Comparative efficacy and safety of alpha-blockers as monotherapy for benign prostatic hyperplasia: a systematic review and network meta-analysis.

Despite the availability of various drugs for benign prostatic hyperplasia (BPH), alpha(α)-blockers are the preferred first-line treatment. However, there remains a scarcity of direct comparisons among various α-blockers. Therefore, this network meta-analysis (NMA) of randomized controlled trials (RCTs) aimed to evaluate the efficacy and safety of α-blockers in the management of BPH. A comprehensive electronic search covered PubMed, Embase, Ovid MEDLINE, and Cochrane Library until August 2023. The primary endpoints comprised international prostate symptom score (IPSS), maximum flow rate (Qmax), quality of life (QoL), and post-void residual volume (PVR), while treatment-emergent adverse events (TEAEs) were considered as secondary endpoints. This NMA synthesized evidence from 22 studies covering 3371 patients with six kinds of α-blockers with 12 dose categories. IPSS has been considerably improved by tamsulosin 0.4 mg, naftopidil 50 mg and silodosin 8 mg as compared to the placebo. Based on the p-score, tamsulosin 0.4 mg had the highest probability of ranking for IPSS, PVR, and Qmax, whereas doxazosin 8 mg had the highest probability of improving QoL. A total of 297 adverse events were reported among all the α-blockers, silodosin has reported a notable number of TEAEs. Current evidence supports α-blockers are effective in IPSS reduction and are considered safer. Larger sample size with long-term studies are needed to refine estimates of IPSS, QoL, PVR, and Qmax outcomes in α-blocker users.

Normative data for insulin-like growth factor-1 (IGF-1) in healthy children and adolescents from India.

BACKGROUND: Serum IGF-1 is an important biochemical tool to diagnose and monitor GH-related disorders. However, ethnic-specific Indian data following consensus criteria for the establishment of normative data, are not available. Our objective was to generate chronological age (CA)-, bone age (BA)- and Tanner stage-specific normative data for IGF-1 in healthy Indian children and adolescents. METHODS: A cross-sectional epidemiological study was conducted in schools and the community, which enrolled apparently healthy children and adolescents with robust exclusion criteria. The outcome measure was serum IGF-1 assessed using an electro-chemiluminescence immunoassay (ECLIA). The 2.5th, 5th, 10th, 25th, 50th (median), 75th, 90th, 95th, and 97.5th centiles for IGF-1 were estimated using generalized additive models. RESULTS: We recruited 2226 apparently healthy participants and following exclusion, 1948 (1006 boys, 942 girls) were included in the final analysis. Girls had median IGF-1 peak at CA of 13 years (321.7 ng/mL), BA of 14 years (350.2 ng/mL) and Tanner stage IV (345 ng/mL), while boys had median IGF-1 peak at CA of 15 years (318.9 ng/mL) BA of 15 years (340.6 ng/mL) and Tanner stage III (304.8 ng/mL). Girls had earlier rise, peak and higher IGF-1 values. The reference interval (2.5th-97.5th percentile) was broader during peri-pubertal ages, indicating a higher physiological variability. CONCLUSION: This study provides ethnicity-specific normative data on serum IGF-1 and will improve the diagnostic utility of IGF-1 in the evaluation and management of growth disorders in Indian children and adolescents.

Comprehensive safety profile of dipeptidyl peptidase-4 inhibitors: a post-marketing study based on FAERS database using signal detection algorithms.

BACKGROUND: Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) have acquired a foothold in managing type 2 diabetes mellitus, but few concerns have arisen regarding their overall safety profile. The aim of this study is to assess the potential risk of DPP-4 inhibitors by analyzing data from the FDA Adverse Event Reporting System (FAERS) database. RESEARCH DESIGN AND METHODS: This is a retrospective study which explored the FAERS database till March 2023 for the collection of safety reports. The disproportionality analysis was performed using signal detection algorithms (SDAs) incorporating frequentist-based data mining approach such as relative reporting ratio (RRR), reporting odds ratio (ROR) and proportional reporting ratio (PRR) with 95% confidence interval (CI). RESULTS: A total of 14,573 adverse event reports were reported in the FAERS public dashboard associated with all the included DPP-4 inhibitors. The computed PRR, ROR, and RRR indicated positive signals for DPP-4 inhibitors with cardiac failure, pancreatitis, pemphigoid, hypoglycemia, acute kidney injury and lactic acidosis. Saxagliptin showed a higher signal score for cardiac failure, while sitagliptin was more associated with pancreatitis. Moreover, alogliptin exhibited an elevated signal score associated with pancreatic carcinoma. CONCLUSION: Several significant disproportionality signals were observed with DPP-4 inhibitors. However, clinicians have to consider the comorbidities and concomitant drugs while prescribing these drugs.

Estimating the active and lifetime prevalence and incidence of epilepsy in Asian Countries: A systematic review and meta-analysis.

OBJECTIVE: In the current era of the World Health Organization's Intersectoral Global Action Plan on Epilepsy and Other Neurological Disorders 2022-2031 (IGAP), precise and updated estimates of epilepsy burden are vital in formulating policies to improve the care of persons with epilepsy, especially in Asian countries with significant treatment gap. Hence, we aimed to consolidate the available data and quantify epilepsy prevalence and incidence estimates in Asian countries. METHODS: We systematically searched PubMed, Embase, Ovid, and Scopus databases from inception until March 2023 for studies reporting epilepsy prevalence and incidence in Asian countries. We applied random effects meta-analysis to generate the pooled prevalence and incidence using the Meta package in R. Additionally, we performed a subgroup meta-analysis to explore the potential sources of heterogeneity. A meta-regression analysis was conducted to examine the trend of epilepsy over time. RESULTS: A total of 99 studies with 100,654,124 participants were included in the meta-analysis. The pooled prevalence was 5.6 per 1000 (95 % confidence interval (CI) 4.4-6.8) for active epilepsy and 6.7 per 1000 (95 % CI 5.7-7.9) for lifetime epilepsy. The pooled incidence rate of epilepsy was 52.5 per 100,000 person-years (95 % CI 42.7-79.4). The subgroup analysis revealed a higher prevalence of active epilepsy (6.7/1000) and lifetime epilepsy (8.6/1000) in West Asia than in other regions. The funnel plot and Egger's test (p-value =<0.0001) revealed publication bias for active epilepsy. CONCLUSION: Our findings highlight a high prevalence of active and lifetime epilepsy in West Asia and emphasize the necessity of implementing and formulating specific strategies to tackle the epilepsy burden in this region. Furthermore, high-quality epidemiological studies incorporating economic burdens and comorbidities associated with epilepsy in Asia are still needed.

Mobile health applications for epilepsy in Indian app stores: A systematic review and content analysis using the mobile app rating scale.

OBJECTIVE: The growing prevalence of smartphones may prompt individuals with epilepsy to pursue unfulfilled healthcare requirements through mobile health (mHealth) apps, but the content and quality of these mHealth apps are rarely analysed. Hence, this study aimed to identify and assess the quality of epilepsy apps for patients with epilepsy (PWE), their caregivers, and healthcare practitioners (HCPs) available in the Play Store and App Store of India. METHODS: We performed a systematic search on the Google Play Store and Apple App Store of India to identify the mHealth apps for epilepsy which were released and updated till May 2023. The identified applications were downloaded and the quality was assessed using a Mobile app rating scale (MARS) for the overall quality, Aesthetics, Engagement, Functionality, and Information by three independent reviewers. The intraclass correlation coefficient (ICC) was calculated to assess the interrater reliability between the reviewers. An unpaired t-test was calculated to analyse the difference in mean scores for Android and iOS applications. RESULTS: The systematic search yielded a total of 2518 apps, out of which 26 were selected for inclusion in the study. Among these, 9 apps were compatible with Android, 11 with iOS, and 6 on both platforms. The mean (SD) MARS score of the apps was 3.5 (0.6) and the ICC for the overall app quality was 0.90 (95% CI: 0.82-0.96). Overall, apps scored highest in functionality (3.9), followed by aesthetics (3.6), information (3.3), and engagement (3.2). Among the included apps, the overall quality score was found to be higher for iOS apps than Android (MD = 0.54; 95% CI: 0.02 - 1.07; p-value: 0.042). CONCLUSION: Our study identified twenty-six mHealth applications for epilepsy that integrated various aspects of epilepsy self-management. The results of this study emphasize the importance of ensuring that current and future applications offer evidence-based information, integrate features that align with patient preferences, and generate evidence regarding the effectiveness of application usage.

Venetoclax adverse event monitoring: a safety meta-analysis of randomized controlled trials and a retrospective evaluation of the FAERS.

Concerns persist about venetoclax's long-term safety in larger populations, with limited evidence of infrequent and delayed adverse events (AEs). The study integrated safety data on venetoclax in leukemia patients from randomized controlled trials (RCTs) and FDA adverse event monitoring system (FAERS). We systematically reviewed RCTs reporting safety outcomes of venetoclax in adult leukemia patients of any gender, either monotherapy or in combination, applying advanced search on databases like PubMed, EMBASE, and ClinicalTrial.gov. The quality assessment was done using the Cochrane Risk of Bias Tool. We utilized a random effect meta-analysis to calculate risk ratio (RR) with 95% confidence intervals (CI). The Open Vigil 2.1 MedDRAv24 was used to search the FAERS database, with data available until September 2023. The disproportionality was calculated using the proportional reporting ratio and the reporting odds ratio. The study protocol for meta-analysis was registered with PROSPERO; CRD42022378006. For the safety meta-analysis, seven RCTs with available AEs were examined. A total of 942 AEs were found associated with the venetoclax group; 79% of them were in grade three or above. Venetoclax significantly increased the risk of neutropenia grade three or above (RR = 1.34, 95% CI: 1.10-1.64, p: 0.0033) compared with the control group. In FAERS, 26,436 patients were reported with AEs associated with venetoclax. Significant signal scores were observed in hematological, cardiac, vascular, and gastrointestinal disorders. 11 out of 30 generated signals, failed to meet the signal criteria upon refinement. The current study updated and improved the safety profile of venetoclax in the post-marketing period, assisting in risk evaluation and mitigation for the best possible patient health care.

Trends estimation of obesity prevalence among South Asian young population: a systematic review and meta-analysis.

The premise for effective prevention and treatment of obesity is the availability of accurate prevalence figures. However, the prevalence of pediatric obesity and overweight in South Asian countries has seldom been analyzed. This article provides a comprehensive review and meta-analysis of studies on overweight and obesity to provide a more precise prevalence estimate. The study protocol was registered on PROSPERO (CRD42022320625). PubMed and Embase databases were comprehensively searched from inception till September 2023. The random-effects model was utilized to derive the pooled prevalence of obesity and overweight. Subgroup meta-analysis was used to assess variations in prevalence estimates across subgroups. A meta-regression analysis was also performed to assess the trend of overweight and obesity over the years. 152 studies were included with 489,525 participants. The pooled prevalence was 12.4 (95% CI 11.1-13.6) for overweight, 6.6% (95% CI 5.6-7.8) for obesity, and 19.3% (95% CI 17.1-21.7) for obesity and overweight. In subgroup analysis, Bangladesh reported a higher prevalence for both obesity (8.9%; 95% CI 4.9-13.9) and overweight (13.6%; 95% CI 9.2-18.8). Meta-regression analysis found a significant association between obesity prevalence and the publication year (ß = 0.004; p = 0.03; R2 = 2.74%). The results of this study indicate a relatively higher prevalence of childhood obesity in South Asia, emphasizing the necessity for large-scale awareness efforts and context-specific preventative methods.

Societal costs of illness for infantile epileptic spasms syndrome and evolutionary cost prediction in the era of WHO's IGAP.

BACKGROUND: To achieve the goal of improving the quality of life for persons with epilepsy within the framework of the WHO's Intersectoral Global Action Plan (IGAP), our study aimed to assess the societal financial burden linked to infantile epileptic spasms syndrome (IESS), ensuring that children afflicted with IESS receive high-quality healthcare without enduring substantial financial constraints. METHODS: Between August 2022 and March 2023, 92 children with IESS (male: female: 2:1), recently diagnosed or previously followed-up, were recruited. We gathered costs for drugs, tests, and medical services, along with legal guardians' monthly income. Total expenditure was determined by multiplying unit costs by the yearly service usage commencing from the onset. Time series analysis was utilised to forecast the financial burden from 2022 to 2032. RESULTS: Clinicians' first choice of treatment was ACTH (n = 60, 65·2%), prednisolone (n = 25, 27·2%), and vigabatrin (n = 7, 7·6%) and the median cost of treatment during the initial year was INR 39,010 [USD 479·2]. The median direct medical, direct non-medical, and indirect cost were INR 31,650 [USD 388·4], INR 6581 [USD 80·8], and INR 10,100 [USD 124·07], respectively. Families lost a median of 12 days of work annually. Drug costs and loss of wages were the key factors in the financial burden. The projected and adjusted figures exhibited an incremental growth rate of 2·6% tri-annually. INTERPRETATION: This pioneering study in developing countries, the first of its kind, evaluates the societal cost, financial hardship, and trajectory of incremental cost in IESS. The primary drivers of the financial burden were pharmacological treatment and family work adjustments. The government shoulders 62% of the financial burden, and projected a triannual growth of 2·6% from 2022 to 2032. Our results rationalize policymakers' focus on incorporating IESS into social security programs, particularly in developing countries.

Identifying Risk Factors and Health Concerns Associated With Chronic Low Back Pain Among Northern Indians: A Community-based Study.

BACKGROUND: Chronic low back pain (CLBP) is a common and significant cause of disability globally. In their lifetime, 70% to 80% of adults will have low back discomfort at some point. Even though CLBP is a very disabling disorder, information about its prevalence and associated factors is sparse in the literature. OBJECTIVES: We aimed to determine the prevalence of CLBP and its risk factors among an adult population, as well as related health concerns and health-seeking behaviors. STUDY DESIGN: Cross-sectional study. SETTING: A tertiary care setting in Chandigarh, India from November 2017 through February 2020. METHODS: Adults of either gender who provided informed consent were included in the study. Sociodemographic and CLBP awareness data were collected using a standard questionnaire. Prevalence was expressed as proportion of sample, with 95% CI. For categorical and quantitative data, the chi squared and independent t test were utilized. Logistic regression was applied to identify significant risk variables and outcomes. A P value of <= 0.05 was considered significant. RESULTS: A total of 2,847 patients were enrolled, with a mean (SD) age of 38 (14) years; 61% of them were men. These patients had a CLBP lifetime prevalence of 16% (95% CI, 15-17; 457/2,847). In addition, 62% (285/457) of these patients visited their doctor/physician more than 10 times and 23% (103/457) sought the advice of 2 physicians to treat their CLBP. Increasing age (odds ratio[OR], 1.040, 95% CI, 1.032-1.049; P < 0.001), being underweight (OR, 3.315; 95% CI, 1.494-7.359; P < 0.003) and increasing pain frequency (OR, 1.616; 95% CI, 1.139-2.293; P < 0.007) were identified as potential CLBP risks. LIMITATIONS: The study was carried out in a single tertiary hospital in northern India; hence its results cannot be extrapolated. Also, we were unable to categorize CLBP based on how severe the symptoms were, such as complaint-only or debilitating. CONCLUSION: An effective, supervised program addressing the younger productive population to maintain a healthy weight, give up smoking, and encourage an active lifestyle should be implemented. KEY WORDS: Chronic low back pain, prevalence, health concerns, risk factors, public health.

Care of Children with Infantile Epileptic Spasms Syndrome and Applicability of Telemedicine Amidst the COVID-19 Pandemic.

This ambispective, observational study evaluated the impact of the COVID-19 pandemic on managing children with Infantile epileptic spasms syndrome (IESS) and the feasibility of telemedicine-based management for IESS. Caregivers of children with IESS were telephonically interviewed using a structured questionnaire and various relevant indices were compared between the study population and a pre-pandemic cohort from the same center. There was a significant increase in diagnostic lag during the pandemic (p = 0.04). Adrenocorticotropic hormone was the first-line antiseizure medication of choice in both cohorts and the response to treatment was also similar. Telemedicine was utilized by around 80% of caregivers and satisfaction rates with telemedicine were high. However, caregivers continued to rate physical consultations higher in preference.

Efficacy and Safety of Dietary Therapies for Childhood Drug-Resistant Epilepsy: A Systematic Review and Network Meta-analysis.

Importance: Despite advances in the understanding of dietary therapies in children with drug-resistant epilepsy, no quantitative comparison exists between different dietary interventions. Objective: To evaluate the comparative efficacy and safety of various dietary therapies in childhood drug-resistant epilepsy. Data Sources: Systematic review and network meta-analysis (frequentist) of studies in PubMed, Embase, Cochrane, and Ovid published from inception to April 2022 using the search terms ketogenic diet, medium chain triglyceride diet, modified Atkins diet, low glycemic index therapy, and refractory epilepsy. Study Selection: Randomized clinical trials comparing different dietary therapies (ketogenic diet, modified Atkins diet, and low glycemic index therapy) with each other or care as usual in childhood drug-resistant epilepsy were included. Abstract, title, and full text were screened independently by 2 reviewers. Data Extraction and Synthesis: Data extraction was conducted following Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline. Cochrane risk-of-bias tool was used to assess the study quality. Effect sizes were calculated as odds ratio with 95% CI using random-effects model. The hierarchy of competing interventions was defined using the surface under the cumulative ranking curve. Main Outcomes and Measures: Short-term (≤3 months) 50% or higher and 90% or higher reduction in seizure frequency and treatment withdrawal due to adverse events were the primary efficacy and safety outcomes. Results: Of 2158 citations, 12 randomized clinical trials (907 patients) qualified for inclusion. In the short term, all dietary interventions were more efficacious than care as usual for 50% or higher seizure reduction (low glycemic index therapy: odds ratio [OR], 24.7 [95% CI, 5.3-115.4]; modified Atkins diet: OR, 11.3 [95% CI, 5.1-25.1]; ketogenic diet: OR, 8.6 [95% CI, 3.7-20.0]), while ketogenic diet (OR, 6.5 [95% CI, 2.3-18.0]) and modified Atkins diet (OR, 5.1 [95% CI, 2.2-12.0]) were better than care as usual for seizure reduction of 90% or higher. However, adverse event-related discontinuation rates were significantly higher for ketogenic diet (OR, 8.6 [95% CI, 1.8-40.6]) and modified Atkins diet (OR, 6.5 [95% CI, 1.4-31.2]) compared with care as usual. Indirectly, there was no significant difference between dietary therapies in efficacy and safety outcomes. Conclusions and Relevance: This study found that all dietary therapies are effective in the short term. However, modified Atkins diet had better tolerability, higher probability for 50% or higher seizure reduction, and comparable probability for 90% or higher seizure reduction and may be a sounder option than ketogenic diet. Direct head-to-head comparison studies are needed to confirm these findings.

Translation, Adaptation, and Validation of Hindi version of Quality of Life of the Infant (QUALIN) for Use in Infants and Toddlers.

OBJECTIVES: To translate Quality of Life of the Infant (QUALIN), cross-culturally adapt the Hindi version of QUALIN (Hi-QUALIN), and evaluate its psychometric properties in children. METHODS: This cross-sectional study was performed at the tertiary-care center in North India over 21 mo (April 2019 to January 2021). Healthy children (aged 3 to 36 mo) visiting the hospital for vaccination, minor ailments, routine health checkup, and accompanying an ill sibling were included. Children with infantile spasms in same age group were also included. Hindi translations were carried out by bilingual translators who could fluently communicate and write in Hindi and English. Standard Hindi was used to avoid the misinterpretation or misunderstanding. Discriminant and Construct validity was determined utilizing the known-groups method and factor analysis. Reliability was analysed as internal consistency and test-retest reliability. RESULTS: Four hundred and sixty-four children were recruited through opportunity sample selection method with statistically significant difference between healthy and unhealthy children in total score of Hi-QUALIN (3-12 mo) and (13-36 mo). Finally, Hi-QUALIN (3-12 mo and 13-36 mo) consisted of 29 and 30 items constituting the five extracted factors respectively. Overall internal consistency was excellent (α = 0.92 and 0.88, respectively). Intra-class correlation coefficients (ICC) were 0.84 (95% CI: 0.78-0.89; p <0.0001) and 0.94 (95% CI: 0.93-0.96; p <0.0001) indicating excellent test-retest reliability. CONCLUSIONS: Hi-QUALIN has good psychometric properties and can be used for health-related quality of life (HRQoL) measurement in young children.

Opioid sparing strategies for perioperative pain management other than regional anaesthesia: A narrative review.

Opioids play a crucial role in pain management in spite of causing increased hospital morbidity and related costs. It may also cause significant risks such as postoperative nausea and vomiting (PONV), sedation, sleep disturbances, urinary retention and respiratory depression (commonly referred to as opioid related adverse effects) in postoperative patients. In order to evade these opioid related side effects and also improve pain management, multimodal analgesia i.e., combination of different analgesics, was introduced more than a decade ago. Both pharmacological and non-pharmacological techniques are available as opioid sparing analgesia. Research from around the world have proved pharmacological techniques ranging from acetaminophen, NSAIDs (non-steroidal anti-inflammatory drugs), N-methyl-D-aspartate receptor antagonists (NDMA), alpha-2 agonists, anticonvulsants such as gamma aminobutyric acid analogues, beta-blockers, capsaicin, lignocaine infusion to glucocorticoids to be effective. On the other hand, non-pharmacological methods include techniques such as cognitive behavioral therapy, transcutaneous electrical nerve stimulation (TENS), electroanalgesia, acupuncture and hypnosis. However, research regarding the effect of these non-pharmacological techniques on pain management is still needed.

Short-term and long-term efficacy and safety of antiseizure medications in Lennox Gastaut syndrome: A network meta-analysis.

PURPOSE: To assess the short-term and long-term comparative efficacy and safety of ASMs for Lennox-Gastaut syndrome (LGS). METHODS: Following a systematic literature search, randomized controlled trial (RCT) and open-label extension (OLE) studies on LGS comparing ASMs with placebo or other ASMs were included. ≥50% reduction in drop seizure frequency from baseline and occurrence of treatment-emergent adverse events (TEAEs) were the primary efficacy and safety outcomes. For short-term outcomes, a network meta-analysis (NMA) reporting odds ratio (OR) with 95% confidence intervals (CIs) and hierarchy of competing interventions [surface under the cumulative ranking curve(SUCRA)] was done. Long-term outcomes were reported as proportion with 95% CIs using the random-effects model. RESULTS: Fifteen studies including 1263 participants with LGS (aged 2-54years) receiving any of six ASMs [cannabidiol (CBD), clobazam (CLB), felbamate (FLB), lamotrigine (LTG), rufinamide (RFM), topiramate (TPM)] or placebo were included. High-dose CLB (1.0 mg/kg/day; CLB_H) [OR: 4.9; 95% CI: 2.3-10.8] was significantly associated with ≥50% reduction in drop seizure frequency as compared with placebo, and achieved the highest-ranking probability (0.89) based on SUCRA values (although there was an overlap between confidence intervals of effect sizes of CLB, RFM and CBD), while high-dose CBD (20 mg/kg/day; CBD_H) [OR: 3.8; 95% CI:1.6-9.0] had significantly higher odds for occurrence of any TEAEs and had the highest-ranking probability (0.85). Furthermore, the long-term treatment with CLB [78%; 95% CI: 70-85%] was associated with a significantly higher proportion of patients with reduction in drop-seizures, and long-term use of CBD [96%; 95% CI: 95-98%] was associated with a higher frequency of TEAEs. CONCLUSION: The study findings suggest that CLB_H, CBD and RFM are the most efficacious and safest in terms of both short and long-term outcomes with CLB_H probably leading the hierarchy. Future head-to-head trials comparing these ASMs are needed.

Effect of anxiety and psychologic stress on periodontal health: a systematic review and meta-analysis.

OBJECTIVE: The primary objective of this meta-analysis (PROSPERO No: CRD42019124695) was to assess the association between psychologic stress, anxiety, and periodontitis. DATA SOURCES: The electronic search was conducted using PubMed, Embase, and Scopus, by three independent reviewers till December 2019. The search was limited to human studies published only in English language. The fixed-effect model and random-effects model were used to obtain the overall mean difference, odds ratio (OR), and its 95% CI for all studies. The heterogeneity was calculated by I2 statistics. The Newcastle--Ottawa scale was used to assess the risk of bias in the included studies. Out of 775 potentially relevant articles, 25 studies were selected for systematic review and only 14 studies could be used for meta-analysis in three subsets. The pooled OR for stress and periodontitis was 1.78, which was statistically highly significant (I2 = 98.6%, P = .00). Mean salivary cortisol levels as a measure of stress in patients with periodontitis was 4.81 nmol/L (I2 = 98.0%, P = .08). State-Trait Anxiety Inventory value was seen as -1.28 (I2 = 0.0%, P = .06) for state anxiety and -0.11 (I2 = 0.0%, P = .85) for trait anxiety in patients with periodontitis. CONCLUSION: The findings indicate a role of psychologic stress and anxiety in the progression of periodontitis.

Health-related quality of life in transplant eligible multiple myeloma patients with or without early ASCT in the real-world setting.

There is no comparative health-related quality of life (HR-QoL) data of transplant eligible (TE) multiple myeloma (MM) patients undergoing early autologous stem cell transplantation (ASCT) and those without in the era of novel drugs. This study prospectively evaluated the serial HR-QoL in TE-MM using the EORTC QLQ-C30 and MY20 questionnaires. Barring the transient worsening in QoL one-month after ASCT, there was a comparable improvement in most QoL domains in both early-ASCT and no-early ASCT cohorts. Post-early-ASCT patients had higher global health scores (71.9 vs. 60.8, p < .05) than no-early ASCT at 12-months. Patients belonging to lower socioeconomic status (SES) were more likely not to undergo ASCT than middle-high SES patients (38.6% vs. 74.5%, p < .05). While age, gender had no impact on QoL, performance status, staging, and induction therapy impacted QoL. This study shows that early ASCT maintains QoL and should be encouraged in all TE-MM patients.

Comparative short-term efficacy and safety of add-on anti-seizure medications in Dravet syndrome: An indirect treatment comparison.

PURPOSE: Although cannabidiol and fenfluramine have been recently approved by the US Food and Drug Administration (FDA) for seizures in children with Dravet syndrome (DS), the comparative efficacy and safety of these and stiripentol as an add-on therapy for DS has not been evaluated in head-to-head trials. The current study aimed to assess the comparative efficacy and safety of add-on anti-seizure medications in DS. METHODS: PubMed and EMBASE database search and a manual search was done using keywords; "antiepileptic", "Dravet syndrome" and "antiseizure". The primary efficacy outcome was ≥50% reduction in convulsive seizure frequency from baseline while the safety outcome was treatment-emergent adverse events (TEAEs). Frequentist approach were used for combining direct and indirect evidence and network plots prepared. The drugs were ranked based on p-scores obtained using the surface under the cumulative ranking (SUCRA). Heterogeneity across studies was calculated by I2 statistic and Q test. RESULTS: Five randomized controlled trials (RCTs) with 565 patients with DS (2-20 years) who received placebo or any of the three active interventions (stiripentol, cannabidiol, and fenfluramine) were included. Compared with placebo, all the three drugs were associated with a significant reduction in convulsive seizure frequency from baseline. Stiripentol had the highest probability ranking for ≥50% reduction in convulsive seizure frequency from baseline [OR: 20.2; 95% CI: 2.1-198.0] and for occurrence of any treatment emergent adverse events (TEAEs) [OR:53.9; 95% CI: 1.4 to 2079.8] followed by fenfluramine and cannabidiol. However, for serious TEAEs, the ranking order was stiripentol followed by cannabidiol and fenfluramine. The trial on stiripentol had limited sample size explaining the wide confidence intervals for the comparative outcomes. CONCLUSION: In this indirect comparison, fenfluramine and stiripentol hadd comparable efficacy but fenfluramine appeareded to be safer in terms of less frequent serious TEAEs. Cannabidiol had relatively lower efficacy and was associated with serious TEAEs. A head-to-head trial between stiripentol, cannabidiol and fenfluramine is the need of the hour.

Efficacy and safety of low-dose naltrexone in painful diabetic neuropathy: A randomized, double-blind, active-control, crossover clinical trial.

BACKGROUND: There is a need for newer therapies for chronic painful diabetic neuropathy as the existing drugs have their own limitations. Clinical trials on low-dose naltrexone (1-5 mg/d) showed efficacy and safety in certain chronic painful conditions, but not in painful diabetic neuropathy. Hence the present study was planned. METHODS: Sixty-seven participants with painful diabetic neuropathy were randomized to receive either 2 mg naltrexone or 10 mg amitriptyline daily following a 2-week run-in period. The participants were followed up every 2 weeks for a total of 6 weeks. Up-titration was done (to 4 mg naltrexone or 25/50 mg amitriptyline) if the pain reduction was less than 20% on the visual analog scale (VAS) during the next follow-up visit. Efficacy was assessed using the change in VAS score at the end of 6 weeks from baseline. Safety was evaluated at each follow-up visit. After 2 weeks of washout period, the participants were crossed over to receive the comparator drug for another 6 weeks with similar evaluations. RESULTS: The difference (confidence interval) in the change in VAS score between groups from baseline was 1.64 (-0.92 to 4.20) in per-protocol analysis and 1.5 (-1.11 to 4.13) in intention-to-treat analysis. Eight and fifty-two adverse events were reported in the naltrexone and amitriptyline groups, respectively (P < .001). The most common adverse events were mild diarrhea with naltrexone and somnolence with amitriptyline. CONCLUSIONS: Low-dose naltrexone exhibited similar efficacy and a superior safety profile compared with amitriptyline in painful diabetic neuropathy.