Efficacy and Safety of Fezolinetant for the Treatment of Menopause-Associated Vasomotor Symptoms: A Meta-analysis.

OBJECTIVE: To evaluate the efficacy and adverse events of fezolinetant for treating vasomotor symptoms (VMS) of menopause. DATA SOURCES: PubMed/MEDLINE, ClinicalTrials.gov , EMBASE, Cochrane Database, Scopus, and WHO International Clinical Trials Registry Platform were searched through June 2023 for publications and randomized controlled trials on fezolinetant compared with placebo in menopausal women who experienced moderate-to-severe VMS. METHODS OF STUDY SELECTION: Our literature search identified 330 articles, of which five studies with six reports were included in our meta-analysis per our eligibility criteria. TABULATION, INTEGRATION, AND RESULTS: The risk of bias was evaluated using Cochrane's RoB 2 (Risk of Bias version 2) tool, quality of evidence was graded using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach, and outcome measures data for effect size were pooled in random-effects model and rated. A total of 2,168 participants from five randomized clinical trials (six reports) were included. Fezolinetant significantly lowered VMS frequency, with pooled mean difference of 2.62 (95% CI, 1.84-3.41). The pooled mean difference for fezolinetant compared with placebo for the MENQOL (Menopause-Specific Quality of Life) measure was -0.60 (95% CI, -0.92 to -0.28), and the mean percentage improvement in VMS frequency was 22.51% (95% CI, 15.35-29.67). Fezolinetant was associated with improvement in sleep quality when compared with placebo. CONCLUSION: Fezolinetant is effective in lowering moderate-to-severe VMS frequency and sleep disturbances in postmenopausal women. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42023427616.

Comparison of efficacy between levonorgestrel intrauterine system and dienogest in adenomyosis: a randomized clinical trial.

Background: Medical management of adenomyosis is an emerging perspective in modern gynecology. Though levonorgestrel intrauterine system (LNG-IUS) and dienogest (DNG) effectively relieve symptoms in adenomyosis, neither has been approved for the same indication. Our study aims to compare the efficacy and safety of these progestins in treating adenomyosis. Objective: To study the efficacy and safety of LNG-IUS versus DNG in patients with symptomatic adenomyosis. Design: Open-labeled, parallel, single-centered, randomized clinical trial. Methods: Patients with adenomyosis-associated pain with or without abnormal uterine bleeding were randomly allocated to either LNG-IUS group or DNG group. The primary outcome was a reduction in painful symptoms after 12 weeks of treatment measured by visual analog scale (VAS) score. Changes in menstrual blood loss (MBL), improvement in quality of life (QoL), and adverse drug reactions were also analyzed. Results: The VAS score significantly decreased from baseline in both groups. The baseline and post-treatment VAS scores in the LNG-IUS group were 6.41 ± 1.07 and 3.41 ± 1.04 (p = <0.001) and in the DNG group, were 6.41 ± 0.95 and 3.12 ± 1.40 (p = <0.001), respectively. A significantly greater proportion of patients in the LNG-IUS group experienced lighter MBL as compared to the DNG group [27/30 (90%) in the LNG-IUS group versus 17/22 (77.2%) in the DNG group (p = 0.006)]. Both the groups had improvement in QOL scores calculated by the World Heath Organisation QOL scale (WHOQOL BREF) questionnaire; however, it was more pronounced in the DNG group [(28.76 ± 30.47 in the LNG-IUS group versus 48.26 ± 44.91 in the DNG group (p = 0.04)]. Both the agents were safe as there were no reported major adverse drug reactions. Conclusion: DNG can be an effective and safe alternative to LNG-IUS for the medical management of adenomyosis. Trial registration: The trial was prospectively registered at the clinical trial registry - India (CTRI) vide CTRI number CTRI/2020/05/025186.

Comparison of effectiveness and safety of Mirena (LNG-IUS) with dienogest for treatment of adenomyosis Adenomyosis is a condition affecting women, typically aged 40­50, but its incidence is rising in younger women, impacting fertility. It causes painful symptoms like dysmenorrhea, dyspareunia, chronic pelvic pain, and heavy menstrual bleeding. Managing symptoms is crucial, and medical approaches include levonorgestrel intrauterine system (LNG-IUS) and dienogest (DNG). LNG-IUS is reversible contraception, approved for eight years, effectively treating symptoms. DNG, a newer progestin, is effective for endometriosis, but evidence for adenomyosis is limited. This single-center, open-label randomized clinical trial compared LNG-IUS and DNG in treating adenomyosis. Women over 20 with pelvic pain were diagnosed using ultrasound and met specific criteria. After informed consent, participants were assigned randomly to LNG-IUS or DNG groups. Treatment outcomes, including pelvic pain, quality of life (QoL), and adverse effects, were assessed over 12 weeks. Out of 84 assessed, 74 women were recruited, with 34 in each group analyzed. After 12 weeks, both groups showed significantly reduced pelvic pain (VAS scores), but no significant difference was found between the groups. LNG-IUS resulted in a significantly greater reduction in heavy menstrual bleeding (HMB), whereas DNG showed better improvement in overall QOL. Adverse effects were similar in both groups, with hot flushes reported in the DNG group. This study is one of the few comparing LNG-IUS and DNG for adenomyosis, finding both effective for symptom relief. Although LNG-IUS was superior in reducing HMB, DNG showed better overall improvement in QoL. Safety profiles were similar. Previous studies support the efficacy of DNG in reducing adenomyosis symptoms. To conclude, both LNG-IUS and DNG effectively alleviate adenomyosis symptoms, with LNG-IUS superior in reducing heavy menstrual bleeding and DNG showing better overall improvement in QOL. DNG is a viable and effective alternative to LNG-IUS.

Comparison of the efficacies of triple, quadruple and sequential antibiotic therapy in eradicating Helicobacter pylori infection: A randomized controlled trial.

BACKGROUND AND AIM: There is regional variation in the eradication rates of Helicobacter pylori (H. pylori) regimens depending on the local antibiotic resistance patterns. The aim of this study was to compare the efficacies of triple, quadruple and sequential antibiotic therapy in eradicating H. pylori infection. METHODS: A total of 296 H. pylori-positive patients were randomized to receive one of the three regimens (triple, quadruple or sequential antibiotic therapy) and eradication rate was assessed by H. pylori stool antigen test. RESULTS: The eradication rates of standard triple therapy, sequential therapy and quadruple therapy were 93%, 92.9% and 96.4%, respectively (p = 0.57). CONCLUSION: Fourteen days of standard triple therapy, 14 days of bismuth-based quadruple therapy and 10 days of sequential therapy are equally efficacious in eradicating H. pylori and all regimens have optimum H. pylori eradication rates. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: CTRI/2020/04/024929.

Comparison of oral triclofos and intranasal midazolam and dexmedetomidine for sedation in children undergoing magnetic resonance imaging (MRI): an open-label, three-arm, randomized trial.

The purpose of this study was to compare the efficacy of oral triclofos (TRI), intranasal midazolam (INM), and intranasal dexmedetomidine (IND) in achieving successful sedation in children undergoing MRI. This open-label, three-arm, randomized trial was conducted in a tertiary care teaching hospital over 18-month period. Children scheduled for MRI were enrolled. Rate of successful/adequate sedation was assessed using the Paediatric Sedation State Scale (PSSS). The primary outcome was the efficacy (successful sedation or sedation rate) of the three drugs. One-hundred and ninety-five children were included for the MRI procedure. IND was found to be superior in terms of achieving successful sedation. INM had a shorter onset and duration of sedation compared to IND and TRI, but with an increased failure rate (88.3%). Keeping INM as the reference group, it was found that the odds of sedation increased 4.1 times on changing from INM to IND (p < 0.01), and 2.26 times on changing from INM to TRI (p < 0.01). Adverse events included nasal discomfort (18.3%) in INM group; and self-limited tachycardia (4.6%) and hypotension (10.8%) in the IND group. CONCLUSION: IND was more efficacious than INM or TRI for procedural sedation in children undergoing MRI without any significant adverse events. CLINICAL TRIAL REGISTRATION: CTRI/2019/01/017257; date registered: 25/01/2019. WHAT IS KNOWN: • Oral triclofos (TRI) and intranasal midazolam (INM) have been used for procedural sedation in children undergoing MRI with variable success; but the experience with intranasal dexmedetomidine (IND) is limited. WHAT IS NEW: • IND provides more effective sedation compared to INM or TRI for procedural sedation in children undergoing MRI, without any significant adverse events.

Awareness, attitude, and practice of materiovigilance among medical professionals at a tertiary care institute of national importance: A cross-sectional study.

Background: Medical faculty and residents have a key role in the reporting of adverse events associated with medical devices. However, at present, there are no published data regarding their knowledge, attitude, and practice about materiovigilance in India. Materials and Methods: This was a cross-sectional questionnaire-based survey done among medical faculty and residents of a tertiary care institution of national importance. The questionnaire consists of 15 questions pertaining to knowledge, attitude, and practice of materiovigilance. Results: The questionnaire was administered to 138 medical faculty and residents, out of which 105 responded constituting a 76% response rate. The mean knowledge score of medical faculty and residents was 2.09 ± 1.06 and 2.07 ± 1.02, respectively, and the difference between the two groups was not statistically significant (P = 0.9). The majority of the participants (92.63%) believed that medical device can cause adverse events; however, very few of them (20.13%) have reported it during their practice. Conclusion: Requisite knowledge and appropriate attitude are essential for developing healthy practice toward reporting of adverse events associated with medical devices. Our study revealed that the knowledge gap exists among medical professionals about the reporting of adverse events and the materiovigilance program. A continuous effort is required to make them aware of the materiovigilance by conducting various training programs such as continuous medical education and workshops by the coordinators of the medical device adverse events monitoring center.

Adverse events following immunization of COVID-19 (Covaxin) vaccine at a tertiary care center of India.

The study aimed to assess the adverse events following COVID-19 vaccine (Covaxin) immunization at a tertiary care institution and also assess the predictors of the adverse events following immunization (AEFI). The prospective observational study was conducted in a tertiary care institute among the Covaxin beneficiaries between June 28 and September 6, 2021. A total of 1826 participants were assessed for any local or systemic adverse events after seven days of vaccination. A telephonic interview was conducted, and the beneficiaries were assessed according to the adverse event grading. A total of 1826 participants were assessed for AEFI, and 544 (29.8%) reported at least one of the AEFI. No severe adverse events were reported, and about 1.6% had moderate AEFI. Pain at the injection site (14.6%), fever (9.7%), and myalgia (5.9%) were the common adverse events reported by the participants. AEFI incidence was higher in the first dose (38.1%) when compared to the second dose (26.4%), and this finding was significant with a p < 0.001. The major factors associated with AEFI were female sex, history of an allergic reaction, presence of comorbidities, acute infection in the past 3 months, and intake of chronic medications. Precaution needs to be taken while vaccinating individuals having allergies, comorbidities, acute infection in the last 3 months, and individuals on chronic medication.

Comparison of Clinical Outcome between Dexamethasone and Methyl Prednisolone in Treatment of Moderate to Severe COVID-19: A Systematic Review and Meta-Analysis.

OBJECTIVE: Though systemic corticosteroid is used for treatment of COVID 19, questions regarding the appropriate dose, duration and type of corticosteroid use still remain unanswered. This study aimed to address, whether choice of systemic corticosteroid significantly influences the clinical outcome of COVID 19 patients. MATERIALS AND METHODS: Studies reporting the comparison between clinical outcome of dexamethasone and methylprednisolone in treatment of COVID 19 were searched from inception till April, 2021. Random-effect model was used. Odd's ratio (OR) and 95% confidence interval was expressed. I2 statistics used for test of heterogeneity. RESULT: Three studies with 373 patients (160 in dexamethasone group and 213 in methyl prednisolone group) were included. Though, statistically significant reduction in all-cause mortality with methyl prednisolone group in comparison to dexamethasone group (OR=1.80, 95%CI: 1.08 to 3.01, P=0.02) estimated, sub group analysis of observational studies did not support the finding (OR=1.60, 95% CI: 0.88 to 2.92, P=0.12). No significant difference in terms of need for invasive ventilator or intensive care unit (ICU) between the 2 groups. The grade of evidence was very low for both the outcomes. Conclusion and Relevance: In the present context, both dexamethasone and methyl prednisolone are equally effective in the management of COVID 19.

Oral Azithromycin Versus Doxycycline in the Treatment of Children With Uncomplicated Scrub Typhus: A Randomized Controlled Trial.

OBJECTIVES: To compare the efficacy of azithromycin versus doxycycline in treatment of children with uncomplicated scrub typhus in terms of percentage of children who attained remission of fever after 72 hours of administration of first dose of the study drug, mean time taken to attain fever defervescence, normalization of laboratory parameters, resolution of hepatosplenomegaly and lymphadenopathy. DESIGN: Interventional, open-labeled randomized controlled trial. STUDY METHODS: Patients admitted with undifferentiated fever in the In-Patient Department (IPD), Department of Paediatrics, All India Institute of Medical Sciences, Bhubaneswar, India, as per the inclusion criteria were randomized and was treated with azithromycin at 10 mg/kg/d in one group and doxycycline at 4.4 mg/kg/d for 5 days in the other group and was assessed based on the primary and secondary objectives. RESULTS: There was no statistically significant difference between the percentage of children who attained remission of fever after 72 hours of administration of azithromycin (98.2%) and doxycycline (96.5%) (P value 0.47) and the average time taken for fever defervescence (azithromycin: 24.53 hours; doxycycline: 25.82 hours; P value 0.36). The odds of attaining fever remission in the doxycycline group as compared with the azithromycin group was 1.01 (95% confidence interval -0.60 to -1.71), which was also statistically not significant. There was less incidence of adverse drug events in the azithromycin group (1.78%) as compared with the doxycycline group (8.6%), which was statistically significant (P value 0.02). CONCLUSION: Azithromycin is equally efficacious in terms of fever defervescence, resolution of clinical signs and laboratory parameters as doxycycline, is safer and better tolerated in children.

Efficacy and safety of abrocitinib for the treatment of moderate-to-severe atopic dermatitis: a meta-analysis of randomized clinical trials.

BACKGROUND: Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disorder. Though corticosteroids are the cornerstone of therapy, the Janus kinase inhibitor abrocitinib has shown promise in recent clinical trials for the treatment of AD. OBJECTIVE: To assess the overall efficacy and safety of abrocitinib in moderate to severe AD. METHODS: All randomized controlled trials (RCTs) evaluating the efficacy and safety of abrocitinib in moderate to severe AD were included in the meta-analysis. RESULTS: The pooled analysis revealed a significant proportion of patients achieving Investigator's Global Assessment (IGA) response (RR = 3.52, 95% CI; 2.78-4.46, p < .00001), Eczema Area and Severity Index (EASI) response (RR = 3.35, 95% CI; 2.54-4.41, p < .00001), and Peak Pruritus Numerical Rating Score (PP-NRS) response (RR = 2.54,95% CI; 1.95-3.30, p < .00001) in abrocitinib arm compared to the placebo arm. Moreover, the pooled analysis also suggested that treatment-emergent adverse events (TAEs) were relatively higher with abrocitinib than placebo (R.R. = 1.17; 95% CI; 1.06-1.29, p = .002). CONCLUSIONS: This meta-analysis showed that abrocitinib had a significant beneficial effect and tolerable adverse effect profile in patients of AD. Dose regimens of 200 and 100 mg seemed to have similar benefits. However, long-term trials are needed for corroboration.Key pointsAbrocitinib is emerging as a potential treatment option for moderate to severe atopic dermatitis.The pooled analysis from 4 RCTs demonstrated significant effectiveness of abrocitinib in both physician and patient-reported outcomes like IGA, EASI, and PP-NRS. The drug was also well-tolerated across the trials.The number needed to treat (NNT) for all efficacy outcomes was low suggesting clinically desirable benefits with the use of abrocitinib. Trial registration: Review registration number PROSPERO database: CRD42021255634.

Diagnostic utility of Ga-68 DOTA-SSTR and F-18 FDG PET/CT in the detection of culprit tumours causing osteomalacia: a systematic review and meta-analysis.

BACKGROUND: Tumour-induced osteomalacia (TIO) or oncogenic osteomalacia is a rare variant of paraneoplastic syndrome secondary to a small benign phosphaturic mesenchymal tumour that secretes phosphaturic substances. Complete tumour excision is often curative. However, the localization of these offending tumours has always remained a challenge because of their small size, slow-growing nature, and presence in atypical locations. We performed a systemic review and meta-analysis on the sensitivity and specificity of F-18 FDG PET/CT and Ga-68 DOTA-SSTR PET/CT to detect tumours causing osteomalacia. METHODS: Pub Med, SCOPUS, the Cochrane Library and Web of Science were searched for articles on F-18 FDG and Ga-68 DOTA-SSTR PET/CT in the detection of culprit tumours in TIO till September 2020. Both retrospective and prospective studies having three or more patients were included. The methodological quality of included studies was assessed using the Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies-2 checklist. A random-effect model was used for the statistical pooling of sensitivity and specificity. Pooled data were presented with 95% confidence intervals (95% CI) and displayed using Forest plots. Heterogeneity was expressed using the I2 statistic. RESULTS: The pooled sensitivity of Ga-68 DOTA-SSTR PET/CT in detecting the culprit tumour derived from all included studies is 86% (95% CI: 79-91%). There is moderate statistical heterogeneity among the included studies (I2 = 72.7%). The pooled sensitivity of F-18 FDG PET/CT in detecting the offending tumour derived from all included studies is 73% (95% CI: 61-84%) with moderate statistical heterogeneity among the included studies (I2 = 45.4%). CONCLUSION: In the detection of offending tumours in TIO, Ga-68 DOTA-SSTR PET/CT has better sensitivity than F-18 FDG PET/CT and should be used as first-line imaging modality due to very high sensitivity.

Role of ivermectin in the prevention of SARS-CoV-2 infection among healthcare workers in India: A matched case-control study.

BACKGROUND: Ivermectin is one among several potential drugs explored for its therapeutic and preventive role in SARS-CoV-2 infection. The study was aimed to explore the association between ivermectin prophylaxis and the development of SARS-CoV-2 infection among healthcare workers. METHODS: A hospital-based matched case-control study was conducted among healthcare workers of AIIMS Bhubaneswar, India, from September to October 2020. Profession, gender, age and date of diagnosis were matched for 186 case-control pairs. Cases and controls were healthcare workers who tested positive and negative, respectively, for COVID-19 by RT-PCR. Exposure was defined as the intake of ivermectin and/or hydroxychloroquine and/or vitamin-C and/or other prophylaxis for COVID-19. Data collection and entry was done in Epicollect5, and analysis was performed using STATA version 13. Conditional logistic regression models were used to describe the associated factors for SARS-CoV-2 infection. RESULTS: Ivermectin prophylaxis was taken by 76 controls and 41 cases. Two-dose ivermectin prophylaxis (AOR 0.27, 95% CI, 0.15-0.51) was associated with a 73% reduction of SARS-CoV-2 infection among healthcare workers for the following month. Those involved in physical activity (AOR 3.06 95% CI, 1.18-7.93) for more than an hour/day were more likely to contract SARS-CoV-2 infection. Type of household, COVID duty, single-dose ivermectin prophylaxis, vitamin-C prophylaxis and hydroxychloroquine prophylaxis were not associated with SARS-CoV-2 infection. CONCLUSION: Two-dose ivermectin prophylaxis at a dose of 300 µg/kg with a gap of 72 hours was associated with a 73% reduction of SARS-CoV-2 infection among healthcare workers for the following month. Chemoprophylaxis has relevance in the containment of pandemic.

Therapeutic potential of ivermectin as add on treatment in COVID 19: A systematic review and meta-analysis.

The current management of COVID-19 is mostly limited to general supportive care and symptomatic treatment. Ivermectin is a broad-spectrum anti-parasitic drug used widely for the treatment of onchocerciasis and lymphatic filariasis. Apart from its anti-parasitic effect it also exhibits antiviral activity against a number of viruses both in vitro and in vivo. Hence, we conducted this systematic review and meta-analysis to assess the currently available data on the therapeutic potential of ivermectin for the treatment of COVID-19 as add on therapy. A total of 629 patients were included in the 4 studies and all were COVID-19 RT-PCR positive. Among them, 397 patients received ivermectin along with usual therapy. The random effect model showed the overall pooled OR to be 0.53 (95%CI: 0.29 to0.96) for the primary outcome (all-cause mortality) which was statistically significant (P=0.04). Similarly, the random effect model revealed that adding ivermectin led to significant clinical improvement compared to usual therapy (OR=1.98, 95% CI: 1.11 to 3.53, P=0.02).  However, this should be inferred cautiously as the quality of evidence is very low. Currently, many clinical trials are on-going, and definitive evidence for repurposing this drug for COVID-19 patients will emerge only in the future.

Effectiveness of Convalescent Plasma Therapy in the Treatment of Moderate to Severe COVID 19 Patients: A Systematic Review and Meta-Analysis.

Though Convalescent plasma therapy (CPT) is being used for management of COVID-19, the evidence is still equivocal. So, we carried out this study to evaluate the currently available data to provide evidence about CPT in COVD-19 patients. RCTs and observational studies with sample size with more than 5 were included in the analysis. Out of 196 studies, 12 studies were selected for systematic review and meta-analysis was carried out for 6 studies having a control arm. For dichotomous values, risk ratio (RR) and 95% confidence interval was expressed. MAIN OUTCOMES: All-cause mortality, clinical improvement by day 7 and viral detection by day 7 were the defined outcome measures before starting of data extraction. RESULT: For 6 studies (2 RCTs and 4 observational studies) with 474 patients, the overall pooled RR for all-cause mortality was 0.61 (95%CI: 0.37 to 0.99. P= 0.04). Only RCTs and only observational studies for all-cause mortality showed pooled RR of 0.60 (95% CI: 0.33 to 1.10, P=0.10) and 0.48 (95% CI: 0.17 to 1.36, P= 0.17) respectively. There was risk of bias in the studies due to randomization process and confounding. Sensitivity analysis was carried out only for observational studies. The overall pooled RR for clinical improvement by day 7 and viral detection by day 7 were 1.12 (95%CI: 0.96 to 1.31, P=0.16) and 0.19 (95%CI: 0.09 to 0.60, P < 0.0001). CONCLUSION AND RELEVANCE: Though the review suggests modest utility of CPT in reducing all-cause mortality, improving clinical outcome, and early viral clearance, it should be interpreted cautiously.

Factors most influencing antibiotic stewardship program and comparison of prefinal- and final-year undergraduate medical students.

BACKGROUND: As future practitioners, undergraduate medical students have a key role in the antimicrobial stewardship program (ASP). However, at present, there are not much data about their knowledge and perception of antibiotic resistance and ASP. METHODS: This was a cross-sectional questionnaire-based survey administered to the prefinal- and final-year undergraduate medical students of a tertiary care institution. RESULTS: One hundred and ninety-seven students participated in our study constituting 70% response rate. The mean difference in knowledge score between prefinal- and final-year students was 0.77 (95% confidence interval: 0.30-1.24, P = 0.0016). Thirty-seven (39.7%) prefinal- and 57 (54.8%) final-year students knew the correct definition of antimicrobial stewardship. Majority of the participants, i.e., 66 (70.9%) prefinal-year and 80 (76.9%) final-year students perceived antibiotic resistance as a public health problem. Principal component analysis revealed the greater role of attitude-related questions. CONCLUSION: Good knowledge and positive attitude are paramount for the effective implementation of the antibiotic stewardship program. Our study revealed that the knowledge gap exists among the undergraduate students about the rational use of the antibiotic stewardship program. It was also revealed that the role of attitude plays a more significant role than knowledge for the proper understanding of the program. A sustained effort is required to make them aware of the rational use of antibiotics by incorporating the knowledge and practice of the ASP into their study curriculum.

Methodological Characteristics of Clinical Trials: Impact of Mandatory Trial Registration.

PURPOSE: Numerous studies across multiple specialties have evaluated the impact of trial registration on quality of study reports and found significant improvements over several domains. However, the impact of mandatory trial registration on the quality of clinical trial protocols remains hitherto unexplored. METHODS: We carried out a retrospective cohort study of clinical trial applications submitted to drug regulatory authority of India for initial review with the objective of comparing methodological characteristics of their protocols. Since trial registration was made mandatory in the country in June 2009, we selected two study periods as between January 2007 to May 2009 (Period I) and July 2009 to December 2011 (Period II). Seventy-five protocols were randomly selected using a computer-generated list for each study period, making a total of 150 protocols. Data on twelve key methodological characteristics were collected including clearly defined primary outcomes, randomization, blinding, use of control group, statistical methods, handling of withdrawals amongst others. RESULTS: More than 3/4th of the trial applications in the two study periods were for new chemical entities and nearly 90% were pharmaceutical industry sponsored studies. Comparing the period before and after implementation of mandatory trial registration, description of clearly defined trial outcomes improved from nearly 42% to 80% (p<0.001), sample size justifications increased from 38% to 70% (p<0.001) and use of allocation concealment improved from 24% to 49% (p=0.001). Marked improvement was also noted for blinding, description of statistical methods and handling of withdrawals and dropouts. Remaining characteristics did not change significantly between the two study periods. The mean cumulative scores for the study protocols improved significantly from 7± 0.296 in the first period to 8.93± 0.346 (p<0.001) in the second period. CONCLUSIONS: Our study found a significant improvement in the methodological quality characteristics of the protocols particularly in elements related to minimization of bias and statistical methods, which could be attributed to mandatory trial registration. Overall, the significant improvement was limited to global clinical trials, and room for improvement was noted for two quality characteristics - proportion of randomized studies and trials adequately describing the generation of allocation sequence.

Predictive Validity of Some Common Animal Models of Bipolar Disorder Using Lithium and Lamotrigine Therapy: An Attempt towards a Battery-Based Approach for the Evaluation of Mood Stabilizers.

OBJECTIVE: To determine the predictive validity of some of the commonly employed models of mania and depression using standard drugs i.e. lithium (70 mg/kg) and lamotrigine (5 mg/kg) in male Wistar rats. METHODS: The depression facet of bipolar disorder was evaluated using forced swim test, tail suspension test, and chronic mild stress test. The models used to evaluate the mania facet of bipolar disorder were isolation-induced aggression test, saccharine preference test, and morphine-sensitized hyperlocomotion test. RESULTS: The immobility time was significantly (p<0.05) reduced by lamotrigine in the tail suspension test and the forced swim test, while lithium caused significant (p<0.05) reduction only in the tail suspension test. Rats exposed to chronic mild stress showed the maximal increment of 1% sucrose consumption at the 3rd week of treatment in both the lithium (p<0.001) and lamotrigine (p<0.01) groups. In the isolation-induced aggression test, the aggressive behaviour of rats was significantly reduced by both lithium [approach (p<0.001), attack (p<0.01), and bite (p<0.01)] and lamotrigine [approach (p<0.001), and attack (p<0.05)]. Neither of the drugs were effective in the saccharine preference test. Only lithium was able to significantly (p<0.05) reduce the crossing parameter in morphine-sensitized rats. CONCLUSION: Our study identifies the chronic mild stress test and isolation-induced aggression test of having the highest predictive validity in the depression and mania facets of bipolar disorder, respectively, and should be a part of a battery of tests used to evaluate novel mood stabilizers.

Self-medication practice and factors influencing it among medical and paramedical students in India: A two-period comparative cross-sectional study.

AIM: Self-medication is widely practiced with varying dimensions in India. This practice has many implications, especially among medical and paramedical students having some knowledge and good exposure to drugs. We conducted a two-period observational study to evaluate the change in knowledge and practice of self-medication, over 5 years of time period, among medical and paramedical students from different parts of India. MATERIALS AND METHODS: A structured questionnaire was administered to medical (MBBS), dental (BDS), and paramedical students, who come to attend pan India annual cultural, literary, and sports event at New Delhi. The study was conducted in two phases (2007 and 2012) in different respondents of same categories (medical and paramedical) of students. Three-hundred and thirty students from 39 colleges in 2007 and 356 students from 38 colleges in 2012 participated in the study. RESULTS: The prevalence of self-medication remained high in both 2007 and 2012 (74.6% and 69.4%), although no significant difference was observed between the two phases (P = 0.14%). Oral antibacterial agents, oral anti-inflammatory agents, and antipyretics were the most common group of drugs used in both phases of study. A significant increase was observed in number of students who took complete course of oral antibiotics (28.3-38.3%, P = 0.01). CONCLUSION: The prevalence of self-medication among undergraduate students remains unaltered over the span of 5 years. Nevertheless, there was a better sensitization toward appropriate antibiotic usage and the practice of responsible self-medication needs to be promoted among future healthcare providers.