Green NiO nanoparticle-integrated PVA-alginate hydrogel: potent nanocatalyst for efficient reduction of anthropogenic water pollutants.

Hydrogel nanocatalyst composed of nickel oxide (NiO) nanoparticles embedded in PVA-alginate hydrogels were potentially explored toward the reduction of anthropogenic water pollutants. The NiO nanoparticles was accomplished via green method using waste pineapple peel extract. The formation of the nanoparticles was affirmed from different analytical techniques such as UV-Vis, FTIR, XRD, TGA, FESEM, and EDS. Spherical NiO nanoparticles were obtained having an average size of 11.5 nm. The nano NiO were then integrated into PVA-alginate hydrogel matrix forming a nanocomposite hydrogel (PVALg@ NiO). The integration of nano NiO rendered an improved thermal stability to the parent hydrogel. The PVALg@ NiO hydrogel was utilized as a catalyst in the reduction of 4-nitrophenol (4-NP), potassium hexacyanoferrate (III), rhodamine B (RhB), methyl orange (MO), and malachite green (MG) in the presence of a reducing agent, i.e., NaBH4. Under optimized conditions, the reduction reactions were completed by 4.0 min and 3.0 min for 4-NP and potassium hexacyanoferrate (III), respectively, and the rate constant was estimated to be 1.14 min-1 and 2.15 min-1. The rate of reduction was found to be faster for the dyes and the respective rate constants were be 0.17 s-1 for RhB, MG and 0.05 s-1 for MO. The PVALg@ NiO hydrogel nanocatalyst demonstrated a recyclability of four runs without any perceptible diminution in its catalytic mettle. The efficacy of the PVALg@ NiO hydrogel nanocatalyst was further examined for the reduction of dyes in real water samples collected from different sources and the results affirm its high catalytic potential. Thus, this study paves the path for the development of a sustainable hydrogel nanocatalyst for reduction of hazardous pollutants in wastewater treatment.

Efficacy and safety of dasotraline in attention-deficit hyperactivity disorder: A systematic review and meta-analysis.

Background and Aim: Pharmacotherapeutic options for attention-deficit hyperactivity disorder (ADHD) are limited due to adverse effects and inadequate efficacy of existing drugs. Clinical trials were conducted on dasotraline in search of a safer and more efficacious alternatives to stimulant agents. This meta-analysis was conducted to evaluate the efficacy and safety of dasotraline in ADHD compared to placebo. Methods: The reviewers extracted data from five relevant clinical trials after a literature search on Medline/PubMed, Embase, Scopus, Google Scholar, and Cochrane databases and Clinical Trial Registries. Quality assessment was done using the risk of bias assessment tool, and the random-effects model was used to estimate the effect size. Sub-group analysis, meta-regression, and sensitivity analysis were done as applicable. PRISMA guidelines were followed in the selection, analysis, and reporting of findings. Results: Dasotraline significantly reduced the ADHD total symptom score (SMD: -0.35; 95% CI: -0.55 to -0.15; P < 0.001), hyperactivity/impulsivity subscale score (SMD: -0.27; 95% CI: -0.44 to -0.11; P = 0.001), inattentiveness sub-scale score (SMD: -0.33; 95% CI: -0.53 to -0.14; P < 0.001), and CGI-S (SMD: -0.25; 95% CI: -0.42 to -0.08; P = 0.003). Sub-group analysis showed a significant reduction of ADHD symptoms in both pediatric and adult age groups. Meta-regression showed a significant association between SMD of ADHD symptom score reduction and the duration of dasotraline therapy. The incidence of decreased appetite showed dose dependence but not the incidence of insomnia. Conclusions: Dasotraline 4 mg (in children) and 6 mg (in adults) can improve the clinical outcome in patients with ADHD by improving symptoms and global functioning with acceptable tolerability.PROSPERO Registration number: CRD42022321979.

Repurposing of dextromethorphan as an adjunct therapy in patients with major depressive disorder: a randomised, group sequential adaptive design, controlled clinical trial protocol.

BACKGROUND: Therapeutic latency, lack of efficacy and adverse drug reactions are the major concerns in current antidepressant therapies. To overcome these treatment hurdles, add-on therapy to conventional antidepressant medications may lead to better therapeutic outcomes. The present randomised controlled trial has been planned to evaluate the efficacy and safety of add-on dextromethorphan to selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder (MDD). METHODS AND ANALYSIS: A randomised, double-blind, add-on, placebo-controlled, group sequential design clinical trial will be conducted on patients with MDD who will be randomly assigned to the control and the test group in a 1:1 ratio. Patients in the test group will get dextromethorphan 30 mg once daily, whereas patients in the control group will receive a placebo once daily as an add-on to ongoing SSRI treatment for 8 weeks. All patients will be evaluated for the primary outcome (change in the Montgomery-Åsberg Depression Rating Scale score) and secondary outcomes (treatment response rate, remission rate, Clinical Global Impression, serum brain-derived neurotrophic factor, serum dextromethorphan and treatment-emergent adverse events) over the period of 8 weeks. Intention-to-treat analysis will be done for all parameters using suitable statistical tools. ETHICS AND DISSEMINATION: This study was approved by the Institutional Ethics Committee of All India Institute of Medical Sciences, Bhubaneswar, India, and the study conformed to the provisions of the Declaration of Helsinki and ICMR's ethical guidelines for biomedical research on human subjects (2017). Written informed consent will be obtained from the participants before recruitment. The results of this study will be published in peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT05181527.

Evaluation of Safety and Efficacy of Add-on Alpha-Lipoic Acid on Migraine Prophylaxis in an Adolescent Population: A Randomized Controlled Trial.

Nutraceuticals like alpha-lipoic acid (ALA) may have potential benefits as prophylactic agents for adolescent migraine, with fewer adverse events than existing medications. The present study was conducted to evaluate the safety and efficacy of add-on ALA for prophylaxis in adolescent migraine. A randomized, open-label, add-on clinical trial was conducted with 60 adolescent migraineurs, who were randomized to receive flunarizine or flunarizine with an add-on ALA. A clinical evaluation of the frequency and severity of migraine, responder rate, Pediatric Migraine Disability Assessment (PedMIDAS) scoring, serum thiol, and serum calcitonin gene-related peptide (CGRP) was performed both at baseline and following 12 weeks of treatment. The frequency of acute attacks of migraine decreased significantly (P = .001) in the test group compared with the control group. The responder rate was found to be significantly higher (80%) in the test group than in the control group (33.3%) (P = .001). The mean monthly migraine headache days in the test group showed a significant reduction (-7.7 days, 95%CI -9.1 to -6.3 days; P = .010). The severity of acute migraine attacks (mild, moderate, severe) also showed a significant reduction in the test group (P = .001). PedMIDAS scores showed significant improvement in the test group (P = .021), in comparison with the control group. Serum thiol levels were significantly increased in the test group (18 mmol/L, 95%CI 13.5 to 36.1 mmol/L; P = .001). Serum CGRP levels showed a significant reduction with adjunctive ALA therapy (-122.4 pg/mL, 95%CI -142.3 to -89.0 pg/mL; P = .006). Add-on ALA with flunarizine as a prophylactic agent for migraine in adolescents can improve clinical outcomes by improving clinical and biochemical parameters.

Effect of regulated add-on sodium chloride intake on stabilization of serum lithium concentration in bipolar disorder: A randomized controlled trial.

OBJECTIVE: Lithium-induced natriuresis may lead to lithium retention and fluctuation of lithium levels during maintenance therapy. Therefore, the present study was conducted to evaluate the effect of add-on sodium chloride on serum lithium levels in bipolar disorder. METHODS: This RCT was conducted in 60 patients with type I bipolar disorder who were randomized into the control group that received lithium carbonate with the advice not to take additional salt (at the table) and the test group that received sachets of sodium chloride (1 g/d) as an add-on to lithium carbonate and were advised to restrict their additional salt intake (at the table) to 1 g/d. After baseline assessments, all patients were followed up at 4 weeks, 8 weeks, and 12 weeks when serum lithium, sodium, and potassium were estimated. Serum creatinine and aldosterone were repeated at 12 weeks. The percentage of patients showing fluctuations in serum lithium level (serum lithium <0.6 mEq/L or >0.8 mEq/L) was considered as the primary outcome measure. RESULTS: In the test group, the fluctuation rate in serum lithium (26.7%) was significantly (p = 0.01) lower than that in the control group (63.3%). Serum lithium values varied significantly across sampling times in the control group but not in the test group. There was a significant difference in serum lithium between the groups at 8 and 12 weeks of follow-up. There were no significant differences in the change in serum sodium, potassium, creatinine, aldosterone, creatinine clearance, and blood pressure within the group and between the groups. A significant positive correlation was found between serum lithium and aldosterone at baseline. CONCLUSIONS: Intake of add-on sodium chloride (1 gm/day) may reduce the fluctuations in serum lithium during the maintenance phase of lithium therapy in type I bipolar disorder. GOV IDENTIFIER: NCT04222816.

Efficacy and Safety of Melatonin as Prophylaxis for Migraine in Adults: A Meta-analysis.

AIMS: To evaluate the efficacy and safety of melatonin for migraine prophylaxis in adults. METHODS: After a comprehensive literature search in the MEDLINE, Cochrane Database, and International Clinical Trial Registry Platform databases, reviewers extracted data from three relevant articles. PRISMA guidelines were followed in the selection, analysis, and reporting of the findings. Quality assessment was performed using the Cochrane risk of bias assessment tool. A random-effects model was used to estimate the effect size, and meta-regression was performed for variables with a likely influence on effect size. Subgroup analysis was performed based on the comparison used in the included studies. RESULTS: Melatonin therapy in migraine was associated with a significantly higher responder rate when compared to both placebo and standard therapy (OR = 1.84; 95% CI: 1.08 to 3.14; P = .03). The results of the meta-analyses indicated that melatonin can achieve a significant reduction in frequency of migraine attacks (MD = 1.00; 95% CI: 0.02 to 1.98; P = .04), migraine attack duration (MD = 5.02; 95% CI: 0. 91 to 9.13; P = .02), use of analgesics (MD = 1.43; 95% CI: 0.38 to 2.48; P = .008), and migraine severity (MD = 1.93; 95% CI: 1.23 to 2.63; P < .0001) over placebo, but had no significant effects in comparison to amitriptyline or valproate. There was no significant difference in the occurrence of common adverse drug reactions, such as drowsiness and fatigue, between the melatonin group and the comparison groups. CONCLUSIONS: Melatonin showed a beneficial prophylactic role in migraine, with a better responder rate in comparison to placebo in reducing migraine severity, mean attack duration, mean attack frequency, and analgesic use, but did not show significant effects in comparison to amitriptyline or valproate.

Efficacy and safety of supraphysiologic doses of levothyroxine for patients with bipolar depression in adults: A systematic review.

BACKGROUND: In bipolar disorder (BD), depression is the most difficult-to-treat dimension and available evidence suggests that add-on supraphysiological doses of levothyroxine may be an effective augmenting agent. AIM: This systematic review has been conducted to evaluate the efficacy and safety of supraphysiologic doses of levothyroxine in bipolar depression in adults. METHODS: After a comprehensive literature search on MEDLINE/PubMed, Scopus, Cochrane databases and International Clinical Trial Registry Platform (ICTRP), reviewers extracted data from eight relevant articles. PRISMA guidelines were followed in the selection, analysis and reporting of findings. Quality assessment was done using the risk of bias assessment and a random effects model was used to estimate effect size. Meta-analysis could not be done due to the lack of randomized, placebo-controlled trials and adequate data. A systematic review was done on eight studies and analysis on the pre-post change in Hamilton depression rating scale score (HDRS) was done for six studies. RESULTS: The random model analysis of pooled effects showed a standardized mean difference of HDRS score by 2.62 (95% CI: 2.21-3.04; p < 0.0001). The responder and remission rates were not significant as reported in one study. Markov chain analysis performed in one study revealed that patients in the levothyroxine group had a significantly greater increase in time in the euthymic state and a decrease in the mixed state. In most of the studies, levothyroxine therapy was well tolerated, with no serious adverse events. CONCLUSION: Add-on supraphysiological dose of levothyroxine has a potential role in attenuating depressive symptoms in bipolar depression, especially in therapy-resistant BD. PROSPERO REGISTRATION NUMBER: CRD42020218456.

Comparative Study of the Effects of Azilsartan and Telmisartan on Insulin Resistance and Metabolic Biomarkers in Essential Hypertension Associated With Type 2 Diabetes Mellitus.

Introduction The complex interplay between the autonomic nervous system, renin-angiotensin-aldosterone system (RAAS), and immunity contributes to the pathogenesis of hypertension in diabetes mellitus. The objective of this study was to investigate and compare the effect of azilsartan and telmisartan on insulin resistance and metabolic biomarkers in patients with both hypertension and type 2 diabetes mellitus. Methods The present study was a prospective, randomized, active-controlled, open-label, parallel-group clinical trial. Patients with grade I or II essential hypertension with type 2 diabetes mellitus were randomized into two groups of 25 patients each. Baseline evaluation of homeostasis model assessment-insulin resistance (HOMA-IR), plasma glucose, insulin, leptin and adiponectin levels, and systolic and diastolic blood pressure (SBP and DBP) of patients was done. Patients were reassessed after 12 weeks of drug therapy with azilsartan 40 mg OD (once daily) or telmisartan 40 mg OD. Results The mean changes in HOMA-IR from the baseline at the end of 12 weeks of treatment were 0.15 (-0.64, 0.94.52) in the azilsartan group and 0.32 (-0.61, 1.26) in the telmisartan group. The mean difference in the changes from the baseline in HOMA-IR between the two groups was 0.3 (-0.87, 1.48), which was not statistically significant. No statistically significant changes were observed between the two groups in metabolic biomarkers (leptin: -0.84, CI: -4.83 to 3.14, and adiponectin: -0.12, CI: -0.62 to 0.37). Systolic (SBP) and diastolic blood pressure (DBP) decreased at the end of the 12-week treatment in both the groups; however, there was no significant difference between the two groups (SBP: -2.6, CI: -10.35 to 5.1, and DBP: -3.0, CI: -7.7 to 1.7). Conclusion Neither azilsartan nor telmisartan had any significant effects on insulin resistance and metabolic biomarkers after 12 weeks of drug therapy in hypertension patients associated with type 2 diabetes mellitus. However, they showed a comparable antihypertensive effect. The adverse effects observed were mild in nature, and their incidence was comparable between the two groups.

Comparative efficacy of mitochondrial agents for bipolar disorder during depressive episodes: a network meta-analysis using frequentist and Bayesian approaches.

RATIONALE: Mitochondrial dysfunctions have emerged as new biological hypothesis and therapeutic target for bipolar disorder. This network meta-analysis has been done to evaluate the comparative efficacy of mitochondrial agents in bipolar depression. METHODS: After a comprehensive literature search on PubMed/MEDLINE, Cochrane databases, and International Trials Registry Platform, efficacy data were extracted from 15 randomized controlled trials. Random-effects meta-analysis was done following both frequentist and Bayesian approaches to pool the effects across the interventions. A network graph was built, relative effects of interventions in respect to one another and placebo were calculated, and treatments were ranked as per P- and SUCRA scores. Change in depression rating score was the primary outcome. Data was entered in contrast level and arm level for frequentist and Bayesian approaches, respectively. RESULTS: Amongst mitochondrial agents, N-acetylcysteine (NAC) was shown to have the highest probability of being the best treatment, followed by coenzyme Q10 and combination therapy of alpha-lipoic acid (ALA) and acetyl-L-carnitine (ALCAR) as depicted by P- and SUCRA scores. In the Bayesian approach, none of the treatments had better efficacy than placebo, but in the frequentist approach, NAC (effect estimate: - 1.18 (95% CI: - 2.05; - 0.31)) was significantly better than placebo. CONCLUSION: Methodically, there may be a difference of magnitude in frequentist and Bayesian approaches, but the direction of effect and ranking probabilities do not differ. We conclude that none of the existing mitochondrial agents showed better efficacy than placebo in bipolar depression regarding depression rating scores.

Efficacy and Safety of Lasmiditan for Acute Treatment of Migraine in Adults: A Meta-Analysis.

Monotherapy with triptans in acute migraine is ineffective in many patients and contraindicated in certain cardiovascular diseases where alternative therapeutic options are necessary to explore. This meta-analysis has evaluated the efficacy and safety of lasmiditan for the treatment of acute migraine in adults. After performing a literature search on MEDLINE/PubMed, Scopus, Cochrane databases, and International Clinical Trial Registry Platform, reviewers assessed eligibility and extracted data from 4 relevant articles. Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed in the selection, analysis, and reporting of findings. A random-effects model was used to estimate effect size. Quality assessment was done using the risk of bias assessment tool and meta-regression for probable variables affecting effect size. Subgroup analysis was done depending on the dose of lasmiditan. Lasmiditan use was associated with a significantly higher percentage of patients with pain freedom (odds ratio [OR], 2.02; 95% confidence interval [CI], 1.72-2.39; P < .00001), sustained pain freedom (OR, 1.93; 95%CI, 1.55-2.39; P <.00001), headache response (OR, 2.05; 95%CI, 1.77-2.36; P < .00001), clinical disability level (OR, 1.36; 95%CI, 1.20-1.55; P < .00001), patients' global impression (OR, 1.88; 95%CI, 1.69-2.10; P < .00001), and significantly lower use of rescue medication (OR, 0.49; 95%CI, 0.38-0.63; P < .00001) compared to placebo. Lasmiditan use was also associated with a higher likelihood of adverse effects like dizziness (OR, 6.54; 95%CI, 4.24-10.07; P < .00001), paresthesia (OR, 4.28; 95%CI, 2.97-6.17; P < .00001), and fatigue (OR, 5.67; 95%CI, 3.78-8.52; P < .00001) compared to placebo. Subgroup analysis showed a dose-dependent effect of lasmiditan on pain freedom, sustained pain freedom, patient's global impression, and occurrence of adverse drug reactions. Prediction probability for effect estimate favoring placebo was calculated to be 0.0017%. Lasmiditan has shown a favorable effect in terms of efficacy and safety in the treatment of an acute attack of migraine in comparison to placebo. Further studies are needed to evaluate long-term safety, efficacy, and use in specific subgroups of patients. PROSPERO Registration Number: CRD42020177838.

Effect of add-on melatonin on seizure outcome, neuronal damage, oxidative stress, and quality of life in generalized epilepsy with generalized onset motor seizures in adults: A randomized controlled trial.

Epilepsy treatment is challenging because of multiple impediments like lack of efficacy of monotherapy, adverse drug reactions, and different comorbidities. Add-on therapy to first-line antiepileptics may be the option to overcome therapeutic hurdles. The present randomized, double-blind, add-on placebo-controlled clinical trial was conducted to evaluate the effect of add-on melatonin in the treatment of generalized epilepsy with generalized onset motor seizure in adults. The control group (n = 52) received add-on placebo, and the test group (n = 52) received add-on melatonin (3 mg/day) with valproate (20 mg/kg in two divided doses). Clinical evaluation of seizure frequency, Chalfont-National Hospital seizure severity scale (NHS3), Pittsburgh sleep quality index (PSQI), quality of life in epilepsy inventory, Epworth sleepiness scale (ESS), and biochemical estimation of serum neuron-specific enolase (NSE) and glutathione reductase were done at baseline and compared with follow-up at 8 weeks. Among 104 patients randomized [mean (SD) age of 27.6 (11.5); 84 (80.8%) male], 88 (84.6%) completed the trial. The responder rate and seizure-free rate in the test group were significantly (p = 0.006 and 0.034) higher than the control group. There was a significantly higher reduction in the frequency of seizures (p = 0.016) and NHS3 (-2.39; 95%CI: -4.56 to -0.21; p = 0.032) in the test group compared to the control group. Similarly, improvement in PSQI (-1.40; 95%CI: -2.64 to -0.15; p = 0.029) was significantly better in the test group. There was no significant difference in the change in ESS (p = 0.621) and quality of life scoring (p = 0.456) between the study groups. The decrease in serum NSE was significantly higher with the test group compared to the control group (-2.01; 95% CI: -3.74 to -0.27; p = 0.024). Add-on melatonin increased serum glutathione reductase significantly (p = 0.038), but there was no significant difference between the groups (p = 0.685). Add-on melatonin with valproate for generalized epilepsy with generalized onset motor seizures in adults can achieve a significantly better clinical outcome by reducing the seizure frequency, severity and attaining a better seizure-free rate in comparison to the control group.

Comparative efficacy and safety of pharmacological interventions for smoking cessation in healthy adults: A network meta-analysis.

Smoking is the leading cause of morbidity and mortality in different non-communicable diseases, and cessation leads to immense health benefits. The present network meta-analysis has been conducted to evaluate and compare the effects of available pharmacological interventions for smoking cessation in adults. A standard meta-analysis protocol was developed and after performing a comprehensive literature search on MEDLINE/PubMed, Cochrane databases, and International Clinical Trials Registry Platform, reviewers extracted data from 97 randomized controlled trials. PRISMA guidelines were followed in data extraction, analysis and reporting of findings. Random effects Bayesian network meta-analysis was done to pool the effects across the interventions. Network graph was built, and for closed triangles in the network graph, node splitting analysis was performed. The primary outcome measure was self-reported biochemically verified smoking abstinence at six months. The number of participants achieving continuous abstinence was reported. Data for the number of participants reporting at least one adverse event was also extracted, if available. Combination of nicotine receptor agonist and nicotine replacement therapy had a significant odd of 4.4 (95%CrI:2.2-8.7), bupropion and nicotine receptor agonist 4.0 (95%CrI:2.1-7.7), bupropion and nicotine replacement therapy 3.8 (95%CrI:2.3-6.2), combination nicotine replacement therapy has an odd of 2.6 (95%CrI:1.8-3.8), and nicotine receptor agonist had a significant odd of 2.7 (95%CrI:2.3-3.2) when compared to placebo (moderate quality of evidence) for continuous abstinence at 6 months. When compared with behavioural therapy, the odds ratio of interventions was not statistically significant. Combination of nicotine receptor agonist and nicotine replacement therapy has the highest probability of being the best treatment for abstinence from smoking.

Effect of Haloperidol and Risperidone on Serum Melatonin and GAP-43 in Patients with Schizophrenia: A Prospective Cohort Study.

OBJECTIVE: Serum melatonin, a biomarker of circadian rhythm, can upregulate Growth-associated protein 43 (GAP-43) which is involved in neural regeneration and plasticity. The present study was conducted to investigate the adequacy of the first-line antipsychotic drugs to improve sleep and circadian rhythm disruptions by assessing the effect of haloperidol and risperidone on serum melatonin and GAP-43 in schizophrenia. METHODS: In this cohort study, 100 schizophrenic patients were recruited, and clinical evaluations were done using the Positive and Negative Syndrome Scale (PANSS) and the Pittsburgh sleep quality index (PSQI). The patients with predominantly positive symptoms taking haloperidol (Group I) and patients with predominantly negative symptoms taking risperidone (Group II) were admitted and serum melatonin, arylalkylamine N-acetyltransferase, GAP-43 and urinary melatonin were estimated. After 8 weeks, all clinical and biochemical parameters were repeated. RESULTS: Serum melatonin (2:00 hours) was significantly decreased in both haloperidol (2.42; 95% confidence interval [95% CI]: 0.67-4.17; p = 0.008) and risperidone group (3.40; 95% CI: 0.54-6.25; p = 0.021). Urinary melatonin was significantly decreased in both haloperidol (p = 0.005) and risperidone group (p = 0.014). PSQI score was significantly increased in both haloperidol (p = 0.001) and risperidone group (p = 0.003). Serum GAP-43 was significantly decreased in both haloperidol and risperidone group (p < 0.001). PANSS decreased significantly in both the groups and there was a significant negative correlation between serum melatonin at 2:00 hours and PANSS (r = -0.5) at baseline. CONCLUSION: Monotherapy with haloperidol and risperidone can achieve symptomatic improvement but cannot improve sleep and circadian rhythm disturbances in schizophrenia.

Effect of canakinumab on clinical and biochemical parameters in acute gouty arthritis: a meta-analysis.

BACKGROUND: Targeted anti-IL-1ß therapy may be a valuable option for the management of gouty arthritis. The present meta-analysis has evaluated the effect of canakinumab, an anti-IL-1ß monoclonal antibody in gouty arthritis. METHODS: A standard meta-analysis protocol was developed and after performing a comprehensive literature search in MEDLINE, Cochrane, and International Clinical Trial Registry Platform (ICTRP), reviewers assessed eligibility and extracted data from three relevant articles. A random-effects model was used to estimate the pooled effect size as the mean difference in Visual Analouge Scale (VAS) score, serum hsCRP, serum Amyloid A, and risk ratio for global assessment between the groups. Quality assessment was done using the risk of bias assessment tool and summary of findings was prepared using standard Cochrane methodology with GradePro GDT. RESULTS: Treatment with canakinumab showed a mean reduction of VAS score by 14.59 mm [95% CI - 19.42 to - 9.77], serum hsCRP by 15.36 mg/L [95% CI 1.62-29.11], serum Amyloid A by 67.18 mg/L [95% CI 17.06-117.31], and improvement in patient global assessment (RR = 1.478; 95% CI 1.29-1.67) and physician global assessment (RR = 1.44; 95% CI 1.28-1.61). The probability that future studies may have a mean difference in VAS score less than zero has been calculated to be 27.3% using a cumulative distribution function (CDF) calculator. CONCLUSION: This meta-analysis shows the beneficial effect of canakinumab over triamcinolone by reducing VAS score, serum hsCRP, serum amyloid A, and improvement in global assessments in acute gouty arthritis.

Effect of lurasidone versus olanzapine on cardiometabolic parameters in unmedicated patients with schizophrenia: a randomized controlled trial.

OBJECTIVE: Patients with schizophrenia are at higher risk of cardiovascular morbidity and mortality than healthy individuals. This study was conducted to compare the effect of lurasidone and olanzapine on cardiometabolic parameters in unmedicated patients with schizophrenia. METHODS: The present study was a randomized open-label, parallel design, active-controlled clinical trial. After recruitment and randomization of 101 patients, a baseline assessment was done by PANSS, SOFAS, lipid profile, fasting blood glucose, HbA1c, serum insulin and serum hs-CRP. HOMA-IR, atherogenic index, coronary risk index and cardiovascular risk indices were calculated as derived parameters. Patients received either lurasidone 80 mg or olanzapine 10 mg as monotherapy and followed up after 6 weeks. RESULTS: There was a significant increase in fasting blood glucose (p < 0.001), HbA1c (p < 0.001) and serum insulin (p < 0.001) after 6 weeks of therapy in both the treatment groups but the difference between the groups was not significant (FBS, p = 0.209; HbA1c, p = 0.209; serum insulin, p = 0.720). Olanzapine showed worsening of lipid profile (p < 0.001) while the same improved with lurasidone (p < 0.001) and the difference between the groups was found to be significant (p < 0.001). Serum HDL level decreased in both the treatment groups (olanzapine, p < 0.001; lurasidone, p < 0.001) but the difference between the groups was not significant (p = 0.333). There was an increase in hs-CRP levels in both the treatment groups (olanzapine, p < 0.001; lurasidone, p < 0.001) with no significant difference between them (p = 0.467). Atherogenic index, coronary risk index and cardiovascular risk index increased significantly in the olanzapine group as compared with the lurasidone group (p < 0.001). CONCLUSION: Lurasidone showed a favourable effect on lipid profile and cardiovascular risk indices over olanzapine. However, long-term studies are needed to establish and generalize the findings. TRIAL REGISTRATION: ClinicalTrials.gov NCT03304457.

Effect of Repetitive Transcranial Magnetic Stimulation on Seizure Frequency and Epileptiform Discharges in Drug-Resistant Epilepsy: A Meta-Analysis.

BACKGROUND AND PURPOSE: The role of low-frequency repetitive transcranial stimulation (rTMS) in drug-resistant epilepsy (DRE) has been conflicting and inconclusive in previous clinical trials. This meta-analysis evaluated the efficacy of rTMS on seizure frequency and epileptiform discharges in DRE. METHODS: A standard meta-analysis protocol was registered in the International Prospective Register of Ongoing Systematic Reviews (PROSPERO: CRD42018088544). After performing a comprehensive literature search using specific keywords in MEDLINE, the Cochrane database, and the International Clinical Trial Registry Platform (ICTRP), reviewers assessed the eligibility and extracted data from seven relevant clinical trials. Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were followed in the selection, analysis, and reporting of findings. A random-effects model was used to estimate the effect size as the mean difference in seizure frequency and interictal epileptiform discharges between the groups. Quality assessment was performed using a risk-of-bias assessment tool, and a meta-regression was used to identify the variables that probably influenced the effect size. RESULTS: The random-effects model analysis revealed a pooled effect size of -5.96 (95% CI= -8.98 to -2.94), significantly favoring rTMS stimulation (p=0.0001) over the control group with regard to seizure frequency. The overall effect size for interictal epileptiform discharges also significantly favored rTMS stimulation (p<0.0001), with an overall effect size of -9.36 (95% CI=-13.24 to -5.47). In the meta-regression, the seizure frequency worsened by 2.00±0.98 (mean±SD, p=0.042) for each week-long lengthening of the posttreatment follow-up period, suggesting that rTMS exerts only a short-term effect. CONCLUSIONS: This meta-analysis shows that rTMS exerts a significant beneficial effect on DRE by reducing both the seizure frequency and interictal epileptiform discharges. However, the meta-regression revealed only an ephemeral effect of rTMS.

Effect of add-on ramelteon therapy on sleep and circadian rhythm disruption in patients with schizophrenia: A randomized controlled trial.

The sleep and circadian rhythm disruptions in schizophrenia are attributed to a decrease in nocturnal melatonin level which may worsen if treated with conventional sedative drugs. This study was planned to evaluate the effects of add-on ramelteon on sleep and circadian rhythm disturbances in schizophrenia. A randomized, rater-blinded clinical trial was conducted on 120 patients with schizophrenia. Patients were categorized into predominantly positive (PG) or negative (NG) symptoms depending on Positive and Negative Syndrome Scale (PANSS) scoring, and then they were randomized into control (haloperidol/risperidone) or test (add-on ramelteon) groups. After recruitment, baseline serum melatonin, serum AANAT, urinary melatonin and Pittsburgh Sleep Quality Index (PSQI) were evaluated. Patients were reassessed after 4 weeks of therapy with antipsychotics with or without ramelteon. A significantly greater increase in night-time melatonin level (PG: 10·19; 95%CI: 1·42 to 18·97; p = 0·024; NG: 18·74; 95%CI: 8·48 to 29·0; p = 0·001), decrease in PSQI scores (PG: -1·57; 95%CI: -2·59 to -0·55; p = 0·003; NG: -2·49; 95%CI: -4·59 to -0·39; p = 0·021), increase in urinary melatonin (PG: 0·20; 95% CI: 0·056 to 0·35; p = 0·008; NG :0·15; 95% CI: 0·01 to 0·29; p = 0·034), increase in serum AANAT (PG: 4·61; 95%CI: 1·34 to 7·87; p = 0·007; NG:3·46; 95%CI: 1·30 to 5·63; p = 0·002) and improvement in PANSS score were found in patients receiving add-on ramelteon. The increase in serum melatonin and decrease in PSQI score were greater with predominantly negative symptom group in comparison to positive symptom group. Ramelteon may be considered as an add-on therapy with antipsychotic drugs for sleep and circadian rhythm disturbances in schizophrenia.

Effect of alpha agonists on the prevention of postparacentesis circulatory dysfunction in patients with refractory or recurrent ascites: a meta-analysis.

Postparacentesis circulatory dysfunction (PCD) is one of the commonest complications encountered in patients with refractory or recurrent ascites. Alpha agonists like clonidine and midodrine have been studied in various clinical trials for the prevention of PCD with varied results. This meta-analysis was done to evaluate the effect of alpha agonists on prevention of PCD in patients of refractory or recurrent ascites. A standard meta-analysis protocol was developed and registered in the International Prospective register of Ongoing Systematic Reviews. After performing a comprehensive literature search in MEDLINE, Cochrane, and International Clinical Trial Registry Platform, reviewers assessed eligibility and extracted data from five relevant articles. Preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines were followed in selection, analysis, and reporting of findings. Random effects model was used to estimate effect size. Quality assessment was done using the risk of bias assessment tool and meta-regression for probable variables affecting effect size. The random effect model analysis revealed a mean reduction of 2.63 ng/ml/h (95% CI: -4.46 to -0.8; P = 0.005) in plasma renin activity (PRA), mean reduction of 255.37 pg/ml (95% CI: -441.23 to -69.5; P = 0.007) in plasma aldosterone levels, and a mean increase of 0.14 mg/dl (95% CI: -0.13 to 0.41; P = 0.32) in serum creatinine levels favouring add-on alpha agonist group. In meta-regression, change in PRA (P = 0.79) and plasma aldosterone (P = 0.93) did not show a significant difference due to variation in follow-up duration across various studies. Add-on alpha agonists bring about a significant reduction in PRA and plasma aldosterone compared to standard medical treatment and thus prevents the occurrence of PCD in patients with refractory or recurrent ascites.

Effect of Sertraline, Dosulepin, and Venlafaxine on Non-BDNF Neurotrophins in Patients With Depression: A Cohort Study.

BACKGROUND: The neurotrophic hypothesis of depression has been mostly studied with a focus on brain-derived neurotrophic factor (BDNF) leading to lack of data on non-BDNF neurotrophins (NTs). The aim of this study was to evaluate the effect of antidepressant drugs on changes in serum nerve growth factor (NGF), neurotrophin 3 (NT-3), and neurotrophin 4 (NT-4). METHODS: A prospective cohort study was conducted on 105 patients with depression who were subgrouped to the group 1 (mild and moderate depression without somatic syndrome treated with sertraline), group 2 (mild and moderate depression with somatic syndrome treated with dosulepin), and group 3 (severe depression without psychotic symptoms treated with venlafaxine). At baseline, the severity of depression (Montgomery-Asberg Depression Rating Scale [MADRS]), serum NGF, NT-3, and NT-4 were estimated. Thirty-five healthy volunteers were recruited as controls for a baseline comparison of NTs. All patients were followed up after 6 weeks to evaluate the changes in NT levels and correlate it with the change in MADRS scores. RESULTS: At baseline, NT levels were significantly lower in patients with depression in comparison with healthy control. In group 1, serum NGF, NT-3, and NT-4 level were found to increase significantly after treatment, whereas changes in groups 2 and 3 were statistically not significant. Montgomery-Asberg Depression Rating Scale score and serum NGF at baseline had an inverse relation (r = -0.648), whereas the change in MADRS score in sertraline group had a positive correlation (r = 0.86) with the change of serum NGF. CONCLUSIONS: Monotherapy with sertraline increased the level of non-BDNF NTs; however, treatment with dosulepin and venlafaxine did not produce any significant changes in patients with depression.