Risk of serious skin and subcutaneous tissue disorders for nimesulide among the pediatric population: a jeopardy identified through the analysis of global individual case safety reports.

BACKGROUND: The safety reports arising currently on nimesulide are divulging the jeopardy of skin and subcutaneous tissue disorders (SSTDs). RESEARCH DESIGN AND METHODS: The global individual case safety reports on nimesulide-induced SSTDs available at VigiBase® were analyzed up to 31 March 2023. Disproportionality analyses viz. Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), and Information Component (IC) were performed to identify the quantitative signals. RESULTS: Out of 33,983,649 de-duplicated cases available in the VigiBase®, 1,664,134 (4.9%) were in pediatrics below 12 years of age. Among these, cases attributed to nimesulide were 251, of which 126 (50.2%) were on SSTDs. Among all the SSTDs reported for nimesulide, the serious reactions like urticaria [PRR = 2.3; lower bound (LB) ROR = 1.7; IC025 = 0.6], Stevens-Johnson syndrome (SJS) [PRR = 28.3; LB ROR = 18.2; IC025 = 3.2], angioedema [PRR = 7.5; LB ROR = 4.5; IC025 = 1.7], and toxic epidermal necrolysis (TEN) [PRR = 27.4; LB ROR = 11.5; IC025 = 1.5] were identified as potential signals. In comparison with non-SSTDs, SSTDs reported for nimesulide were significantly higher among children (2-11 years, 90.5%), from India (38.9%), and by the physician (60.3%). CONCLUSIONS: Identifying the giant quantitate association between nimesulide and serious & life-threatening reactions like SJS and TEN, precautionary measures need to be taken by the regulatory authorities to prevent nimesulide-induced SSTDs among the pediatric population.

Risk of pancreatitis and pancreatic carcinoma for anti-diabetic medications: findings from real-world safety data analysis and systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The existing evidence from pre- and post-marketing studies is conflicting on the risk of pancreatic events for anti-diabetic medications. RESEARCH DESIGN AND METHODS: A retrospective case/non-case study was conducted by using spontaneous reports on pancreatic events for anti-diabetic medications from the FDA Adverse Event Reporting System (FAERS) and VigiBase. Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), and Information Component (IC) were calculated by a disproportionality analysis. Furthermore, PubMed, Google Scholar, Scopus, and ClinicalTrials.gov were systematically searched for randomized controlled trials (RCTs) on anti-diabetic drugs with pancreatic outcomes. RESULTS: The FAERS data analysis found strong signals on incretin mimetics causing pancreatic events, with sitagliptin having the highest risk [PRR = 24.2, lower bound (LB) ROR = 24.4, IC025 = 4.4 for pancreatitis, and PRR = 15.4, LB ROR = 14.9, IC025 = 3.8 for pancreatic carcinoma]. Empagliflozin was the most pancreatitis-risk sodium-glucose co-transporter-2 inhibitor [PRR = 4.0, LB ROR = 3.5, IC025 = 1.8]. VigiBase reiterated these findings and identified some new signals for novel anti-diabetics. Meta-analysis revealed that the incidence of pancreatitis and pancreatic carcinoma with anti-diabetic medications was insignificant. However, compared to the placebo/active comparator, gliptins had a higher risk of acute pancreatitis (OR 1.44; 95% CI 1.03, 2.01; P = 0.03). CONCLUSION: Evidence from the post-marketing safety data analysis identified a strong association between incretin mimetics and pancreatic events. Fewer events in RCTs may justify insignificant meta-analysis results.

We conducted this research to identify the risk of pancreatitis and pancreatic carcinoma among anti-diabetic medications from pre-and post-marketing evidence available from clinical trials data and pharmacovigilance databases (FAERS, VigiBase). A disproportionality analysis of pharmacovigilance data was done to statistically check whether the selected drug-event pairs were frequently reported from the database (known as a 'signal'). We performed further signal refinement analysis using OpenVigil 2.1 on the generated signals to check whether the signal sustains even after removing co-prescribed medications possessing the same risk. Also, conducted a systematic review of randomized controlled trials for evidence generation regarding the pancreatic safety of the medications. The findings from real-world data indicated that, among all anti-diabetics, incretin mimetics and sulfonylurea compounds produced signals for both pancreatitis and pancreatic carcinoma. Notable pancreatitis risk was also identified for newer anti-diabetics like SGLT-2 inhibitors. The findings from the meta-analysis of clinical trials indicated a 44% risk of DPP-4 inhibitors in causing acute pancreatitis and a 60% risk of GLP-1 agonists in elevating the lipase level, compared to placebo/active comparator. Thus, the study raises concerns over the risk of pancreatitis and pancreatic carcinoma among the users of anti-diabetic medications, especially incretin mimetics.

Prevalence of Cognitive Decline in Type 2 Diabetes Mellitus Patients: A Real-World Cross-Sectional Study in Mysuru, India.

The goal of this research is to study the prevalence of cognitive impairment in diabetes mellitus (DM) patients and establish the necessity of detecting and treating it early in these patients. A cross-sectional study was conducted at a tertiary care hospital in Mysuru for 4 months examined diabetic patients (test) and nondiabetic subjects (control) for cognitive decline using the Montreal Cognitive Assessment (MoCA) tool. Cognitive functions such as visuospatial/executive function, naming, attention, language, abstraction, delayed recall, and orientation were assessed in both groups. The diabetic group showed a significantly lower total MoCA score than the non-diabetic group (18.99 ± 0.48 and 26.21 ± 0.46, respectively; p < 0.001). Assessment of scores in diabetic patients demonstrated the significant influence of age demographics on cognitive impairment (p-value < 0.001). Furthermore, a higher proportion of diabetic patients displayed cognitive impairment despite a higher score in a single subdomain, making it evident that diabetes is diverse and multifactorial in origin, where oxidative stress and inflammatory responses play a predominant role. This study suggested that the local T2DM population residing in Mysuru (India) has a high prevalence of cognitive impairment, evident from poor performance in almost all cognitive domains assessed by MoCA. Future studies could examine the generalizability of cognitive function findings in diabetic patients across diverse geographic regions and ethnic groups, as well as investigate interventions such as lifestyle modifications and medication to prevent or delay cognitive decline in those with diabetes.

Impact of medical conditions and medications received during pregnancy on adverse birth outcomes: A hospital-based prospective case-control study.

Purpose: In view of the raising rate of adverse birth outcomes (ABOs) across the globe, this study was conducted to assess the impact of medical conditions and medications received during pregnancy on ABOs. Materials and Methods: A prospective case-control study was conducted at the Department of Obstetrics and Gynecology of a tertiary care hospital over a period of 3 years from July 2015 to June 2018. Liveborn and stillborn neonates included in the study were categorized into cases and controls based on the presence or absence of composite ABOs, respectively. Binary logistic regression analysis was used to identify the risk factors for ABOs among medical conditions and medications received by mothers during their current pregnancy. Results: Among 1214 neonates included in the study, 556 (45.8%) were identified with composite ABOs, the majority were low birth weight (320 [26.4%]) and preterm birth 300 (24.7%). After adjusting for confounding factors, it was identified that hypertension (adjusted odds ratio [aOR] 7.3), oligohydramnios (aOR 3.9), anemia (aOR 3.2), nifedipine (aOR 10.0), nicardipine (aOR 5.3), and magnesium sulfate (aOR 5.3) were the risk factors for overall and specific ABOs like preterm birth and low birth weight. It was also identified that the early detection and management of hypertension with antihypertensives like labetalol and methyldopa can reduce the risk of preterm birth by 93% and 88%, respectively. Conclusion: Medical conditions such as hypertension, oligohydramnios, and anemia and medications such as nifedipine, nicardipine, and magnesium sulfate during pregnancy were identified as the risk factors for overall and specific ABOs like preterm birth and low birth weight.

Effect of L-Carnosine in Patients with Age-Related Diseases: A Systematic Review and Meta-Analysis.

INTRODUCTION: L-carnosine has been found to have multimodal activity. AIM: The aim of this review was to find out the efficacy of L-carnosine in patients with age-related diseases. METHODS: Clinical studies evaluated the effect of L-carnosine on cancer, cardiovascular disease, diabetes, and neurodegenerative disorders were searched in electronic bibliographic databases. The protocol has been registered with PROSPERO (CRD42022314033). The revised Cochrane risk of bias tool for randomized trials was used to assess all of the reports for risk of bias. RevMan 5.4 was used to conduct the meta-analysis. RESULTS: Following the screening process, 14 papers were selected for systematic review, with 9 of them being qualified for meta-analysis. Many of the included studies showed that L-carnosine has potential therapeutic activity in age related diseases. Results from the meta-analysis showed that in diabetes mellitus, HbA1c [mean difference (MD) 95% CI = -1.25 (-2.49, -0.022); p = 0.05; p = 0.001; I2 = 85%] and fasting blood sugar (FBS) [MD 95% CI = -12.44 (-22.44, -2.44); p = 0.01; p = 0.40; I2 = 0%] and in neurodegenerative disorder, Wechsler Memory Scale Logical Memory 2 (WMS-LM2) [MD 95% CI = 1.34 (0.83, 1.85); p < 0.00001; p = 0.43; I2 = 0%], showed statistically significant difference, favoring the L-carnosine group over the control group. While in neurodegenerative disorder, Alzheimer 's Disease Assessment Scale (ADAS) [MD 95% CI = 0.98 (-1.55, -0.42); p = 0.0007; p = 0.86; I2 = 0%] and Back Depression Inventory (BDI) [MD 95% CI = -1.12 (-1.87, -0.37); p = 0.003; p = 0.73; I2 = 0%] showed statistically significant difference, favoring the control group over L-carnosine group. CONCLUSIONS: Clinical studies were conducted to manage chemotherapy induced toxicities and there are no clinical studies available for its anti-cancer use, and the current evidence does not support its use in the treatment of cardiovascular disease.

Effect of garlic extract on markers of lipid metabolism and inflammation in coronary artery disease (CAD) patients: A systematic review and meta-analysis.

Several preclinical studies have focused on the beneficial effects of garlic on cardiovascular diseases, but the results were inconsistent. We performed a systematic review and meta-analysis on the effect of garlic powder tablets and aged garlic extract (AGE) in CAD patients, mainly focusing on blood pressure, coronary artery calcification, lipid profile, and inflammatory markers. We searched PubMed, Cochrane CENTRAL, and Google Scholar to identify randomized controlled trials which examined garlic's effect on CAD patients. The standardized mean difference with 95% CI was calculated using fixed-effect or random-effect models. Garlic has shown statistically significant changes of HDL (SMD = 0.18; 95% CI = -0.00 to 0.37; p = .05); LDL (SMD = -0.27; 95% CI = -0.46 to -0.08; p = .004), apolipoprotein-A (SMD = 0.68; 95% CI = 0.24 1.13; p = .002), C-RP (SMD = -0.59; 95% CI = -0.92 to -0.25; p = .0007), IL-6 (SMD = -1.08; 95% CI = -2.17 to 0.01; p = .05), homocysteine (SMD = -0.66; 95% CI = -1.04 to -0.28; p = .0007) and CAC score (SMD = -1.61; 95% CI = -2.66 to -0.57; p = .003). In the case of subgroup analysis, the overall effect was significantly effective in reducing TC, LDL levels and improving HDL levels in CV risk patients. Our study findings provide consistent evidence that intake of garlic reduces CVD risk factors. However, garlic could be considered a safe natural medicine to debilitate inflammation in CAD patients.

Efficacy, safety, and tolerability of isoniazid preventive therapy for tuberculosis in people living with HIV.

OBJECTIVE: The aim of this study was to systematically assess the efficacy, safety, and tolerability of isoniazid preventive therapy (IPT) for tuberculosis (TB) in people with HIV (PWH). DESIGN: A systematic review and meta-analysis. METHODS: A thorough literature search was performed using PubMed, Cochrane CENTRAL, and Google Scholar from their inception to June 30, 2021. All randomized controlled trials (RCTs) investigating the efficacy, safety, or tolerability of IPT on PWH compared with placebo or active comparators were included in the study. The heterogeneity among the studies was identified by using the I2 statistic and Cochran's Q test. RESULTS: Out of the 924 nonduplicate RCTs identified through database searching and other sources, 26 studies comprising 38 005 patients were included. The overall effect estimate identified the reduction of active TB incidence [odds ratio (OR) 0.69; 95% confidence interval (95% CI) 0.57-0.84; P  < 0.001], but not all-cause mortality (OR 0.91; 95% CI 0.82, 1.02; P  = 0.10) with IPT compared with the control. In addition, no significant association was identified between the use of IPT and the risk of peripheral neuropathy (OR 1.50; 95% CI 0.96-2.36; P  = 0.08) and hepatotoxicity (OR 1.21; 95% CI 0.97-1.52; P  = 0.09). CONCLUSION: This systematic review and meta-analysis identified a significant reduction in the incidence of active TB, but not all-cause mortality, among PWH who received IPT compared with the control. Lesser number of outcomes may be the reason for nonsignificant results in terms of safety outcomes of IPT. Therefore, there is a need for extensive and long-term studies to address these issues further, especially in TB/HIV endemic areas.

SGLT2 inhibitors associated pancreatitis: signal identification through disproportionality analysis of spontaneous reports and review of case reports.

BACKGROUND: In recent times, pancreatitis has been one of the most frequently reported adverse events for sodium-glucose cotransporter-2 (SGLT2) inhibitors. AIM: To evaluate the potential association between SGLT2 inhibitors and the risk of pancreatitis by analyzing the spontaneous reports through disproportionality analysis and reviewing case reports. METHOD: A retrospective case/non-case study was conducted using spontaneous reports from the FDA Adverse Event Reporting System (FAERS), VigiBase, and the Canadian Adverse Reaction Database (CARD). Disproportionality analysis was performed by calculating the Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), and the Information Component (IC). In parallel, a review of case reports was conducted on SGLT2 inhibitors-induced pancreatitis. RESULTS: A total of 524, 510, and 40 spontaneous reports of pancreatitis suspected to be caused by SGLT2 inhibitors were identified from FAERS, VigiBase, and CARD, respectively. Through the disproportionality analysis of FAERS data, a signal was identified between the SGLT2 inhibitors and pancreatitis, with empagliflozin having highest risk [PRR = 3.9; Lower Bound (LB) ROR = 3.4; IC025 = 1.7], followed by canagliflozin [PRR = 3.6; LB ROR = 3.2; IC025 = 1.6], and dapagliflozin [PRR = 3.2; LB ROR = 2.7; IC025 = 1.4]. VigiBase and CARD data analyses reiterated the findings of FAERS. Thirteen case reports identified from a systematic literature search strengthened these findings and highlighted the importance of physical examination and laboratory parameters for the early diagnosis of pancreatitis. CONCLUSION: The current study found a potential risk of pancreatitis with the use of SGLT2 inhibitors. There is an urgent need to thoroughly investigate the same and take the necessary action to avoid or minimize the risk.

Comparative efficacy and safety of oral nifedipine with other antihypertensive medications in the management of hypertensive disorders of pregnancy: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Hypertensive disorders of pregnancy are the most frequently occurring medical condition during pregnancy, resulting in fetal and/or maternal morbidity and mortality. This meta-analysis compared the efficacy and safety of nifedipine with other antihypertensive medications used in hypertensive disorders of pregnancy. METHODOLOGY: A comprehensive search was performed using PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar. The meta-analysis was carried out using Review Manager Software, and the pooled effect estimate was generated as standardized mean difference and odds ratio with 95% confidence interval and two-sided P -value. RESULTS: The meta-analysis was comprised of 22 randomized control trials with 2595 participants. It was found that meantime and number of doses required to achieve target blood pressure were lower in the nifedipine group ( P  < 0.05). Even though it is statistically insignificant, fetal APGAR (Appearance, Pulse, Grimace, Activity, and Respiration) scores less than seven favors nifedipine intervention. Furthermore, none of the fetal or maternal secondary outcomes were found significant. CONCLUSION: Nifedipine was found to be more effective than other antihypertensive medications to reduce blood pressure, particularly in patients with severe hypertension. However, future clinical studies, including real-world data are necessary to establish the safety profile of nifedipine concerning the fetal outcomes in hypertensive pregnant women.

Antifungal therapy in the management of fungal secondary infections in COVID-19 patients: A systematic review and meta-analysis.

OBJECTIVES: The prevalence of fungal secondary infections among COVID-19 patients and efficacy of antifungal therapy used in such patients is still unknown. Hence, we conducted this study to find the prevalence of fungal secondary infections among COVID-19 patients and patient outcomes in terms of recovery or all-cause mortality following antifungal therapy (AFT) in such patients. METHODS: We performed a comprehensive literature search in PubMed®, Scopus®, Web of Sciences™, The Cochrane Library, ClinicalTrial.gov, MedRxiv.org, bioRxiv.org, and Google scholar to identify the literature that used antifungal therapy for the management fungal secondary infections in COVID-19 patients. We included case reports, case series, prospective & retrospective studies, and clinical trials. Mantel Haenszel random-effect model was used for estimating pooled risk ratio for required outcomes. RESULTS: A total of 33 case reports, 3 case series, and 21 cohort studies were selected for final data extraction and analysis. The prevalence of fungal secondary infections among COVID-19 patients was 28.2%. Azoles were the most commonly (65.1%) prescribed AFT. Study shows that high survival frequency among patients using AFT, received combination AFT and AFT used for >28 days. The meta-analysis showed, no significant difference in all-cause mortality between patients who received AFT and without AFT (p = 0.17), between types of AFT (p = 0.85) and the duration of AFT (p = 0.67). CONCLUSION: The prevalence of fungal secondary infections among COVID-19 patients was 28.2%. The survival frequency was high among patients who used AFT for fungal secondary infections, received combination AFT and AFT used for >28 days. However, meta-analysis results found that all-cause mortality in COVID-19 patients with fungal secondary infections is not significantly associated with type and duration of AFT, mostly due to presence of confounding factors such as small number of events, delay in diagnosis of fungal secondary infections, presence of other co-infections and multiple comorbidities.

Macrolides versus placebo for chronic asthma.

BACKGROUND: Asthma is a chronic disease in which inflammation of the airways causes symptomatic wheezing, coughing and difficult breathing. Macrolides are antibiotics with antimicrobial and anti-inflammatory activities that have been explored for the long-term control of asthma symptoms. OBJECTIVES: To assess the effects of macrolides compared with placebo for managing chronic asthma. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register up to March 2021. We also manually searched bibliographies of previously published reviews and conference proceedings and contacted study authors. We included records published in any language in the search. SELECTION CRITERIA: We included randomised controlled clinical trials (RCTs) involving both children and adults with asthma treated with macrolides versus placebo for four or more weeks. Primary outcomes were exacerbation requiring hospitalisation, severe exacerbations (exacerbations requiring emergency department (ED) visits or systemic steroids, or both), symptom scales, asthma control questionnaire (ACQ, score from 0 totally controlled, to 6 severely uncontrolled), Asthma Quality of Life Questionnaire (AQLQ, with score from 1 to 7 with higher scores indicating better QoL), rescue medication puffs per day, morning and evening peak expiratory flow (PEF; litres per minutes), forced expiratory volume in one second (FEV1; litres), bronchial hyperresponsiveness, and oral corticosteroid dose. Secondary outcomes were adverse events (including mortality), withdrawal, blood eosinophils, sputum eosinophils, eosinophil cationic protein (ECP) in serum, and ECP in sputum. DATA COLLECTION AND ANALYSIS: Two review authors independently examined all records identified in the searches then reviewed the full text of all potentially relevant articles before extracting data in duplicate from all included studies. As per protocol, we used a fixed-effect model. We conducted a sensitivity analysis for analyses with high heterogeneity (I2 greater than 30%). GRADE was used to assess the certainty of the body of evidence. MAIN RESULTS: Twenty-five studies met the inclusion criteria, randomising 1973 participants to receive macrolide or placebo for at least four weeks. Most of the included studies reported data from adults (mean age 21 to 61 years) with persistent or severe asthma, while four studies included children. All participants were recruited in outpatient settings. Inclusion criteria, interventions and outcomes were highly variable. The evidence suggests macrolides probably deliver a moderately sized reduction in exacerbations requiring hospitalisations compared to placebo (odds ratio (OR) 0.47, 95% confidence interval (CI) 0.20 to 1.12; studies = 2, participants = 529; moderate-certainty evidence). Macrolides probably reduce exacerbations requiring ED visits and/or treatment with systemic steroids (rate ratio (RaR) 0.65, 95% CI 0.53 to 0.80; studies = 4, participants = 640; moderate-certainty evidence). Macrolides may reduce symptoms (as measured on symptom scales) (standardised mean difference (SMD) -0.46, 95% CI -0.81 to -0.11; studies = 4, participants = 136 ; very low-certainty evidence). Macrolides may result in a little improvement in ACQ (SMD -0.17, 95% CI -0.31 to -0.03; studies = 5, participants = 773; low-certainty evidence). Macrolides may have little to no effect on AQLQ (mean difference (MD) 0.24, 95% CI 0.12 to 0.35; studies = 6, participants = 802; very low-certainty evidence). For both the ACQ and the AQLQ the suggested effect of macrolides versus placebo did not reach a minimal clinically important difference (MCID, 0.5 for ACQ and AQLQ) (ACQ: low-certainty evidence; AQLQ: very low-certainty evidence). Due to high heterogeneity (I2 > 30%), we conducted sensitivity analyses on the above results, which reduced the size of the suggested effects by reducing the weighting on the large, high quality studies.  Macrolides may result in a small effect compared to placebo in reducing need for rescue medication (MD -0.43 puffs/day, 95% CI -0.81 to -0.04; studies = 4, participants = 314; low-certainty evidence). Macrolides may increase FEV1, but the effect is almost certainly below a level discernible to patients (MD 0.04 L, 95% CI 0 to 0.08; studies = 10, participants = 1046; low-certainty evidence). It was not possible to pool outcomes for non-specific bronchial hyperresponsiveness or lowest tolerated oral corticosteroid dose (in people requiring oral corticosteroids at baseline). There was no evidence of a difference in severe adverse events (including mortality), although less than half of the studies reported the outcome (OR 0.80, 95% CI 0.49 to 1.31; studies = 8, participants = 854; low-certainty evidence). Reporting of specific adverse effects was too inconsistent across studies for a meaningful analysis. AUTHORS' CONCLUSIONS: Existing evidence suggests an effect of macrolides compared with placebo on the rate of exacerbations requiring hospitalisation. Macrolides probably reduce severe exacerbations (requiring ED visit and/or treatment with systemic steroids) and may reduce symptoms. However, we cannot rule out the possibility of other benefits or harms because the evidence is of very low quality due to heterogeneity among patients and interventions, imprecision and reporting biases. The results were mostly driven by a well-designed, well powered RCT, indicating that azithromycin may reduce exacerbation rate and improve symptom scores in severe asthma. The review highlights the need for researchers to report outcomes accurately and according to standard definitions. Macrolides can reduce exacerbation rate in people with severe asthma. Future trials could evaluate if this effect is sustained across all the severe asthma phenotypes, the comparison with newer biological drugs, whether effects persist or wane after treatment cessation and whether effects are associated with infection biomarkers.

Prevalence, Risk Factors, and Cost Burden of Fall-Related Hospital Admissions in india.

OBJECTIVE: To assess prevalence, risk factors, and cost burden of fall-related hospital admissions among older people in India. Previous studies conducted in India have not focused on the number of fall-related hospital admissions.
DESIGN: A prospective observational study was carried out over 12 months. Socio-demographic, medical and medication details were collected from the patients, medical records, and treating physicians.
SETTING: The study was conducted in internal medicine, orthopedics, and emergency departments of a tertiary care teaching hospital in Mysuru, Southern India.
PARTICIPANTS: Patients 60 years of age or older, of any gender, admitted to hospital were included in this study.
MAIN OUTCOME MEASURE: Prevalence of fall-related hospital admission, fall-related hospital admission associated with medication use, and direct cost incurred due to fall-related hospital admission.
RESULTS: A total of 1,036 patients [Males 53.6%] with a mean (SD) age of 69.3 (8.1) years were included in the study. A total of 188 patients were admitted due to falling with the prevalence of 18.1%. The majority of patients fell due to environmental factors [105 (55.8%)]. Among medication-related falls (20), the majority were associated with the use of antihyperglycemics and antihypertensives. Increasing age, female gender, and multiple comorbidities were identified as risk factors for fall-related hospital admissions.
CONCLUSIONS: Falls are a common reason for hospital admission among older populations. Clinicians need to focus on modifiable risk factors to reduce the prevalence of falls and advise patients and their caregivers about appropriate self-care behaviors.

Effect of L-Carnosine in children with autism spectrum disorders: a systematic review and meta-analysis of randomised controlled trials.

Autism spectrum disorders (ASD) are an emerging health problem worldwide. So far, no definite cure for ASD exists. L-Carnosine is an amino acid containing ß-alanine and L-histidine which has been proposed to have neuroprotective, antioxidant and anti-convulsive properties that may benefit affected children with this disorder. This review aimed to assess the effect of L-Carnosine in the management of ASD in children. We systematically reviewed randomised controlled trials (RCTs) which documented the effect of L-Carnosine in children with ASD. A literature search was performed in PubMed, Cochrane Library, Google Scholar, ClinicalTrials.gov, Clinical Trial Registry-India databases from inception to December 20, 2020. Articles were selected based on pre-set inclusion/exclusion criteria. The primary outcomes were changes in social, communication and behavioural responses and the secondary outcomes were improvement in sleep disorders, gastrointestinal problems, oxidative stress markers and adverse effects. Jadad scale was used to assess the quality of RCTs and modified Cochrane risk of bias tool was used to check the risk of bias of the included studies. The meta-analysis was reported based on the fixed-effects model. Four double-blinded, placebo-controlled, RCTs and one open label trial with a total of 215 participants were selected for the review. All the trials were methodological of high quality according to the Jadad scale. The modified Cochrane risk of bias tool showed a low to high risk of bias. Results from the meta-analysis of three studies showed no significant difference between L-Carnosine and placebo groups in the Gilliam autism rating scale (GARS) (MD = - 2.57; 95% CI - 10.30, 5.16, p = 0.52) and in its socialisation (MD = - 1.51; 95% CI - 6.16, 3.14, p = 0.53), behaviour (MD = - 0.48; 95% CI - 4.82, 3.87, p = 0.83) and communication (MD = - 3.94; 95% CI - 10.00, 2.11, p = 0.20) subscales as well as the childhood autism rating scale (CARS) (MD = - 0.88; 95% CI - 6.96, 5.20; p = 0.78). Current data do not support the use of L-Carnosine in the management of children with ASD due to a low number of studies and sample size available. Further studies are warranted to know the effect of L-Carnosine for ASD management.

Knowledge, beliefs, and practice of pregnant women regarding medication use during pregnancy: a hospital-based cross-sectional study.

The purpose of this study was to assess the knowledge, beliefs, and practice (KBP) of pregnant women on medication use during pregnancy, and to identify the factors influencing KBP. A cross-sectional study was conducted in the Department of Obstetrics & Gynaecology of a tertiary care hospital over a period of nine months. Pregnant women receiving at least one medication were included in the study. A 19-item questionnaire was developed, validated, and used for assessing the KBP of pregnant women. Logistic regression analysis was used to identify the factors influencing the KBP. A total of 422 pregnant women with a mean (SD) age of 24.6 (4.05) years were included in the study. Pregnant women were having less knowledge on 'unsafe medications' and 'important medications' during pregnancy, wrong belief on 'stopping all medications during pregnancy', and less practice of 'asking Pharmacist how to take medications'. It was identified hat the age, education, occupation, and area of living were the factors influencing the knowledge and practice of pregnant women on medication use. This study identified the need for improvement in knowledge and practice of pregnant women who are young, having nil or low level of education, no occupation, and living in rural areas.IMPACT STATEMENTWhat is already known on this subject? Knowledge and beliefs on medication use play a vital role in medication adherence among pregnant women. Crisis in rural healthcare along with socio-demographic conditions and literacy status of Indian women may have contributed to the lack of understanding about use of medications during pregnancy.What the results of this study add? The knowledge of pregnant women was found to be insufficient on 'unsafe medications' and 'important medications' during pregnancy. Majority of the pregnant women believe that it is better for the foetus if they 'stop taking all medications during pregnancy'. 'Not asking Pharmacist how to take medications' is one important practice in India contributes less knowledge on medication use.What the implications are of these findings for clinical practice and/or further research? There is a need for improvement in knowledge and practice of medication use among pregnant women who are young, having nil or low level of education, no occupation, and living in rural areas.

Knowledge and beliefs towards universal safety precautions during the coronavirus disease (COVID-19) pandemic among the Indian public: a web-based cross-sectional survey.

Background: The novel coronavirus disease 2019 (COVID-19) is considered the most serious global health threat in recent times. As there is a current lack of approved treatments and vaccines, universal safety precautions (USPs) must be taken to deal with this emergency. Objective: The aim of this study was to assess the knowledge and beliefs of the Indian public with regard to USPs during the COVID-19 pandemic. Methods: A cross-sectional, web-based survey was conducted during March 2020. A 20-item self-administered questionnaire was developed, validated and distributed using Google Forms through social media networks. Binary logistic regression analysis was used to identify the factors influencing knowledge regarding COVID-19 USPs. Results: Of the 1117 individuals who participated in the survey, the mean age was 28.8 ± 10.9 years, 32.9% had a post-graduate education, 45% had a professional job, and 40% belonged to the upper-middle economic class. Overall, the mean correct response scores were 63% for USP knowledge and 83% for USP beliefs. All the sociodemographic variables were significantly (p < 0.001) associated with the USP knowledge levels. Importantly, students were less likely to have a lower level of USP knowledge compared with the other occupations (odds ratio 0.35, 95% CI 0.23-0.53; p < 0.001). Conclusion: Although the knowledge and beliefs of the Indian public towards USPs are encouraging, there is a need for long-term educational interventions as the dynamics and severity of COVID-19 rapidly change. These findings could guide public health authorities to make and implement precautionary measures to combat this pandemic.

Efficacy and Safety of Non-Steroidal Anti-Androgens in Patients with Metastatic Prostate Cancer: Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Prostate cancer (PCa) is the sixth primary cause of cancer death. However, conflicts are present about the efficacy and safety of Non-steroidal anti-androgens (NSAA) for its treatment. The aim of this study was to assess the efficacy and safety of NSAAs versus any comparator for the treatment of advanced or metastatic PCa (mPCa). METHODS: MEDLINE and the Cochrane Library were searched. References of included studies and clinicaltrials.gov were also searched for relevant studies. Only English language studies after 1990 were considered for review. Randomized controlled trials (RCTs) examining the efficacy and safety of NSAAs as compared with any other comparator including surgery or chemotherapy in mPCa patients were included. The outcomes include efficacy, safety and the tolerability of the treatment. The Cochrane Risk of Bias Assessment Tool was used for quality assessment. Two authors were independently involved in the selection, extraction and quality assessment of included studies and disagreements were resolved by discussion or by consulting a third reviewer. RESULTS: Fifty-eight out of 1307 non-duplicate RCTs with 29154 patients were considered for the review. NSAA showed significantly better progression-free survival [PFS] (Hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.46-0.78; P=0.0001), time to distant metastasis or death [TTD] (HR, 0.80; 95% CI 0.73-0.91; P<0.0001), objective response (Odds ratio [OR], 1.64; 95% CI 1.06-2.54; P=0.03) and clinical benefits (OR, 1.33; 95% CI 1.08-1.63; P=0.006) as compared to the control group. There was no significant difference observed between the groups in terms of overall survival (HR, 0.95; 95%CI, 0.87-1.03; P=0.18) and time to progression (HR, 0.93; 95% CI 0.77-1.11; P=0.43). Treatment-related adverse events were more with the NSAA group, but the discontinuation due to lack of efficacy reason was 43% significantly lesser than the control group in patients with mPCa. Rest of the outcomes were appeared to be non-significant. CONCLUSION: Treatment with NSAA was appeared to be better efficacious with respect to PFS, TTD, and response rate with considerable adverse events when compared to the control group in patients with metastatic PCa.

Prevalence and Predictors of Self-Medication Practices in India: A Systematic Literature Review and Meta-Analysis.

BACKGROUND: Self-Medication (SM) is a practice of using medications to treat selfdiagnosed symptoms without a legitimate prescription by a health care professional. Alongside posing a burden on a patient, SM practices are associated with certain unfavourable health conditions such as drug-resistance, adverse effects, drug-interactions, including death. OBJECTIVE: To systematically review and quantify the prevalence of SM practices and its associated factors in India. METHODS: A comprehensive systematic search was performed using scientific databases such as PubMed and Cochrane library for the peer-reviewed research articles that were conducted in India without any language and date restrictions. Studies which were cross-sectional by design and assessing the prevalence and predictors of SM practices in India were considered for the review, and all the relevant articles were screened for their eligibility. RESULTS: Of 248 articles, a total of 17 articles comprising of 10,248 participants were included in the meta-analysis. Overall, the mean prevalence of SM practices in India was observed to be 53.57%. Familiarity with the medication appears to be a major reason to practice SM (PR: 30.45; 95% Confidence Interval [CI]: 17.08-43.82; 6 studies), and the practice was noticed more among individuals from a middle-lower class family with a prevalence rate of 26.31 (95%CI: 2.02-50.60; P<0.0001). Minor ailments were the primary reason for practicing SM (PR: 42.46; 95%CI: 21.87- 63.06), among which headache was the most commonly reported (PR: 41.53; 95%CI: 18.05-65.02). CONCLUSION: Self-medication practices are quite frequent in India. While NSAIDs and anti-allergens are the most frequently utilized self-medicated drugs used for headache and cold and cough.

Impact of preterm birth and low birth weight on medical conditions, medication use and mortality among neonates: a prospective observational cohort study.

BACKGROUND: There is a paucity of studies conducted in India on neonatal outcomes of preterm birth and low birth weight. Hence, we aimed to assess the impact of preterm birth and low birth weight on medical conditions, medication use and mortality among neonates. METHODS: A prospective observational cohort study was conducted at the neonatal intensive care unit (NICU) over a period of 9 months. Neonates of either sex, admitted to NICU and who received at least one medication were enrolled in the study. Perinatal and demographic data, reason(s) for NICU admission, diagnoses, medications prescribed, medication-related problems, discharge status and the direct medical cost were documented and analyzed. RESULTS: Four hundred and five neonates were included in the study: 60.5% were boys, 32.7% were preterm and 44.2% were born underweight. Neonatal sepsis (n = 125, 16.7%), unconjugated hyperbilirubinemia (n = 83, 11.1%) and respiratory distress syndrome (n = 62, 8.3%) were the most common medical conditions and were significantly more common among preterm and underweight neonates. Nearly half of the medications prescribed were anti-infectives for systemic use (n = 1310, 47.4%). The mean number of medications received by neonates increased from term to extremely preterm (5.2-15.0) and normal birth weight to extremely low birth weight (5.0-14.9). Mortality rate was significantly higher among extremely preterm (66.7%), and very preterm (15.2%) neonates compared to term (2.9%) neonates. The median direct medical cost for NICU admission was INR 21,430 (USD 331). CONCLUSION: Medical conditions, medications prescribed and mortality rate were significantly higher among preterm and underweight neonates admitted to NICU.

Valproic acid and Stevens-Johnson syndrome: a systematic review of descriptive studies.

Valproic acid (VPA) is a commonly used antiepileptic drug (AED). Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis are the rare but fatal cutaneous adverse drug reactions for VPA. We aimed to identify and critically evaluate all the literature of SJS in association with VPA and to describe the clinical features of the condition. A literature search was conducted in MEDLINE/PubMed from inception to December 2017 and updated in July 2018 without any restrictions, and the references of included studies were also searched. The descriptive studies discussing any patients who experienced SJS followed by the use of VPA alone or along with any other AED for its main indication were included. Two authors were independently involved in the study selection and data extraction. Disagreements were resolved by consensus or by the discussion with a third reviewer. A total of 19 studies including 17 case reports and two case series of 98 were included in the review. In all studies, the dose of VPA ranged from 100 mg/day to a maximum dose of 1,000 mg/day and was administered for indications including epilepsy, seizures, schizophrenic affective disorders, and bipolar disorder. The mortality seen with severe cutaneous adverse drug reactions can be decreased by immediate withdrawal of opposing medications, providing symptomatic relief, and offering supportive care, all of which are the mainstay of controlling the condition. It is essential for healthcare professionals to be aware of the importance of monitoring SJS or any other cutaneous reactions followed by the use of valproic acid even though the incidence is low, but it is injurious to the patient.

Assessment of impact of pharmacophilia and pharmacophobia on medication adherence in patients with psychiatric disorders: A cross-sectional study.

AIMS: To investigate the impact of pharmacophilia and pharmacophobia on medication adherence among patients with psychiatric disorders. MATERIALS AND METHODS: A cross-sectional, observational study was conducted in the Department of Psychiatry over a period of 2 months. Patients above 18 years of age with a psychiatric diagnosis as per the International Classification of Diseases 10 and receiving at least one psychotropic medication (any medication capable of affecting the mind, emotions, and behavior) for >1 month were enrolled in the study. Patients who were critically ill, on magico-religious treatment (beliefs prevalent in a particular culture concerning various supernatural influences operating in the environment), diagnosis of dementia, or mental retardation and patients from whom reliable history of illness cannot be obtained were excluded from the study. Drug attitude inventory scale was used to classify patients into pharmacophilic and pharmacophobic groups. Medication adherence rating scale was used to identify the extent of medication adherence. RESULTS: Among 176 patients included, 110 were found to be pharmacophilic and 54 were pharmacophobic. The number of hospitalizations (P < 0.03) and adverse drug reactions (P < 0.001) were found to be higher in pharmacophobic group as compared to pharmacophilic group. Antipsychotics were found to be most commonly prescribed medications among pharmacophobic group (P < 0.001). In this study, patients who had pharmacophilia were found to be have higher adherence score (mean score: 6.98) than patients with pharmacophobia (mean score: 2.9), with P< 0.001. CONCLUSIONS: This study concluded that pharmacophobia toward psychopharmacological agents can significantly reduce the medication adherence among patients with psychiatric disorders.