Empowering Nursing Students to Prevent Medication Error-Related Harms: A Step Toward Improving Patient Safety.

Aim: Existing gaps in nursing curriculum particularly related to medication management such as administration and monitoring increase the propensity of nurses to commit medication errors during clinical practice. The present training program was conducted with an aim to sensitize and educate undergraduate nursing students on medication errors' related aspects. Methods: The participants were students pursuing bachelors nursing degree course (second and third year). The training "Medication errors: Role of Nurse practitioners" comprised of blended teaching methods such as theme lectures, hands on training exercises, small group case­based learning, role plays, and nursing officer's practical experiences. The participants' knowledge and perception about medication errors were assessed at baseline (pre-intervention phase) and 1 week after program (post-intervention phase) with the help of a structured self-administered questionnaire in English language. Results: A total of 110 nursing students participated in the program. Post program there was a consistent increase in the number of correct responses to all knowledge-based questions with a significant improvement in knowledge scores from baseline [Baseline: (mean ± SD) 12.62 ± 2.33; Post-training: 18.52 ± 2.22; P < .001]. There was a positive change in the perception about medication errors among students. The participants rated the overall quality of program as excellent [66 (60%)] or very good [40 (36.4%)]. More than 90% agreed on its applicability in their future practice. Conclusions: The training was quite successful in educating nursing students on medication errors. There is a constant need to educate nurses and other healthcare providers including doctors and pharmacists on medication safety related aspects with an ultimate goal to improve patient safety.

Cutaneous adverse drug reactions notified by pharmacovigilance in a tertiary care hospital in north India.

CONTEXT: Medication-related adverse events, apart from causing significant morbidity and mortality, increase the healthcare cost burden and lead to early treatment discontinuations. OBJECTIVES: Knowing the fact that cutaneous adverse drug reactions (cADRs) are most frequent, this study was conducted with an aim to describe their clinical profiles and preventive strategies. METHODS: All adverse drug reaction (ADR) forms filled from January 2012 to January 2013 were scrutinised and forms with cADRs analysed and assessed for causality, preventability and severity. RESULTS: Of 400 ADR forms, 109 included cADRs. Sixty-eight percent patients were males and mean ± SD age was 35 ± 18 years. Rash, Steven-Johnson syndrome and toxic epidermal necrolysis were the most common presentations. Most frequent culprit drugs included antibiotics and anti-inflammatory agents. Causality was probable or possible in majority. Ninety percent cases were "not preventable". Majority of the patients had mild to moderate reactions and recovered completely after medical management. CONCLUSIONS: Pharmacovigilance, with special attention to monitoring and reporting of cADRs must be encouraged. As major bulk of cADRs result from physician prescribed drugs, awareness on part of the physician can help in their timely detection and management, thereby restricting the associated damage.

The Availability of Essential Antimicrobials in Public and Private Sector Facilities: A Cross-Sectional Survey in a District of North India.

(1) Background: There is a need to assess the availability of essential antimicrobials, as the availability of an antimicrobial is a critical element of its rational use. We aimed to assess the availability of antimicrobials listed in the National List of Essential Medicines 2015, India (primary list), and a selected (secondary) list comprised of agents indicated for commonly encountered infectious illnesses in various healthcare settings and to identify the reasons for their non-availability. (2) Methods: A cross-sectional survey of 25 public, private, and other sector pharmacies was carried out in Rohtak, a district of the North Indian state of Haryana, from April to June 2022. (3) Results: Most of the antimicrobials surveyed were optimally available in various sector pharmacies with the exception of benzathine benzylpenicillin, benzylpenicillin, cloxacillin, cefazolin, cefuroxime, cefadroxil, amphotericin B, and antimalarials. The most frequent reasons for limited availability were low demand, no prescriptions, and the non-listing of drugs in the state's essential medicine list. (4) Conclusions: Enough evidence needs to be generated with respect to the status of availability of essential antimicrobials from different regions of India as well as other lower-middle-income countries to devise measures for ascertaining better availability of these agents, especially antibiotics at regional, national, and global scales.

Linguistic adaptation and validation of All Aspects of Health Literacy Scale (AAHLS): A health literacy assessment tool for use in Hindi-speaking population.

Background Health literacy plays an important role in determining healthcare and medication outcomes. There is a lack of an appropriate, validated scale to assess health literacy status among the Hindi-speaking population. We translated and validated the English version of the All Aspects of Health Literacy Scale (AAHLS) into Hindi. Methods We translated the scale as per WHO guidelines on translation and adaptation of instruments. We did preliminary pilot testing in 30 bilingual subjects and evaluated cross-language concordance of the scale. The final translated scale so obtained after cross-cultural adaptation was tested in a validation study on 130 subjects from the outpatient department of internal medicine in which test-retest repeatability, construct validity, discriminant validity and internal consistency were assessed. Analysis was done using paired t-test, one-way ANOVA, Cronbach α and intra-class correlation coefficient. Results An excellent correlation between Hindi and English versions of the scale for various factors ensured cross-language concordance. Hundred percentage response rate was observed in the validation study. The scale showed good internal consistency (Cronbach α=0.99). The difference in total mean AAHLS score was not statistically significant across different age groups, genders and educational levels. Factor analysis showed a positive correlation among four factors/components of health literacy. For test-retest reliability, the intra-class correlation coefficient for all the items in different factors was significant (range 0.88-1.00; p<0.0001). Significant association of critical literacy sub-scores with functional (r=0.274, p=0.002) and communicative (r=0.283, p=0.001) sub-scores revealed a good construct validity. Conclusion The Hindi translated version of the AAHLS scale is a valid and reliable tool to assess health literacy in the Hindi-speaking population.

An educational program on antimicrobial resistance and stewardship for staff nurses in a public tertiary care hospital in India.

BACKGROUND: Nurses, the largest group among healthcare professionals, hold a pivotal position to positively influence antimicrobial management by virtue of being in constant touch with patients and their widespread engagement in multiple activities relating to antimicrobial use. However, the existing gap in nursing curriculum particularly in areas related to antimicrobial resistance and optimal use of these agents limits the clinical application of nurses' skills and pose barrier to their contribution towards achieving desirable outcomes in patient care. This training program was conducted to increase the nurses' awareness on antimicrobial resistance (AMR) and sensitize them on their role in optimal antimicrobial management and stewardship activities. METHODS: Training comprised of 4 modules focussing on topics like key concepts on antimicrobials, AMR, infection prevention and control, antibiotic allergy, optimal use of antibiotics and antimicrobial stewardship (AS). The participants' knowledge at baseline and 1 week after program were assessed. RESULTS AND CONCLUSIONS: 190 nurses participated in the program. Post program there was a consistent increase in the number of correct responses to all knowledge-based questions pertaining to 4 modules. A significant improvement in knowledge scores for all modules from baseline was also seen. The participants rated the overall quality of program as very good and agreed on its applicability in their practice. The training program was quite successful in educating nurses on critical issues related to AMR and AS. Nurses need to be constantly trained and sensitized for their potential contributions in the field of AMR and stewardship.

Drug Utilization Research and Predictors of Outcomes in the Intensive Care Unit of a Tertiary Care Hospital: A Prospective Observational Study.

BACKGROUND: Multiple drugs are commonly prescribed to intensive care unit (ICU) patients owing to the disease profile, multiple organ dysfunction, prophylaxis, management of stress ulcers, nosocomial infections, etc. This study aimed to evaluate the drug utilization patterns and factors influencing mortality and duration of stay in ICU patients.  Methodology: A prospective observational study was conducted in the ICU of our tertiary care hospital, Postgraduate Institute of Medical Sciences, Rohtak. Data was collected from treatment charts of patients using a structured pretested proforma. World Health Organization Anatomical Therapeutic Chemical/Defined Daily Dose (WHO ATC/DDD) methodology and core prescribing indicators were used to assess drug utilization data. The effect of different variables on mortality and duration of stay in the ICU was evaluated using regression analysis. RESULTS: An average of 8.78 drugs were prescribed per patient. Among the 922 prescriptions, anti-infectives, anti-inflammatory drugs, and drugs acting on the gastrointestinal tract were the most frequent medication classes prescribed. Polypharmacy and trade name prescribing were common. For most of the drugs, the prescribed daily dose corresponded to the WHO-DDD except ceftriaxone and levofloxacin. Age, presence of cardiac disorders, and Glasgow Coma Scale (GCS) score at admission directly correlated with mortality while the use of diuretics had a negative correlation with the duration of ICU stay.  Conclusions: There is a need to rationalize drug therapy in the ICU with regard to limiting polypharmacy and emphasizing generic drug name prescribing and adherence to the essential drug list. Antibiotic prescription patterns, in particular, deserve a special focus keeping in mind the multitude of factors demanding aggressive antibiotic use in critically ill intensive care patients.

WHO-Point Prevalence Survey of Antibiotic Use Among Inpatients at a Core National Antimicrobial Consumption Network Site in North India: Findings and Implications.

Data on Point Prevalence Surveys (PPSs) in India are limited yet. We report findings of a PPS conducted in a core "National Antimicrobial Consumption Network site" under National Centre for Disease Control - WHO project "Point prevalence survey of antimicrobial consumption at healthcare facilities." A cross-sectional survey was conducted as per the "WHO methodology for PPS on antibiotic use in hospitals" in a tertiary care hospital in India in December 2021. Data were collected using predesigned and pretested questionnaire in separate hospital, ward, and patient forms. Eight hundred two inpatients (excluding ICUs) were covered out of whom 299 (37.3%) were on antibiotics with 11.7% receiving 3 or more antibiotics. Surgical prophylaxis (SP) (42.5%) and community acquired infections (32.8%) were the most common indications for antibiotic use. Of the patients, 92.5% received SP for more than 24 hrs. Most commonly prescribed antibiotics were penicillins with beta-lactamase inhibitors (22.3%). Of the total antibiotic prescriptions, 81.5% were from WHO essential medicines list and 12% from "not recommended" WHO AWaRe classification. Of the antibiotic prescriptions, 84.6% were parenteral. Few prescriptions complied with standard treatment guidelines (1.9%), documented indication for antibiotic use (11.6%), and stop/review date (4.4%) in notes. Double anaerobic cover accounted for 6.8% of the total prescriptions. Some identified areas for improvement were: formulation of hospital antibiotic guidelines, promoting culture of sending cultures, improvement in surgical antibiotic prophylaxis, decreasing use of antibiotic combinations and double anaerobic cover, fostering IV to oral switch of antibiotics, and ensuring effective communication among health care workers by documenting adequate information in medical notes.

Awareness Regarding Antimicrobial Resistance and Antibiotic Prescribing Behavior among Physicians: Results from a Nationwide Cross-Sectional Survey in India.

(1) Background: Understanding the physicians' knowledge, attitudes, and antimicrobial prescribing behavior is a crucial step towards designing strategies for the optimal use of these agents. (2) Methods: A cross-sectional online survey was conducted among clinicians across India between May and July 2022 using a self-administered questionnaire in English comprising 35 questions pertaining to demographic characteristics, knowledge, attitude, and practices domains. (3) Results: A total of 544 responses were received from 710 physicians contacted. Sixty percent of participants were males, with mean age of 34.7 years. Mean ± Standard Deviation scores for knowledge, attitude, and practices domains were 8 ± 1.6, 20.2 ± 3.5, and 15.3 ± 2.1, respectively. Higher scores were associated with basic [odds ratio (95% Confidence Interval), p value: 2.95 (1.21, 7.2), 0.02], medical and allied sciences [2.71 (1.09, 6.67), 0.03], and central zone [3.75 (1.39, 10.12), 0.009]. A substantial proportion of dissatisfactory responses were found regarding hospital antibiograms, antibiotics effective against anaerobes, WHO AWaRe (access, watch, and reserve) classification of antibiotics, and the role of infection prevention and control (IPC) measures in the containment of antimicrobial resistance (AMR). (4) Conclusions: There is a need to sensitize and educate clinicians on various issues related to antimicrobial use, such as antibiograms, double anaerobic cover, IPC practices, and guideline-based recommendations, to curb the AMR pandemic.

Causes of DMARD withdrawal following ADR within 6 months of initiation among Indian rheumatoid arthritis patients.

The present study was conducted in Indian rheumatoid arthritis (RA) patients prescribed disease-modifying anti-rheumatic drugs (DMARDs) to determine the incidence and type of adverse drug reactions (ADRs) leading to their withdrawal in the initial 6 months of therapy. This was considered important as pharmacogenetic variations in the pattern of RA in different populations and genetic differences in efficacy and safety to drugs demand separate studies to be conducted in different populations. Hospital records were used to identify 1,000 consecutive patients with RA fulfilling the American College of Rheumatology criteria and having at least 6-month follow-up. Age, gender, duration of arthritis, drug usage and ADR-related drug withdrawal were recorded from the charts. Most of the patients were put on single DMARD. Combined use of DMARD was less frequent and non-use of DMARD was common; however, disease control was good. The commonest DMARD used in our hospital was hydroxychloroquine 444 (44%) and the commonest combination used was methotrexate with hydroxychloroquine by 55 (6%). Sulphasalazine use showed preference to young and males. Supportive drugs used were NSAIDs by 883 (88%), corticosteroids by 646 (65%), paracetamol by 594 (59%) and amitriptyline by 88 (9%). Incidence of ADR-related DMARD withdrawal was maximum with leflunomide 2/15 (13.33%) followed by methotrexate 9/116 (7.76%), sulphasalazine 6/185 (3.24%), chloroquine 3/131 (2.29%) and hydroxychloroquine 8/444 (1.8%). Severity and symptomatology of disease, genetic pattern of patients, financial status, previous experience of the clinicians and patients, availability of drugs, patient expectations and compliance were the main factors that lead to a difference in pattern of therapy in our patients compared to other population.

Immune checkpoint inhibitors as neoadjuvant therapy in early triple-negative breast cancer: A systematic review and meta-analysis.

Context: Immune checkpoint inhibitors combined with chemotherapy are being evaluated in neoadjuvant settings in early triple-negative breast cancer (TNBC). Aim: To evaluate efficacy and safety of checkpoint inhibitors in early TNBC. Methods: Electronic search was done using PubMed, EMBASE, Google Scholar, Cochrane Central Register of Controlled Trials and clinicaltrials.gov to identify relevant articles till October 31, 2020. Clinical trials evaluating checkpoint inhibitors as neoadjuvant therapy in early-stage TNBC were included. Outcomes assessed included pathologic complete response (pCR), event-free survival (EFS), and safety. Statistical Analysis Used: Meta-analysis was conducted using Cochrane review manager (RevMan) version 5.4. Randomized controlled trials (RCTs) were assessed for quality using Cochrane Collaboration risk of the bias assessment tool, version 2.0 (ROB-2). GRADE analysis was done to assess the overall quality of evidence for all outcomes. Results: Out of 116 studies screened, 5 RCTs were included in meta-analysis. Compared to control group, programmed death-1 (PD-1)/programmed death-ligand 1 (PDL-1) inhibitor group was associated with significant increase in rate of pCR (odd ratio [OR] =1.71 [1.38-2.11]; P < 0.00001) and EFS (1.77 [1.21-2.60]; P = 0.003). There was a significant increase in risk of serious adverse events (risk ratio [RR] =1.53 [1.28-1.83]; P < 0.00001), adverse events of special interest (AESI) of any grade (RR: 1.5 [1.34-1.69], P < 0.00001) and grade 3 or higher AESI (RR: 2.8 [1.87-4.19], P < 0.00001) with PD-1/PDL-1 inhibitors compared to control. Conclusions: PD-1/PDL-1 inhibitors in combination with neoadjuvant chemotherapy for early TNBC show significant improvement in pCR irrespective of PDL-1 status and cancer stage.

Pharmacotherapy of heart failure with normal ejection fraction (HFNEF)--a systematic review.

AIM: The pharmacotherapy for heart failure with normal ejection fraction (HFNEF) is not as well defined as that for the treatment for heart failure with reduced ejection fraction (HFREF). Studies of the various drugs given for HFNEF have revealed conflicting results. The aim of this systematic review was to determine whether there is any benefit with pharmacotherapy in HFNEF in terms of cardiac outcomes. METHODS: Electronic and printed sources were searched until August 2010 for randomized controlled clinical trials (RCTs) comparing drug therapy with placebo in HFNEF. Weighted mean difference and pooled odds ratio (OR) with 95% confidence intervals were calculated. RESULTS: A total of six RCTs including 8410 patients with a mean follow-up period of 21 months were included in the analysis. Although there were no significant differences in all cause mortality between the two groups (pooled OR 0.95, 95% CI 0.79, 1.13, P= 0.55), the subgroup analysis revealed a slight but non significant advantage with the ß-adrenoceptor blocker group. There was no significant difference between the two groups in terms of cardiovascular mortality, hospitalization, worsening heart failure, ejection fraction, E : A ratio, deceleration time and E : E' ratio. CONCLUSION: There was no significant benefit of pharmacotherapy in HFNEF. This might have been because of a lack of stringent inclusion criteria for patients in the trials and lower power of the studies. Hence trials with well defined inclusion criteria, better power, longer follow-up periods and with echocardiographic parameters as endpoints are required to shed further light on this topic.

Evaluation of effect of isoflavone on thyroid economy & autoimmunity in oophorectomised women: a randomised, double-blind, placebo-controlled trial.

BACKGROUND AND OBJECTIVES: The potential of soy isoflavones to interfere with thyroid function has been reported. However, there are limited data regarding their effect on thyroid function and autoimmunity in surgical menopausal women. The present study aimed to evaluate the effect of isoflavones on thyroid function and autoimmunity, menopausal symptoms, serum follicle stimulating hormone (FSH) and estradiol levels in oophorectomised women. METHODS: A randomized, double blind, placebo-controlled trial was conducted in 43 oophorectomised women to evaluate the effect of soy isoflavones (75 mg/day for 12 wk) on serum thyroid profile (free T3, free T4, TSH, TBG and anti-TPO antibody titres) assessed at baseline, 6 and 12 wk after randomization. Assessment was also done for menopause symptom score (MSS) three weekly, and FSH and estradiol levels at baseline and at study completion. RESULTS: There was a significant alteration in free T3 levels in the group receiving isoflavones (4.05 ± 0.36, 4.12 ± 0.69 and 3.76 ± 0.55 pmol/l at baseline, 6 and 12 wk, respectively; P=0.02). However, the mean change in various thyroid parameters at 12 wk from baseline was not significantly different between the two groups. MSS was also significantly decreased at 9 and 12 wk from baseline with isoflavones (12.47 ± 8.15, 9.35 ± 5.23 and 9 ± 5.14 at baseline, 9 and 12 wk respectively; P=0.004) with significant improvement in urogenital symptoms compared to placebo. Isoflavones did not significantly affect other parameters during study period. There were no serious adverse events reported and the proportion of patients experiencing adverse events was similar between the two groups. INTERPRETATION AND CONCLUSIONS: Modest reduction in serum free T3 levels in the isoflavone group in the absence of any effect on other thyroid parameters might be considered clinically unimportant.

Repurposing old molecules for new indications: Defining pillars of success from lessons in the past.

Drug repurposing or studying existing drugs for potential therapeutic utility in newer indications has been identified as an attractive option for treating a number of diseases. Various strategies of drug repurposing include serendipitous observation of drug's unexpected effects, directing the failed investigational drugs to new indications and currently adopted systematic approach to identify, screen and develop existing drug molecules for new off-label indications. Drug repurposing is able to constructively overcome the bottleneck restraints encountered during traditional de novo drug development process in grounds of timelines, cost and resources. However, success rates of drug repurposing programs are not very impressive. Through a meticulous examination of some failed repurposing attempts we aimed to identify key factors leading to high attrition rate in such studies. Based on the fundamental elements of knowledge and evaluation, we have defined four pillars toward improving success rate in drug repurposing programs viz. sound knowledge of the repurposed drug's pharmacological characteristics (pillar 1: drug pharmacology); drug formulation considerations in new indication (pillar 2: drug formulation); evaluation in representative biological assays with translational potential (pillar 3: evaluation in biological assays); and robust clinical trial methodologies including biomarker driven approach to provide conclusive evidence of repurposed drug's efficacy in new indication (pillar 4: clinical evaluation). In addition to the pharmacological challenges, certain regulatory concerns, including lack of clear guidelines for evaluation and market exclusivity pose hurdles in the application of drug repurposing, which may however be overcome to a great extent by adopting some strategies as discussed in this review.

Inhaled route and anti-inflammatory action of ivermectin: Do they hold promise in fighting against COVID-19?

In an effort to curb the global pandemic due to coronavirus, the scientific community is exploring various treatment strategies with a special emphasis on drug repurposing. Ivermectin, an anti-helminthic drug is also being proposed for treatment and prevention of COVID-19. Ivermectin has demonstrated broad spectrum antiviral activity against both DNA and RNA viruses. Due to its potential to interfere with transport of SARS-CoV-2 nucleocapsid protein to nucleus, it is being proposed to have antiviral activity against this virus as well which has been confirmed in an in-vitro study. However, in-vitro to in-vivo extrapolation studies indicate an inability to achieve the desired IC50 levels of ivermectin after oral administration of doses up to 10 times higher than the approved anti-helminthic dose. In a modelling simulation study, drug accumulation in the lungs was noticed at levels having potential antiviral activity. It is hypothesised that inhaled formulation of ivermectin may be effective against SARS-CoV-2. Therefore, ivermectin administered via inhalational route needs to be explored for potential beneficial role in COVID-19 in preclinical and clinical studies. We also hypothesise the possibility of drug having anti-inflammatory action in coronavirus associated severe respiratory illness based on few in-vitro and in-vivo reports which however needs to be confirmed clinically.

Reno-protective potential of sodium glucose cotransporter-2 (SGLT2) inhibitors: Summary evidence from clinical and real-world data.

Type 2 diabetes mellitus is an independent risk factor for renal impairment, developing in due course to end-stage kidney disease (ESKD). Such progressive renal damage is related to an increased predisposition to cardiovascular events and mortality. Even with intensive glycemic control and use of nephro-protective renin angiotensin system (RAS) blockers, rise in the worldwide prevalence of diabetic kidney disease remains tenacious. Identifying drugs with potential to halt progressive renal damage is the pressing priority at present. Sodium glucose cotransporter 2 (SGLT2) inhibitors, by virtue of their glucose-lowering and additional pleotropic effects, such as weight reduction, blood pressure lowering, anti-inflammatory, anti-fibrotic effects etc. are postulated to affect systemic and intrarenal hemodynamic mechanisms in a favorable manner which ultimately contribute to beneficial processes in the kidney. The promising reno-protective efficacy of these drugs is further highlighted by a reduction in development/progression of albuminuria and stabilization of renal function associated with their use. In particular, recent cardiovascular and kidney disease focused outcome trials have effectively demonstrated reduced rates of ESKD and other hard renal end-points, including doubling of serum creatinine, renal transplantation, death due to renal causes etc. with SGLT2 inhibitors. In this review, we dig further deep into the proposed reno-protective benefit furnished by this class of drugs by summarizing the evidence generated from clinical trials and large real-world studies. Current guideline recommendations and probability of reno-protection being influenced by factors, such as diabetic status, baseline renal function, RAS blockade is also explored to discuss their intended use in clinical settings.

Zolpidem for Insomnia: A Double-Edged Sword. A Systematic Literature Review on Zolpidem-Induced Complex Sleep Behaviors.

BACKGROUND: Being a nonbenzodiazepine, zolpidem is believed to have a favorable side-effect profile and is widely prescribed for insomnia. However, in the past few years, numerous neuropsychiatric adverse reactions, particularly complex sleep behaviors (CSBs), have been reported with zolpidem. OBJECTIVE: To conduct a systematic review of zolpidem-associated CSBs. DATA SOURCES: An electronic search was conducted using MEDLINE, Embase, PubMed, and Cochrane database of systematic reviews to extract relevant articles till July 2020. STUDY ELIGIBILITY CRITERIA: Any type of literature article (case report, case series, and observational or interventional study) reporting CSBs associated with zolpidem. RESULTS: In this review, we present aggregate summarized data from 148 patients presenting with zolpidem-induced CSBs (79 patients from 23 case reports and 5 case series; 69 patients out of 1454 taking zolpidem [4.7%] from three observational clinical studies). Various types of CSBs associated with zolpidem were reported, most common being sleepwalking/somnambulism and sleep-related eating disorder. On causality assessment, around 88% of cases were found to have a probable association with zolpidem. LIMITATIONS: Extraction of data from observational studies and spontaneous reports, due to nonavailability of any randomized controlled trials relevant to the study objective. CONCLUSION AND IMPLICATION OF KEY FINDINGS: Zolpidem-induced CSBs, although not very common, may develop when the drug is used at therapeutic doses for insomnia. Doctors need to be alert to monitor such adverse effects of zolpidem and exercise caution while prescribing it.

Systematic review and meta-analysis of efficacy and safety of hydroxychloroquine and chloroquine in the treatment of COVID-19.

Repurposed drugs like hydroxycloroquine (HCQ) and chloroquine (CQ) are being tested for potential therapeutic role in COVID-19. We aimed to evaluate efficacy and safety of HCQ and CQ in COVID-19. Using PubMed, EMBASE, medRxiv, Google Scholar, clinicaltrials.gov, electronic search was carried out to identify relevant articles till June 2020 with re-evaluation in last week of November 2020. Observational and interventional clinical studies comparing efficacy of CQ or HCQ to standard management or other drug/s for SARS-CoV-2 infection patients were included. Cochrane review manager version 5.3 was used for synthesis of meta-analysis results. For randomized controlled trials, risk of bias was assessed using Cochrane Collaboration risk of bias assessment tool, version 2.0 (ROB-2). ROBINS-I was used for quality assessment of observational studies. Overall evidence quality generated by review was graded as per GRADE Recommendation. A total of 903 studies were screened. Nineteen studies were included in synthesis of meta-analysis with total of 4,693, 1,626, and 6,491 patients in HCQ/CQ, HCQ/CQ + AZ and control groups, respectively. HCQ/CQ treatment was associated with significantly increased rates of virological cure (OR = 2.08, 95%CI = 1.36-3.17; P = 0.0007) and radiological cure (OR = 3.89, 95%CI = 1.35 - 11.23; P = 0.01) compared to control. HCQ/CQ had no difference in unadjusted mortality rate (unadjusted OR = 0.98 95% CI = 0.70-1.37, P = 0.89, random effect model) and adjusted hazard ratio for mortality (adjusted HR = 1.05, 95%CI = 0.86--1.29; P = 0.64). However, a significant increase in odds of disease progression (OR = 1.77, 95%CI = 1.46-2.13; P < 0.00001) and QT prolongation (OR = 11.15, 95%CI = 3.95-31.44; P < 0.00001) was noted. The results with HCQ/CQ and azithromycin combination were similar to HCQ/CQ mono-therapy. In the light of contemporary evidence on effectiveness of HCQ/CQ, judicious and monitored use of HCQ/CQ for treatment of COVID-19 patients is recommended in low to middle income countries with emphasis on no mortality benefit. Registration number of Systematic review. Register in PROSPERO database: cRD42020187710.

Evaluation of antihyperalgesic effect of curcumin on formalin-induced orofacial pain in rat.

The present study was planned to evaluate the role of curcumin in the formalin-induced orofacial pain in rats that mimics typical human orofacial pain. Adult Wistar rats of either sex received an injection of 50 microL of 5% v/v subcutaneous formalin injection into one vibrissal pad and consequent facial grooming behavior was monitored. Animals exhibited two distinct periods of nocifensive grooming: (a) an acute phase lasting 0-6 min; and (b) a tonic phase lasting 6-45 min. The analgesic response of curcumin was observed at doses of 25, 50, 100, 200, 400 and 600 mg/kg i.p., administered 15 min prior to formalin injection. Another group received subanalgesic dose of diclofenac (0.2 mg/kg) and curcumin 25 mg/kg. Curcumin and diclofenac were administered 15 and 5 min prior to formalin injection respectively. Curcumin produced a dose-dependent inhibition of facial grooming in both acute and tonic phases compared to vehicle and potentiated the subanalgesic dose of diclofenac. The study results for the first time demonstrated the per se antinocifensive effect of curcumin and also exhibited a synergistic interaction with the subanalgesic dose of an NSAID in the facial pain model. More studies are necessary to elucidate the mechanisms of curcumin in this model of pain.

Evaluation of efficacy of metoprolol in patients having heart failure with preserved ejection fraction: A randomized, double-blind, placebo-controlled pilot trial.

BACKGROUND: There is a lack of evidence-based therapies for the treatment of heart failure (HF) with preserved ejection fraction (HFpEF). Beta blockers may provide some benefit in HFpEF due to their proven role in HF with reduced ejection fraction. AIM: The main objective of the present study was to evaluate the efficacy of controlled-release metoprolol (metoprolol succinate) in HFpEF. MATERIALS AND METHODS: This was an investigator-initiated, randomized, double-blind, placebo-controlled, 14-week pilot study with metoprolol succinate as a study drug. Dose titration protocol was used with optional upward titration of doses ranging from 25 to 100 mg. The end points included clinical, echocardiographic, biochemical (N-terminal pro-B-type natriuretic peptide and serum carboxy-terminal propeptide of procollagen type I), and quality of life (QoL) (SF-36) parameters. RESULTS: Twenty patients were enrolled in each of the treatment arms. An improvement in New York Heart Association class and exercise capacity was seen in both treatment arms. The mean change in various echocardiographic and biochemical parameters between the two groups was statistically insignificant. A significant improvement in some QoL parameters was observed in both the groups. No serious adverse events were seen. CONCLUSION: Hence, this pilot study showed that metoprolol succinate possibly has some beneficial role in HFpEF as reflected by improvement in some parameters. The findings highlight the need of a larger study with longer follow-up to provide a definitive answer.