The Pregnancy Tele-yoga Module to Combat Stress, Anxiety, and Depression Associated with Pregnancy: An Exploratory Open-label Multicentric Study.

Purpose: Untreated stress, anxiety, and depression during the perinatal period can lead to adverse maternal and infant outcomes. Yoga, the practice of body-mind-spirit techniques has been shown to reduce stress, anxiety, and depression. Aims: The aim of the study was to examine the feasibility and limited efficacy of the 4-week practice of pregnancy tele-yoga module (PTYM) delivered and monitored through an online platform. Methodology: A multicentric, open-label, exploratory study was conducted in the antenatal clinics (ANCs) of three tertiary care hospitals in India. Pregnant women between 13 and 32 weeks of gestation were invited to participate. PTYM was taught by the trained research staff. A YouTube link demonstrating the PTYM developed by the researchers was shared with consenting participants. Using the Yoga Performance Assessment (YPA), research staff monitored the online performance of the PTYM. Pre- and postintervention, women were assessed using the Depression, Anxiety, and Stress Scale-21 (DASS-21). Results: Preintervention, among 162 consented pregnant women, anxiety (62.34%) was the most common mental health condition, followed by stress (55.55%) and depression (45.67%). YPA at the end of week 1, week 2, week 3, and week 4 was 19.45, 21.35, 24.15, and 28.45, respectively. Postintervention anxiety, stress, and depression persisted in 19.78%, 11.44%, and 10.41% of women. Pregnant women with stress (DASS-21 ≥15; n = 90), anxiety (DASS-21 ≥8; n = 101), and depressive (DASS-21 ≥10; n = 74) symptoms after undergoing 4 weeks of PTYM reported significant reduction in the scores. Conclusion: The current study demonstrated the feasibility and limited efficacy of PTYM in ANCs of a tertiary care hospital in India.

Health-related quality of life and its determinants among cancer patients: evidence from 12,148 patients of Indian database.

BACKGROUND: Cancer survivors experience a decrement in health-related quality of life (HRQoL) resulting from the disease as well as adverse effects of therapy. We evaluated the HRQoL of cancer patients, stratified by primary cancer site, stage, treatment response and associated adverse events, along with its determinants. METHODS: Data were collected from 12,148 patients, sampled from seven purposively chosen leading cancer hospitals in India, to elicit HRQoL using the EuroQol questionnaire comprising of 5-dimensions and 5-levels (EQ-5D-5L). Multiple linear regression was used to determine the association between HRQoL and various socio-demographic as well as clinical characteristics. RESULTS: Majority outpatients (78.4%) and inpatients (81.2%) had solid cancers. The disease was found to be more prevalent among outpatients (37.5%) and inpatients (40.5%) aged 45-60 years and females (49.3-58.3%). Most patients were found to be in stage III (40-40.6%) or stage IV (29.4-37.3%) at the time of recruitment. The mean EQ-5D-5 L utility score was significantly higher among outpatients [0.630 (95% CI: 0.623, 0.637)] as compared to inpatients [0.553 (95% CI: 0.539, 0.567)]. The HRQoL decreased with advancing cancer stage among both inpatients and outpatients, respectively [stage IV: (0.516 & 0.557); stage III (0.609 & 0.689); stage II (0.677 & 0.713); stage I (0.638 & 0.748), p value < 0.001]. The outpatients on hormone therapy (B = 0.076) showed significantly better HRQoL in comparison to patients on chemotherapy. However, palliative care (B=-0.137) and surgery (B=-0.110) were found to be associated with significantly with poorer HRQoL paralleled to chemotherapy. The utility scores among outpatients ranged from 0.305 (bone cancer) to 0.782 (Leukemia). Among hospitalized cases, the utility score was lowest for multiple myeloma (0.255) and highest for testicular cancer (0.771). CONCLUSION: Older age, lower educational status, chemotherapy, palliative care and surgery, advanced cancer stage and progressive disease were associated with poor HRQoL. Our study findings will be useful in optimising patient care, formulating individualized treatment plan, improving compliance and follow-up.

Cost-Effectiveness of Novel Agent Regimens for Transplant-Eligible Newly Diagnosed Multiple Myeloma Patients in India.

BACKGROUND: Survival outcomes for multiple myeloma have improved dramatically since the introduction of novel therapeutic agents. While these drugs are highly effective in improving survival outcomes and quality of life in patients with multiple myeloma, they come at a significant cost. We assessed the cost-effectiveness of bortezomib-based triplet or quadruplet drug regimens in isolation and followed by autologous hematopoietic stem cell transplantation (AHSCT) for the treatment of newly diagnosed multiple myeloma (NDMM) in the Indian context. METHODS: A Markov model was developed to assess the health and economic outcomes of novel drug regimens with and without AHSCT for the treatment of NDMM in India. We estimated the lifetime quality-adjusted life-years (QALYs) and costs in each scenario. The incremental cost-effectiveness ratios (ICERs) were computed and compared against the current willingness-to-pay threshold of a one-time per capita gross domestic product of ₹146,890 (US$1,927.70) for India. Parameter uncertainty was assessed through Monte Carlo probabilistic sensitivity analysis. RESULTS: Among seven treatment sequences, the VCd (bortezomib, cyclophosphamide, dexamethasone) alone arm has the lowest cost and health benefits as compared to four treatment sequences, namely VTd (bortezomib, thalidomide, dexamethasone) alone, VRd (bortezomib, lenalidomide, dexamethasone) alone, VRd plus AHSCT and DVRd (Daratumumab, bortezomib, lenalidomide, dexamethasone) plus AHSCT. It was found that VTd plus AHSCT and VCd plus AHSCT arms were extendedly dominated (ED) by combination of two alternative treatments. Among the five non-dominated strategies, VRd has a lowest incremental cost of ₹ 2,20,093 (US$2,888) per QALY gained compared to VTd alone followed by VRd plus AHSCT [₹3,14,530 (US$4,128) per QALY gained] in comparison to VRd alone. None of the novel treatment sequences were found to be cost-effective at the current WTP threshold of ₹1,46,890 (US$1,927.7). CONCLUSION: At the current WTP threshold of one-time per capita GDP (₹ 146,890) of India, VRd alone and VRd plus AHSCT has 38.1% and 6.9% probability to be cost-effective, respectively. Reduction in current reimbursement rates of novel drugs, namely VRd, lenalidomide, and pomalidomide plus dexamethasone under national insurance program and societal cost of transplant by 50%, would make VRd plus AHSCT and VTd plus AHSCT cost-effective at an incremental cost of ₹40,671 (US$34) and ₹97,639 (US$1,281) per QALY gained, respectively.

Practical Clinical Consensus Guidelines for the Management of Cancer Associated Anemia in Low- and Middle-Income Countries.

Purvish M. ParikhCancer-associated anemia (CAA) remains a major unmet need that compromises overall survival (OS) and quality of life (QoL). Currently, available guidelines do not take into consideration the unique challenges in low- and middle-income countries (LMIC). Our CAA patients have to battle preexisting impaired nutritional status, depleted body iron stores, financial limitations, and difficulty in having easily accessible affordable healthcare. Hence, we fulfilled the need of guidelines for LMIC. A group of subject experts were put together, given background literature, met in a face-to-face discussion, voted using Delphi process, and finally agreed on the contents of this guideline document. As many as 50% of cancer patients will have significant anemia (hemoglobin < 10 g/dL) at initial diagnosis. It is most commonly seen with gastrointestinal malignancies, head and neck cancers, and acute leukemias. The hemoglobin falls further after initiation of cancer directed therapy, due to chemotherapy itself or heightened nutritional deficiency. Its evaluation should include tests for complete blood count, red blood cell morphology, reticulocyte count, Coombs test, and levels of vitamin B12 and folic acid. Iron status should be monitored using test to measure serum iron, total iron binding capacity, transferring saturation, and serum ferritin levels. A minimum of 50% of cancer patients with anemia require iron supplements. The preferred mode of therapy is with intravenous (IV) iron using ferric carboxymaltose (FCM). Most patients respond satisfactorily to single dose of 1000 mg. It is also safe and does not require use of a test dose. Significant anemia is found in at least half of all cancer patients in India, South Asian Association for Regional Cooperation region, and other LMIC countries. Its awareness among healthcare professionals will prevent it from remaining undiagnosed (in up to 70% of all cancer patients) and adversely affecting OS and QoL. The benefits of treating them with IV iron therapy are quick replenishment of iron stores, hemoglobin returning to normal, better QoL, and avoiding risk of infections/reactions with blood transfusions. Many publications have proven the value of single-dose FCM in such clinical situations. CAA has been proven to be an independent prognostic factor that adversely affects both QoL and OS in cancer patients. Use of FCM as single IV dose of 1000 mg is safe and effective in the majority of patients with CAA.

Financial toxicity of cancer treatment in India: towards closing the cancer care gap.

Background: The rising economic burden of cancer on patients is an important determinant of access to treatment initiation and adherence in India. Several publicly financed health insurance (PFHI) schemes have been launched in India, with treatment for cancer as an explicit inclusion in the health benefit packages (HBPs). Although, financial toxicity is widely acknowledged to be a potential consequence of costly cancer treatment, little is known about its prevalence and determinants among the Indian population. There is a need to determine the optimal strategy for clinicians and cancer care centers to address the issue of high costs of care in order to minimize the financial toxicity, promote access to high value care and reduce health disparities. Methods: A total of 12,148 cancer patients were recruited at seven purposively selected cancer centres in India, to assess the out-of-pocket expenditure (OOPE) and financial toxicity among cancer patients. Mean OOPE incurred for outpatient treatment and hospitalization, was estimated by cancer site, stage, type of treatment and socio-demographic characteristics. Economic impact of cancer care on household financial risk protection was assessed using standard indicators of catastrophic health expenditures (CHE) and impoverishment, along with the determinants using logistic regression. Results: Mean direct OOPE per outpatient consultation and per episode of hospitalization was estimated as ₹8,053 (US$ 101) and ₹39,085 (US$ 492) respectively. Per patient annual direct OOPE incurred on cancer treatment was estimated as ₹331,177 (US$ 4,171). Diagnostics (36.4%) and medicines (45%) are major contributors of OOPE for outpatient treatment and hospitalization, respectively. The overall prevalence of CHE and impoverishment was higher among patients seeking outpatient treatment (80.4% and 67%, respectively) than hospitalization (29.8% and 17.2%, respectively). The odds of incurring CHE was 7.4 times higher among poorer patients [Adjusted Odds Ratio (AOR): 7.414] than richest. Enrolment in PM-JAY (CHE AOR = 0.426, and impoverishment AOR = 0.395) or a state sponsored scheme (CHE AOR = 0.304 and impoverishment AOR = 0.371) resulted in a significant reduction in CHE and impoverishment for an episode of hospitalization. The prevalence of CHE and impoverishment was significantly higher with hospitalization in private hospitals and longer duration of hospital stay (p < 0.001). The extent of CHE and impoverishment due to direct costs incurred on outpatient treatment increased from 83% to 99.7% and, 63.9% to 97.1% after considering both direct and indirect costs borne by the patient and caregivers, respectively. In case of hospitalization, the extent of CHE increased from 23.6% (direct cost) to 59.4% (direct+ indirect costs) and impoverishment increased from 14.1% (direct cost) to 27% due to both direct and indirect cost of cancer treatment. Conclusion: There is high economic burden on patients and their families due to cancer treatment. The increase in population and cancer services coverage of PFHI schemes, creating prepayment mechanisms like E-RUPI for outpatient diagnostic and staging services, and strengthening public hospitals can potentially reduce the financial burden among cancer patients in India. The disaggregated OOPE estimates could be useful input for future health technology analyses to determine cost-effective treatment strategies.

Cost-Effectiveness of the First Line Treatment Options For Metastatic Renal Cell Carcinoma in India.

PURPOSE: Tyrosine kinase inhibitors such as sunitinib and pazopanib are the mainstay of treatment of metastatic renal cell carcinoma (mRCC) in India. However, pembrolizumab and nivolumab have shown significant improvement in the median progression-free survival and overall survival among patients with mRCC. In this study, we aimed to determine the cost-effectiveness of the first-line treatment options for the patients with mRCC in India. METHODS: A Markov state-transition model was used to measure the lifetime costs and health outcomes associated with sunitinib, pazopanib, pembrolizumab/lenvatinib, and nivolumab/ipilimumab among patients with first-line mRCC. Incremental cost per quality-adjusted life-year (QALY) gained with a given treatment option was compared against the next best alternative and assessed for cost-effectiveness using a willingness to pay threshold of one-time per capita gross-domestic product of India. The parameter uncertainty was analyzed using the probabilistic sensitivity analysis. RESULTS: We estimated the total lifetime cost per patient of ₹ 0.27 million ($3,706 US dollars [USD]), ₹ 0.35 million ($4,716 USD), ₹ 9.7 million ($131,858 USD), and ₹ 6.7 million ($90,481 USD) for the sunitinib, pazopanib, pembrolizumab/lenvatinib, and nivolumab/ipilimumab arms, respectively. Similarly, the mean QALYs lived per patient were 1.91, 1.86, 2.75, and 1.97, respectively. Sunitinib incurs an average cost of ₹ 143,269 ($1,939 USD) per QALY lived. Therefore, sunitinib at current reimbursement rates (₹ 10,000 per cycle) has a 94.6% probability of being cost-effective at a willingness to pay threshold of 1-time per capita gross-domestic product (₹ 168,300) in the Indian context. CONCLUSION: Our findings support the current inclusion of sunitinib under India's publicly financed health insurance scheme.

Clinical pharmacologist from the eyes of a clinical pharmacologist: a questionnaire-based survey.

INTRODUCTION: Management of a clinical condition is patient centric. Interdisciplinary coordination plays an influential role in patient management. Pharmacology deals with the study of drugs. Clinical pharmacology deals with applied aspects of pharmacology in addition to clinical research. METHODOLOGY: We set up a survey to assess the perceptions of clinical pharmacologists (CPs) regarding their roles and about clinical pharmacology courses in India. The survey was administered via a Google questionnaire sent via LinkedIn, Email, or WhatsApp to 100 CP's working in India. RESULTS: Respondents to the questionnaire were working as CPs. They were either postgraduate in pharmacology (MD pharmacology (doctor of medicine in pharmacology) 60.2%) or had a super-specialization degree in clinical pharmacology (DM clinical pharmacology (doctorate in medicine in clinical pharmacology) (34.7%)) or other pharma postgraduates. They were working in pharmaceutical companies (41.8%), hospitals (26.5%), or academic institutions (30.6%). When the responses from the respondents were stratified by qualification or experience, they showed that most of the CPs felt that the CPs played a significant role in academia, pharmaceutical organizations, hospitals, and drug regulatory bodies. CONCLUSIONS: All the CPs opined that training during the postgraduation course was not sufficient to be qualified as CP. There was no consensus among the CPs on the benefit of existing certification courses in clinical research. However, they felt that the centres offering these courses should be accredited, and the curriculum should be uniform. Respondents opined that CPs' patient management role could be improved by collaborating with clinicians and organizing workshops and conferences.

Role of ADME gene polymorphisms on imatinib disposition: results from a population pharmacokinetic study in chronic myeloid leukaemia.

PURPOSE: Imatinib is a substrate of CYP3A4, ABCB1 and ABCG2, and is known to have wide variability in pharmacokinetics (PK). At the same time, a clear relationship between drug levels and response also exists for imatinib in chronic myeloid leukaemia (CML). Therefore, pharmacogenetic-based dosing of imatinib is an attractive proposition. This study aims to characterize the population pharmacokinetics of imatinib in order to identify significant covariates including pharmacogenetic variants. METHODS: Forty-nine patients with CML were enrolled in the study after being on imatinib for at least 4 consecutive weeks. Steady-state pharmacokinetic sampling was performed either in a sparse (4 samples each, n = 44) or intensive manner (9 samples each, n = 5). An additional pharmacogenetic sample was also collected from all patients. Plasma imatinib levels were estimated using a validated HPLC method. Pharmacogenetic variants were identified using the PharmacoScan array platform. Population pharmacokinetic analysis was carried out using NONMEM v7.2. Seven SNPs within CYP3A4, ABCB1 and ABCG2 genes were evaluated for covariate effect on the clearance of imatinib. RESULTS: Imatinib PK was well characterized using a one-compartment model with zero-order absorption. The clearance and volume of distribution were found to be 10.2 L/h and 389 L respectively. Only SNP rs1128503 of the ABCB1 gene had a small but insignificant effect on imatinib clearance, with a 25% reduction in clearance observed in patients carrying the polymorphism. Twenty-three out of forty-nine patients (47%) carried the polymorphic allele, of whom 17 were heterozygous and six were homozygous. CONCLUSION: Our study conclusively proves that genetic polymorphisms in the CYP3A4 and ABC family of transporters do not have any role in the personalized dosing of imatinib in CML.

Cost Effectiveness of Ribociclib and Palbociclib in the Second-Line Treatment of Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer in Post-Menopausal Indian Women.

BACKGROUND: In this study, we evaluate the cost and outcomes of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) plus fulvestrant, fulvestrant alone, and conventional chemotherapy as the second-line therapy for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC) in India. METHODS: Using a Markov model, the clinical effectiveness of managing HR+, HER2- MBC in postmenopausal women with either a CDK4/6i (either ribociclib or palbociclib) and fulvestrant, fulvestrant alone, and chemotherapy (single-agent paclitaxel or capecitabine) was measured in terms of quality-adjusted life-years (QALYs). The costs were estimated from two different points of view: scenario I, as per the prevailing market prices of the drugs; and scenario II, as per the reimbursement rates set up by the publicly financed national health insurance scheme. Incremental cost per QALY gained with a given treatment option was compared against the next best alternative and was assessed for cost effectiveness using a threshold of 1-time the per capita gross domestic product (GDP) in India from a societal perspective. RESULTS: In scenario I, an MBC patient was found to incur a lifetime cost of Indian Rupees (₹) 2.54 million ($34,644), ₹2.53 million ($34,496), ₹512,598 ($6,984), ₹326,026 ($4,442) and ₹237,115 ($3,230) for the ribociclib and palbociclib combination arms, fulvestrant monotherapy, single-agent paclitaxel and the single-agent capecitabine treatment arms, respectively. The lifetime cost for CDK4/6i (ribociclib and palbociclib) combination therapy, fulvestrant monotherapy, paclitaxel, and capecitabine arms was estimated to be ₹1.94 million ($26,459), ₹1.92 million ($26,220), ₹315,387 ($4,296), ₹187,392 ($2,553) and ₹153,263 ($2,088), respectively, in scenario II. The mean QALYs lived per MBC patient with CDK4/6i (either ribociclib or palbociclib) combination therapy, fulvestrant, paclitaxel and capecitabine were estimated to be 1.4, 1.0, 0.9 and 0.7, respectively. None of the treatment arms are cost effective at current prices and reimbursement rates at a threshold of 1-time the per capita GDP of India. However, a 78% reduction in the current market price or a 72% reduction in the reimbursement rate of fulvestrant in the government-funded insurance program will make it a cost-effective treatment option for HR+, HER2- MBC patients in India. CONCLUSION: CDK4/6i (ribociclib and palbociclib) therapy is not a cost-effective treatment option for MBC patients. A 72% reduction in the reimbursement rate for fulvestrant monotherapy will make it a cost-effective treatment option in the Indian context.

Concurrent chemoradiation and brachytherapy alone or in combination with nelfinavir in locally advanced cervical cancer (NELCER): study protocol for a phase III trial.

INTRODUCTION: In locally advanced cervical cancer, nodal, local and distant relapse continue to be significant patterns of relapse. Therefore, strategies to improve the efficacy of chemoradiation are desirable such as biological pathway modifiers and immunomodulating agents. This trial will investigate the impact of nelfinavir, a protease inhibitor that targets the protein kinase B (AKT) pathway on disease-free survival (DFS). METHODS AND ANALYSIS: Radiosensitising effect of nelfinavir in locally advanced carcinoma of cervix is a single-centre, open-label, parallel-group, 1:1 randomised phase-III study. Patients aged over 18 years with a diagnosis of carcinoma cervix stage III are eligible for the study. After consenting, patients will undergo randomisation to chemoradiation and brachytherapy arm or nelfinavir with chemoradiation and brachytherapy arm. The primary aim of the study is to compare the difference in 3-year DFS between the two arms. Secondary aims are locoregional control, overall survival, toxicity and quality of life between the two arms. Pharmacokinetics of nelfinavir and its impact on tumour AKT, programmed cell death ligand 1, cluster of differentiation 4, cluster of differentiation 8 and natural killer 1.1 expression will be investigated. The overall sample size of 348 with 1 planned interim analysis achieves 80% power at a 0.05 significance level to detect a HR of 0.66 when the proportion surviving in the control arm is 0.65. The planned study duration is 8 years. ETHICS AND DISSEMINATION: The trial is approved by the Institutional Ethics Committee-I of Tata Memorial Hospital, Mumbai (reference number: IEC/0317/1543/001) and will be monitored by the data safety monitoring committee. The study results will be disseminated via peer-reviewed scientific journals, and conference presentations. Study participants will be accrued after obtaining written informed consent from them. The confidentiality and privacy of study participants will be maintained. TRIAL REGISTRATION NUMBER: The trial is registered with Clinical Trials Registry-India (CTRI/2017/08/009265) and ClinicalTrials.gov (NCT03256916).

Cost Effectiveness of Bevacizumab Plus Chemotherapy for the Treatment of Advanced and Metastatic Cervical Cancer in India-A Model-Based Economic Analysis.

PURPOSE: Patients with advanced and metastatic cervical cancer have a poor prognosis with a 1-year survival rate of 10%-15%. Recently, an antiangiogenic humanized monoclonal antibody bevacizumab has shown to improve the survival of these patients. This study was designed to assess the cost effectiveness of incorporating bevacizumab with standard chemotherapy for the treatment of patients with advanced and metastatic cervical cancer in India. METHODS: Using a disaggregated societal perspective and lifetime horizon, a Markov model was developed for estimating the costs and health outcomes in a hypothetical cohort of 1,000 patients with advanced and metastatic cervical cancer treated with either standard chemotherapy alone or in combination with bevacizumab. Effectiveness data for each of the treatment regimen were assessed using estimates from Gynecologic Oncology Group 240 trial. Data on disease-specific mortality in metastatic cervical cancer, health system cost, and out-of-pocket expenditure were derived from Indian literature. Multivariable probabilistic sensitivity analysis was undertaken to account for parameter uncertainty. RESULTS: Over the lifetime of one patient with advanced and metastatic cervical cancer, bevacizumab along with standard chemotherapy results in a gain of 0.275 (0.052-0.469) life-years (LY) and 0.129 (0.032-0.218) quality-adjusted life-years (QALY), at an additional cost of $3,816 US dollars (USD; 2,513-5,571) compared with standard chemotherapy alone. This resulted in an incremental cost of $19,080 USD (7,230-52,434) per LY gained and $34,744 USD (15,782-94,914) per QALY gained with the use of bevacizumab plus standard chemotherapy. CONCLUSION: Addition of bevacizumab to the standard chemotherapy is not cost effective for the treatment of advanced and metastatic cervical cancer in India at a threshold of 1-time per-capita gross domestic product.

Dose dependent slurred speech and laryngopharyngeal dysesthesia due to oxaliplatin.

INTRODUCTION: Oxaliplatin is a platinum containing alkylating agent commonly used in the management of colorectal cancers. The most common dose-limiting toxicity of oxaliplatin is peripheral neuropathy, which can be severe enough to cause treatment discontinuation. We present a case of dysarthria and laryngopharyngeal dysesthesia (LPD) that developed during the first dose of oxaliplatin, which showed dose-dependent reduction in severity in subsequent cycles. CASE REPORT: A 52-year-old female patient with adenocarcinoma of rectum (pT4N2M0) was prescribed oxaliplatin (130 mg/m2) and capecitabine(2000mg/m2). She developed heaviness in the tongue, slurred speech, jaw pain, perioral paresthesia within 30 min after the end of 3 h infusion of oxaliplatin in the first cycle. The symptoms subsided without any sequelae in two days. However, in the subsequent cycles as the dose of the oxaliplatin was reduced, similar symptoms reappeared but were of reduced in severity. No dysesthesia symptoms were observed in the 4th cycle when the oxaliplatin was administered at 85 mg/m2. MANAGEMENT AND OUTCOME: As and when the patient developed symptoms - slurred speech, jaw pain during the first three cycles, she was managed with inj. Hydrocortisone (100 mg i.v.) and one ampoule of pheniramine (45 mg i.v.). DISCUSSION: Occurrence of laryngopharyngeal dysesthesia due to oxaliplatin does not warrant drug withdrawal, dose titration can be helpful, thereby preventing the drug withdrawal for the patient management.

Effect of the Pandemic on Quality-of-Life Data Collection in Prostate Cancer Patients.

PURPOSE: To understand the difficulties that happen during the quality of life (QoL) data collection in a pandemic and provide measures to overcome them. METHODS: We analyzed the recruitment and follow-up data of patients in one of our ongoing study whose aim was to collect the Adverse drug reactions and QoL (at regular intervals) in prostate cancer patients who were on docetaxel. Before the pandemic, we could enroll 31 patients in the study over four months. We analyzed the difficulties experienced by these patients and consultants in collecting QoL data during the pandemic, especially in situations with limited availability of resources and also where the patients are not technologically advanced. RESULTS: Due to the pandemic, we could not recruit a single new patient into the study. Complete QoL assessments were available in only two patients, and the disease progressed in five patients. QoL assessment was not possible in 19 of 31 enrolled patients. More than 44% of the enrolled patients had difficulty commuting to the hospital despite transport services to hospitals. Due to the risk of acquiring COVID19 infection during traveling to the hospital, follow-ups were affected. CONCLUSION: There should be increased support for novel technologies that can successfully capture and transfer patients' QoL data to the treating consultant.

Yoga Program for Type 2 Diabetes Prevention (YOGA-DP) Among High-Risk People: Qualitative Study to Explore Reasons for Non-participation in a Feasibility Randomized Controlled Trial in India.

Background: Yoga-based interventions can be effective in preventing type 2 diabetes mellitus (T2DM). We developed a Yoga program for T2DM prevention (YOGA-DP) among high-risk people and conducted a feasibility randomized controlled trial (RCT) in India. The objective of this study was to identify and explore why potential participants declined to participate in the feasibility RCT. Methods: An exploratory qualitative study, using semi-structured interviews, was conducted at a Yoga center in New Delhi, India. Fourteen people (10 women and four men) who declined to participate in the feasibility RCT were interviewed, and 13 of them completed the non-participant questionnaire, which captured their socio-demographics, diets, physical activities, and reasons for declining. Results: Three types of barriers were identified and explored which prevented participation in the feasibility RCT: (1) personal barriers, such as lack of time, perceived sufficiency of knowledge, preferences about self-management of health, and trust in other traditional and alternative therapies; (2) contextual barriers, such as social influences and lack of awareness about preventive care; and (3) study-related barriers, such as lack of study information, poor accessibility to the Yoga site, and lack of trust in the study methods and intervention. Conclusions: We identified and explored personal, contextual, and study-related barriers to participation in a feasibility RCT in India. The findings will help to address recruitment challenges in future Yoga and other RCTs. Clinical Trial Registration:www.ClinicalTrials.gov, identifier: CTRI/2019/05/018893.

Development of National Cancer Database for Cost and Quality of Life (CaDCQoL) in India: a protocol.

INTRODUCTION: The rising economic burden of cancer on healthcare system and patients in India has led to the increased demand for evidence in order to inform policy decisions such as drug price regulation, setting reimbursement package rates under publicly financed health insurance schemes and prioritising available resources to maximise value of investments in health. Economic evaluations are an integral component of this important evidence. Lack of existing evidence on healthcare costs and health-related quality of life (HRQOL) makes conducting economic evaluations a very challenging task. Therefore, it is imperative to develop a national database for health expenditure and HRQOL for cancer. METHODS AND ANALYSIS: The present study proposes to develop a National Cancer Database for Cost and Quality of Life (CaDCQoL) in India. The healthcare costs will be estimated using a patient perspective. A cross-sectional study will be conducted to assess the direct out-of-pocket expenditure (OOPE), indirect cost and HRQOL among cancer patients who will be recruited at seven leading cancer centres from six states in India. Mean OOPE and HRQOL scores will be estimated by cancer site, stage of disease and type of treatment. Economic impact of cancer care on household financial risk protection will be assessed by estimating prevalence of catastrophic health expenditures and impoverishment. The national database would serve as a unique open access data repository to derive estimates of cancer-related OOPE and HRQOL. These estimates would be useful in conducting future cost-effectiveness analyses of management strategies for value-based cancer care. ETHICS AND DISSEMINATION: Approval was granted by Institutional Ethics Committee vide letter no. PGI/IEC-03/2020-1565 of Post Graduate Institute of Medical Education and Research, Chandigarh, India. The study results will be published in peer-reviewed journals and presented to the policymakers at national level.

Validation of a novel causality assessment scale for adverse events in non-small cell lung carcinoma patients treated with platinum and pemetrexed doublet chemotherapy.

AIM: Accurate causality assessment (CA) of adverse events (AEs) is important in clinical research and routine clinical practice. The Naranjo scale (NS) used for CA lacks specificity, leading to a high rate of false positive causal associations. NS is a simple scale for CA; however, its limitations have reduced its popularity in favour of other scales. We therefore attempted to improvise the algorithm by addressing specific lacunae in NS. METHODS: We attempted to modify the existing NS by (a) changing the weightage given to certain responses, (b) achieving higher resolution to certain responses for delineating drug related and unrelated AEs and (c) modifying the slabs for classification of association as 'likely' and 'unlikely'. The new scale, named as the Sharma-Nookala-Gota (SNG) algorithm, was evaluated in a training set of 19 AEs in a tertiary care cancer hospital in western India, and further validated in a set of 104 AEs. Consensus of four physician opinion was taken as gold standard for comparison. RESULTS: Of the 19 AEs in the training set, 6 were described by the treating physician as 'not related' and 13 as related to the drug. The SNG algorithm had 100% concordance with physician opinion, whereas the NS had only 73.7% concordance. NS showed a tendency to misclassify AEs as 'related' when they were indeed 'not related'. In the validation set of 104 AEs, NS and SNG algorithms misclassified 30 and 2 AEs, respectively, leading to a concordance of 70.2% and 98.1%, respectively, with physician opinion. CONCLUSION: Decisive modifications of the NS resulted in the SNG scale, with superior specificity while retaining sensitivity against the gold standard. PLAIN LANGUAGE SUMMARY: SNG algorithm - A novel tool for causality assessment of adverse drug reactions Adverse events (AEs) can cause increased morbidity, hospitalisation, and even death. Hence it is essential to recognise AEs and to establish their correct causal relationship to a drug. Many causality assessment methods, scales and algorithms are available to assess the relationship between an AE and a drug. The Naranjo algorithm is most commonly employed in spite of its many drawbacks as it is simple to use. Concerns have been raised regarding the performance of the scale, and researchers have tried to answer them, but none of them could address all issues satisfactorily. We too experienced many problems while using it in our routine clinical practice and in clinical trials. For instance, the Naranjo scale is non-specific and shows a bias toward implicating the drug as the causal factor for AEs. This improper assessment has often led to drug discontinuation, thereby compromising the efficacy of treatment. Hence, we modified the existing Naranjo scale to a new one (the Sharma-Nookala-Gota - SNG algorithm) to address these shortcomings. We piloted the SNG causality assessment algorithm in patients suffering from AEs due to various drugs. The SNG algorithm was found to have good concordance with the physicians' assessment of causality. As a next step, we validated the SNG algorithm in patients receiving a standard drug combination of pemetrexed and carboplatin for lung cancer combination. Out of the 104 AEs observed in 65 patients, the SNG causality assessment algorithm showed good concordance (except in two cases) with the physicians' decision of causality assessment, while the Naranjo algorithm was not so successful. Hence, the SNG algorithm can be a better guide for causality assessment of AEs.

Van der Waals contacted MoOx staked ZnO/GaN vertical heterostructured ultraviolet light emitting diodes.

Since the discovery of two dimensional (2D) materials, there has been a gold rush for van der Waals integrated 2D material heterostructure based optoelectronic devices. Van der Waals integration involves the physical assembly of the components of the device. In the present work, we extended van der Waals integration from 2D materials to three-dimensional (3D) materials, and herein we uniquely designed a van der Waals contacted light emitting diode based on MoOx staked ZnO/GaN heterostructure. The presence of the MoOx layer between n-type ZnO and p-type GaN leads to the confinement of electrons and an increase in the electron charge density at n-type ZnO. The n-type MoOx, a well-known hole injection layer, favors the availability of holes at the ZnO site, leading to the efficient recombination of electrons and holes at the ZnO site, which results in predominant high-intensity UV-EL emission around 380 nm in both forward and reverse bias.

Randomized, Parallel Group, Open-Label Bioequivalence Trial of Intramuscular Pegaspargase in Patients With Relapsed Acute Lymphoblastic Leukemia.

PURPOSE: Pegylated asparaginase is comparatively safer than native asparaginase in the management of acute lymphoblastic leukemia (ALL). However, the high price and nonavailability in low- and middle-income countries limits its use. In 2014, the first generic of pegaspargase (Hamsyl) was approved in India for use as a second-line treatment option for ALL. The aim of this study was to assess whether the generic pegaspargase (the test product) was bioequivalent with the reference product (Oncaspar). PATIENTS AND METHODS: This study was an open-label, parallel-group, comparative pharmacokinetic study in pediatric patients with relapsed ALL receiving their first dose (1,000 IU/m2) of pegaspargase administered intramuscularly. Patients were randomly assigned 1-to-1 to either the test or the reference product. The 2 formulations were considered equivalent if the 90% CIs for area under the plasma asparaginase activity-time curve (AUC0-t) geometric mean test-to-reference ratio was within 75% to 133%. RESULTS: Twenty-nine patients (6-18 years of age) were enrolled in this study, of whom 24 completed the study criteria and were considered for safety analysis (5 patients were ineligible for the assessment). Three patients were excluded from analysis, because of presence of anti-asparaginase antibodies, leaving 21 patients who were considered for bioequivalence pharmacokinetics data. The point estimate of AUC0-t for the test-to-reference ratio was 95.05 (90% CI, 75.07% to 120.33%). Maximum plasma concentration, trough concentrations (day 14), half-life, volume of distribution, drug clearance, and changes in the asparagine and glutamine levels were not significantly different between products. Adverse events were comparable in both groups. CONCLUSION: Generic and reference pegaspargase had equivalent pharmacokinetics with comparable safety. This could be a safe and cost-effective alternative for patients with ALL, especially in low- and middle-income countries.

Clinical pharmacokinetics of 3-h extended infusion of meropenem in adult patients with severe sepsis and septic shock: implications for empirical therapy against Gram-negative bacteria.

BACKGROUND: Optimal anti-bacterial activity of meropenem requires maintenance of its plasma concentration (Cp) above the minimum inhibitory concentration (MIC) of the pathogen for at least 40% of the dosing interval (fT > MIC > 40). We aimed to determine whether a 3-h extended infusion (EI) of meropenem achieves fT > MIC > 40 on the first and third days of therapy in patients with severe sepsis or septic shock. We also simulated the performance of the EI with respect to other pharmacokinetic (PK) targets such as fT > 4 × MIC > 40, fT > MIC = 100, and fT > 4 × MIC = 100. METHODS: Arterial blood samples of 25 adults with severe sepsis or septic shock receiving meropenem 1000 mg as a 3-h EI eight hourly (Q8H) were obtained at various intervals during and after the first and seventh doses. Plasma meropenem concentrations were determined using a reverse-phase high-performance liquid chromatography assay, followed by modeling and simulation of PK data. European Committee on Antimicrobial Susceptibility Testing (EUCAST) definitions of MIC breakpoints for sensitive and resistant Gram-negative bacteria were used. RESULTS: A 3-h EI of meropenem 1000 mg Q8H achieved fT > 2 µg/mL > 40 on the first and third days, providing activity against sensitive strains of Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter baumannii. However, it failed to achieve fT > 4 µg/mL > 40 to provide activity against strains susceptible to increased exposure in 33.3 and 39.1% patients on the first and the third days, respectively. Modeling and simulation showed that a bolus dose of 500 mg followed by 3-h EI of meropenem 1500 mg Q8H will achieve this target. A bolus of 500 mg followed by an infusion of 2000 mg would be required to achieve fT > 8 µg > 40. Targets of fT > 4 µg/mL = 100 and fT > 8 µg/mL = 100 may be achievable in two-thirds of patients by increasing the frequency of dosing to six hourly (Q6H). CONCLUSIONS: In patients with severe sepsis or septic shock, EI of 1000 mg of meropenem over 3 h administered Q8H is inadequate to provide activity (fT > 4 µg/mL > 40) against strains susceptible to increased exposure, which requires a bolus of 500 mg followed by EI of 1500 mg Q8H. While fT > 8 µg/mL > 40 require escalation of EI dose, fT > 4 µg/mL = 100 and fT > 8 µg/mL = 100 require escalation of both EI dose and frequency.