Ocular adverse events associated with platins: a disproportionality analysis of pharmacovigilance data and extensive systematic review of case reports.

BACKGROUND: Anti-cancer drugs, particularly platinum-based chemotherapy drugs, have been showing ocular adverse events (OAEs) in patients undergoing chemotherapy, which is concerning due to the potential impact on patient's quality of life and the ability to continue effective cancer treatment. RESEARCH DESIGN AND METHODS: A retrospective case/non-case study was conducted using spontaneous reports on OAEs by platins from the FDA Adverse Event Reporting System (FAERS) database. A disproportionality analysis was performed by calculating the Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), and the Information Component (IC) to identify OAE signals for platinum-based chemotherapy drugs. In parallel, a review of case reports for OAEs from platins was conducted by a systematic literature search in PubMed and Google Scholar. RESULTS: Using disproportionality analysis, 69 signals were identified for platinum-based chemotherapy drugs and OAEs (carboplatin: 42, oxaliplatin: 16, cisplatin: 11). Choroidal infarction [PRR = 215.1; χ2 = 4527.1; lower bound (LB) ROR = 140.7; IC025 = 5.1] and orbital hemorrhage [PRR = 120.0; χ2 = 300.5; LB ROR = 35.1; IC025 = 1.3] were the strong signals identified for carboplatin. Optic disc hyperemia [PRR = 208.2; χ2 = 742.5; LB ROR = 74.1; IC025 = 2.2] and blindness cortical [PRR = 23.7; χ2 = 382.5; LB ROR = 14.8; IC025 = 3.1] were the signals identified for oxaliplatin and cisplatin, respectively. A total of 32 case reports of OAEs from platinum-based chemotherapy drugs were identified through a systematic search in PubMed and Google Scholar, strengthening the association. CONCLUSION: The study revealed a potential risk of OAEs when using platinum-based chemotherapy drugs as an anticancer medication.

The study aimed to investigate the risk of ocular adverse events (OAEs) associated with platinum-based chemotherapy drugs, namely cisplatin, carboplatin, and oxaliplatin. Analyzed data from pharmacovigilance databases and conducted a systematic review of case reports to identify and understand these potential risks.The Pharmacovigilance analysis revealed many reports detailing OAEs related to these platinum-based drugs. Notable findings included signals indicating serious adverse events such as blindness, retinal toxicity, and optic nerve damage. Further refinement of these signals, considering the influence of concurrent medications, confirmed the association between platinum drugs and OAEs.Additionally, the systematic review of case reports provided insights into specific OAEs observed in patients receiving platinum-based chemotherapy. Common adverse events included vision impairment, retinal issues, and tunnel vision, with some patients experiencing irreversible vision loss.The study highlighted the importance of recognizing and monitoring OAEs in platinum-based chemotherapy patients. It emphasized the need for healthcare providers to assess patients' ocular histories carefully before treatment and for regulatory authorities to incorporate relevant findings into drug safety guidelines. Overall, the research enhances patient care and safety in cancer treatment by providing comprehensive information on the ocular toxicity associated with platinum-based chemotherapy drugs.

Characteristics of isoniazid-induced psychosis: a systematic review of case reports and case series.

PURPOSE: Isoniazid, a first-line antitubercular drug, is associated with nervous system adverse drug reactions such as seizures, peripheral neuropathy, and psychosis. This systematic review of case reports and case series aimed to characterize the demographic, social, and clinical factors associated with isoniazid-induced psychosis in patients with active tuberculosis (TB) and those who received isoniazid for latent TB infection (LTBI). METHODS: We comprehensively searched the Embase, PubMed, and Scopus databases to identify relevant studies published between the date of inception of the database and June 2024. RESULTS: A total of 28 studies, including 21 case reports and 7 case series involved 37 patients who developed isoniazid-induced psychosis. A higher frequency of isoniazid-induced psychosis was observed during the first 2 months of treatment, with a relatively early onset observed among patients aged 18 years or less. Delusions and/or hallucinations are the common symptoms of isoniazid-induced psychosis. Psychomotor disturbances, disorganized speech or formal thought disorder, disorganized or abnormal behaviour, and neuropsychiatric symptoms (sleep disturbances, hostility or aggression, confusion, affective symptoms, anxiety symptoms, and cognitive difficulties) were the other symptoms observed in the included studies. More than 80% of cases rechallenged with isoniazid resulted in the recurrence of psychotic symptoms. CONCLUSION: Patients with TB and LTBI should be assessed for psychotic and neuropsychiatric symptoms during isoniazid therapy, mainly in the first 2 months. Further research is required to understand the impact of underlying risk factors, such as genetic predisposition and isoniazid pharmacokinetics, as well as the clinical utility and dosage recommendations of pyridoxine for managing isoniazid-induced psychosis.

Efficacy and safety of luseogliflozin in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

PURPOSE: Owing to the absence of the most recent evidence on the efficacy and safety of luseogliflozin, our study aimed to conduct a systematic review and meta-analysis of luseogliflozin in patients with type 2 diabetes mellitus. METHODS: A comprehensive search of electronic databases like PubMed, Cochrane CENTRAL, and Google Scholar was performed from the inception to the 31st of August 2023 to identify the randomized controlled trials (RCTs) that examined the glucose and body weight lowering efficacy and safety outcomes of luseogliflozin in comparison with control or other active treatments. The fixed or random-effect model was used based on the heterogeneity identified using the I2 statistic and Cochran's Q test. RESULTS: Out of 50 non-duplicate articles identified through database searching, 8 RCTs (11 studies) with 1922 patients were included in this study. The efficacy outcomes like HbA1c (MD: -0.59%; 95% CI: -0.90, -0.29; P < 0.001), FPG (MD: -16.01 mg/dL; 95% CI: -19.46, -12.57; P < 0.001), PPG (MD: -36.63 mg/dL; 95% CI: -43.71, -29.55; P < 0.001) and body weight (MD: -1.66 kg; 95% CI: -2.23, -1.12; P < 0.001) were significantly reduced with luseogliflozin compared to the control group. Regarding the safety outcomes, there was no statistically significant difference between the two groups for hypoglycemia (OR: 1.14; 95% CI: 0.70, 1.84; P = 0.60). However, pollakiuria (OR: 4.08; 95% CI: 1.71, 9.69; P < 0.001) and any ADRs (OR: 2.04; 95% CI: 1.33, 3.14; P < 0.001) were significantly higher in the luseogliflozin group compared to the control. CONCLUSION: The current study identified a significant improvement in efficacy outcomes of HbA1c, FPG, PPG, and body weight in the luseogliflozin group. Non-significant safety results may be due to a smaller population size and fewer studies. Hence, long-term multicentric RCTs are needed to identify the safety and efficacy in a diversified population.

Assessment of disease pattern and drug utilization among neurology intensive care unit patients in a developing country: an observational analysis.

OBJECTIVE: This study aimed to assess the disease pattern and drug utilization among admitted patients in a tertiary-care hospital's neurology intensive care unit (neuro ICU). METHODS: A prospective observational cohort study was conducted between August 2022 and January 2023. Patients of any age and gender admitted to the neuro ICU were included, but those who declined to participate were excluded. Demographics, clinical, and medication details were consistently gathered and maintained until discharge. The World Health Organization (WHO)/International Network of Rational Use of Drugs (INRUD) prescribing indicators and the Anatomical Therapeutic Chemical (ATC) classification/Defined Daily Dose (DDD) system were used to evaluate drug use. RESULTS: A total of 516 patients were included, predominantly male (65.1%), with an average age of 54.62 ± 15.02 years. The most common diagnosis was stroke [72.3%, comprised of hemorrhagic (46.7%) and ischemic (25.6%)], followed by seizure disorders (6.6%), and central nervous system infections (5.4%). Patients received an average of 7.8 medications, 32.3% prescribed by generic name, 16.0% antibiotics, 74.1% injections, and 100% essential drugs. A (28.5%), C (19.2%), N (17.3%), J (19.2%), B (13.5%), and R (2.3%) were commonly prescribed ATC classes of medications. Number of DDDs was maximum for pantoprazole and furosemide. Based on discharged status, 41.0% were discharged on request, 24.8% against medical advice, 23.8% routine, and 10.2% mortality during hospitalization. CONCLUSION: Our study reveals a high prevalence of hemorrhagic stroke, especially among men, diverging from global ischemic stroke trends. Irregular hypertension treatment is the primary cause, exacerbated by low healthcare knowledge in rural areas, where patients often discharge on request, probably due to poor socio-economic conditions. Urgent public awareness campaigns and further research are needed to address this elevated hemorrhagic stroke incidence.

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.

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.

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.

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.

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.