Assessment of Potential Drug-drug Interactions (pDDIs) and Their Risk Factors Among Hospitalized Cardiac Patients in a Tertiary-care Center of Central India: A Retrospective Record-based Study.

Background: Patients with cardiovascular disorders (CVD) possess multiple comorbidities and are prone to be prescribed multiple drugs, thus predisposing them to various drug-drug interactions (DDIs). Objective: This study was carried out to assess the potential-DDIs (pDDIs) among the drugs prescribed to hospitalized patients with CVD and associated factors. Method: It was a retrospective study conducted with the help of the medical records department. Medical records of all the patients admitted to the cardiology department of our tertiary care center from January 1st, 2019, to December 31st, 2019, were included for analysis using Lexicomp, an up-to-date drug interaction screening tool. The pDDIs were divided into classes A, B, C, D, and X, and those belonging to classes D or X were considered clinically significant. Multiple logistic regression was used to analyze the association between the factors associated with and the occurrence of clinically significant pDDIs, with a P-value < .05 considered statistically significant. Results: Almost all the records reflected (335/338) at least 1 pDDI. A total of 4966 pDDIs were detected, of which the majority belonged to category C (75.3%), and 5.1% of pDDIs were clinically significant. The patients who were prescribed more than 10 drugs per day (OR = 2.46; 95% CI: 1.27-4.82; P = .008), prescribed parenteral formulation (OR = 1.84; 95% CI: 1.57-2.21; P < .0001), or had a diagnosis of acute coronary syndrome (OR = 2.33; 95% CI:1.1-5.12; P = .03) were associated with clinically significant pDDIs. Other factors, that is, female sex, use of fixed-dose combinations, and the triad of diabetes mellitus, hypertension, and dyslipidemia, were positively associated with clinically significant pDDIs. Conclusion: Even though every patient had at least 1 pDDI, the prevalence of clinically significant pDDIs was relatively less. Use of >10 drugs/day, parenteral formulation, patients with acute coronary syndrome were significantly associated with clinically significant pDDIs.

Trial Sequential Analysis and Meta-Analysis of Olanzapine in Pediatric Patients for Chemotherapy-Induced Nausea and Vomiting (CINV).

Background and Objective: Olanzapine (OLZ) containing regimens are approved in adults for chemotherapy-induced nausea and vomiting (CINV) receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC), and the same has not been approved in the pediatric population. In order to generate data regarding the efficacy and safety of OLZ as an adjunct to the standard of care (SoC) for CINV in pediatric patients receiving HEC/MEC, the review authors performed this systematic review and meta-analysis. Methods: A systematic literature search was performed through the databases Cochrane Library, Pub Med, and clinicaltrials.gov, from inception to September 2023, using keywords: "chemotherapy" and "olanzapine," "nausea" and "vomiting." Randomized clinical trials published in English that analyzed the efficacy and safety of olanzapine as an adjunct to SoC were included. The essential outcomes included in this study were the proportion of patients with no emesis in the acute and delayed phase, patients with no nausea in the acute and delayed phase, the proportion of patients requiring rescue medication, and the proportion of patients with reduced CNS arousal. Results: In the OLZ group, a greater number of patients had no emesis both in the acute and delayed phase (RR = 1.22; 95% CI = 1.09-1.37; P = .0004); and (RR = 1.23; 95% CI = 0.92-1.63; P = .16) respectively. Similarly, a higher number of patients showed no nausea both in the acute and delayed phase (RR = 1.08; 95% CI = 0.78-1.48; P = .66) and (RR = 1.12; 95% CI = 0.79-1.61; P = .52) respectively. The use of rescue medication was significantly less in the OLZ group (RR = 0.62; 95% CI = 0.42-0.91; P = .01). More patients experienced reduced CNS arousal in the OLZ group (RR = 2.97; 95% CI = 2.02-4.38; P < .0001). Conclusions: Olanzapine as an adjunct to the SoC may be effective in acute emesis, which may also reduce the use of rescue medication. Reduced CNS alertness was the significant adverse effect observed. For other endpoints, more studies are required to substantiate its role in CINV.

Olanzapine-Samidorphan for Schizophrenia: A Systematic Review and Meta-Analysis.

Background and Objective: United States Food and Drug Administration (USFDA) recently approved a novel combination of olanzapine-samidorphan (OLZSAM) for managing olanzapine-associated adverse events (weight gain) in adult patients with schizophrenia and bipolar disorder. To opine about the safety and efficacy of OLZSAM, authors performed a systematic review and meta-analysis to convene justifiable evidence. Methods: A thorough literature search was performed through the databases Embase, Cochrane Library, PubMed, and clinicaltrials.gov, from inception to September 2022, with the keywords: 'olanzapine and samidorphan' and schizophrenia; and "ALKS3831" and "lybalvi." Clinical trials published in English that analyzed the efficacy and safety of OLZSAM were included. The significant outcomes included in this study were change from baseline (CFB) in Positive and Negative Syndrome Scale (PANSS) at the end of the study, the proportion of patients with weight gain at the end of the study, the proportion of patients with at least one adverse event, and the incidence of drug discontinuation due to adverse events. Results: The change in PANSS score at the end of the study was comparable among groups receiving OLZSAM and olanzapine alone: standardized mean difference (SMD) = 0.04; 95% CI = -0.09 to 0.17; p = 0.57. The OLZSAM group reported less incidence of weight gain: risk ratio (RR) = 0.91; 95% CI = 0.62-1.34; p = 0.63, and any adverse event: RR = 0.99; 95% CI = 0.90-1.09; p = 0.81. Drug discontinuation incidence was higher in the OLZSAM group: RR = 1.22; 95% CI = 0.84-1.79; p = 0.30. Conclusions: The combination OLZSAM showed comparable efficacy to olanzapine alone in schizophrenia patients, with relatively less incidence of weight gain and adverse events; however, the drug discontinuation due to adverse events was more in the OLZSAM group.

Assessment of knowledge, attitude and practice of fixed-dose combinations amongst attending physicians and residents: a cross-sectional evaluation.

Background: Fixed-dose combinations (FDCs) were brought into the market with the intent of providing benefits primarily to patients and physicians. Nevertheless, despite their multiple advantages, they have their own set of drawbacks, especially regarding irrational FDCs. If physicians continue to prescribe them, prohibiting their sale would become all the more challenging. This cross-sectional survey study was planned to comprehend the level of knowledge, attitude and practice of physicians regarding such FDCs at a tertiary care teaching institute of western Uttar Pradesh, India. Methodology: A pre-validated questionnaire was communicated electronically to all the attending physicians. For data analysis, descriptive statistics were applied and a χ2 test was performed for inter-group comparison. Results: Amongst the 108 respondents, participation was almost comparable from both medical and surgical branches, with most participants being junior residents (58%). Even with sound knowledge of FDCs, only 46.30% of them were aware of banned FDCs. Similarly, only 6.48% could correctly identify the disadvantages associated with the use of FDCs, and 33.18% could correctly recognize irrational FDCs. This finding was consistently reflected in their attitude and practice and only 15.74% of respondents cross-referenced FDCs with the available literature. Furthermore, despite 88.89% of respondents checking for rationality of FDCs before prescribing them, a compendium of irrational FDCs is routinely prescribed. Conclusion: To amend these shortcomings in prescribing of irrational FDCs, some recommendations are proposed by the authors herein.

Trofinetide in Rett syndrome: A brief review of safety and efficacy.

Rett syndrome (RTT) is a rare genetic neurological disorder that primarily affects girls and is caused by mainly mutations in the methyl-CpG-binding protein 2 (MECP2) gene, leading to critical issues in normal brain function. The condition has a global prevalence of 5 to 10 cases per 100,000 females, and there is currently no cure for RTT. However, therapy is available to manage the symptoms and improve quality of life. Trofinetide, an insulin-like growth factor 1, was originally developed as a stroke medication and progressed to Phase II clinical trials, where it exhibited favorable safety and efficacy profiles by improving several core RTT symptoms. Recently, Trofinetide received the US Food and Drug Administration (FDA) approval and orphan drug designation for the treatment of RTT, making it the first approved drug for this rare genetic disorder. It has also shown to be safe, well-tolerated and with no known drug interactions. These findings suggest that Trofinetide is a promising treatment option for individuals with RTT.

Physician's knowledge, attitude and practice of fixed drug combinations: Can we recognize the lacunae?

Objective: The Indian pharmaceutical market is flooded with different fixed drug combinations (FDCs), many of which lack a rational justification. The study aimed to assess the knowledge, attitude, and practice (KAP) regarding FDCs among the physicians of a tertiary-care teaching center. Method: The target sample size for this cross-sectional study was calculated as 75, and the study was conducted between February and August 2020 by using a content-validated questionnaire. Descriptive statistics had been utilized for data analysis, and Chi-square test had been applied for intergroup comparison (with P < 0.05 considered to be significant). Results: The mean age of the physicians who participated in this survey was 33.2 years. While 44% of them could identify all the potential advantages of using FDCs, only 09% could correctly recognize all the disadvantages associated with the same. Among the list of rational and irrational FDCs, only 49% could single out the irrational ones. And though the majority (83%) of the respondents do check for the rationality of FDCs before prescribing them, still out of 25 most commonly prescribed FDCs, 16 lacked any scientific justification for combination, and 09 (out of 16) had been banned by the Government of India. Conclusion: The outcome of this cross-sectional questionnaire-based study reflects the deficit in the knowledge regarding FDCs, as well as incoherence among the knowledge, attitude, and prescription practice. Though the physicians have cultivated a healthy attitude towards prescribing FDCs, the same is not reflected in their practice. In order to rectify these disparities, the authors have proposed certain recommendations within this article.

The Profile of Use of Rituximab in Tertiary Care Hospitals of Central India.

Background: Rituximab, one of the most commonly used biologics, was once approved by the United States Food and Drug Association (US FDA) for the management of different systemic autoimmune disorders, and it is now used extensively in managing off-label indications. There is a scarcity of data regarding its utilization pattern in India. Objective: To assess rituximab usage pattern in two tertiary care hospitals of Central India. Methods: A cross-sectional, retrospective study was performed to analyze the data of patients from two tertiary care centers of Central India who had received rituximab between 2019 and 2021. The usage was categorized either for FDA-approved indications or for off-label indications. Multiple logistic regression was applied to evaluate which factors would influence the use of rituximab for an FDA-approved indication. Results: A total of 79 medical records of patients. The majority of the patients (77.2%) had received rituximab for an FDA-approved indication. The most common approved and off-label indications detected were non-Hodgkin's lymphoma and autoimmune disorders, respectively. The use of rituximab for an FDA-approved indication was associated with increased age (adjusted odds ratio [AOR] = 1.04, 95% confidence interval [CI] = 0.99-1.1), male sex: AOR = 2.55, 95% CI = 0.74-9.93, malignancy: AOR = 9.39, 95% CI = 1.46-76.12, and diabetes: AOR = 1.38, 95% CI = 0.19-13.74. Conclusions: The use of rituximab was more common for an FDA-approved indication rather than for an off-label indication. Factors such as advancing age, male sex, and malignancy were frequently associated with the FDA-approved use of rituximab.

Ditans vs Gepants: A Systematic Review and Indirect Network Meta-Analysis for Comparative Analysis of Efficacy and Safety.

BACKGROUND: An acute attack of migraine, incapacitates the migraineurs, and is widely prevalent. And to warden off its symptoms, recently two groups of drugs have been approved and launched. OBJECTIVE: The aim of this systematic review and indirect meta-analysis is to evaluate and summarize the effectiveness of these pharmacological interventions in managing the aforesaid disease. MATERIAL AND METHODS: An extensive literature search was done through Cochrane library, Pub Med, clincialtrials.gov, for a period of 5 years (2015-2020), using key words: lasmiditan; ubrogepant; rimegepant; and acute migraine. Randomized double-blind phase III clinical trials, published in English language, were included which explored the efficacy and safety of these drugs. The outcomes of this meta-analysis included proportion of patients' headache, most bothersome symptoms free, and no disability at all at 2 h post-dose, with sustained pain freedom 2-24 h, and experiencing any adverse event. An indirect network meta-analysis was also conducted to determine the comparative effectiveness of these drugs. RESULTS: A total of seven RCTs involving 7266 patients were included. In general, the new drugs demonstrated better result in all the efficacy parameters. The adverse events were observed in treatment group compared to placebo. While in the indirect comparison, lasmiditan emerged to be superior in all the outcomes, except for sustained pain freedom 2-24 h (rimegepant was better). The adverse events were more with lasmiditan. CONCLUSION: All the newer drugs have shown significant improvement in the outcomes analyzed. Lasmiditan appears to be superior among the newer drugs in efficacy; however it has more adverse effects.

Istradefylline Versus Opicapone for "Off" Episodes in Parkinson's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: In recent times, the US-FDA approved istradefylline and opicapone as an adjunct to levodopa/carbidopa for managing the "off" episodes in Parkinson's disease. PURPOSE: Current meta-analysis was performed to determine the safety and efficacy of these drugs in the management of "off" episodes and to recognize which among them would provide therapeutic benefits clinically. METHODS: A thorough literature search was performed through the Cochrane Library, PubMed, and clinicaltrials.gov for a period from January 2003 to October 2020, with the following keywords: Istradefylline, KW-6002, opicapone, BIA 9-1067, and Parkinson's disease. Those randomized, double-blind placebo/active comparator-controlled trials that analyzed the efficacy and safety of istradefylline and opicapone and that were published in the English language were included. In this analysis, the outcomes focused on the least square mean change in "off" time and Unified Parkinson's Disability Rating Scale (UPDRS) III score from baseline to the end of the study, and the incidence of treatment-emergent adverse events (TEAEs) and dyskinesia. RESULTS: Both drugs have shown significant reduction in "off" time duration (mean difference [MD] = -0.70; 95% CI [-1.11, -0.30]; P < 0.001 for istradefylline and MD = -0.85; 95% CI [-1.09, -0.61]; P < .001 for opicapone). Istradefylline showed significant improvement in UPDRS III (MD = -1.56; 95% CI [-2.71, -0.40]; P < .008), but the same was not observed with opicapone (MD = -0.63; 95% CI [-1.42, -0.15]; P < .12). The incidence of TEAEs and dyskinesia reportedly were higher in the intervention group rather than with the placebo, (risk ratio RR =1.11, 95% CI [1.02,1.20] for istradefylline and RR =1.12, 95% CI [1.00,1.25] for opicapone, and for dyskinesia particularly, the incidence was higher with opicapone as compared to istradefylline (RR = 3.47, 95% CI [2.17, 5.57], and RR = 1.77, 95% CI [1.29, 2.44], respectively). CONCLUSIONS: Both drugs were comparable in efficacy; however, istradefylline seemed to be better in reducing the UPDRS III score. Although the incidence of TEAEs and dyskinesia were higher with both the drugs, the incidence of dyskinesia was more in the opicapone group.

The outlook of doctors toward telemedicine: A cross-sectional study of knowledge, awareness, and attitude in central India.

BACKGROUND: In an underdeveloped country like India where there are varied constraints in accessing healthcare, telemedicine can prove to be instrumental in providing access to the scant medical resources and infrastructures. The irony lies in its underutilization, which is multifactorial. OBJECTIVE: The present research was planned to evaluate the level of awareness, knowledge, and attitude toward telemedicine among the faculty members of tertiary-care teaching centers in Chhattisgarh, India. METHODS: A questionnaire-based survey was conducted to collect appropriate data, which were utilized for analysis as well as various intergroup analyses (among different designations, age groups, sex, and worksite). The data have been presented as median and percentage, while for intergroup comparison Mann-Whitney Test was performed. RESULTS: Among the 115 respondents, only 34% were females. The mean age was around 40.7 years, and 58% were <40 years of age. Their median scores of awareness, knowledge, and attitude were estimated to be 06, 14, and +9, respectively. No statistically significant difference was observed in the awareness, knowledge, and attitude among the faculty members belonging to different designations, age groups, and worksites. CONCLUSIONS: Though, in general, the faculty members have demonstrated a favorable attitude toward the use of telemedicine yet most of them scored below the median mark. Furthermore, the estimated level of knowledge and awareness was also mediocre.

Retrospective Analysis of Drug Prescription Statistics in a Tertiary Care Center in India: Recommendations for Promoting Prudent Utilization of Drugs.

OBJECTIVE: Drug utilization studies provide information regarding the drug usage pattern in hospital settings, which can be used to promote cost-efficient uses of drugs. The present observational retrospective study was conducted to evaluate the drug utilization pattern in a tertiary care center in India and create a baseline consumption data for the drugs, simultaneously identifying targets for improving drug prescribing pattern. METHODS: The current retrospective cross-sectional study was conducted at All India Institute of Medical Sciences Raipur, wherein the 217 medical records of different departments for August 2019 were chosen randomly (using systematic random sampling) for evaluation. The information was extracted from medical records regarding the basic demographic details, drug strength, route, and total amount, and eventually, the World Health Organization (WHO) core indicators were estimated. Drug utilization data were assessed using the WHO Anatomical Therapeutic Chemical/Defined Daily Dose (ATC-DDD) methodology. Potential drug-drug interactions were also analyzed. FINDINGS: Most of the records analyzed were of male patients (56.2%). Drugs prescribed by their generic name were 50%. Prescriptions containing injection and antimicrobials were 68.1% and 83.6%, respectively. 49.3% of the patients had received a fixed-dose combination, and 60.9% of drugs belonged to the National List of Essential Medicines 2015. A total of 15 potential drug interactions were found. CONCLUSION: Calculated prescribed daily dose of most of the antimicrobials and other groups of drugs was close to the WHO-DDD. Trade name prescription and polypharmacy were very common. Antibiotics accounted for the majority of drug costs.