Patient-reported outcomes with selpercatinib treatment in patients with RET-driven cancers in the phase I/II LIBRETTO-001 trial.

BACKGROUND: This post-hoc retrospective study describes long-term patient-reported outcomes (PROs) for REarranged during Transfection (RET)-altered non-small-cell lung cancer (NSCLC), medullary thyroid cancer (MTC), non-MTC thyroid cancer (TC), and tumor agnostic (TA) patients (Data cut-off: January 2023) from the LIBRETTO-001 trial. PATIENTS AND METHODS: Patients completed the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30). Patients with MTC also completed a modified version of the Systemic Therapy-Induced Diarrhea Assessment Tool (mSTIDAT). The proportion of patients with improved, stable, or worsened status after baseline was reported. PROs were summarized at 3 years (cycle 37) post-baseline for the NSCLC and MTC cohorts, and at 2 years (cycle 25) post-baseline for the TC and TA cohorts. Time-to-event outcomes (time to first improvement or worsening and duration of improvement) were reported. RESULTS: The baseline assessment was completed by 200 (63.3%), 209 (70.8%), 50 (76.9%), and 38 (73.1%) patients in the NSCLC, MTC, TC, and TA cohorts, respectively. The total compliance rate was 80%, 82%, 70%, and 85%, respectively. Approximately 75% (NSCLC), 81% (MTC), 75% (TC), and 40% (TA) of patients across all cohorts reported improved or stable QLQ-C30 scores at year 3 (NSCLC and MTC) or year 2 (TC and TA) with continuous selpercatinib use. Across cohorts, the median time to first improvement ranged from 2.0 to 19.4 months, the median duration of improvement ranged from 1.9 to 28.2 months, and the median time to first worsening ranged from 5.6 to 44.2 months. The total compliance rate for the mSTIDAT was 83.7% and the proportion of patients with MTC who reported diarrhea on the mSTIDAT was reduced from 80.8% at baseline to 35.6% at year 3. CONCLUSIONS: A majority of patients with RET-driven cancers improved or remained stable on most QLQ-C30 domains, demonstrating favorable health-related quality of life as measured by the QLQ-C30 during long-term treatment with selpercatinib.

Factors Affecting the Utilization of Delivery Care Services in Eastern Nepal.

Background Maternal health has been the utmost priority program implemented by the Government of Nepal, popularly known as the Aama program. The achievement of sustainable development goals in 2030 underlay the utilization of maternal and health care services. Institutional delivery is one of the key focused indicators to measure the country's efficacy in delivering maternal and health care service utilization. The study was conducted in eastern Nepal focusing on the factors affecting institutional delivery. Objective To assess the relationship of demographic, socio-cultural, and socio-behavioral factors with the utilization of delivery care services and to assess factors other than demographic, socio-cultural and socio-behavioral affecting the perception towards health services, accessibility to health services, and utilization of delivery care services. Method This study was cross-sectional and descriptive. A total of 401 recently delivered women were taken for the face-to-face interview. A multistage sampling technique has been taken to select the sample household as a primary sampling unit. Ethical approval has been obtained from Nepal Health Research Council. Result In the multivariate model, education level, family type of women, perceptions and awareness about the health facilities (should a pregnant woman go for a medical check-up, and quality of service of private health institutions is better than public health institutions were found to have a significant influence on the behaviors related to institutional delivery. Conclusion Our study stated that perception of quality of care, regular access to health services, receiving a higher level of education, and living in the joint family are very important which tend to improve the other determining factors for utilization of delivery care service in eastern Nepal.

High success and low recurrence with shorter treatment regimen for multidrug-resistant TB in Nepal.

SETTING: Nine drug-resistant TB centres, some of them supported by Damien Foundation in Nepal where >80% of multidrug-resistant/rifampicin-resistant TB (MDR/RR-TB) patients are treated. OBJECTIVE: To assess the uptake, effectiveness and safety of the 9-12-month shorter treatment regimen (STR) in MDR/RR-TB patients registered from January 2018 to December 2019. DESIGN: This was a cohort study involving secondary programme data. RESULTS: Of 631 patients, 301 (48.0%) started and continued STR. Key reasons for ineligibility to start/continue STR were baseline resistance or exposure to second-line drugs (62.0%), contact with extensively drug-resistant TB (XDR-TB) or pre-XDR-TB (7.0%) patients and unavailability of STR drugs (6.0%). Treatment success was 79.6%; unsuccessful outcomes were death (12.0%), lost to follow-up (5.3%), failure (2.7%) and not evaluated (0.7%). Unsuccessful outcomes were significantly associated with HIV positivity and patient age ⩾55 years, with adjusted relative risk of respectively 2.39 (95% CI 1.52-3.77) and 3.86 (95% CI 2.30-6.46). Post-treatment recurrence at 6 and 12 months was respectively 0.5% and 2.4%. Serious adverse events (SAEs) were seen in 15.3% patients - hepatotoxicity and ototoxicity were most common. CONCLUSION: STR had a modest uptake, high treatment success and low post-treatment recurrence. For proper detection and management of SAEs, improving pharmacovigilance might be considered. Availability of rapid diagnostic test for second-line drugs is crucial for correct patient management.

CADRE: Neuf centres de traitement de la TB pharmacorésistante, dont certains sont financés par Action Damien au Népal où >80% des patients atteints de TB multirésistante/résistante à la rifampicine (MDR/RR-TB) sont traités. OBJECTIF: Évaluer l'utilisation, l'efficacité et l'innocuité d'un schéma thérapeutique plus court (STR) de 9-12 mois chez les patients atteints de MDR/RR-TB enregistrés de janvier 2018 à décembre 2019. MÉTHODE: Étude de cohorte comprenant des données programmatiques secondaires. RÉSULTATS: Sur 631 patients, 301 (48,0%) ont démarré et poursuivi un STR. Les raisons principales d'inéligibilité à l'instauration/la poursuite d'un STR étaient une résistance initiale ou une exposition aux médicaments de deuxième intention (62,0%), un contact avec des patients atteints de TB ultrarésistante (XDR-TB) ou de pré-XDR-TB (7,0%) et la non-disponibilité des médicaments pour le STR (6,0%). Le taux de réussite thérapeutique était de 79,6%. Les résultats liés à la non-réussite thérapeutique étaient décès (12,0%), perte de vue (5,3%), échec thérapeutique (2,7%) et absence d'évaluation (0,7%). Les résultats liés à la non-réussite thérapeutique étaient significativement associés à l'infection par le VIH et aux patients âgés ⩾55 ans avec un risque relatif ajusté de 2,39 (IC 95% 1,52­3,77) et de 3,86 (IC 95% 2,30­6,46), respectivement. Le taux de récidive post-traitement à 6 et 12 mois était de 0,5% et 2,4%, respectivement. Des évènements indésirables graves (SAE) ont été observés chez 15,3% des patients, le plus souvent hépatotoxicité et ototoxicité. CONCLUSION: Le STR a été associé à une utilisation modérée, à une réussite thérapeutique élevée et à un faible taux de récidive post-traitement. Pour une détection et une prise en charge adéquates des SAE, l'amélioration de la pharmacovigilance peut être envisagée. La disponibilité de tests diagnostiques rapides pour les médicaments de deuxième intention est essentielle à une prise en charge adéquate des patients.

Assessment of Short Term Cardiovascular Risk Among 40 Years and Above Population in a Selected Community of Kathmandu, Nepal.

BACKGROUND: Cardiovascular disease (CVD) risk assessment is effective for identifying whether people are at low or high risk of CVD events. It is also useful for determining the intensity of intervention. People with low risk of CVD can take more benefit by lifestyle modifications, whereas people at high risk need pharmacological intervention in addition. But, there is dearth of related study in Nepal. Therefore, this study aimed to assess short term CVD risk prediction in selected community of Kathmandu, Nepal. METHODS: We conducted a cross-sectional study in Sitapaila Village Development Committee, Kathmandu, Nepal between November 2014 and April 2015. We, first selected the household randomly to enroll 347 participants with 18 to 70 years of age, and later assessed the short term CVD risk prediction among ≥ 40 years age group using WHO/ISH chart. RESULTS: The mean age of respondents was 52 years. The majority of participants were female (58.4%), homemakers (45.2%), from Newar ethnic group (31.9%), and without formal education (42.8%). Smoking was present in 21.7% of respondents, diabetes in 19.9 %, and hypertension in 53.6%. The ≥10% CVD risk was seen in 14.6% (95% CI: 9.2, 20) of the respondents. It was significantly associated with age (p<0.001), education (p=0.027), smoking (p = 0.002), cholesterol level (p = 0.021), systolic hypertension (p <001), and diabetes (p = 0.019). CONCLUSIONS: The study population is in high risk of developing CVDs in near future. Lifestyle modifications and pharmaceutical interventions to manage the risk factors among study population are highly recommended.

Study of fasting serum lipid and lipoproteins profile in type-II diabetic patients attending NMCTH.

Dyslipidemia is one of the primary causes for cardio vascular disease (CVD) and development of myocardial infarction (MI) which often leads to coronary artery disease (CAD). The elevated level of total cholesterol (TC), triglycerides (TG), low-density lipoproteins-cholesterol (LDL-C), and lowered high-density lipoprotein-cholesterol (HDL-C) are the predictable risk factor for CAD with type-II diabetic patient. The present study was undertaken taken with an objective to frame out the lipid profile in type-II diabetic patients attending OPD (outpatient department) of Nepal Medical College Teaching Hospital (NMCTH) Jorpati, Kathmandu. Samples of 148 individuals with age varying from 30-73 were analyzed. Out of which 96 patients were diabetic and 52 were control group. The mean +/- SD (mg/dl) levels of Cholesterol, TG and LDL-C were found significantly higher compared to non-diabetic, and these are statistically significant when compared with healthy control group. The study concludes that the study of accessing fasting lipid profile in type-II diabetic will be a tool of accessing risk for cardiovascular and other coronary artery complications.

Impact evaluation of uterine prolapse surgery in Nepalese women.

BACKGROUND: The problem of uterine prolapse exists throughout Nepal and negatively affects women's health and quality of life (QOL). The Government of Nepal recognizes it as a priority problem. METHODS: This study was conducted in eight districts to examine the status and problems of women who have undergone prolapse surgery. Qualitative and quantitative methods were used to examine the issues of prolapse. Survey method was used to administer the questionnaire. RESULTS: Sixty-six percent women reported pelvic organ prolapse at an early age. The mean age of its occurrence was 28 years. In the hill/mountain districts, 52% women among the non-poor and 72% among the poor went to health camps for surgery indicating that the camps were fulfilling the demands of the poor. Majority (>75%) of them from remote districts went to health camps for surgery indicating the camps were more beneficial to women in remote areas. Counseling was weak in the health camps and the use of IEC materials was minimal. Majority had improved health status after surgery. The incidence of post-surgery problems were as follows: 10.1% in government hospitals, 11.1% in non-government hospitals and 15.1% in health camps. CONCLUSIONS: Despite improved performance of health camps, the program for prolapse management still seems weak due to lack of ownership of local health institutions and lack of proper coordination among the stakeholders/ partners. However, these camps need to be scaled up for the benefit of the unreached population.

The influence of ethnic origin on the skin photoageing: Nepalese study.

Ethnic and genetic differences modify skin structure and function. Skin photoageing is becoming one of the most studied cosmetological topics. However, there are relatively few data available to evaluate the effect of ethnic skin origin on the degree of photoageing, particularly among people inhabiting sunny and hot climate as in South Asia. Two hundred and forty participants, enrolled in the study conducted in Pokhara valley, Nepal, were classified into four different age categories viz. below 30, 30-50, 50-60 and above 60 years. Participants answered the questioner regarding their age, gender, ethnic origin, occupation, skin characteristics, lifestyle factors, type of cosmetic and skin care products used, drug treatment and personal skin condition evaluation. Skin hyperpigmentation and the degree of wrinkling, the two most important parameters related to photoageing, were particularly evaluated in two ethnic groups, namely Aryan-origin and Mongolian-origin participants. The study showed that Aryan-origin ethnic skin was more wrinkled and darker than that of Mongolian. Male skin was found to be darker than the female skin, which might be the result of the use of sun-protective cosmetic products among women. Smoking was found to increase the degree of wrinkling; however, no differences related to ethnic origin in relation to smoking were observed. This study indicates the need to further evaluate the differences in skin response to daily exposure to strong sun among various ethnic-origin inhabitants.

Association of cardiovascular risk factors in hypertensive subjects with metabolic syndrome defined by three different definitions.

INTRODUCTION: Different authorities have put forward their criteria to define metabolic syndrome (MetS). The aim of this study was to find the prevalence of MetS in hypertensive individuals by the available three different definitions from National Cholesterol Education Program (NCEP), International diabetes Federation (IDF) and WHO and their association with other cardiac risk factors. METHODS: After anthropometric measurements fasting blood was analyzed for glucose, lipids, high sensitivity C-reactive protein (hsCRP) and anti-oxidized LDL antibody in 150 hypertensive individuals. A ten-year coronary heart disease risk was predicted using the Framingham risk score (FRS). RESULTS: The prevalence of MetS was 54.7 % by NCEP, 42.0 % by IDF) and 18.7 % by WHO. As many as 63.4 % had MetS by any definition, while only 9.4 % fulfilled all the criteria of the three definitions. The association of cardiac risk factors also varied according to the definition used. hsCRP was significantly elevated in MetS compared to non-MetS. Body mass index, waist circumference and HDL-C were associated in MetS defined by NCEP and IDF. FRS was higher in MetS defined by Adult Treatment Panel and WHO definitions. An increase in urine albumin and a decrease in eGFR were associated with MetS individuals defined by WHO only. CONCLUSION: There is a wide variation in the prevalence of MetS and associated cardiac risk factors according to three different definitions used. The different cardiac risk factors among MetS also vary with the definitions used. However, hsCRP and emerging risk factor are significantly elevated in hypertensive individuals with MetS as defined by all definitions.

In-vitro assessment of cell-mediated immunity by demonstrating effector-t cells for diagnosis of tuberculosis in Nepalese subjects.

The immune response against mycobacterium tuberculosis (MTB) is cell mediated. T-cells become sensitized when they encounter MTB antigens and subsequently activated effector T-cells produce a number of cytokines including interferon- gamma (INF-gamma) to fight the infecting organisms. Demonstration of either production of INF-gamma or presence of effector T-cells sensitized to MTB specific antigens in vitro can be diagnostic for TB infection. Aim of this study was to determine the efficacy of commercially available T-SPOT.TB kit which is used for the in vitro diagnosis of TB infection and to determine if this test has any cross reactivity in leprosy patients. Blood sample was taken from 30 sputum AFB positive, 30 sputum AFB negative healthy controls and 10 cases of paucibacillary leprosy patients. The blood samples were processed to separate peripheral blood mononuclear cells. The final cell suspensions were cultured along with MTB specific antigens namely- Early Secretory Antigenic Target (ESAT-6) and Culture Filtrate Protein (CFP 10) along with negative and positive controls. The production of INF-gamma was demonstrated by enzyme linked immunospot (ELISPOT) assay technique. All AFB positive samples produced INF-gamma after exposure to MTB specific antigens. 4 (16.6%) of healthy controls were also found reactive for INF-gamma. The sensitivity and "specificity" for active disease of the ELISPOT (T-SPOT.TB) in respect to AFB microscopy was 100% and 85.7% respectively. Assessment of CMI against tuberculosis, by demonstrating effector T-cell sensitized to MTB antigens can be use to aid the diagnosis of tuberculosis. T-SPOT.TB has no cross reactivity with leprosy patients.

Use of protein: creatinine ratio in a random spot urine sample for predicting significant proteinuria in diabetes mellitus.

Present study was undertaken during a period of 6 months (September 2008-February 2009) to see an correlation of 24 hours urine protein estimation with random spot protein-creatinine (P:C) ratio among a diabetic patients. The study comprised of 144 patients aged 30-70 years, recruited from Kantipur hospital, Kathmandu. The 24-hr urine sample was collected, followed by spot random urine sample. Both samples were analyzed for protein and creatinine excretion. An informed consent was taken from all participants. Sixteen inadequately collected urine samples as defined by (predicted creatinine--measured creatinine)/predicted creatinine > 0.2 were excluded from analysis. The Spearman's rank correlation between the spot urine P:C ratio and 24-hr total protein were performed by the Statistical Package for Social Service. At the P:C ratio cutoff of 0.15 and reference method (24-hr urine protein) cutoff of 150 mg/day, the correlation coefficient was found to be 0.892 (p < 0.001). The area under ROC curve at different cutoffs was 0.88 at 95.0% CI. The sensitivity and specificity of the P:C ratio to detect significant proteinuria at the cutoff of 0.15 are 96.6% and 74.4%. So the P:C ratio can predict significant proteinuria in diabetic subjects, avoiding the inconvenient 24-hr urine collection but the cutoff should be carefully selected for different patients group under different laboratory procedures and settings.