The safety and immunogenicity of a bivalent conjugate vaccine against Salmonella enterica Typhi and Paratyphi A in healthy Indian adults: a phase 1, randomised, active-controlled, double-blind trial.

BACKGROUND: Enteric fever caused by Salmonella enterica Typhi and Salmonella Paratyphi A is an important public health problem, especially in low-income and middle-income countries with limited access to safe water and sanitation. We present results from, to our knowledge, the first ever human study of a bivalent paratyphoid A-typhoid conjugate vaccine (Sii-PTCV). METHODS: In this double-blind phase 1 study, 60 healthy Indian adults were randomly assigned (1:1) to receive a single intramuscular dose of either Sii-PTCV or typhoid conjugate vaccine (Typbar-TCV). Safety was assessed by observing solicited adverse events for 1 week, unsolicited events for 1 month, and serious adverse events (SAEs) over 6 months. Immunogenicity at 1 month and 6 months was assessed by measuring anti-capsular polysaccharide antigen Vi (anti-Vi) IgG and IgA against Salmonella Typhi and anti-lipopolysaccharide (LPS) IgG against Salmonella Paratyphi A by ELISA, and functional antibodies using serum bactericidal assay (SBA) against Salmonella Paratyphi A. This study is registered with Clinical Trial Registry-India (CTRI/2022/06/043608) and is completed. FINDINGS: 60 participants were enrolled. Of these 60 participants, 57 (95%) participants were male and three (5%) participants were female. Solicited adverse events were observed in 27 (90%) of 30 participants who received Sii-PTCV and 26 (87%) of 30 participants who received Typbar-TCV. The most common local solicited event was pain in 27 (90%) participants who received Sii-PTCV and in 23 (77%) participants who received Typbar-TCV. The most common solicited systemic event was myalgia in five (17%) participants who received Sii-PTCV, whereas four (13%) participants who received Typbar-TCV had myalgia and four (13%) had headache. No vaccine-related unsolicited adverse events or SAEs were reported. The seroconversion rates on day 29 were 96·7% (95% CI 82·8-99·9) with Sii-PTCV and 100·0% (88·4-100·0) with Typbar-TCV for anti-Vi IgG; 93·3% (77·9-99·2) with Sii-PTCV and 100·0% (88·4-100·0) with Typbar-TCV for anti-Vi IgA; 100·0% (88·4-100·0) with Sii-PTCV and 3·3% (0·1-17·2) with Typbar-TCV for anti-LPS (paratyphoid); and 93·3% (77·9-99·2) with Sii-PTCV and 0% (0·0-11·6) with Typbar-TCV for SBA titres (paratyphoid). Paratyphoid anti-LPS immune responses were sustained at day 181. INTERPRETATION: Sii-PTCV was safe and immunogenic for both typhoid and paratyphoid antigens indicating its potential for providing comprehensive protection against enteric fever. FUNDING: Serum Institute of India.

A phase I clinical study to assess safety and immunogenicity of yellow fever vaccine.

Yellow fever, a mosquito-borne flavivirus infection, is an important public health problem in Africa and Latin America. A Yellow Fever vaccine (YFV) was developed and tested in a study in India. This was a Phase I, open-label, randomized, controlled study where healthy adults received SII YFV intramuscularly (SII YFV IM), SII YFV subcutaneously (SII YFV SC) or STAMARIL® (Sanofi-Pasteur) in 1:1:1 ratio. They were followed for solicited reactions for 10 days and unsolicited events for 28 days and serious adverse events for 3 months. YF-neutralizing antibodies were measured at baseline and on Days 10, 14, 28. A total of 60 adults were enrolled in the study. The proportion of participants with solicited reactions was 10%, 40%, and 25% in SII YFV SC, SII YFV IM, and STAMARIL® arms, respectively. No causally related unsolicited events or any serious adverse event was reported. After vaccination, the seroconversion was 94.44%, 100%, and 100%, in the three arms respectively. The post-vaccination geometric mean titers were similar in the study arms. The new YFV was found safe and immunogenic by IM as well as SC routes. The vaccine can be tested in further phases of clinical studies.

Critical appraisal of published research papers - A reinforcing tool for research methodology: Questionnaire-based study.

BACKGROUND AND OBJECTIVES: Critical appraisal of published research papers is routinely conducted as a journal club (JC) activity in pharmacology departments of various medical colleges across Maharashtra, and it forms an important part of their postgraduate curriculum. The objective of this study was to evaluate the perception of pharmacology postgraduate students and teachers toward use of critical appraisal as a reinforcing tool for research methodology. Evaluation of performance of the in-house pharmacology postgraduate students in the critical appraisal activity constituted secondary objective of the study. MATERIALS AND METHODS: The study was conducted in two parts. In Part I, a cross-sectional questionnaire-based evaluation on perception toward critical appraisal activity was carried out among pharmacology postgraduate students and teachers. In Part II of the study, JC score sheets of 2nd- and 3rd-year pharmacology students over the past 4 years were evaluated. RESULTS: One hundred and twenty-seven postgraduate students and 32 teachers participated in Part I of the study. About 118 (92.9%) students and 28 (87.5%) faculties considered the critical appraisal activity to be beneficial for the students. JC score sheet assessments suggested that there was a statistically significant improvement in overall scores obtained by postgraduate students (n = 25) in their last JC as compared to the first JC. CONCLUSION: Journal article criticism is a crucial tool to develop a research attitude among postgraduate students. Participation in the JC activity led to the improvement in the skill of critical appraisal of published research articles, but this improvement was not educationally relevant.

Minocycline in Alcohol Withdrawal Induced Anxiety and Alcohol Relapse in Rats.

INTRODUCTION: Anxiety and negative sensations due to alcohol withdrawal are factors leading to alcohol relapse and addiction. Minocycline, an antibiotic, can decrease alcohol consumption in rats, however, its effects on alcohol withdrawal anxiety and relapse have not been studied. MATERIAL AND METHODS: Part 1: Forced alcohol drinking in gradually increasing concentration was administered till day 22 in rats. Effect of drugs on anxiety was assessed using elevated plus maze (EPM) and two-chambered box apparatus, after removal of alcohol. Part 2: For relapse, an alcohol deprivation effect model was used, rats were continuously offered alcohol and water for 4 consecutive weeks in a two-bottle choice paradigm, followed by 2 weeks of alcohol deprivation. Effect of drugs on alcohol consumption during the first hour of alcohol reintroduction was assessed. Animals were sacrificed and whole brain Tumor Necrosis Factor (TNF) α was estimated. RESULTS: Part 1: Anxiety at 3 hours was significantly lower following minocycline (20 mg/kg i.p.) or diazepam compared to vehicle control. Part 2: Acute administration of minocycline (5,10 and 20 mg/kg, i.p.) suppressed alcohol consumption significantly (p value<0.05) as compared to vehicle control. A significant decrease in whole brain TNF α was observed in animals treated with minocycline compared to untreated animals. CONCLUSION: Minocycline attenuates alcohol withdrawal anxiety and disrupts alcohol relapse.

Adherence of Observational Studies Published in Indian Journals to STRO BE Statement.

PURPOSE AIM: Quality of reporting is very important in medical research. To ensure a uniform and detailed reporting of observational studies experts came out with a checklist of items, named 'Strengthening the Reporting of Observational Studies in Epidemiology' (STROBE). The present study examines the adherence of observational studies published in selected Indian journals from 2011-2015 to STROBE Statement. METHOD: 7 open access Indian journals, belonging to different specialities were selected. All the observational studies were assessed by 5 independent reviewers for the adherence to STROBE checklist as 'yes, partly and no'. The completeness of reporting was also assessed. RESULTS: A total of 271 articles were examined. Only 10 items (Abstract, Background/rationale, Objectives, Study Setting, Data sources/ measurement, Quantitative variables, number of Participants at each stage, Characteristics of study participants, Key results) out of the 22 items and their subdivisions of STROBE were adhered to, in more than 70% of articles. Other 10 items (bias, subgroup analysis, addressing missing data, sensitivity analysis, reason for nonparticipation, flow diagram, missing data) had adherence in less than 30% of the articles. The completeness of reporting was 50.5%, 49.12% and 43.06% in cross sectional, cohort and case control study, respectively. CONCLUSION: The overall reporting was suboptimal. The completeness of reporting did not differ in the three types of observational study designs.

Prescription pattern and awareness of disease and treatment in patients of Parkinson's disease.

AIM: This cross-sectional study aimed to evaluate the prescription pattern, awareness of disease and treatment in patients with Parkinson's disease (PD). MATERIALS & METHODS: A total of 100 PD patients, attending a tertiary care hospital in Mumbai were included. Prescriptions were analyzed and awareness was evaluated using a questionnaire. RESULTS: The mean number of anti-Parkinson agents (APA) prescribed was 1.52 ± 0.65. Number of APA strongly correlated with disease duration (ρ = 0.818; p < 0.001). Many APA were underutilized (prescribed daily dose/defined daily dose < 1). There was no awareness of all items on symptoms and alternative therapeutic options. Awareness of disease impairments (32%), long-term complications (28%), dosing regimen (46%) and follow-up (36%) was poor. CONCLUSION: More than one APA is commonly prescribed in PD patients. Awareness of disease and treatment of PD is poor among the patients.

Drug Utilization in Neonatal Intensive Care Unit of a Tertiary-care Hospital in Mumbai, India.

OBJECTIVE: To study the prescription pattern (using applicable WHO indicators), cost analysis and off-label use of drugs in neonatal intensive care unit (NICU) of a tertiary-care hospital. METHODS: The prescriptions of 460 neonates admitted to a NICU during July 2014-March 2015 were studied prospectively. RESULTS: Of 460 neonates, 54.8% were preterm and 73% were low birth weight (LBW). The mean (SD) prescription items per neonate were 5.7 (3.6). Overall off-label use was 12.3%, while 38% neonates received at least one off-label drug. Of 326 off-label drugs, antibiotics (69.6%) followed by non-steroid anti-inflammatory drugs (7%) were commonly used. Premature and LBW babies required more drugs with higher cost and longer stay, compared to full term and normal weight babies (P<0.01), while the pattern of off-label use was similar across both these categories (P>0.05). CONCLUSION: Off-label antibiotics use was common, and prescribing practices were uniform in NICU.

Evaluation of effect of minocycline on rewarding potential and alcohol relapse in place preference model in mice.

INTRODUCTION: Medical management for alcohol abuse has limitations. Alcohol consumption activates N-methyl-d-aspartate receptors and release of nitric oxide which can be inhibited by minocycline as it readily crosses blood brain barrier and may have effect on alcohol consumption. Thus, study objective is to evaluate the effect of minocycline on rewarding property, extinction and the reinstatement phenomenon induced by alcohol in a model of conditioned place preference (CPP) in mice. METHODOLOGY: To evaluate rewarding effects of alcohol, CPP procedure consisted of 4 parts, including adaptation (day 1), pre-conditioning test (day 2), conditionings with alcohol (days 3, 5, 7 and 9) or saline (days 4, 6, 8 and 10) and postconditioning test (day 11) conducted on 11 consecutive days. The groups included were saline treated group (alcohol control), naltrexone - 1mg/kg (positive control), and minocycline in the doses of 10, 30 and 50mg/kg. To evaluate the effect of minocycline on alcohol relapse, CPP procedure consisted 6 parts, the first 4 were the same as enumerated above followed by extinction (days 12-16) and reinstatement phase (day 17). RESULTS: The time spent in alcohol paired compartment by different groups, revealed that minocycline and naltrexone significantly attenuated alcohol-induced place preference compared to alcohol control (p<0.05). Pretreatment with minocycline and naltrexone blocked reinstatement of extinguished CPP. CONCLUSION: Minocycline may have a role in attenuating the rewarding property of alcohol and prevent alcohol relapse.

A cross-sectional study to assess the incompatible dietary behavior of patients suffering from skin diseases: A pilot study.

BACKGROUND: Ayurveda implies the importance of diet and dietary habits in various human diseases. Confirmatory evidence regarding role of diet and dietary practices in diseases of skin are lacking. OBJECTIVES: To assess incompatible dietary behavior in acne, psoriasis, fungal infections, and vitiligo patients using a questionnaire tool. MATERIALS AND METHODS: A questionnaire-based, cross-sectional case control study was conducted in the skin out-patient department of a tertiary care hospital. Patients were enrolled in each diseased group and their control groups. Perception of patients regarding the role of diet in skin diseases was evaluated. Study participants were subjected to 2 validated questionnaires to assess consumption of incompatible diet and incompatible dietary habits. RESULTS: Diet was perceived to be more important in patients of acne compared to their controls (P < 0.05). Mean composite score regarding the assessment of consumption of incompatible diet of acne (19.594 ± 4.613 vs. 16.719 ± 3.457, P = 0.006) and psoriasis (17.531 ± 2.688 vs. 16.281 ± 2.630, P = 0.0497) patients was higher than their controls. Mean composite score regarding assessment of incompatible dietary habits was higher in acne (19.031 ± 4.589 vs. 15.688 ± 4.645, P = 0.0054), psoriasis (18.875 ± 5.014 vs. 15 ± 3.069, P = 0.0009), and fungal infection (16.469 ± 3.538 vs. 14.5 ± 2.627, P = 0.0115) patients compared to controls. Mean composite scores of both the questionnaires in vitiligo patients were similar to controls. CONCLUSION: Scores for consumption of incompatible diet and dietary habits were found to be higher in acne and psoriasis patients compared to controls. Patients with fungal infections had higher scores for the presence of incompatible dietary habits but similar scores for the consumption of incompatible diet, whereas both scores in patients of vitiligo were similar to controls.

Evaluation of package inserts of Ayurveda drug formulations from Mumbai city.

INTRODUCTION: Package insert (PI) is a vital document accompanying a prescribed medication to provide information to the prescriber and end-user at a glance. Studies regarding PIs of Ayurvedic medicines in accordance with standard guidelines are lacking. AIM: Present study was undertaken to evaluate PI of Ayurveda drugs. MATERIALS AND METHODS: PIs of Ayurveda drugs were obtained from five randomly selected Ayurveda medical shops located in three main zones of Mumbai. From each medical shop, a range of 15-20 PI was planned to be collected for different formulations. It was decided to collect a minimum fifty PIs/group for equitable distribution of various formulations in period of January-June2013. Checklist was prepared, and content validity was achieved. Final validated checklist contained a total of 13 items, and the presence or absence of information pertaining to these items on the PI was evaluated. Any other additional information present on PI was also noted. Each item was analyzed and expressed as percentages. RESULTS: The information on 258 PIs included: Name of ingredients (67%), quantity of ingredients (47.27%), route of administration (86.8%), dosage form (86.8%), indications (18%), dose (18%), contraindications (18%), side effects (9%), shelf life (5.81%), storage conditions (11%), and manufacturers name with contact details (34%). CONCLUSION: PIs accompanying Ayurveda medicinal products in India are deficient in information required to be furnished by them.