Prevalence, Attributes, and Risk Factors of QT-Interval-Prolonging Drugs and Potential Drug-Drug Interactions in Cancer Patients: A Prospective Study in a Tertiary Care Hospital.

Introduction Cancer chemotherapy regimens include multiple classes of adjuvant drugs as supportive therapy. Because of the concurrent intake of other drugs (like antiemetics, antidepressants, analgesics, and antimicrobials), there is a heightened risk for possible QT interval prolongation. There is a dearth of evidence in the literature regarding the usage of QT-prolonging anticancer drugs and associated risk factors that have the propensity to prolong QT interval. The purpose was to explore the extent of the use of QT-interval-prolonging drugs and potential QT-prolonging drug-drug interactions (QT-DDIs) in cancer patients attending OPD in a tertiary-care hospital. Methods This was a hospital-based, cross-sectional, observational study. Risk stratification of QT-prolonging drugs for torsades de pointes (TdP) was done by the Arizona Center for Education and Research on Therapeutics (AzCERT)/CredibleMeds-lists, and potential QT-DDIs were determined with four online DDI-checker-software. Results In 1331 cancer patients, the overall prevalence of potential QT-prolonging drug utilization was 97.3%. Ondansetron, pantoprazole, domperidone, and olanzapine were the most frequent QT-prolonging drugs in cancer patients. The top six antineoplastics with potential QT-prolonging and torsadogenic actions were capecitabine, oxaliplatin, imatinib, bortezomib, 5-fluorouracil, and bendamustine. Evidence-based pragmatic QTc interval prolongation risk assessment tools are imperative for cancer patients. Conclusion This study revealed a high prevalence of QT-prolonging drugs and QT-DDIs among cancer patients who are treated with anticancer and non-anticancer drugs. As a result, it's critical to take precautions, stay vigilant, and avoid QT-prolonging in clinical situations. Evidence-based pragmatic QTc interval prolongation risk assessment tools are needed for cancer patients.

Safety and efficacy of Vitamin D3 supplementation with Imatinib in Chronic Phase- Chronic Myeloid Leukaemia: an Exploratory Randomized Controlled Trial.

OBJECTIVES: The study aimed to compare early molecular response (EMR) rates at 3 months of imatinib therapy with and without vitamin D3 supplementation in patients newly diagnosed with chronic-phase chronic myeloid leukaemia (CML-CP). The secondary objective was to assess the effects of vitamin D3 on complete haematological response (CHR) and its safety. DESIGN: Double-blind, placebo-controlled, exploratory randomised trial. SETTING: Tertiary care hospital in northern India. PARTICIPANTS: Treatment-naive patients with chronic phase chronic myeloid leukaemia (n=62) aged >12 years were recruited from January 2020 to January 2021. Patients with progressive disease, pregnancy and hypercalcaemia were excluded. INTERVENTION: Oral vitamin D3 supplementation (60 000 IU) or matched placebo was given once weekly for an initial 8 weeks along with imatinib after randomisation with 1:1 allocation ratio. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was to compare EMR (defined as BCR-ABL1 transcript level ≤10%, international scale) at 3 months. The secondary outcomes were to compare effect of the intervention on CHR, correlation of 25(OH)2D3 levels with treatment response and safety according to Common Terminology Criteria for Adverse Events (CTCAE) version 5. RESULTS: At baseline, 14.5% of the patients had normal vitamin D3 levels. EMR at 3 months was attained in 24 patients (82.7%) of the vitamin D3 group and 21 (75%) of the placebo group (OR 1.6, 95% CI 0.37 to 7.37, p=0.4). A significant difference in vitamin D3 levels from baseline to the end of study was observed. Patients with vitamin D3 supplementation did not achieve higher CHR in comparison with placebo (OR 1.3, 95% CI 0.25 to 7.23, p=1.0). Vitamin D3 levels were not significantly correlated with BCR-ABL1 levels. No dose-limiting toxicities were observed. CONCLUSION: Vitamin D3 levels were low among patients with CML-CP in this study. Vitamin D3 supplementation with imatinib therapy did not have significant effect on EMR or CHR. Further clinical trials could be undertaken to assess the effective dosage and duration of vitamin D3 supplementation in these patients. TRIAL REGISTRATION NUMBER: CTRI/2019/09/021164.

Tenofovir-based first-line regimen in newly diagnosed HIV-patients: An experience from a Tertiary Care Hospital in India.

Introduction: India has a huge burden of HIV/AIDS infection. Tenofovir-based first-line therapy is the preferred treatment for newly diagnosed cases of HIV infection. Materials and Methods: The present prospective study was done among newly diagnosed cases of HIV infection. The patients were followed up for 6 months from the day of enrollment. Sociodemographic parameters, CD4 counts, and adverse drug reactions (ADRs) were analyzed at baseline and after 6 months. Bivariate and multivariate logistic regression was performed with the occurrence of ADRs as outcome variable. Results: In this study, 67 patients were enrolled with a mean age of 32.75 (±14.39) years. Mean CD4 count at the start of treatment was 241.5/mm3. The mean difference in CD4 count was 383.05/mm3 (standard deviation = 274.9). Dizziness, tingling, numbness of extremities, and muscle cramps were the most common adverse effects. On multivariate logistic regression, the occurrence of ADRs was seen to be significantly higher only in illiterate patients. Conclusion: The present study highlights the importance of long-term follow-up of the patients on antiretroviral therapy. Adequate monitoring of the treatment parameters is of utmost importance.

Morbidity Profile and Healthcare Service Utilization Pattern Among Geriatric Population in the Rural Himalayan Region of Uttarakhand, India: A Cross-Sectional Study.

OBJECTIVES: The increasing elderly population, along with their health problems, is a matter of concern, especially in the difficult terrains of the hilly Himalayan region of northern India. Hence, the present study was conducted to assess the healthcare-seeking behavior of the elderly and adherence to medication. METHODS: The present community-based cross-sectional study was conducted on 250 elderly participants by a consecutive sampling method. Data were collected during the months of July 2021 to October 2021 after obtaining institutional ethical clearance. Bivariate logistic regression was done to assess factors associated with healthcare services utilization patterns and adherence to medications in chronic diseases. Significant factors were then analyzed with a multivariate logistic regression model. Variables with p-value <0.05 on multivariate analysis were considered statistically significant. RESULTS: The mean age of the study participants was 67.2 (±8.09) years, and 52% were males. Chronic illness was diagnosed in 45.6% participants. Only 121 (48.4%) participants were aware of health insurance schemes among whom 95 (38%) were registered. Appropriate healthcare-seeking behavior for acute illness episodes was seen in 68.9% of participants. A government healthcare facility was the most preferred facility. Low adherence to chronic disease medication was seen in 41.2%. Participants registered under any health insurance scheme had higher adherence to medications (OR=0.36; 95% CI, 0.15-0.86; p-value=0.02). CONCLUSIONS: The majority of the participants preferred government healthcare facilities. Registration under any health insurance scheme was found to significantly influence adherence to medications. Further qualitative studies can be of paramount importance in understanding the perspectives of the geriatric population in the study area.

Association of Serum Hepcidin With Preeclampsia: A Systematic Review and Meta-Analysis.

The objective of the present systematic review and meta-analysis was to compare the levels of serum hepcidin in women who developed pre-eclampsia with those who did not. The databases PubMed, Embase, Scopus, Cochrane, and references of retrieved articles published till September 2020 were searched with no language restriction. Mean differences in iron regulating protein (hepcidin) were compared using a random-effects model based on the level of heterogeneity. A total of 760 individuals were included in the analysis from seven studies. The pooled estimate showed that mean hepcidin levels were significantly higher in women who developed pre-eclampsia [0.3 ng/ml, 95% confidence interval (CI): 0.01-0.59, p=0.003] as compared to women who did not develop pre-eclampsia. Further research can be done to assess the levels of various iron parameters in different trimesters of pregnancy and their association with pre-eclampsia.

A prospective study to evaluate antimicrobial prescribing pattern among admitted patients in hilly Himalayan region of northern India.

BACKGROUND AND AIM: Global scenario of antimicrobial (AM) utilization depicts 20-50% inappropriateness. Majority of the hospital admissions are due to unwanted effects because of non-judicial usage of these drugs. The present study focuses on utilization pattern of antimicrobials (AMs) in a tertiary care hospital in northern India. MATERIALS AND METHODS: A prospective observational study was conducted over a period of one year in seven departments of a tertiary care hospital in hilly Himalayan region. Aim of the study was to analyze the AM utilization pattern using World Health Organization (WHO) indicators and instruments. RESULTS: A total 700 prescriptions were analyzed in the present study. Injectable antibiotics (71%) followed by oral (29%) were most commonly prescribed. Beta lactams (79%) were the most frequently used antibiotic class. Most commonly prescribed AM was Ceftriaxone (30%). Majority of the time AMs were given empirically (44.8%), where most common indication was respiratory infections (42%). Culture and sensitivity tests were done for guiding curative therapy in 34.71% cases. The average duration of patient hospital stay was 8.81 days in the study population. The mean duration of prescribed antimicrobial treatment was 5.12 days. On an average 1.93 AMs were prescribed per patient. AMs were prescribed by International nonproprietary name (INN) in 62.19% of the admissions. The most common AM related adverse drug reaction was gastritis (96%) and skin rash (4%) with Amoxicillin + clavulanic acid being the most common causative agent. Total antimicrobial consumption was 148.24 DDD/100 bed days with Medicine department showing the highest consumption (36.25/100 bed days). CONCLUSION: The present study is the first and largest antimicrobial utilization study in the hilly Himalayan region of northern India. Our study found an urgent need for improvement of prescribing patterns, patient care indicators and strict adherence to standard guidelines.

Frequency of anemia and micronutrient deficiency among children with cleft lip and palate: a single-center cross-sectional study from Uttarakhand, India.

BACKGROUND: Children with cleft lip and/or palate can be undernourished due to feeding difficulties after birth. A vicious cycle ensues where malnutrition and low body weight precludes the child from having the corrective surgery, in the absence of which the child fails to gain weight. This study aimed to identify the proportion of malnutrition, including the deficiency of major micronutrients, namely iron, folate and vitamin B12, in children with cleft lip and/or palate and thus help in finding out what nutritional interventions can improve the scenario for these children. METHODS: All children less than 5 years with cleft lip and/or cleft palate attending our institute were included. On their first visit, following were recorded: demographic data, assessment of malnutrition, investigations: complete blood count and peripheral blood film examination; serum albumin, ferritin, iron, folate, and vitamin B12 levels. RESULTS: Eighty-one children with cleft lip and/or palate were included. Mean age was 25.37± 21.49 months (range, 3-60 months). In 53% of children suffered from moderate to severe wasting, according to World Health Organization (WHO) classification. Iron deficiency state was found in 91.6% of children. In 35.80% of children had vitamin B12 deficiency and 23.45% had folate deficiency. No correlation was found between iron deficiency and the type of deformity. CONCLUSION: Iron deficiency state is almost universally present in children with cleft lip and palate. Thus, iron and folic acid supplementation should be given at first contact to improve iron reserve and hematological parameters for optimum and safe surgery.

Drug related adverse pregnancy outcomes at a tertiary care hospital from the foothills of Himalayas: A Prospective observational study.

CONTEXT AND AIM: Safety of drug usage during pregnancy is of utmost importance. Unrestricted usage of drugs may lead to undesirable and unpredictable pregnancy outcomes. This study was designed to detect drug-related adverse pregnancy outcomes, perform prescription audit and develop a pregnancy drug registry. METHODS AND MATERIALS: A prospective observational study was conducted at a tertiary care hospital in northern India. Pregnant females attending antenatal clinic, irrespective of their duration of pregnancy were included in the study over a period of 1 year. The participants were followed up monthly during their pregnancy till the pregnancy outcome. Adverse pregnancy outcomes were evaluated and causality assessment was done using the WHO-UMC scale. STATISTICAL ANALYSIS: Descriptive and inferential statistical tools were used for appropriate variables. Regression model was used to establish relationship between factors proposed to be responsible for adverse pregnancy outcomes. Presence of adverse pregnancy outcome was used as an independent variable. Microsoft Excel and Strata (version 12) were used for statistical analysis. RESULTS: A total 326 pregnant women were screened out of which 305 were included in the final analysis. Mean age of participants was 27.82 (±4.51) years. Pre-existing comorbidities were present in 4.26% of participants. Average number of drugs per participant was 6.32 (±1.94). Most drugs prescribed to participants were from FDA category B (49.23%) and category A (33.60%). Mean ADR reported per patient was 1.16 (±1.18) with involvement of musculoskeletal (56.42%) and gastrointestinal (7.16%) being most frequent. Adverse pregnancy outcomes were reported in 25 participants among which IUGR (24%) followed by IUD (20%) and ectopic pregnancy (16%) were most frequently observed. Multivariate logistic regression showed number of comorbidities (P = 0.037) and number of drugs consumed during pregnancy (P = 0.02) to be statistically significantly associated with occurrence of adverse pregnancy outcome. CONCLUSIONS: Pregnancy registries have been instrumental in detection of signals for further research in drug-related adverse outcomes. Inappropriate usage of drugs has been shown to be associated with adverse pregnancy outcomes. Our study warrants need for further well-designed studies on adverse pregnancy outcomes in larger patient populations.

Safety and efficacy of antiviral combination therapy in symptomatic patients of Covid-19 infection - a randomised controlled trial (SEV-COVID Trial): A structured summary of a study protocol for a randomized controlled trial.

OBJECTIVES: 1. To compare the safety and efficacy of Hydroxychloroquine with Ribavirin and standard treatment in patients with non-severe COVID-19 infection 2. To compare the safety and efficacy of standard treatment, Lopinavir-ritonavir with Ribavarin, and Hydroxychloroquine with Ribavirin in patients with severe COVID-19 infection TRIAL DESIGN: The study is an Open label, Parallel arm design, stratified randomised controlled trial. Patients will be categorised as non-severe or severe based on predefined criteria. Those who satisfy all inclusion criteria and no exclusion criteria in the respective categories, will be randomly assigned to one of the three treatment groups in a ratio of 1:1 in the non-severe category and 1:1:1 in the severe category. PARTICIPANTS: The trial will be undertaken in a tertiary care center of the country where both Covid and non-Covid patients are getting treated. All patients who are confirmed positive and admitted will be screened for the eligibility criteria and will be enrolled in the study after a written informed consent. Patients will be categorised as non-severe or severe based on predefined criteria. INCLUSION CRITERIA (ALL REQUIRED): 1. Age ≥18 years at time of participation in the study 2. Laboratory (RT-PCR) confirmed infection with SARS-CoV-2 3. Symptomatic (severe or non-severe) Covid-19 disease 4. Willingness of study participant to accept randomization to any assigned treatment arm EXCLUSION CRITERIA: 1. Use of medications that are contraindicated with Lopinavir/Ritonavir, Hydroxychloroquine/Chloroquine, or Ribavirin and that cannot be replaced or stopped 2. Patient already on antiretroviral therapy with Lopinavir-Ritonavir based regimen or on Hydroxychloroquine/Chloroquine or on Ribavirin 3. Any known contraindication to test drugs such as retinopathy and QT prolongation 4. Known allergic reaction or inability to take orally of Lopinavir-ritonavir, Hydroxychloroquine/ Chloroquine, Ribavarin 5. Pregnant or breastfeeding females 6. Receipt of any experimental treatment for 2019-nCoV (off-label, compassionate use, or trial related) within 30 days prior to participation in the present study or want to participate after enrolment INTERVENTION AND COMPARATOR: Two therapeutic interventions for non-severe category and three for severe category as described below NON-SEVERE TREATMENT ARMS (NS-GROUP): Treatment Arm Drug A Standard Treatment (STNS) B Hydroxychloroquine 400 mg twice on first day followed by 400 mg per oral daily for 10 days + Ribavirin (1.2 g orally as a loading dose followed by 600mg orally every 12 hours) for 10 days + Standard Treatment (STNS) Standard Treatment for non-severe cases (STNS): Strict Isolation, Standard Precautions (Hand hygiene, Cough Etiquette, Wear surgical mask), Hydration, Proper Nutrition, Supportive Pharmacotherapy (Antipyretic, Antiallergic, Cough Suppressant), Treatment of Comorbid Diseases, Oseltamivir (75 mg BD) for patients who are tested positive for H1N1. SEVERE GROUP TREATMENT ARMS (S-GROUP): Treatment Arm Drug A Standard Treatment (STs) B Hydroxychloroquine 400mg BD on day1 followed by 400 mg once daily + Ribavirin (1.2 g orally as a loading dose followed by 600mg orally every 12 hours) for 10 days + Standard Treatment (STs) C Lopinavir(200mg) + Ritonavir (50mg) two tablets twice daily+ Ribavirin (1.2g orally as a loading dose followed by 600mg orally every 12 hours) for 10 days + Standard Treatment (STs)6 Standard Treatment for severe patients (STs): Strict Isolation, Standard Precautions (Hand hygiene, Cough Etiquette, Wear surgical mask), Fluid Therapy, Supportive Pharmacotherapy (Antipyretic, Antiallergic, Cough Suppressant), Oxygen supplementation (As required), Invasive ventilation (As required), Antibiotic agents for other associated infections (according to 2019 ATS/IDSA guidelines for non-ICU and ICU patients), Vasopressor support, Renal-replacement therapy, Treatment of Comorbid Diseases, Oseltamivir (75 mg BD) for patients who are tested positive for H1N1. MAIN OUTCOMES: Primary endpoints: (1) Time to Clinical recovery (TTCR) defined as the time (in hours) from initiation of study treatment (active or placebo) until normalisation of fever, respiratory rate, oxygen saturation, and alleviation of cough, sustained for at least 72 hours. (2) Time to SARS-CoV-2 RT-PCR negative in upper respiratory tract specimen, time to laboratory recovery of each organ involvement. Secondary Endpoints: All causes mortality, Frequency of respiratory progression (defined as SPO2≤ 94% on room air or PaO2/FiO2 <300mmHg and requirement for supplemental oxygen or more advanced ventilator support), time to defervescence (in those with fever at enrolment), frequency of requirement for supplemental oxygen or non-invasive ventilation, frequency of requirement for mechanical ventilation, frequency of serious adverse events as per DAIDS table grade of severity. Outcomes are monitored for 28 days from the time of enrolment into the study OR until the patient is discharged or death whichever is longer. RANDOMIZATION: The randomization will be done using a secured central computer-based randomization using a secure website using a central, computer-based randomisation program in a ratio of 1:1 in the non-severe category and 1:1:1 in the severe category. BLINDING (MASKING): This is an open labelled study i.e. Study assigned treatment will be known to the research team, the investigators and participants. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Since it is an exploratory trial as COVID-19 being a new disease, all patients who came under the purview of the inclusion criteria within the study period (5 months duration of the recruitment period of the total 6 months duration of the study i.e. from the month of June, 2020 to October 2020) and who have consented for the study will be included. TRIAL STATUS: Protocol version:1.0 Recruitment start: June 3rd, 2020 (Ongoing) Recruitment finish (expected): October 31st, 2020 TRIAL REGISTRATION: Clinical Trial Registry of India (CTRI): CTRI/2020/06/025575 . Registration on 03 June 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this letter serves as a summary of the key elements of the full protocol.

COVID-19 and tuberculosis co-infection: a neglected paradigm.

COVID-19 has been affecting mankind round the globe. The incidence of this infectious disease of respiratory origin is constantly on rise. Another infectious disease widely prevalent is tuberculosis (TB). During past corona virus pandemics of Severe Acute Respiratory Syndrome and Middle East Respiratory Syndrome, coinfection with TB was seen. We present this review as the co-infection of COVID-19 with TB has not been assessed yet, imposing a greater global threat. We suggest few measures to be implemented without delay for effectively screening the suspects of co-infection and also follow up of non-suspect patients in the post-pandemic phase.

A study of adherence to antiretroviral therapy in a tertiary care hospital at Allahabad, India.

INTRODUCTION: India has a large proportion of the global HIV-infected patients. Antiretroviral therapy (ART) is the cornerstone of HIV treatment. Antiretroviral drugs are highly toxic and lead to diverse adverse drug reactions (ADRs). Adherence to medications plays a prominent role in success of the therapy. This prospective study was done to study the adherence and analyze its associated factors. METHODOLOGY: The present study was conducted at ART Centre, Swarup Rani Hospital, Allahabad, Uttar Pradesh, India. Selection of the patients was done based on systematic random sampling method. Baseline enrollment was done over 2 months and follow-up was done monthly over 6 months. Information regarding sociodemographic profile, ART regimen, occurrence of ADRs, adherence to ART and factors affecting adherence was collected. Bivariate logistic regression was done to analyze the association of selected variables with adherence. RESULTS: This study enrolled 163 participants among which 152 participants completed the study. During the study period, 94 participants reported the occurrence of at least one ADR. Nonadherence to ART therapy was seen in 31.6% of patients. The most common reason was forgetting to take the medicine (21.8%) followed by occurrence of ADRs (18.3%). No statistically significant association of nonadherence was found with the selected variables. CONCLUSION: Comprehensive research to assess nonadherence to ART therapy is the need of the hour. Policy formulations ought to be made to assess and promote effective adherence to enhance the longevity and quality of life of people living with HIV/AIDS. Concerted efforts by government and intersectoral collaboration are further needed to sustain promotive measures.