD = 5.87). Outcomes of multivariable analyses demonstrated various factors associated with symptoms of psychological distress, including age (β = −0.122, 95 % CI = −0.218; −0.026), education (β =2.694, 95 % CI = 0.274; 5.115), severity of drug abuse (Drug Abuse Screening Test-10-DAST10)(β = 0.262, 95 % CI = 0.022;0.502), and family functioning (Adaptability, Partnership, Growth, Affection and Resolve-APGAR) (β = −0.525, 95 % CI = −0.787; −0.264). High psychological distress symptoms are common in patients with substance use disorder in Nepal. Demographics (age, education), behavioral (drug abuse severity), and psychosocial factors (family functionality) were associated with psychological distress symptoms. If confirmed by future longitudinal studies such characteristics may assist in identifying groups at risk for co-morbid psychological distress symptoms among patients with substance use disorders. Future treatment approaches for substance use disorders should address co-existing mental illness in Nepal.

Global, regional, national, and selected subnational levels of stillbirths, neonatal, infant, and under-5 mortality, 1980–2015: A systematic analysis for the Global Burden of Disease Study 2015

Abstract: Background Established in 2000, Millennium Development Goal 4 (MDG4) catalysed extraordinary political, financial, and social commitments to reduce under-5 mortality by two-thirds between 1990 and 2015. At the country level, the pace of progress in improving child survival has varied markedly, highlighting a crucial need to further examine potential drivers of accelerated or slowed decreases in child mortality. The Global Burden of Disease 2015 Study (GBD 2015) provides an analytical framework to comprehensively assess these trends for under-5 mortality, age-specific and cause-specific mortality among children under 5 years, and stillbirths by geography over time. Methods Drawing from analytical approaches developed and refined in previous iterations of the GBD study, we generated updated estimates of child mortality by age group (neonatal, post-neonatal, ages 1–4 years, and under 5) for 195 countries and territories and selected subnational geographies, from 1980–2015. We also estimated numbers and rates of stillbirths for these geographies and years. Gaussian process regression with data source adjustments for sampling and non-sampling bias was applied to synthesise input data for under-5 mortality for each geography. Age-specific mortality estimates were generated through a two-stage age–sex splitting process, and stillbirth estimates were produced with a mixed-effects model, which accounted for variable stillbirth definitions and data source-specific biases. For GBD 2015, we did a series of novel analyses to systematically quantify the drivers of trends in child mortality across geographies. First, we assessed observed and expected levels and annualised rates of decrease for under-5 mortality and stillbirths as they related to the Soci-demographic Index (SDI). Second, we examined the ratio of recorded and expected levels of child mortality, on the basis of SDI, across geographies, as well as differences in recorded and expected annualised rates of change for under-5 mortality. Third, we analysed levels and cause compositions of under-5 mortality, across time and geographies, as they related to rising SDI. Finally, we decomposed the changes in under-5 mortality to changes in SDI at the global level, as well as changes in leading causes of under-5 deaths for countries and territories. We documented each step of the GBD 2015 child mortality estimation process, as well as data sources, in accordance with the Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings Globally, 5·8 million (95% uncertainty interval [UI] 5·7–6·0) children younger than 5 years died in 2015, representing a 52·0% (95% UI 50·7–53·3) decrease in the number of under-5 deaths since 1990. Neonatal deaths and stillbirths fell at a slower pace since 1990, decreasing by 42·4% (41·3–43·6) to 2·6 million (2·6–2·7) neonatal deaths and 47·0% (35·1–57·0) to 2·1 million (1·8-2·5) stillbirths in 2015. Between 1990 and 2015, global under-5 mortality decreased at an annualised rate of decrease of 3·0% (2·6–3·3), falling short of the 4·4% annualised rate of decrease required to achieve MDG4. During this time, 58 countries met or exceeded the pace of progress required to meet MDG4. Between 2000, the year MDG4 was formally enacted, and 2015, 28 additional countries that did not achieve the 4·4% rate of decrease from 1990 met the MDG4 pace of decrease. However, absolute levels of under-5 mortality remained high in many countries, with 11 countries still recording rates exceeding 100 per 1000 livebirths in 2015. Marked decreases in under-5 deaths due to a number of communicable diseases, including lower respiratory infections, diarrhoeal diseases, measles, and malaria, accounted for much of the progress in lowering overall under-5 mortality in low-income countries. Compared with gains achieved for infectious diseases and nutritional deficiencies, the persisting toll of neonatal conditions and congenital anomalies on child survival became evident, especially in low-income and low-middle-income countries. We found sizeable heterogeneities in comparing observed and expected rates of under-5 mortality, as well as differences in observed and expected rates of change for under-5 mortality. At the global level, we recorded a divergence in observed and expected levels of under-5 mortality starting in 2000, with the observed trend falling much faster than what was expected based on SDI through 2015. Between 2000 and 2015, the world recorded 10·3 million fewer under-5 deaths than expected on the basis of improving SDI alone. Interpretation Gains in child survival have been large, widespread, and in many places in the world, faster than what was anticipated based on improving levels of development. Yet some countries, particularly in sub-Saharan Africa, still had high rates of under-5 mortality in 2015. Unless these countries are able to accelerate reductions in child deaths at an extraordinary pace, their achievement of proposed SDG targets is unlikely. Improving the evidence base on drivers that might hasten the pace of progress for child survival, ranging from cost-effective intervention packages to innovative financing mechanisms, is vital to charting the pathways for ultimately ending preventable child deaths by 2030. Funding Bill & Melinda Gates Foundation.

Cheaper Options in the Prevention of Chemotherapy-Induced Nausea and Vomiting

Abstract: Chemotherapy-induced nausea and vomiting (CINV) is a common challenge in oncology practice for which there are expensive guideline-based treatment options. Although supportive care in cancer adds significantly to the overall cost, the discussion of unaffordability of anticancer treatment frequently only revolves around the targeted drugs and immunotherapies. In this review, we highlight the available cost-saving strategies and recent updates in preventing CINV in patients with cancer. This is the first work, to our knowledge, to review specifically the less expensive alternatives in CINV prevention, which is particularly important for those working in resource-limited settings. Whereas patients in these settings often cannot afford expensive antiemetics, we now have the science to offer cheaper, more affordable options without necessarily compromising efficacy.

Should low-income countries invest in breast cancer screening?

Abstract: With the increase in incidence and mortality of breast cancer in low-income countries (LICs), the question of whether LICs should promote breast cancer screening for early detection has gained tremendous importance. Because LICs have limited financial resources, the value of screening must be carefully considered before integrating screening programs into national healthcare system. Mammography-the most commonly used screening tool in developed countries-reduces breast cancer-specific mortality among women of age group 50-69, but the evidence is not so clear for younger women. Further, it does not reduce the overall mortality. Because the women in LICs tend to get breast cancer at younger age and are faced with various competing causes of mortality, LICs need to seriously evaluate whether mammographic screening presents a good value for the investment. Instead, we suggest a special module of clinical breast examination that could provide similar benefits at a very low cost. Nevertheless, we believe that LICs would obtain a much greater value for their investment if they promote primary prevention by tobacco cessation, healthier food and healthier lifestyle campaigns instead.

Safety and Efficacy of Azathioprine as a Second Line Therapy for Primary Immune Thrombocytopenic Purpura.

Abstract: Introduction: Immune thrombocytopenic purpura remains common blood disease in Nepal. Azathioprine is an oral immunosupressive medicine which has been used widely in various autoimmune disease and solid organ transplant patients. It is inexpensive, easily available and well tolerated medicine. This study was carried out to evaluate efficacy and safety of azathioprine as a second line medicine for primary ITP patients who were refractory to steroid therapy.Methods: The observational, pre-post study was conducted at Government of Nepal Civil Service Hospital, Kathmandu from January to October 2014. Twenty four primary ITP patients who were steroid refractory were treated with Azathioprine. Patients were termed steroid refractory if platelet counts were less than 30,000/ul on day 21st of steroid therapy. From day 22 onwards oral azathioprine 2mg/kg was started and steroids were tapered 10mg/week and stopped. Platelet counts of more than 30000/ul after one month of stopping steroid, while still on azathioprine, were termed response to azathioprine. Platelet count of more than 100,000/ul was termed complete response. The associations among age, gender, duration and platelets counts were analyzed by chi square test and Fisher's exact test (when individual cell frequency was less than 5). The comparison of platelets counts among the start and day 90 of Azathioprine therapy was performed by the paired t-test. Results: The study showed that there was not significant association among age and gender of the patients and their platelets count on the start of Azathioprine therapy (p value 0.354 and 0.725 respectively) and on day 90 of Azathioprine therapy (p value 0.082 and 0.762 respectively). The duration-wise comparisons of platelets count on both the start and day 90 of Azathioprine therapy were significant (p values 0.029 and 0.008 respectively). The paired comparison among platelets count on the start and day 90 of Azathioprine therapy was highly significant (p value 0.000).Conclusions: The study showed the therapeutic implication of azathioprine in ITP patients. It also showed that efficacy of azathioprine was comparable with other modes of treatment. In low income countries like Nepal azathioprine can be considered as second line treatment for steroid refractory ITP patients.Keywords: Immune thrombocytopenic purpura; autoimmune disease; steroids; azathioprine; Nepal. | PubMed

Negative trials in ovarian cancer: is there such a thing as too much optimism?

Abstract: Recently, two clinical trials of novel agents in metastatic ovarian cancer were published: a phase 3 study of nintedanib and a phase 2 study of volasertib. There seemed to be discordance between the results and conclusions in the publication of both these trials. Despite not very optimistic results, the studies concluded optimistically in favor of the new agents under study. Using these examples, we point out the discrepancies and the risks of concluding optimistically based on statistical significance when the actual benefit is minimal. We also appeal against conducting large phase 3 trials that require significant resources without good phase 2 evidence for doing so.

Same Data; Different Interpretations

Abstract: Interpretation of oncology clinical trial data are not always straightforward or consistent. Similar trial results with disparate interventions may be interpreted differently by the oncology community. One of the main reasons for this discrepancy is the debate regarding what is the appropriate end point for demonstration of efficacy of cancer drugs. There is no doubt that overall survival (OS) is the best parameter to judge the utility of any intervention, and it is free from bias in ascertainment and measurement; but for conditions with few treatment options and dire outcomes, the need for new agents is high and the oncology community sometimes settles on a surrogate end point that, in many cases, is progression-free survival (PFS). It is easy to understand why PFS is favored among the researchers: It occurs early and is not influenced by postprogression therapy. At the same time, it would make little sense to have an agent that reduces chances of dying of cancer but increases off-target deaths; hence, the need for verification of OS. Phase III trials that report on significant PFS benefits without OS prolongation become the apples of discord in the oncology community. In this commentary, we present three examples from lung, ovarian, and breast cancers and demonstrate how the oncology community interprets similar data differently. Finally, we take our best guess as to why this phenomenon happens.

TKI-induced pure red cell aplasia: first case report of pure red cell aplasia with both imatinib and nilotinib

Abstract: Tyrosine-kinase inhibitors (TKIs) represent the only hopes for long-term survival for patients with chronic myeloid leukaemia (CML) and gastrointestinal stromal tumours. Thus, uninterrupted use of TKIs is of importance in such patients. Pure red cell aplasia (PRCA) is a rare disorder, not previously known to be associated with TKIs. We present, to the best of our knowledge, the first case of a patient with CML who developed PRCA secondary to both imatinib and nilotinib. Although PRCA was controlled on withdrawal of TKI, TKI continuation in the patient with CML is important. So we treated him with prednisone, but his haemoglobin started to drop on resumption of imatinib. He was changed to nilotinib but again developed PRCA, which did not improve with steroids. We treated him with cyclosporine and were able to reintroduce nilotinib at a reduced dose without further complications. This case report makes physicians aware of this rare complication of TKIs and also provides encouragement that PRCA could be controlled and TKI continued.

Continuous versus intermittent docetaxel for metastatic castration resistant prostate cancer

Abstract: Docetaxel (DTX) is a standard chemotherapeutic agent for metastatic castration resistant prostate cancer (mCRPC). However, given a number of toxicities associated with DTX, considerable debate exists regarding the optimal number of DTX cycles to be administered in this setting. In clinic, it is a usual practice to continue DTX until toxicities or disease progression precludes its administration. Therefore, we undertook a comprehensive review of the literature on intermittent versus continuous chemotherapy administration in this setting. Although there is no head-to-head comparison of these two approaches, our review discovered many studies which show that intermittent approach is a very feasible and attractive option with lower toxicities and better quality of life. Because of the availability of many newer agents that can be used post-docetaxel, stopping DTX early seems to be more appropriate with introduction of docetaxel or newer agents upon progression. This review summarizes the data from available studies regarding the feasibility and controversies of intermittent docetaxel in prostate cancer.

Antifungal prophylaxis with Amphotericin B deoxycholate emulsified in lipids for acute myeloid leukemia patients treated in low economy countries.

Abstract: Invasive fungal infection (IFI) is a common cause of morbidity and mortality in patients with acute myeloid leukemia (AML) [1,2]. Standard prophylaxis for fungal infections with fluconazole during ...

Use of donated clotting factors for surgeries on haemophilic patients in a resource-constrained country: a kind donor, good outcome, change of practice and future directions.

Abstract: nomics 2007; 25: 1007–29. 8 Polyanskaya T, Zorenko V, Karpov E, Sampiev M, Mishin G, Vasiliev D. Experience of recombinant activated factor VII usage during surgery in patients with haemophilia with inhibitors. Haemophilia 2012; 18: 997–1002. 9 Sadeghi N, Kahn D, Syed D et al. Comparative Biochemical and Functional Studies on a Branded Human Recombinant Factor VIIa and a Biosimilar Equivalent Product. Clin Appl Thromb Hemost 2014; 20: 565– 72. 10 Faranoush M, Abolghasemi H, Toogeh G et al. A comparison between recombinant activated factor VII (Aryoseven) and Novoseven in patients with congenital factor VII deficiency. Clin Appl Thromb Hemost 2015; 21: 724–8.

Inspiration amidst the challenges: the first report of successful bone marrow transplantation in the Himalayan country Nepal

Abstract: Since the first successful haematopoietic stem cell transplant (HSCT) in the late 1950s, HSCT has been established as a standard of care in many benign and malignant haematological disorders (Copelan, 2006; Appelbaum, 2007). In 2006 alone, a total of 50 417 HSCTs were performed worldwide, the majority of which were in Europe (48%) and the Americas (36%) (Gratwohl et al, 2010). Nepal, unknown to many until the recent devastating earthquake, is a small low-income country in South Asia sandwiched between India and China. The health care system of Nepal is overwhelmed with communicable diseases, such as diarrhoea, typhoid and tuberculosis. Under such circumstances, haematological disorders receive the least attention and priority from the government. The dire lack of health facilities, manpower and health insurance, the rapidly increasing cost of novel treatment, poverty, illiteracy and challenging geography frustrates even the most optimistic of physicians. Amidst those adversities and challenges, we started our first HSCT services in November 2012 [India and China started in late 1980s (Advani & Saikia, 1987; Lu et al, 1990)] through our private efforts at Nobel Hospital, Kathmandu. Between November 2012 and May 2014, five multiple myeloma (MM) patients and one patient with relapsed diffuse large B cell lymphoma (DLBCL) were eligible for autologous SCT. One MM patient had his transplant deferred due to inadequate stem cell collection. We report, for the first time, our outcomes and experiences with these five patients (four MM, one DLBCL) who underwent HSCT in Nepal. Three MM patients received bortezomib, doxorubicin and dexamethasone induction regimen while one received lenalidomide-dexamethasone. All achieved a very good partial response and were considered for HSCT. The stage IIIB DLBCL patient, who had an International Prognostic Index score of 3, opted for CHOP chemotherapy due to unaffordability of rituximab and achieved partial remission as assessed by computerized tomography. He was planned for radiotherapy but relapsed. He then received three cycles of ifosfamide, carboplatin and etoposide (ICE), achieving complete remission (CR). He was then scheduled for autologous HSCT (Table I). All MM patients were followed-up monthly. Protein electrophoresis, immunofixation electrophoresis and light chain ratio evaluation was done every 3 months. All patients achieved CR at 3 months. Three patients maintained CR at 1 year of follow-up. The DLBCL patient was followed monthly for 2 months and every 2 months thereafter. Patient was in CR for 7 months but then relapsed at 8 months posttransplant with an additional disseminated tuberculosis infection. He succumbed to infection at 9 months post-transplant. Our experience shows that HSCT services are feasible even in low-economy countries. We used standard category 1 induction regimens for our MM patients; rituximab was not given to the DLBCL patient for financial reasons. MM patients tolerated the standard conditioning regimen of melphalan although this was complicated by mucositis and febrile neutropenia, which were manageable. After 1 year of follow-up, three patients are still in CR. Our DLBCL patient relapsed immediately after completing the sixth cycle of chemotherapy and thus was a candidate for HSCT (Gugliemi et al, 1998). He achieved CR after 3 cycles of ICE and therefore we pursued HSCT. Cost is an important issue in the feasibility of HSCT in low-income countries. Autologous HSCT costs approximately

Disparities in the availability of and access to antiemetics recommended by the international antiemetic guidelines in Serbia, Japan, and Nepal.

Abstract: 117 Background: Guideline-consistent antiemetic therapy requires 4 classes of antiemetics (AEs) to be available and accessible for the optimal prevention of chemotherapy induced nausea and vomiting (CINV): serotonin3 receptor antagonists (5HT3RAs), neurokinin 1 receptor antagonists (NK1RAs), dopamine receptor antagonists (DOPRAs) and dexamethasone. To evaluate disparities in the availability and accessibility of AEs recommended by the international antiemetic guidelines for the prevention of CINV inpatients treated in governmental hospitals in Nepal (low), Serbia (upper-middle) and Japan (high-income). Methods: Availability was evaluated by the formulary availability and marketing authorization (MA) in Serbia (RS), Japan (JP) and Nepal (NP). Accessibility was assessed by the National Health Insurance Fund (NHIF) coverage in Serbia and Japan and by the affordability in Nepal. Off-label use of medications is not legitimate in Serbia and Japan. Results: Barriers are presented in Table. Serbia has no access t...

Adoptive cell therapy and modulation of the tumour microenvironment: new insights from ASCO 2016.

Abstract: Immuno-oncology has changed the landscape of cancer treatment in recent years. Immune checkpoint inhibitors (ICI) have shown survival advantage with long term remissions in a variety of cancers. However, there is another approach to harnessing the power of the immune system in combating cancer: the adoptive cell therapy (ACT) strategy. Although ACT is restricted to small specialized centres and has yet to deliver as much success as ICI, some important results were presented at this year’s ASCO meeting. Important lessons have been learned from these studies, including the prospects and challenges ahead. In this editorial, we summarize the important studies on ACT presented at the ASCO 2016 meeting and discuss the way forward.