Impact of suspected adverse drug reactions on mortality and length of hospital stay in the hospitalised patients: a meta-analysis.

PURPOSE: To estimate the risk of mortality and length of stay in hospitalised patients who have experienced suspected adverse drug reactions (ADRs) as compared to patients who did not experience suspected ADRs. METHODS: A systematic literature search was conducted on databases for observational and randomised controlled studies conducted in any inpatient setting that reported deaths and/or length of hospital stay in patients who had suspected ADRs and did not have suspected ADRs during hospitalisation. PRISMA guidelines were strictly followed during the review. The methodological quality of included studies was assessed using a tool designed by Smyth et al. for the studies of adverse drug reactions. The meta-analytic summary of all-cause mortality was estimated using odds ratio-OR (95% CI) and length of stay using mean difference-MD (95% CI). Both outcomes were pooled using a random effect model (DerSimonian and Laird method). Subgroup and meta-regression were performed based on study variables: study design, age group, study ward, study region, types of suspected ADRs (ADRAd-suspected ADRs that lead to hospitalisation and ADRIn-suspected ADRs that occur following hospitalisation), study duration, sample size and study period. The statistical analysis was conducted through the 'Review manager software version 5.4.1 and JASP (Version 0.14.1)'. RESULTS: After screening 475 relevant articles, 55 studies were included in this meta-analysis. Patients having suspected ADRs had reported significantly higher odds of all-cause mortality [OR: 1.50 (95% CI: 1.21-1.86; I2 = 100%) than those patients who did not have suspected ADRs during hospitalisation. Study wards, types of suspected ADRs and sample size were observed as significant predictors of all-cause mortality (p < 0.05). Patients having suspected ADRs had reported significantly higher mean difference in hospital stay [MD: 3.98 (95% CI: 2.91, 5.05; I2 = 99%) than those patients who did not have suspected ADRs during hospitalisation. Types of suspected ADRs and study periods were observed as significant predictors of length of stay (p < 0.05). CONCLUSION: Suspected ADRs significantly increase the risk of mortality and length of stay in hospitalised patients. SYSTEMATIC REVIEW REGISTRATION: CRD42020176320.

Drug-related deaths among inpatients: a meta-analysis.

PURPOSE: To estimate the prevalence of drug-related deaths with regard to total hospital mortality and to explore the heterogeneity in its estimation through subgroup analysis, univariate and multivariate analysis. METHODS: Two investigators independently searched the PubMed and Google Scholar databases with appropriate key terms to identify observational and randomised studies assessing drug-related problems. The prevalence of drug-related deaths was estimated using a double arcsine method. The heterogeneity was explored through subgroup and univariate analysis for the following study characteristics: study design, age group, study ward, study region, types of drug-related problems, study duration, sample size and study period. The study variables showing significant effects were further explored through a multivariable regression model. The percentage of preventable drug-related deaths was explored as a secondary objective. RESULTS: Of the 480 full-text articles assessed, 23 studies satisfying the selection criteria were included. The mean percentage of drug-related deaths was 5.6% (95% CI: 3.8-7.6%; I2 = 96%). The univariable analysis showed study design (regression coefficient: 4.31) and study wards (regression coefficient: - 6.37) as heterogeneity modifiers. In the multivariable model, only the study ward was considered a significant predictor of drug-related deaths (regression coefficient: - 5.78; p = 0.04). The mean percentage of preventable drug-related deaths was 45.2% (95% CI: 33.6-57.0%; I2 = 60%). CONCLUSION: Drug-related problems are an important cause of mortality. The variability in its estimation could be explained by admission wards.

Efficacy and safety of lopinavir-ritonavir in COVID-19: A systematic review of randomized controlled trials.

BACKGROUND: Lopinavir-ritonavir is a repurposed drug for coronavirus disease-2019 (COVID-19). In this study, a pooled effect of lopinavir-ritonavir on mortality, virological cure, radiological improvement and safety profile in COVID-19 patients has been evaluated. METHODS: The databases were searched for comparative randomized controlled studies evaluating the efficacy and/or safety of lopinavir-ritonavir in COVID-19 patients. The mortality outcome was pooled as a risk difference (RD) with 95% CI. The virological cure, radiological improvement and adverse events were pooled as risk ratio (RR) with 95% CI. All outcomes were pooled using the Mantle-Hanzle method random effect model. The heterogeneity was assessed using the I2 test. RESULTS: Out of 82 full text assessed, seven studies were included in the analysis. The included studies had five different control interventions: supportive care (n=4), umifenovir (arbidol) (n=2), navaferon (recombinant anti-tumour and anti-virus protein) (n=1), lopinavir-ritonavir+novaferon (n=1) and lopinavir-ritonavir+interferon beta 1b+ribavirin (n=1). Lopinavir-ritonavir group did not show significant difference in mortality [RD: 0.00 (95% CI: -0.01, 0.02), I2=0], virological cure [RR: 1.06 (95% CI: 0.85, 1.31), I2=0%], radiological improvement [RR: 0.81 (95% CI: 0.62, 1.05)] and adverse events [RR: 2.59 (95% CI: 0.17, 38.90), I2=75%] than supportive care. Similarly, no difference was observed for any efficacy outcomes between lopinavir-ritonavir and other control interventions. We observed significantly high risk of adverse events with lopinavir-ritonavir as compared to umifenovir [RR: 2.96 (95% CI: 1.42-6.18); I2=0%]. CONCLUSION: There is no benefit of the addition of lopinavir-ritonavir to the standard care in COVID-19 patients.

Comparison of effectiveness of interventions in reducing mortality in patients of toxic epidermal necrolysis: A network meta-analysis.

BACKGROUND: Limited evidence is available about effectiveness and choice of immunomodulating treatment modalities for toxic epidermal necrolysis (TEN). AIMS: To compare the effectiveness of interventions to reduce mortality in patients of toxic epidermal necrolysis through network meta-analysis. METHODS: Studies were retrieved using PubMed, Google Scholar and Cochrane Database of Systematic Reviews from inception to September 18, 2018. Only English language articles were considered. Observational and randomized controlled studies having ≥ 5 TEN patients in each intervention arm were included. Two investigators independently extracted study characteristics, intervention details and mortality data. Bayesian network meta-analysis was performed using the Markov chain Monte Carlo (MCMC) approach through the random effect model. The ranking analysis was done to provide a hierarchy of interventions. The consistency between direct and indirect evidence was assessed through node spit analysis. The primary outcome was to compare the mortality [Odds ratio OR (95% credibility interval CrI)] among all treatment modalities of TEN. RESULTS: Twenty-four studies satisfying the selection criteria were included. The network analysis showed improved survival with cyclosporine as compared to supportive care [OR- 0.19 (95% CrI: 0.05, 0.59)] and intravenous immunoglobulin [OR- 0.21 (95% CrI: 0.05, 0.76)]. The hierarchy of treatments based on "surface under the cumulative ranking curves" (SUCRA) value were cyclosporine (0.93), steroid+intravenous immunoglobulin (0.76), etanercept (0.59), steroids (0.46), intravenous immunoglobulin (0.40), supportive care (0.34) and thalidomide (0.02). No inconsistencies between direct and indirect estimates were observed for any of the treatment pairs. LIMITATIONS: Evidence is mainly based on retrospective studies. CONCLUSION: The use of cyclosporine can reduce mortality in TEN patients. Other promising immunomodulators could be steroid+intravenous immunoglobulin combination and etanercept.

Does Adding of Hydroxychloroquine to the Standard Care Provide any Benefit in Reducing the Mortality among COVID-19 Patients?: a Systematic Review.

Hydroxychloroquine has been promoted for its use in treatment of COVID-19 patients based on in-vitro evidences. We searched the databases to include randomized and observational studies evaluating the effect of Hydroxychloroquine on mortality in COVID-19 patients. The outcome was summarized as odds ratios (OR) with a 95% confidence interval (CI).We used the inverse-variance method with a random effect model and assessed the heterogeneity using I2 test. We used ROBINS-I tool to assess methodological quality of the included studies. We performed the meta-analysis using 'Review manager software version 5.3'. We identified 6 observationalstudies satisfying the selection criteria. In all studies, Hydroxychloroquine was given as add on to the standard care and effect was compared with the standard care alone. A pooled analysis observed 251 deaths in 1331 participants of the Hydroxychloroquine arm and 363 deaths in 1577 participants of the control arm. There was no difference in odds of mortality events amongst Hydroxychloroquine and supportive care arm [1.25 (95% CI: 0.65, 2.38); I2 = 80%]. A similar trend was observed with moderate risk of bias studies [0.95 (95% CI: 0.44, 2.06); I2 = 85%]. The odds of mortality were significantly higher in patients treated with Hydroxychloroquine + Azithromycin than supportive care alone [2.34 (95% CI: 1.63, 3.34); I2 = 0%]. A pooled analysis of recently published studies suggests no additional benefit for reducing mortality in COVID-19 patients when Hydroxychloroquine is given as add-on to the standard care. Graphical Abstract.

Mortality among patients due to adverse drug reactions that occur following hospitalisation: a meta-analysis.

PURPOSE: To estimate the prevalence of mortality among patients that develop adverse drug reactions during hospitalisation (ADRIn), to examine heterogeneity through subgroup analysis and to identify system-organ class (SOC) and their causative drugs. METHODS: Two investigators searched PubMed, Google Scholar and related bibliography for studies reporting ADRIn-related mortality data. The primary outcome was to compute overall prevalence of fatal ADRIn (95% CI) using double arcsine method. We explored the heterogeneity (I2) in its estimation based on study design, study population and data collection methods. The secondary outcomes were the pattern of fatal reactions and their causative drugs. PROSPERO register number-CRD42018090331. RESULTS: Out of 349 full text assessed, 48 studies satisfying the selection criteria were included. The fatal ADRIn prevalence was 0.11% (95% CI 0.06-0.18%; I2 = 93%). The fatal ADRIn prevalence ranged from 0.03% (I2 = 0%) in all ages to 0.27% (I2 = 90%) in elderly population studies. Elderly studies varied for all study characteristics. Among study wards, a higher trend of prevalence was observed in 'internal medicine and ICU' (0.46%, I2 = 51%) and 'neonatal/paediatric ward and ICU' (0.34%, I2 = 58%) studies. The commonly involved SOC were 'gastrointestinal disorders' (28.79%), 'blood and lymphatic system disorders' (19.69%) and 'renal and urinary disorders' (13.64%). Most commonly observed causative drug-fatal ADRIn pairs were antithrombotics and nonsteroidal anti-inflammatory drugs induced gastrointestinal bleeding, and antineoplastic agents induced cytopenia. CONCLUSION: ADRIn is an important cause of mortality. Age groups and study wards have important influence on prevalence of fatal ADRIn and its heterogeneity across studies. Few class drugs contribute to sizable proportion of ADRIn-related mortality.

Mortality among patients due to adverse drug reactions that lead to hospitalization: a meta-analysis.

PURPOSE: The aim of this study was to estimate the prevalence of mortality among patients due to adverse drug reactions that lead to hospitalisation (fatal ADRAd), to explore the heterogeneity in its estimation through subgroup analysis of study characteristics, and to identify system-organ classes involved and causative drugs for fatal ADRAd. METHODS: We identified prospective ADRAd-related studies via screening of the PubMed and Google Scholar databases with appropriate key terms. We estimated the prevalence of fatal ADRAd using a double arcsine method and explored heterogeneity using the following study characteristics: age groups, wards, study region, ADR definitions, ADR identification methods, study duration and sample size. We examined patterns of fatal ADRAd and causative drugs. RESULTS: Among 312 full-text articles assessed, 49 studies satisfied the selection criteria and were included in the analysis. The mean prevalence of fatal ADRAd was 0.20% (95% CI: 0.13-0.27%; I2 = 93%). The age groups and study wards were the important heterogeneity modifiers. The mean fatal ADRAd prevalence varied from 0.01% in paediatric patients to 0.44% in the elderly. Subgroup analysis showed a higher prevalence of fatal ADRAd in intensive care units, emergency departments, multispecialty wards and whole hospitals. Computer-based monitoring systems in combination with other methods detected higher mortality. Intracranial haemorrhage, renal failure and gastrointestinal bleeding accounted for more than 50% of fatal ADRAdcases. Warfarin, aspirin, renin-angiotensin system (RAS) inhibitors and digoxin accounted for 60% of fatal ADRAd. CONCLUSIONS: ADRAd is an important cause of mortality. Strategies targeting the safer use of warfarin, aspirin, RAS inhibitors and digoxin could reduce the large number of fatal ADRAdcases.

Prevalence and pattern of antipsychotic induced movement disorders in a tertiary care teaching hospital in India - a cross-sectional study.

OBJECTIVES: To assess prevalence and pattern of movement disorders among patients taking antipsychotic medications. METHODS: This cross-sectional, intensive monitoring (patient interview, case record form review and clinical examination) study was conducted in patients taking antipsychotic drugs irrespective of duration for the development of movement disorders. The psychiatrist used Modified Simpson-Angus Scale score (10-item scale), Barnes' rating scale and Abnormal Involuntary Movement Scale to diagnose parkinsonism, akathisia and tardive dyskinesia, respectively. We assessed movement disorders for the preventability and seriousness. RESULTS: The overall prevalence of antipsychotic induced movement disorders was 5.67% (95% CI: 4.19-7.62). The prevalence of parkinsonism, akathisia and tardive dyskinesia was 5.10% (95% CI: 3.71-6.98), 0.85% (95% CI: 0.39-1.84) and 0.57% (95% CI: 0.22-1.45), respectively. There was a trend of high proportions of movement disorders in extreme of age group, female gender, patients treated with conventional antipsychotics, on poly therapy, patients of epilepsy with psychosis, schizophrenia and bipolar mood disorder. The movement disorder was lowest with quetiapine (2.02%). CONCLUSIONS: The higher use of atypical antipsychotics had reduced the occurrence of movement disorders in our setup.

Adverse drug reactions reporting by undergraduate medical students in a tertiary care teaching hospital of India: Content and quality analysis in comparison to physician reporting.

BACKGROUND: An important challenge to spontaneous reporting system is underreporting. The sensitization and involvement of undergraduate medical students can reduce underreporting in pharmacovigilance program. OBJECTIVE: To analyze the clinical characteristics and reporting quality of adverse drug reactions (ADRs) by undergraduate medical students in comparison with physicians' reporting. METHODS: We sensitized the second professional year undergraduate medical students about pharmacovigilance and asked them to submit reports of ADR observed during their clinical posting from January to December 2015. We compared students' reports with those sent by physicians (Department of Medicine and Allied Branches, Paediatric, Obstetrics and Gynaecology) of our institute during the same time period. We included ADRs of "certain," "probable," or "possible" categories as per the World Health Organization causality definitions in analysis of both groups. We excluded "unlikely," "unclassified," and "unclassifiable" causality ADRs from the analysis due to questionable association of reactions with suspected drugs. We collected data of demographics, pattern of ADRs, causative drugs, seriousness, other clinical characteristics, and quality of reporting. RESULTS: We analyzed a total number of 176 students' reports having 269 ADRs and 143 physicians' reports covering 180 ADRs. The students predominantly reported ADRs of single drug suspect (84.09% vs. 43.35%), "probable" causality (63.94% vs. 21.11), and augmented type reactions (67.29% vs. 55%) than physicians. Both groups did not differ in reporting of serious reactions (6.25% vs. 9.09%). Students most frequently suspected gastrointestinal disorders (35.68%), whereas physicians most frequently reported skin and appendages disorders (41.11%). Students and physicians more commonly suspected ADRs due to systemic anti-infective (33.64%) and nervous system (42.07%) class of drugs, respectively. The quality analysis suggested no substantial difference in most domains of ADR reporting among both groups. CONCLUSION: Students' reported valuable and clinically relevant ADRs. Medical students should be exposed to ADR reporting during their clinical teaching posting and should be actively involved in pharmacovigilance program to improve detection rate.

Efficacy and safety of aceclofenac in osteoarthritis: A meta-analysis of randomized controlled trials.

OBJECTIVE: To analyze the effects on pain, function, and safety of aceclofenac compared with other nonsteroidal anti-inflammatory drugs (NSAIDs) or pain relief medications in patients with osteoarthritis. MATERIAL AND METHODS: Two investigators independently searched the database. We included randomized controlled trials evaluating efficacy and/or safety of aceclofenac compared with control interventions (NSAIDs or acetaminophen) in patients with osteoarthritis. We did not include placebo, opioid analgesics, NSAID combinations, and topical analgesics for the control groups. We summarized the efficacy data as standardized mean differences (SMD) with 95% confidence intervals (CI) and safety outcomes as risk ratios (RR) with 95% CI using the inverse variance random effect model. We assessed the heterogeneity by the I2 test. We used the GRADE approach to evaluate the quality of the evidence for all outcome parameters. RESULTS: We included 9 trials (8 double blind and 1 single blind) that evaluated pain (7 trials), function (8 trials) and safety (7 trials). We observed no significant difference in pain reduction between aceclofenac and control interventions [SMD: -0.30 (-0.62, 0.01); I2=88%; GRADE evidence- low]. Aceclofenac was more beneficial than control interventions in improving physical function [SMD: -0.27 (-0.50, -0.03); I2=88%; GRADE evidence- low]. We observed less gastrointestinal adverse events for aceclofenac than in control interventions [RR 0.69 (95% CI: 0.57, 0.83); I2=12%; GRADE evidence- moderate]. We observed no difference in overall adverse events occurrence and dropout rate between aceclofenac and control interventions. CONCLUSION: We observed that aceclofenac was beneficial over control analgesics for function improvement and to minimize gastrointestinal adverse events. Our findings could be biased due to the heterogeneity of the sample, the fact that the trials were small and methodological issues.

Hospitalizations due to preventable adverse reactions-a systematic review.

PURPOSE: The study aimed to measure the percentage of preventable adverse drug reactions that lead to the hospitalization (PADRAd) and to explore the heterogeneity in its estimation through subgroup analysis of study characteristics. METHODS: Two investigators independently searched in electronic databases and related bibliography for prospective studies involving PADRAd. We excluded studies investigating medication errors and spontaneous and retrospective reporting. The primary outcome was PADRAd percentage. To explore the heterogeneity, we performed subgroup analysis based on study region, wards, age groups, adverse drug reaction (ADR) definitions, preventability assessment, ADR identification methods, study duration and sample size. We explored fatal PADRAd and causative drugs as a secondary outcome. We used the generic inverse variance method with random effect model to compute meta-analytic summary. RESULTS: Of the 68 full-text articles assessed, we included 22 studies. The mean PADRAd percentage was 45.11 % (95 % CI = 33.06-57.15; I 2 = 99 %). Studies including elderly (63.31 %) and all age groups (49.03 %) showed higher percentages than paediatric population (16.40 %). Studies examining all hospital populations showed higher percentages than specific wards. We observed high percentages in studies using Edwards and Aronson as an ADR definition and Hallas et al. as a preventability assessment tool. After age group adjustment, ADR detection methods did not show significant difference. The fatal PADRAd percentage was 1.58 % (95 % CI = -0.60 to 3.76; I 2 = 47 %). Paediatric and elderly studies showed a different causative drug pattern. CONCLUSION: Variation in PADRAd across the studies can be explained by difference in study populations and data collection methods. Extrapolation of preventable reactions should be carried out considering all these factors with caution.

Incidence of Adverse Drug Reactions in Indian Hospitals: A Systematic Review of Prospective Studies.

This systematic review estimated the incidence of ADRs that lead to hospitalization (ADRAd) and that developed during hospitalization (ADRIn) and factors affecting in Indian population. Two independent investigators searched the electronic databases describing ADRs. Due to high heterogeneity, incidence of ADRAd and ADRIn were presented as median (interquartile range-IQR). We performed the subgroup analysis of incidence based on characteristics of the included studies. The meta-analysis (generic inverse variance method with random effect model) was possible for the fatal ADR incidence. The risk factors for ADRs were also explored from the included studies. We used 'Review manager software version 5.0' and 'Graph Pad Prism version 6.0' for the analysis. Of 77 fully evaluated references, 21 prospective studies were selected. The median incidence of ADRAd and ADRIn were 2.85% (IOR: 1.25 - 3.93%) and 6.34% (IQR: 3.36 - 16.37%), respectively. The subgroup analysis found high incidence rate with studies conducted in intensive care units, elderly age groups, with intensive monitoring, duration of > 1 year and multidisciplinary team. The fatal ADR incidence was 0.08% (95% CI: 0.00-0.15%). Important risk factors for ADRs included elderly, female sex and polypharmacy. The hospitalized patients have a significant burden of ADRs. The multiple factors may have affected their occurrence.

Adverse drug reactions in a psychiatric department of tertiary care teaching hospital in India: Analysis of spontaneously reported cases.

The epidemiological data are limited for the spontaneous adverse drug reaction (ADR) reporting system in psychiatry and its comparison with intensive monitoring studies in terms of causative drugs, seriousness, preventability and drug interactions. This spontaneous ADR reporting study was carried out over a period of three years in the psychiatry department. We adopted WHO definition for an ADR, Naranjo's algorithm for causality, WHO-ADR terminology for the labeling of involved organ-system, International conference on harmonisation (ICH) E2A guidelines for seriousness, modified Schumock and Thornton's criteria for preventability and Medscape drug interaction checker for drug interactions. Two subgroup analyses were performed to find out the risk factors for the serious and preventable reactions. A total of 97 ADRs from 67 patients were included for analysis. The incidence of 'overall' and 'serious ADRs were 0.69% (95% CI: 0.54%, 0.88%) and 0.18% (95% CI: 0.12-0.29%), respectively. The females experienced more ADRs than males. The most commonly reported ADR, incriminated pharmacology group and drug, were extrapyramidal movement disorders (22.68%), atypical antipsychotics (35.62%) and escitalopram (13.91%), respectively. One out of five and one out three reactions were considered as 'serious' and 'preventable', respectively. The drug interactions contributed in 34.02% reactions. The factors significantly associated with 'serious' reactions were typical antipsychotics [OR: 5.47 (1.68, 17.87)], central and peripheral nervous system disorders [OR: 24.00 (5.12, 112.5)] and extrapyramidal reactions [OR: 14.03 (4.43, 44.43)]. The polypharmacy [OR: 5.85 (1.90, 18.03)] was significantly associated with 'preventable' reactions. The spontaneous reporting system is efficient to detect serious reactions and preventable reactions.

Efficacy and safety of lornoxicam vs ibuprofen in primary dysmenorrhea: a randomized, double-blind, double dummy, active-controlled, cross over study.

OBJECTIVES: Study was planned to evaluate the efficacy and safety of lornoxicam in moderate to severe menstrual pain due to primary dysmenorrhea. STUDY DESIGN: This doubled blind, double dummy, randomized, comparable study of lornoxicam versus ibuprofen was conducted at Sir Takhtsinghji General Hospital, Bhavnagar, Gujarat, India. Total 57 primary dysmenorrhea participants having mean age±standard deviation (SD) of 19.2±2.08 were analyzed. The participants were randomly allocated to either lornoxicam 8 mg or ibuprofen 400mg two times a day for maximum of three days on two consecutive menstrual periods. The different medication was taken on each cycle. The analgesic efficacy was compared by a total area under pain relief score to 4 and 8h, pain intensity difference, sum of pain intensity difference to 4 and 8h, peak pain intensity difference to 4 and 8h, peak pain relief to 4 and 8h, total medication consumption, rescue medication and participant global evaluation. Adverse effects were recorded in both groups. RESULTS: In both treatments, efficacy parameters were significantly reduced at measured time points as compared to baseline. No significant difference was observed between lornoxicam and ibuprofen in terms of efficacy parameters: total area under pain relief to 4h (8.0±2.6 vs 8.3±2.7), total area under pain relief to 8h (22.4±4.6 vs 23.0±4.4), sum of pain intensity difference to 4h (-5.7±1.9 vs -6.0±2.0), sum of pain intensity difference to 8h (-17.5±3.3 vs -17.8±3.5), peak pain relief to 4h (3.4±0.8 vs 3.5±0.8), peak pain relief to 8h (3.9±0.5 vs 3.9±0.4), peak pain intensity difference to 4h (-2.6±0.7 vs -2.7±0.7), peak pain intensity difference to 8h (-3.3±0.6 vs -3.3±0.6). Total medication consumption, a requirement of rescue medication and global evaluation of efficacy were comparable in both groups. The incidence of adverse effect was also similar in both groups. CONCLUSIONS: Lornoxicam appears to be a new therapeutic agent for the treatment of primary dysmenorrhea.

Drug-induced anaphylactic reactions in Indian population: A systematic review.

BACKGROUND: Epidemiological data on drug-induced anaphylactic reactions are limited in India and are largely depending on studies from developed countries. AIM: The aim was to analyze the published studies of drug-induced anaphylaxis reported from India in relation with causative drugs and other clinical characteristics. MATERIALS AND METHODS: The electronic databases were searched for Indian publications from 1998 to 2013 describing anaphylactic reactions. The information was collected for demographics, set up in which anaphylaxis occurred, causative drugs, incubation period, clinical features, associated allergic conditions, past reactions, co-morbid conditions, skin testing, IgE assays, therapeutic intervention and mortality. Reactions were analyzed for severity, causality, and preventability. Data were extracted and summarized by absolute numbers, mean (95% confidence interval [CI]), percentages and odds ratio (OR) (95% CI). RESULTS: From 3839 retrieved references, 52 references describing 54 reactions were included. The mean age was 35.31 (95% CI: 30.52-40.10) years. Total female patients were 61.11%. Majority reactions were developed in perioperative conditions (53.70%), ward (20.37%) and home (11.11%). The major incriminated groups were antimicrobials (18.52%), nonsteroidal antiinflammatory drugs-(NSAIDs) (12.96%) and neuromuscular blockers (12.96%). Common causative drugs were diclofenac (11.11%), atracurium (7.41%) and ß-lactams (5.96%). Cardiovascular (98.15%) and respiratory (81.48%) symptoms dominated the presentation. Skin tests and IgE assays were performed in 37.03% and 18.52% cases, respectively. The fatal cases were associated with complications (OR =5.04; 95% CI: 1.41-17.92), cerebral hypoxic damage (OR =6.80; 95% CI: 2.14-21.58) and preventable reactions (OR =14.33; 95% CI: 2.33-87.97). CONCLUSION: Antimicrobials, NSAIDs, and neuromuscular blockers are common causative groups. The most fatal cases can be prevented by avoiding allergen drugs.

Montmorillonite Poly-L-Lactide Microcomposites of Procainamide for controlled drug delivery: In vitro and In vivo evaluation.

The research work reported in this paper is extension of our previous findings related to intercalation of procainamide hydrochloride, an antiarrythmia drug in interlayer gallery of Na(+)-clay (montmorillonite). The microcomposite particles prepared from procainamide-montmorillonite hybrid and poly L-lactide were characterised by scanning electron microscope and atomic force microscopy analysis. In vitro drug release study in simulated intestinal fluid showed controlled release pattern up to ~72 h and significant reduction in the drug release in gastric environment. In vivo pharmacokinetics and biodistribution in rats showed that the plasma/tissue drug levels were within therapeutic window as compared with free drug. The data from toxicity biomarker estimations and clinical biochemistry/haematological parameters showed significant reduction in drug toxicity when formulated in montmorillonite/poly L-lactide as compared with free drug, which is of considerable value in achieving improved therapy with reduced side effects.

Antitubercular effect of 8-[(4-Chloro phenyl) sulfonyl]-7-Hydroxy-4-Methyl-2H-chromen-2-One in guinea pigs.

OBJECTIVE: TO EVALUATE THE ANTITUBERCULAR EFFICACY AND SAFETY OF NEW CHEMICAL ENTITY (NCE): 8-[(4-Chloro phenyl) sulfonyl]-7-Hydroxy-4-Methyl-2H-chromen-2-One (CSHMC) in guinea pigs. MATERIALS AND METHODS: This pilot study was carried out in guinea pigs. They were infected with M. tuberculosis H(37)Rv (1.5 × 10(4) cfu/guinea pig) via intramuscular route. After 30 days, infections were confirmed in 6 guinea pigs by histopathology of spleen, lung, and liver. After that CSHMC (5 and 20 mg/kg) was administered for 1 month and its effect was compared with vehicle, rifampicin (60 mg/kg) and isoniazid (30 mg/kg). Efficacy of CSHMC was evaluated on the basis of histopathologic scoring of lesion in lung, spleen, liver, and safety on the basis of measuring hemogram, liver and renal function parameters. RESULTS: Isoniazid, rifampicin, and CSHMC (20 mg/kg) significantly reduce the median lesion score in lung, spleen, and liver as compared to disease control group. Reduction in median lesion score for lung and spleen were not statistically significant for CSHMC 5 mg/kg. CSHMC (20 and 5 mg/kg) did not produce any changes in hemogram, liver and renal function parameters with respect to normal values. CONCLUSIONS: CSHMC had shown significant antitubercular efficacy comparable to isoniazid and rifampicin and did not show hematological, hepato- and nephrotoxicity.

Protective Effect of Ethanol Extract of Gymnosporia montana (Roth) Bemth. in Paracetamol-induced Hepatotoxicity in Rats.

The aim of the present study was to explore the hepatoprotective activity of the ethanol extract of leaves of Gymnosporia montana (Roth) Bemth. (Family: Celastraceous) against paracetamol-induced hepatotoxicity. Hepatotoxicity in Wistar rats was induced by a single intraperitoneal dose of 500 mg/kg of paracetamol and studied by comparing parameters such as serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, alkaline phosphatase and histopathological examination of liver. Pre and post-treatment with ethanol extract of Gymnosporia montana (Roth) Bemth. at doses of 50 and 100 mg/kg was studied by comparing the above mentioned parameters with silymarin (100 mg/kg) as standard. Both doses of ethanol extract of Gymnosporia montana (Roth) Bemth. were found to be hepatoprotective. Extract at the dose of 100 mg/kg produced effects comparable to those of silymarin. The present study indicates that alcohol extract of Gymnosporia montana (Roth) Bemth. possessed significant hepatoprotective activity.

Effect of pantoprazole and its interactions with vecuronium on the neuromuscular junction.

OBJECTIVE: To study the effect of pantoprazole on neuromuscular transmission and its interactions with vecuronium at the neuromuscular junction (NMJ). MATERIALS AND METHODS: Effect of pantoprazole on neuromuscular transmission (2 muM - 16 mM) and reversal of neuromuscular blockade by pantoprazole and vecuronium with neostigmine (3.3 muM), 3,4-diaminopyridine (0.25 mM), KCl (6 mM), and CaCl(2) (10 mM) were studied by the indirect and direct stimulated preparation of rat phrenic nerve hemidiaphragm. Cumulative reponse curves (CRC) of vecuronium (1 muM to 32 muM) were studied in the absence and presence of 32 muM, 64 muM, and 128 muM pantoprazole. Time for head drop by vecuronium infusion was recorded in the absence and presence of acute and chronic administration of pantoprazole (1.9 mg/kg) in rabbits. RESULTS: Pantoprazole potentiated the basal contractile twitch responses at a lower concentration followed by neuromuscular blockade at a higher concentration. The neuromuscular blockade was not reversed by neostigmine (3.3 muM), 3,4-diaminopyridine (0.25 mM), KCl (6 mM), and CaCl(2) (10 mM). Pantoprazole potentiated the vecuronium-induced neuromuscular blockade. It decreased the total time for complete blockade in rat phrenic nerve hemidiaphragm preparation (P < 0.05) and decreased the time for the head drop in rabbits with vecuronium infusion (P < 0.0001). CONCLUSION: Pantoprazole has a direct neuromuscular blocking action. It has the potential to interact with vecuronium.