Exploring the Clinical Features, Management of Hypertension, and Predictors of Severity in Hospitalized Hypertensive COVID-19 Patients.

Background Hypertension significantly contributes to the severity, prolonged hospitalization, the need for intensive care, and mortality of COVID-19 patients. However, the data is still evolving. This study investigated the predictors of severity among hypertensive COVID-19 patients. Methodology This cohort study included 333 hospitalized hypertensive COVID-19 patients at the Indus Hospital, Karachi, Pakistan, from April 2021 to October 2021. The study evaluated the clinical features, antihypertensive therapy, and predictors of severity. A multivariable binary logistic regression model was used to determine severity predictors using IBM SPSS Statistics for Windows, Version 27.0 (Released 2020; IBM Corp., Armonk, NY, USA). Results The majority of hypertensive COVID-19 patients were females (54.7%), aged <65 years (55.8%), and coexisted with diabetes mellitus (56.5%). The independent predictors of severity were male (aOR 2.65, 95% CI, 1.08-6.51; p < 0.033), fever (aOR 3.52, 95% CI, 1.24-9.92; p = 0.017), shortness of breath (aOR 4.49, 95% CI, 1.73-11.63; p = 0.002), oxygen saturation (<90%) (aOR 87.39, 95% CI, 19.15-398.75; p < 0.001), and D-dimer (>0.5 mcg/ml) (aOR 3.03, 95% CI, 1.19-7.71; p = 0.020). Conclusions Our study concluded that males with fever before admission, shortness of breath, lower oxygen saturation, and elevated D-dimer are the predictors of severity among hypertensive COVID-19 patients.

Semi-physiological Pharmacokinetic Model of Clozapine and Norclozapine in Healthy, Non-smoking Volunteers: The Impact of Race and Genetics.

BACKGROUND AND OBJECTIVES: Clozapine is the medication of choice for treatment-resistant schizophrenia. However, it has a complex metabolism and unexplained interindividual variability. The current work aims to develop a pharmacokinetic model of clozapine and norclozapine in non-smokers and assess the impact of demographic and genetic predictors. METHODS: Healthy volunteers were recruited in a population pharmacokinetic study. Blood samples were collected at 30 min and 1, 2, 3, 5 and 8 h following a single flat dose of clozapine (12.5 mg). The clozapine and norclozapine concentrations were measured via high-performance liquid chromatography-ultraviolet method. A semi-physiological pharmacokinetic model of clozapine and norclozapine was developed using nonlinear mixed-effects modeling. Clinical and genetic predictors were evaluated, including CYP1A2 (rs762551) and ABCB1 (rs2032582), using restriction fragment length polymorphism. RESULTS: A total of 270 samples were collected from 33 participants. The data were best described using a two-compartment model for clozapine and a two-compartment model for norclozapine with first-order absorption and elimination and pre-systemic metabolism. The estimated (relative standard error) clearance of clozapine and norclozapine were 27 L h-1 (31.5 %) and 19.6 L h-1 (30%), respectively. Clozapine clearance was lower in sub-Saharan Africans (n = 4) and higher in Caucasians (n = 9) than Asians (n = 20). Participants with CYP1A2 (rs762551) (n = 18) and ABCB1 (rs2032582) (n = 12) mutant alleles had lower clozapine clearance in the univariate analysis. CONCLUSIONS: This is the first study to develop a semi-physiological pharmacokinetic model of clozapine and norclozapine accounting for the pre-systemic metabolism. Asians required lower doses of clozapine as compared with Caucasians, while clozapine pharmacokinetics in sub-Saharan Africans should be further investigated in larger trials.

The Impact of an Educational Intervention on Enhancing Clinical Knowledge of Physicians and Pharmacists Regarding Statins and Monitoring Parameters: The Experience of a Tertiary Teaching Hospital.

Introduction: Understanding the latest guideline recommendations is crucial for healthcare professionals to apply statin therapy effectively. Thus, the purpose of this study was to evaluate the efficacy of an educational intervention in enhancing the awareness and understanding of physicians and pharmacists concerning risk assessment of Atherosclerotic cardiovascular disease (ASCVD) and the role of statin therapy. Methods: This pre- and post-intervention study was conducted in Sana'a, Yemen's capital city, at the University of Science and Technology Hospital. The study was done between 11/2021-12/2021, and two separate educational sessions were held. The McNemar's test and Wilcoxon signed-rank test were employed as necessary. Results: Participants' awareness of the Framingham CVD risk calculator improved significantly from 40.4% pre-intervention to 78.7% post-intervention. Similarly, understanding of the parameters used in the 10-year ASCVD Risk calculator rose from 46.8% pre-intervention to 76.6% post-intervention. The ability to identify high, moderate, and low-intensity statin therapy, for instance, increased from 34% to 63.8% post-intervention. Regarding statins' contraindications, safety, and efficacy monitoring parameters, pre-intervention knowledge was unsatisfactory, and the educational intervention improved it significantly (p <0.05). For physicians, the median ASCVD risk assessment knowledge score was significantly improved from 4 (IQR = 3-5) pre-intervention to 7 (6.25-8) immediately post-intervention, while the statin therapy clinical knowledge median score significantly improved from 3 (1.25-6.5) to 9 (7.25-14.75) post-education intervention, p-values were 0.002 and 0.003; respectively. For pharmacists, a similar significant improvement (p <0.05) in the overall knowledge scores for both ASCVD risk assessment and statin therapy was noted. Conclusion: The educational intervention improved participants' knowledge of statin therapy and ASCVD risk assessment. Therefore, further education lectures and training programs through continuing medical education on the up-to-date guidelines' recommendations should be regularly implemented to raise awareness and improve the clinical knowledge and appropriateness of statins use in clinical settings. .

Predictive model of recurrent ischemic stroke: model development from real-world data.

Background: There are established correlations between risk factors and ischemic stroke (IS) recurrence; however, does the hazard of recurrent IS change over time? What is the predicted baseline hazard of recurrent IS if there is no influence of variable predictors? This study aimed to quantify the hazard of recurrent IS when the variable predictors were set to zero and quantify the secondary prevention influence on the hazard of recurrent ischemic stroke. Methods: In the population cohort involved in this study, data were extracted from 7,697 patients with a history of first IS attack registered with the National Neurology Registry of Malaysia from 2009 to 2016. A time-to-recurrent IS model was developed using NONMEM version 7.5. Three baseline hazard models were fitted into the data. The best model was selected using maximum likelihood estimation, clinical plausibility, and visual predictive checks. Results: Within the maximum 7.37 years of follow-up, 333 (4.32%) patients had at least one incident of recurrent IS. The data were well described by the Gompertz hazard model. Within the first 6 months after the index IS, the hazard of recurrent IS was predicted to be 0.238, and 6 months after the index attack, it reduced to 0.001. The presence of typical risk factors such as hyperlipidemia [HR, 2.22 (95%CI: 1.81-2.72)], hypertension [HR, 2.03 (95%CI: 1.52-2.71)], and ischemic heart disease [HR, 2.10 (95%CI: 1.64-2.69)] accelerated the hazard of recurrent IS, but receiving antiplatelets (APLTs) upon stroke decreased this hazard [HR, 0.59 (95%CI: 0.79-0.44)]. Conclusion: The hazard of recurrent IS magnitude differs during different time intervals based on the concomitant risk factors and secondary prevention.

Physicians and pharmacists' clinical knowledge of statin therapy and monitoring parameters, and the barriers to guideline implementation in clinical practice.

BACKGROUND: Millions of individuals worldwide use statins, and their significant impact on cardiovascular disease (CVD) has been well-established. However, a lack of knowledge about the up-to-date guideline recommendations regarding statin therapy is a common barrier to implementation in clinical practice. Therefore, the present study aimed to assess the current clinical knowledge about statin therapy and its monitoring parameters. Also, we evaluated the barriers to cholesterol management guideline implementation in Yemen. METHODS: This observational cross-sectional study was conducted over four months, from June/2021 to September/2021, in Sana'a, Yemen. A validated questionnaire was distributed face-to-face to 650 participants (350 physicians and 300 pharmacists). Physicians and pharmacists from governmental and private hospitals and those working in private clinics or community pharmacies were included in the study. RESULTS: A total of 496 participants filled out the survey, with 22 being excluded due to incomplete data. So, the study has an overall response rate of 72.9% (474). The majority of pharmacists (81.8%) and physicians (78.7%) could not identify the patient group that needed ASCVD risk assessment before statin therapy initiation. Although a significant proportion of respondents knew of the fact that high-intensity statins are recommended for patients with ASCVD (65.4%) and primary hypercholesterolemia (58.4%), the majority of physicians and pharmacists could not identify the high (61.6% and 66.7.3%, respectively) and moderate statin-intensity doses (72.2% and 68.6%, respectively). Only 21.9% of all respondents knew that atorvastatin and rosuvastatin can be administered at any time of the day. Similarly, a low overall rate of respondents (19.6%) knew that atorvastatin does not need dose adjustment in chronic kidney diseases, with a statistically significant difference in knowledge between physicians and pharmacists (12.5% vs. 25.6%, p <0.001, respectively). Notably, only 39.2% of participants were aware that statins are not safe to use during breastfeeding. Around half of respondents (52.3%) correctly identify the duration (4 to 12 weeks) at which LD-C measuring is recommended after therapy initiation or dose change. The lowest knowledge scores for respondents were related to statin-drug interactions. Age, experience, degree, and previous guideline exposure were all significantly associated with the knowledge scores (p <0.05). The four most perceived barriers to implementing cholesterol management guidelines were no audit on adherence to the guidelines in the workplace (73.4%), insufficient resources to adequately implement and follow up on the guideline's recommendations (73.6%), patient's financial status (75.7%), and lack of familiarity about the guideline's latest recommendations (63.3%). CONCLUSION: Physicians and pharmacists had suboptimal clinical knowledge regarding statin therapy, dose intensities, drug-drug interaction, contraindications, and monitoring parameters. Therefore, physicians' and pharmacists' educational interventions regarding the up-to-date recommendation about statins are recommended.

Efficacy and Safety of Sitagliptin in the Treatment of COVID-19.

Background: Coronavirus disease 2019 (COVID-19) is associated with a high risk of mortality especially among diabetes mellitus (DM) patients. Effective treatments against COVID-19 can complement the vaccination effort worldwide. Many review articles studied the effects of the dipeptidyl peptidase 4 (DPP-4) inhibitors among COVID-19 patients and found conflicting results. This heterogeneity may be due to different systemic pleiotropic effects of different DPP-4 inhibitors. Sitagliptin appears to be one of the good DPP-4 inhibitors that have antiinflammatory and antithrombotic effect. Therefore, this review assessed the benefits and safety of sitagliptin in the treatment of COVID-19. Methods: A detailed literature review using the electronic databases of Pubmed and Google Scholar was conducted during July and August 2021 to find out studies that published in English language and discussed the role of sitagliptin for COVID-19 patients. Results: 14 articles were eligible and thus included in this narrative review. Nine of these articles agreed to the benefit of sitagliptin in the treatment of COVID-19, while 3 studies considered sitagliptin as non useful or even risky, and one study was neutral in its conclusion towards the usage of sitagliptin in COVID-19. Only one study focused on the safety of sitagliptin and found that it is safe. Conclusion: Sitagliptin has anti-inflammatory, antifibrotic and antiapoptotic properties; such effects may be beneficial in reducing risks of COVID-19. Sitagliptin has good safety and fair benefits to reduce mortality among DM patients with COVID-19. Further randomized clinical trials are needed to confirm these benefits especially among patients without DM.

Risk assessment of atherosclerotic cardiovascular diseases before statin therapy initiation: Knowledge, attitude, and practice of physicians in Yemen.

BACKGROUND: Risk evaluation of atherosclerotic cardiovascular disease (ASCVD) remains the cornerstone of primary prevention. The cardiovascular risk assessment can guide the decision-making on various preventive measures such as initiating or deferring statin therapy. Thus, our study aimed to assess the physicians' knowledge, attitude, and practices regarding atherosclerotic cardiovascular diseases risk assessment. Also, we evaluated the physician-patient discussion and counseling practices before statin therapy initiation in concordance with recommendations from the latest clinical practice guideline. METHODS: A cross-sectional study was conducted between November 2020 and January 2021. A self-administered questionnaire was distributed to 350 physicians (GPs, residents, specialists, and consultants). Two trained pharmacists distributed the questionnaires in 5 major tertiary governmental hospitals and more than ten private hospitals. Also, private clinics were targeted so that we get a representative sample of physicians at different workplaces. RESULTS: A total of 270 physicians filled the questionnaire out of 350 physicians approached, with 14 being excluded due to high missing data, giving a final response rate of 73%. Participants had suboptimal knowledge and practices with a high positive attitude toward atherosclerotic cardiovascular diseases risk assessment. The knowledge and practices were higher among consultants, participants from the cardiology department, those with experience years of more than nine years, and those who reported following a specific guideline for cholesterol management or using a risk calculator in their practice. Notably, the risk assessment and counseling practices were lower among physicians who reported seeing more patients per day. CONCLUSION: Physicians had overall low knowledge, suboptimal practices, and a high positive attitude toward cardiovascular risk assessment. Therefore, physicians' training and continuing medical education regarding cholesterol management and primary prevention clinical practice guidelines are recommended. Also, the importance of adherence to clinical practice guidelines and their impact on clinical outcomes should be emphasized.

Prevalence and predictors of clinically significant statin-drug interactions among Yemeni patients taking statins for primary and secondary prevention of cardiovascular disease.

BACKGROUND: Statins are extensively used in clinical practice for the primary and secondary prevention of cardiovascular diseases. Statins are usually taken in combination with other medications. This may increase the risk of statin-drug interactions. The study aimed to evaluate the prevalence, patterns, and predictors of clinically significant statin-drug interactions among patients on statin therapy. MATERIAL AND METHODS: A cross-sectional study was conducted at the cardiology, endocrine, and internal medicine outpatient clinics in four tertiary care hospitals in Sana'a, Yemen. Lexicomp Drug Interaction database was used to analyze the prescriptions for potential statin-drug interactions. Binary and multivariable logistic regression were utilized for analysis. RESULTS: Of the total number of patients (634), 114 individuals (18%) had a total of 122 statin-drug interactions. According to Lexicomp risk classification, 102 (83.6%) DDIs were class C (monitor therapy), 19 (15.6%) were class D (therapy modification), and only one (0.8%) class X (avoid combination). Simvastatin use was significantly associated with the presence of category D and X DDIs (15.9% vs. 1.6%, p < .001). Polypharmacy (OR = 2.571, p < .001) and having ≥3 comorbidities (OR = 2.512, p < .001) were the only variables associated with the presence of statin-drug interactions (C, D, and/or X). CONCLUSION: Patients with polypharmacy and those with three or more comorbidities had a higher risk for statin-drug interactions. Therefore, routine screening by physicians and pharmacists for potential interactions should occur before prescribing or dispensing any medication to avoid clinically significant statin-drug interactions.

Population pharmacokinetics analyses of rifampicin in adult and children populations: A systematic review.

AIMS: Rifampicin has become an essential component as the first-line therapy for pulmonary tuberculosis (PTB). Several population pharmacokinetic (PK) studies on rifampicin in adult and child populations have been studied previously, therefore the aims of the systematic review were (i) to summarize the relevant published studies and significant covariates that influence the PK of rifampicin across different populations, and (ii) to identify any knowledge gap that requires additional research in the future. METHODS: A total of 121 relevant population PK articles were systematically identified using PubMed and Scopus from inception to October 2021. Review articles, in-vitro and physiological methods, animal studies and noncompartmental analysis were excluded. RESULTS: Nineteen studies, of which 16 involved adults, two involved children, and one involved both adults and children, were included in the review. The structural model of rifampicin can be described as one compartment with a transient compartment absorption model and first-order elimination in most of the studies. Pharmaceutical formulation, body weight, gender, pregnancy status, diabetes and nutritional supplementation were found to be the significant covariates that affect the PK parameters. External validation of the developed PK model was only conducted in two studies. CONCLUSIONS: The source of variability for PK parameters of rifampicin remains inconsistent and poorly understood even though there were many potential covariates investigated in the selected studies. Exploring other possible factors and implementing a strict sampling strategy by considering the induction effects might uncover precise and reliable information. Furthermore, external validation should be frequently conducted to produce better predictability of model performance.

Time-Dissociated Pharmacokinetic Pharmacodynamic Model of Cyclosporine Among Malaysian Renal Transplant Recipients.

BACKGROUND: Cyclosporine is an essential component of many immunosuppressive regimens. However, its pharmacokinetic and pharmacodynamic (PKPD) modeling has not been widely investigated. This study aims to develop a time-dissociated PKPD model of cyclosporine in renal transplant patients. METHODS: Medical records of renal transplant patients at Penang General Hospital were retrospectively analyzed. A time-dissociated PKPD model with covariate effects was developed using NONMEM to evaluate renal graft function response, quantified as estimated glomerular filtration rate (eGFR), toward the cyclosporine cumulative exposure (area under the concentration-time curve). The final model was integrated into a tool to predict the potential outcome. Individual eGFR predictions were evaluated based on the clinical response recorded as acute rejection/nephrotoxicity events. RESULTS: A total of 1256 eGFR readings with 2473 drug concentrations were obtained from 107 renal transplant patients receiving cyclosporine. An Emax drug effect with a linear drug toxicity model best described the data. The baseline renal graft level (E0), maximum effect (Emax), area under the concentration-time curve achieving 50% of the maximum effect, and nephrotoxicity slope were estimated as 12.9 mL·min-1·1.73 m-2, 50.7 mL·min-1·1.73 m-2, 1740 ng·h·mL-1, and 0.00033, respectively. The hemoglobin level was identified as a significant covariate affecting the E0. The model discerned acute rejection from nephrotoxicity in 19/24 cases. CONCLUSIONS: A time-dissociated PKPD model successfully described a large number of observations and was used to develop an online tool to predict renal graft response. This may help discern early rejection from nephrotoxicity, especially for patients unwilling to undergo a biopsy or those waiting for biopsy results.

Knowledge, attitude, perceived barriers, and practices among pharmacists regarding risk assessment of cardiovascular disease: a cross-sectional study in Yemen.

BACKGROUND: Risk evaluation of atherosclerotic cardiovascular diseases can guide the decision-making on various preventive measures, such as initiating or deferring statin therapy. Pharmacists can play an active part in the risk evaluation and primary prevention of atherosclerotic cardiovascular diseases. Thus, our study aimed to assess the pharmacists' knowledge, attitude, perceived barriers, and practices regarding risk assessment of atherosclerotic cardiovascular disease. MATERIALS AND METHODS: A cross-sectional study was conducted among 500 pharmacists using a structured validated questionnaire between November 2020 and February 2021. The Mann-Whitney and Kruskal-Wallis tests were used to analyze the data. RESULTS: A total of 456 pharmacists completed the questionnaire out of 500 distributed (91.2% response rate). Over 60% of participants responded with never or rarely for two out of five cardiovascular diseases (CVD) prevention practices. The lowest pharmacist-patient counseling practices were for side effects of statin medication (14.5%) and reviewing the patient's medications to avoid potential statin-drug interactions (31.8%). Participants had a high positive attitude (median = 34 out of 40). The three major barriers for risk assessment were the lack of support (74.8%), the lack of resources (70.6%), and inadequate training (48.7%). Interestingly, having ≤75 customers a day, community pharmacies, PharmD degree, age ≥30 years, and experience ≥6 years were significantly associated (p < .05) with higher CVD prevention activities and counseling practices. CONCLUSION: Pharmacists have a high positive attitude toward CVD risk assessment. However, they had insufficient knowledge and only provided limited activities and counseling services for CVD prevention and statin therapy. Participants perceived several barriers to CVD risk assessment services in pharmacies. Therefore, it is necessary to remove these impediments for pharmacists to be more involved in CVD risk assessment and prevention. Also, continuing medical education and adequate training for pharmacists are required.

A Repeated Time-to-Positive Symptoms Improvement among Malaysian Patients with Schizophrenia Spectrum Disorders Treated with Clozapine.

Clozapine remains the drug of choice for resistant schizophrenia. However, its dose-response relationship is still controversial. The current investigation aimed to develop a repeated time-to-positive symptoms improvement following the onset of clozapine treatment in Malaysian schizophrenia spectrum disorder patients. Data from patients' medical records in the Psychiatric Clinic, Penang General Hospital, were retrospectively analyzed. Several parametric survival models were evaluated using nonlinear mixed-effect modeling software (NONMEM 7.3.0). Kaplan-Meier-visual predictive check (KM-VPC) and sampling-importance resampling (SIR) methods were used to validate the final model. A total of 116 patients were included in the study, with a mean follow-up of 306 weeks. Weibull hazard function best fitted the data. The hazard of positive symptoms improvement decreased 4% for every one-year increase in age over the median of 41 years (adjusted hazard ratio (aHR), 0.96; 95% confidence intervals (95% CI), (0.93-0.98)). However, patients receiving a second atypical antipsychotic agent had four-folds higher hazard (aHR, 4.01; 95% CI, (1.97-7.17)). The hazard increased 2% (aHR, 1.02; 95% CI, (1.01-1.03)) for every 1 g increase in the clozapine six months cumulative dose over the median of 34 g. The developed model provides essential information on the hazard of positive symptoms improvement after the first clozapine dose administration, including modifiable predictors of high clinical importance.

Population-based Study Comparing Predictors of Ischemic Stroke Recurrence After Index Ischemic Stroke in Non-elderly Adults with or without Diabetes.

BACKGROUND AND PURPOSE: Factors associated with ischemic stroke (IS) recurrence and the contribution of pharmacological treatment as secondary preventions among nondiabetics especially in the non-elderly population are unclear and not widely investigated. This was a population-based study that aimed to identify recurrent IS predictors and to determine the possible impact of secondary preventive medications on the IS recurrence in non-elderly adults with or without diabetes. METHODS: Data of 3386 patients <60 years old who had a history of index IS were extracted from the Malaysian National Neurology Registry (NNEUR) from 2009 to 2016. Recurrent IS was defined as any IS event recorded after the index IS in the NNEUR database. Multivariate logistic regression analysis was performed by using SPSS version 22. RESULTS: Ischemic heart disease (IHD) was the significant predictor of IS recurrence in non-elderly adults both with or without diabetes (adjusted odds ratio (AOR) of 3.210; 95%CI: 1.909-5.398 and 2.989; 95%CI: 1.515-5.894) respectively). Receiving antiplatelet as secondary stroke prevention (AOR: 0.194; 95%CI: 0.046-0.817) and continuation of antidiabetic medication after the index IS event (AOR: 0.510; 95%CI: 0.298-0.872) reduced the odds of IS recurrence only in non-elderly diabetic adults. Among non-elderly adults without diabetes, hyperlipidemia and every increased in 1 mmHg of systolic blood pressure significantly increased the odds of IS recurrence following the indexing event (AOR: 1.796; 95%CI: 1.058-3.051 and 1.009; 95%CI: 1.002-1.016 respectively). CONCLUSION: IHD was found as the main predictor of IS recurrence regardless of diabetes status in non-elderly adults after the index IS event. Receiving antidiabetic and antiplatelet medications upon discharge after index IS were significant predictors of recurrent IS in non-elderly diabetic adults. A proper randomized clinical trial may be required to determine the impact of secondary preventive medication on IS recurrence, especially in non-elderly adults.

The association between cigarette smoking and efavirenz plasma concentration using the population pharmacokinetic approach.

AIMS: Efavirenz is still widely used as the preferred first-line antiretroviral agent in middle- and low-income countries, including Malaysia. The efavirenz population pharmacokinetic profile among HIV-positive smokers is still unknown. We aimed to assess the association of smoking with efavirenz and the differences in HIV clinical outcomes. METHODS: A total of 154 stable HIV-positive patients on efavirenz in northern Malaysia were recruited with a sparse sampling for this multicentre prospective cohort study. The association between smoking and efavirenz pharmacokinetic parameters was determined using the nonlinear mixed-effect model. A mixture model of clearance was adopted to describe the metaboliser status because genetic data are unavailable. The effect of smoking on HIV clinical markers (CD4, CD4/CD8 ratio and viral blips) for at least 2 years after the antiretroviral initiation was also investigated. RESULTS: Our data were best fitted with a 1-compartment mixture model with first-order absorption without lag time. Smoking significantly associated with higher clearance (ß = 1.39; 95% confidence interval: 1.07 to 1.91), while weight affected both clearance and volume. From the mixture model, 20% of patients were in the slow clearance group, which mimic the genotype distribution of slow metaboliser. An efavirenz dose reduction is not recommended for smokers ≥60 kg with normal metabolism rate. Smoking significantly associated with slower normalisation of CD4 and CD4/CD8 ratio. CONCLUSIONS: HIV-positive smokers presented with significantly higher efavirenz clearance and unfavourable clinical outcomes. Close monitoring of adherence and clinical response among smokers is warranted.

Phytochemical screening and enzymatic and antioxidant activities of Erythrina suberosa (Roxb) bark.

BACKGROUND: This study aimed to evaluate the phytochemicals screening of Erythrina suberosa (Roxb) bark and to analyze the enzymatic activities of its various organic fractions. MATERIALS AND METHODS: Crude methanolic fraction of E. suberosa (Roxb) bark and its respective fractions were screened for the presence of different phytochemicals with different reagents. On the basis of increasing order of polarity, different organic solvents were used to obtain different fractions. Enzymatic studies were performed on crude methanolic extract of the plant. All the assays were performed under standard in vitro conditions. RESULTS: The phytochemical analysis shows the presence of alkaloids, phenols, triterpenoids, phytosterols, and flavonoids. Phenolic compounds and flavonoids are the major constituents of the plant. In anticholinesterase assay, the percent inhibition of standard drug (eserine) was 91.27 ± 1.17 and the half maximal inhibitory concentration (IC50) was 0.04 ± 0.0001. For α-glucosidase inhibition, the IC50 value for Dichloromethane fraction was 8.45 ± 0.13, for Methanol fraction it was 64.24 ± 0.15, and for aqueous fraction it was 42.62 ± 0.17 as compared with standard IC50 that is 37.42 (acarbose). Furthermore, results show that all fractions have potential against anti-urease enzyme, but DCM fraction of crude aqueous extract has significant IC50 value (45.26 ± 0.13) than other fractions. CONCLUSION: Keeping in view all the results, it is evident that the plant can be used in future for formulating effective drugs against many ailments. Secondary metabolites and their derivatives possess different biological activities, for example, .g. flavonoids in cancer, asthma, and Alzheimer. Furthermore, the extracts of this plant can be used in their crude form, which is an addition to the complementary and alternative treatment strategies.

In vitro cytotoxic and antimicrobial activities of Erythrina suberosa (Roxb) bark.

BACKGROUND: The study was focused on evaluating cytotoxic and antimicrobial activities of Erythrina suberosa (Roxb.) bark through in vitro pharmacological screening. MATERIALS AND METHODS: The bark was extracted using different solvents, for example, dichloromethane, ethyl acetate, methanol, and aqueous for obtaining the organic fractions. These organic fractions were then evaluated for their cytotoxic and antimicrobial activity compared with the standard. Cefixime was used as the standard for antibacterial assay, whereas clotrimazole was used as the standard for antifungal activities. Bacterial strains used were Staphylococcus aureus and methicillin-resistant S. aureus (MRSA), whereas for antifungal activities Candida albicans, Candida parapsilosis, and Candida krusei strains were used. RESULTS: The organic fractions obtained were evaluated for their cytotoxic and antimicrobial activities. In cytotoxic assay (Brine shrimp lethality assay), dichloromethane fraction was the most potent with LD50 of 47.63, whereas aqueous, methanol, and ethyl acetate fractions showed LD50 of 121.74, 422.2, and 201.96, respectively. Similarly, for antibacterial assay, dichloromethane fraction showed 32.2mm zone of inhibition against MRSA in comparison with standard cefixime (zone of inhibition, 30.5mm). A minimal zone of inhibition with crude saponins (13.1 and 12.2mm) was observed against C. albicans in comparison to standard (cefixime) with a zone of inhibition of 28.5mm. No prominent results were observed against C. parapsilosis and C. krusei strains. CONCLUSION: The study was based on the plant from Indo-Pak origin, and it has shown some prominent cytotoxic and antibacterial activities. Although the results of this study have provided a basic idea about the efficacy of plant extract, still more explanatory and high-scale studies can be beneficial for elaborating the cytotoxic and antimicrobial activities of this plant.

Risk factors for mortality among COVID-19 patients.

AIMS: COVID-19 is a current global pandemic. However, comprehensive global data analyses for its mortality risk factors are lacking. The current investigation aimed to assess the predictors of death among COVID-19 patients from worldwide open access data. METHODS: A total of 828 confirmed cases of COVID-19 with definite outcomes were retrospectively identified from open access individual-level worldwide data. Univariate followed by multivariable regression analysis were used to evaluate the association between potential risk factors and mortality. RESULTS: Majority of the patients were males 59.1% located in Asia 69.3%. Based on the data, older age (adjusted odds ratio (aOR), 1.079; 95% confidence intervals (95% CI), 1.064-1.095 per year increase), males (aOR, 1.607; 95% CI, 1.002-2.576), patients with hypertension (aOR, 3.576; 95% CI, 1.694-7.548), diabetes mellitus (aOR, 12.234; 95% CI, 4.126-36.272), and patients located in America (aOR, 7.441; 95% CI, 3.546-15.617) were identified as the risk factors of mortality among COVID-19 patients. CONCLUSIONS: Males, advanced age, hypertension patients, diabetes mellitus patients, and patients located in America were the independent risk factors of death among COVID-19 patients. Extra attention is required to be given to these factors and additional studies on the underlying mechanisms of these effects.

Gender differences in the modifiable risk factors associated with the presence of prediabetes: A systematic review.

BACKGROUND: Prediabetes is a risk state for the future development of type 2 diabetes. Previously, it was evident that the risk factors for diabetes differ by gender. However, conclusive evidence regarding the gender difference in modifiable risk factors associated with the presence of pre-diabetes is still lacking. AIMS: To systematically identify and summarize the available literature on whether the modifiable risk factors associated with prediabetes displays similar relationship in both the genders. METHODS: A systematic search was performed on electronic databases i.e. PubMed, EBSCOhost, and Scopus using "sex", "gender", "modifiable risk factors" and "prediabetes" as keywords. Reference list from identified studies was used to augment the search strategy. Methodological quality and results from individual studies were summarized in tables. RESULTS: Gender differences in the risk factor association were observed among reviewed studies. Overall, reported association between risk factors and prediabetes apparently stronger among men. In particular, abdominal obesity, dyslipidemia, smoking and alcohol drinking habits were risk factors that showed prominent association among men. Hypertension and poor diet quality may appear to be stronger among women. General obesity showed stringent hold, while physical activity not significantly associated with the risk of prediabetes in both the genders. CONCLUSIONS: Evidence suggests the existence of gender differences in risk factors associated with prediabetes, demands future researchers to analyze data separately based on gender. The consideration and the implementation of gender differences in health policies and in diabetes prevention programs may improve the quality of care and reduce number of diabetes prevalence among prediabetic subjects.

Population Pharmacokinetic Modeling of Cyclosporine Among Malaysian Renal Transplant Patients: An Evaluation of Methods to Handle Missing Doses in Conventional Drug-Monitoring Data.

Cyclosporine is a primary drug in transplant immunosuppression regimens. It has a narrow therapeutic index and variable pharmacokinetic behavior. This study aimed to develop a population pharmacokinetic model of cyclosporine in Malaysian renal transplant recipients as well as to evaluate the performances of different methodsfor handling missing doses. A total of 2804 concentrationts predose and 2 hours after doses were collected retrospectively from 113 renal transplant patients on cyclosporine in Penang General Hospital. Model structure and pharmacokinetic parameters were estimated using nonlinear mixed-effects modeling software. Missing doses were handled using different methods to evaluate their performance. Covariate analysis was performed using stepwise forward addition (P < .05) followed by backward elimination (P < .001). Prediction-corrected visual predictive check and sampling-importance resampling methods were used to validate the final model. A 1-compartment model with first-order absorption and elimination best fitted the data. All methods to handle missing doses performed well with the missing dose method being superior to other methods and thus was applied in the final model. Cyclosporine clearance (CL/F) was estimated as 15.1 L/h, and volume of distribution (V/F) was 108 L. Postoperative time, sex, and calcium channel blockers were identified as significant covariates on CL/F, whereas sex and cholesterol level were identified as significant covariates on V/F. This is the first population pharmacokinetic model developed in Malaysian renal transplant patients using a large sample with an evaluation of different methods to handle missing doses in less informative conventional therapeutic drug-monitoring data.

Population Pharmacokinetics of Clozapine: A Systematic Review.

BACKGROUND AND OBJECTIVE: Clozapine is a second-generation antipsychotic drug that is considered the most effective treatment for refractory schizophrenia. Several clozapine population pharmacokinetic models have been introduced in the last decades. Thus, a systematic review was performed (i) to compare published pharmacokinetics models and (ii) to summarize and explore identified covariates influencing the clozapine pharmacokinetics models. METHODS: A search of publications for population pharmacokinetic analyses of clozapine either in healthy volunteers or patients from inception to April 2019 was conducted in PubMed and SCOPUS databases. Reviews, methodology articles, in vitro and animal studies, and noncompartmental analysis were excluded. RESULTS: Twelve studies were included in this review. Clozapine pharmacokinetics was described as one-compartment with first-order absorption and elimination in most of the studies. Significant interindividual variations of clozapine pharmacokinetic parameters were found in most of the included studies. Age, sex, smoking status, and cytochrome P450 1A2 were found to be the most common identified covariates affecting these parameters. External validation was only performed in one study to determine the predictive performance of the models. CONCLUSIONS: Large pharmacokinetic variability remains despite the inclusion of several covariates. This can be improved by including other potential factors such as genetic polymorphisms, metabolic factors, and significant drug-drug interactions in a well-designed population pharmacokinetic model in the future, taking into account the incorporation of larger sample size and more stringent sampling strategy. External validation should also be performed to the previously published models to compare their predictive performances.