Efficacy and Safety of MAO-B Inhibitors Safinamide and Zonisamide in Parkinson's Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND OBJECTIVE: In Parkinson's disease, safinamide and zonisamide are novel monoamine oxidase-B inhibitors with a dual mechanism of action involving the inhibition of sodium and calcium channels and the subsequent release of glutamate. The aim of this systematic review and meta-analysis was to examine the efficacy and safety of both drugs compared with placebo on motor symptoms, cognitive function, and quality of life in patients with Parkinson's disease. METHODS: We searched MEDLINE, EMBASE, Cochrane Central, Scopus, PsycINFO, and trials registries up to March 2023 for randomized controlled trials of adults with Parkinson's disease administered either safinamide or zonisamide and published in English. We excluded single-arm trials or if neither the efficacy nor safety outcomes of interest were reported. Primary outcomes were the change from baseline in Unified Parkinson's Disease Rating Scale section III (UPDRS-III) and serious adverse events. Secondary outcomes included a change from baseline in OFF-time, Parkinson's Disease Questionnaire 39 to evaluate quality of life, and Mini-Mental State Examination for cognitive function assessment. The meta-analysis was conducted using Review Manager 5.4.1. Random-effect models were used to calculate the pooled mean differences (MDs) and risk ratios with 95% confidence intervals (CIs). Subgroup analyses by medication, doses, Parkinson's disease stage, and risk of bias were conducted. We assessed the risk of bias using the Cochrane's risk of bias tool. Sensitivity analysis was conducted, and publication bias were evaluated. This meta-analysis was not externally funded, and the protocol is available on the Open Science Framework Registration ( https://doi.org/10.17605/OSF.IO/AMNP5 ). RESULTS: Of 3570 screened citations, 16 trials met inclusion criteria (4314 patients with Parkinson's disease). Ten safinamide trials were conducted in several countries. Six zonisamide trials were included, five of which were conducted in Japan and one in India. UPDRS Part III scores were significantly lower with both monoamine oxidase-B inhibitors than with placebo (MD = -  2.18; 95% CI -  2.88 to -  1.49; I 2 =63%; n = 14 studies). A subgroup analysis showed a significant improvement in UPDRS-III in safinamide (MD = -  2.10; 95% CI -  3.09 to -  1.11; I2 = 71%; n = 8 studies) and zonisamide (MD = -  2.31; 95% CI -  3.35 to -  1.27; I2 = 52%; n = 6 studies) compared with placebo. Monoamine oxidase-B inhibitors significantly decreased OFF-time compared with placebo. No significant differences in cognitive function (Mini-Mental State Examination), whereas an improvement in quality of life (Parkinson's Disease Questionnaire 39 scores) was observed. There was no significant difference in incidence rates of serious adverse events among all examined doses of zonisamide and safinamide compared with placebo. Two trials were reported as a high risk of bias and sensitivity analyses confirmed the primary analysis results. CONCLUSIONS: Evidence suggests that novel monoamine oxidase-B inhibitors not only improve motor symptoms but also enhance patients' quality of life. The meta-analysis showed that both medications have a similar safety profile to placebo with regard to serious adverse events. The overall findings emphasize the effectiveness of safinamide and zonisamide in the treatment of Parkinson's disease as adjunct therapy. Further long-term studies examining the impact of these medications on motor and non-motor symptoms are necessary.

Health-related quality of life variation by socioeconomic status: Evidence from an Iranian population-based study.

BACKGROUND: Health-Related Quality of Life (HRQoL) values based on the accurate and reliable European Quality of Life Five Dimension (EQ-5D) questionnaire gives health-state utilities as a helpful data set for studying socio-demographic and socio-economic inequalities in health status in the general population. We aimed to do a population-based study to see how HRQoL varies by socio-demographics and socioeconomic status (SES). MATERIALS AND METHODS: The study was a cross-sectional population-based study in Shiraz, Iran's southwest. Data was gathered utilizing a personal digital assistant (PDA). A trained interviewer administered the EQ-5D questionnaire to a representative sample of 1036 inhabitants. Principal component analysis (PCA) was used to create SES indices. Because of the skewed distribution, quantile regression was utilized to model the quartiles of HRQoL values. STATA 12.0 was used to perform all statistical analyses. P <0.05 was considered statistically significant. RESULTS: In 1036 study respondents, women had a mean HRQoL of 0.67 ± 0.28, whereas men had a mean HRQoL of 0.78 ± 0.25. Gender and age remained significant in all quartiles of HRQoL value. Participants with insurance showed 0.14 and 0.08 higher HRQoL values in the first and second HRQoL quartiles than those without coverage, respectively. Education [95% CI: 0.034, 0.111)], economy [95% CI: 0.013, 0.077], and assets [95% CI: 0.003, 0.069] all had an impact on HRQoL value in the lowest quintile. CONCLUSION: In all quartiles of HRQoL value, women had lower reported HRQoL than men. Insurance programs aimed at more disadvantaged groups with poorer HRQoL may help to minimize inequity. Education, economics, and assets all had an impact on the lower quartiles of HRQoL value, emphasizing the importance of general policies in determining public health status.

Acute kidney injury in COVID-19 patients receiving remdesivir: A systematic review and meta-analysis of randomized clinical trials.

OBJECTIVES: Remdesivir is an antiviral agent with positive effects on the prognosis of Coronavirus Disease (COVID-19). However, there are concerns about the detrimental effects of remdesivir on kidney function which might consequently lead to Acute Kidney Injury (AKI). In this study, we aim to determine whether remdesivir use in COVID-19 patients increases the risk of AKI. METHODS: PubMed, Scopus, Web of Science, the Cochrane Central Register of Controlled Trials, medRxiv, and bioRxiv were systematically searched until July 2022, to find Randomized Clinical Trials (RCT) that evaluated remdesivir for its effect on COVID-19 and provided information on AKI events. A random-effects model meta-analysis was conducted and the certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation. The primary outcomes were AKI as a Serious Adverse Event (SAE) and combined serious and non-serious Adverse Events (AE) due to AKI. RESULTS: This study included 5 RCTs involving 3095 patients. Remdesivir treatment was not associated with a significant change in the risk of AKI classified as SAE (Risk Ratio [RR]: 0.71, 95% Confidence Interval [95% CI] 0.43‒1.18, p = 0.19, low-certainty evidence) and AKI classified as any grade AEs (RR = 0.83, 95% CI 0.52‒1.33, p = 0.44, low-certainty evidence), compared to the control group. CONCLUSION: Our study suggested that remdesivir treatment probably has little or no effect on the risk of AKI in COVID-19 patients.

Antiseizure medication use during pregnancy and neonatal growth outcomes: A systematic review and meta-analysis.

AIMS: We aimed to systematically synthesize the current published literature on neonatal growth outcomes associated with antiseizure medication (ASM) use during pregnancy. METHODS: We searched seven databases, from inception to 23 March 2022. We investigated small for gestational age (SGA) and low birth weight (LBW) as primary outcomes and birth weight, birth height, cephalization index and head circumference as secondary outcomes. The primary analysis included pregnant people exposed to any ASM compared with unexposed pregnant people. Subgroup analysis included ASM class analysis, within epilepsy group analysis and polytherapy compared to monotherapy. RESULTS: We screened 15 720 citations and included 65 studies in the review. Exposed pregnant people had a significantly increased risk of SGA relative risk (RR) 1.33 (95% CI 1.18 to 1.50, I2 74%), LBW RR 1.54 (95% CI 1.33 to 1.77, I2 67%), and decreased birth weight with a mean difference (MD) of -118.87 (95% CI -161.03 to -76.71, I2 42%) g. A non-significant risk change in birth height and head circumference was observed. In subgroup analysis, ASM polytherapy, within epilepsy and ASM class analysis were also associated with an increased risk of SGA and LBW. CONCLUSIONS: This meta-analysis demonstrates that pregnant people exposed to ASMs have a significantly increased risk of adverse fetal growth outcomes including SGA and LBW and decreased birth weight compared to unexposed pregnant people. Polytherapy was associated with higher risks compared to monotherapy. Additional studies are warranted on specific ASM risks.

Prescription trends of antiseizure medications before and during the COVID-19 pandemic.

Introduction: Given the lack of evidence on how the COVID-19 pandemic impacted antiseizure medication (ASM) use, we examined the trends of ASMs before and during COVID-19. Methods: We conducted a population-based study using provincial-level health databases from Manitoba, Canada, between 1 June 2016 and 1 March 2021. We used interrupted time series autoregressive models to examine changes in the prevalence and incidence of ASM prescription rates associated with COVID-19 public health restrictions. Results: Among prevalent users, the COVID-19 pandemic led to a significant increase in new-generation ASMs with a percentage change of 0.09% (p = 0.03) and a significant decrease in incidence use of all ASMs with a percentage change of -4.35% (p = 0.04). Significant trend changes were observed in the prevalent use of new-generation ASMs (p = 0.04) and incidence use of all (p = 0.04) and new-generation ASMs (p = 0.02). Gabapentin and clonazepam prescriptions contributed 37% of prevalent and 54% of incident use. Conclusion: With the introduction of public health measures during COVID-19, small but significant changes in the incident and prevalent use of ASM prescriptions were observed. Further studies are needed to examine whether barriers to medication access were associated with potential deterioration in seizure control among patients. Conference presentation: The results from this study have been presented as an oral presentation at the 38th ICPE, International Society of Pharmacoepidemiology (ISPE) annual conference in Copenhagen.

Preterm birth and stillbirth rates associated with socioeconomic disparities during COVID-19 pandemic: a population-based cross-sectional study.

BACKGROUND: Conflicting evidence exists on the impact of the COVID-19 pandemic restrictions on preterm birth (PTB) and stillbirth rates. We aimed to evaluate changes in PTB and stillbirth rates before and during the pandemic period and assess the potential effect modification of socioeconomic status (SES). METHODS: Using the linked administrative health databases from Manitoba, Canada, we conducted a cross-sectional study among all pregnant women, comparing 3.5 years pre-pandemic (1 October 2016 to 29 February 2020) to the first year of the pandemic (1 March 2020 to 31 March 2021). We used generalised linear models to assess the quarterly rates of PTB (<37 weeks) and stillbirths. We calculated the predicted trends based on pre-pandemic period data. Finally, we evaluated the PTB and stillbirth rates among lower and higher SES pregnant women (average annual household income) using subgroup analysis and interaction models. RESULTS: We examined 70 931 pregnancies in Manitoba during the study period. The risk of PTB increased by 7.7% (95%CI 1.01 to 1.13) and stillbirths by 33% (95% CI 1.08 to 1.64) during the pandemic period. Following COVID-19 restrictions implemented in March 2020, there were increases in the quarterly rates of both PTB (immediate increase (ß2)=1.37; p=0.0247) and stillbirths (immediate increase (ß2)=0.12; p=0.4434). Among the lower income groups, the pandemic restrictions resulted in an immediate relative increase in PTB and stillbirth rates by 20.12% (immediate increase (ß2)=3.17; p=0.0057) and 27.19% (immediate increase (ß2)=0.48; p=0.0852). However, over the pandemic, the overall PTB rate significantly decreased as a rebound effect by 0.85% per quarter (p=0.0004), whereas the overall stillbirth rate did not decrease significantly (slope decrease (ß3) =-0.01; p=0.8296) compared with the pre-pandemic period. The quarterly rates during the pandemic among the higher income group decreased by 0.39% (p=0.1296) for PTB and increased by 0.07% (p=0.1565) for stillbirth. We observed an effect modification by SES for PTB rates (p=0.047). CONCLUSION: While the onset of COVID-19 pandemic restrictions was not associated with significant effects on stillbirth rates, we observed an immediate and rebound effect on PTB rates. The impact of COVID-19 on preterm birth was dependent on SES, with higher influence on families with lower SES. Further studies are needed to detect future trend changes during pandemic waves after 2021 and assess potential underlying mechanisms.

Sex differences among users of NSAIDs and opioids during COVID-19 Pandemic.

BACKGROUND: Sex-based inequalities in healthcare have been exposed and amplified during the COVID-19 pandemic. However, few studies have reported sex differences in medication utilization and no studies have examined sex differences in prescribed non-steroidal anti-inflammatory drugs (NSAIDs) and opioids utilization. AIM: To compare the utilization patterns of prescribed NSAIDs and opioids between males and females in Manitoba, Canada during the COVID-19 pandemic. METHOD: A cohort of incident and prevalent users of prescribed NSAIDs and opioids was created. Interrupted times series analysis using autoregressive models were used to evaluate the quarterly change in the prevalent and incident users before and after COVID-19 restrictions were applied (first quarter of 2020). RESULTS: COVID-19 restrictions were associated with a significant decrease in the utilization of prescribed NSAIDs and opioids in all users, followed by a revert to the pre-pandemic trends. Among female prevalent and incident NSAIDs users, there was a significant change in trend after COVID-19 restrictions were introduced (ß3 = 0.087 and 0.078, P = 0.023 and 0.028, respectively). However, there was non-significant change in trend among male prevalent and incident NSAIDs and opioids users during the pandemic. CONCLUSION: In this study, a significant sharp decline in the use of prescribed NSAIDs and opioids was shown in both sexes at the onset of the pandemic. However, a significant upward trend is observed in female NSAIDs users as restrictions began to be lifted.

Evaluation of the Factors Associated with Prescribed and Non-Prescribed Medicine: A Population-Based Study.

OBJECTIVES: Several factors influence medication patterns. The purpose of this study was to look into the role of social determinants in the use of prescribed and non-prescribed medications in a population-based setting of people over 18 in a southern metropolis of Iran (Shiraz) for 2 years. STUDY DESIGN: Prospective population-based cross-sectional. METHODS: This descriptive and cross-sectional survey was done in 2018-2020. A total of 1016 participants were randomly selected based on their postal codes and recruited to the study. The demographic characteristics (age, sex, and education), social profiles (insurance, supplementary insurance, health status, and daily exercise plan), and outpatient visits (family/general physician or specialist/ subspecialist) were recorded by gathering sheets. Descriptive analyses and multinomial logistic analyses were carried out using SPSS software. RESULTS: The medication use pattern was classified into three categories: non-prescribed type I, non-prescribed type II, and prescribed. The mean age of participants was 45.54 ± 15.82 years. The results indicated that most of them took their medication without a prescription (non-prescribed type II). However, people who had insurance and referred to a family physician commonly used the prescribed medications. This study also found that patients who visited a family doctor or a general practitioner used fewer prescribed drugs than those who visited a specialist. CONCLUSION: This study describes social determinants as additional effective factors in health services that influence the use of prescribed and non-prescribed medications in Shiraz. These evidence- based findings can help policymakers to plan the best programs.

Acute kidney injury in COVID-19 patients receiving remdesivir: A systematic review and meta-analysis of randomized clinical trials

Abstract Objectives: Remdesivir is an antiviral agent with positive effects on the prognosis of Coronavirus Disease (COVID-19). However, there are concerns about the detrimental effects of remdesivir on kidney function which might consequently lead to Acute Kidney Injury (AKI). In this study, we aim to determine whether remdesivir use in COVID-19 patients increases the risk of AKI. Methods: PubMed, Scopus, Web of Science, the Cochrane Central Register of Controlled Trials, medRxiv, and bio-Rxiv were systematically searched until July 2022, to find Randomized Clinical Trials (RCT) that evaluated remdesivir for its effect on COVID-19 and provided information on AKI events. A random-effects model metaanalysis was conducted and the certainty of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation. The primary outcomes were AKI as a Serious Adverse Event (SAE) and combined serious and non-serious Adverse Events (AE) due to AKI. Results: This study included 5 RCTs involving 3095 patients. Remdesivir treatment was not associated with a significant change in the risk of AKI classified as SAE (Risk Ratio [RR]: 0.71, 95% Confidence Interval [95% CI] 0.43‒1.18, p = 0.19, low-certainty evidence) and AKI classified as any grade AEs (RR = 0.83, 95% CI 0.52‒1.33, p = 0.44, low-certainty evidence), compared to the control group. Conclusion: Our study suggested that remdesivir treatment probably has little or no effect on the risk of AKI in COVID-19 patients.

Drug utilization patterns before and during COVID-19 pandemic in Manitoba, Canada: A population-based study.

BACKGROUND: The COVID-19 pandemic has led the Canadian provincial governments to take unprecedented measures, including restrictions to healthcare services and pharmacists. Limited evidence exists on changes in prescription trends in Canada during the pandemic period. OBJECTIVES: To examine the trend of prescription medications' utilization before and during COVID-19, among incident and prevalent users in the general population. We examined 18 major classes of medications. METHODS: We used the administrative health databases from the province of Manitoba, Canada, to conduct a province-wide cross-sectional study. Incident and prevalent use was compared between two time periods; pre-COVID-19: July 2016-March 2020 and during COVID-19: April 2020-March 2021. Interrupted time series analysis using autoregressive models was used to quantify the change in level and slope in quarterly medication use among incident and prevalent users. RESULTS: The quarterly study population ranged from 1,353,485 to 1,411,630 Manitobans. The most common comorbidities were asthma (26.67%), hypertension (20.64%), and diabetes (8.31%). On average, the pandemic restrictions resulted in a 45.55% and 12.17% relative decline in the aggregated utilization of all drugs among both incident and prevalent users, respectively. Subclass analysis showed a 46.83%, 23.05%, and 30.98% relative drop among incident users of antibiotics, cardiovascular drugs and opioids use, respectively. We observed a significant slope increase during COVID-19 among the quarterly cardiovascular, antidiabetics, alpha-1 blockers, and statins incident users compared to the pre-COVID-19 period. We noted a significant decrease in level among NSAIDs, opioids, and antibiotic prevalent users, however, no significant changes in slope were observed. CONCLUSION: Our findings show a significant impact of COVID-19 measures on prescription trends in the general population. The observed decline among several medication classes was temporary. Further research is needed to monitor prescription trends and better understand if those changes were associated with increased health services and worsened outcomes.

Evaluation of factors that influenced the length of hospital stay using data mining techniques.

BACKGROUND: length of stay (LOS) is the time between hospital admission and discharge. LOS has an impact on hospital management and hospital care functions. METHODS: A descriptive, retrospective study was designed on about 27,500 inpatients between March 2019 and 2020. Required data were collected from six wards (CCU, ICU, NICU, General, Maternity, and Women) in a teaching hospital. Clinical data such as demographic characteristics (age, sex), type of ward, and duration of hospital stay were analyzed by the R-studio program. Violin plots, bar charts, mosaic plots, and tree-based models were used to demonstrate the results. RESULTS: The mean age of the population was 40.8 ± 19.2 years. The LOS of the study population was 2.43 ± 4.13 days. About 60% of patients were discharged after staying one day in the hospital. After staying one day in the hospital, 67% of women were discharged. However, 23% of men were discharged within this time frame. The majority of LOS in the CCU, ICU, and NICU ranged from 5 to 9 days.; In contrast, LOS was one day in General, Maternity, and Woman wards. Due to the tree plot, there was a different LOS pattern between Maternity-Women and the CCU-General-ICU-NICU wards group. CONCLUSION: We observed that patients with more severe diseases hospitalized in critical care wards had a longer LOS than those not admitted to critical care wards. The older patient had longer hospital LOS than the younger. By excluding Maternity and Woman wards, LOS in the hospital was comparable between males and females and demonstrated a similar pattern.

Utilization of Pharmacokinetic/Pharmacodynamic Modeling in Pharmacoepidemiological Studies: A Systematic Review on Antiarrhythmic and Glucose-Lowering Medicines.

Introduction: In human pharmacology, there are two important scientific branches: clinical pharmacology and pharmacoepidemiology. Pharmacokinetic/pharmacodynamic (PK/PD) modeling is important in preclinical studies and randomized control trials. However, it is rarely used in pharmacoepidemiological studies on the effectiveness and medication safety where the target population is heterogeneous and followed for longer periods. The objective of this literature review was to investigate how far PK/PD modeling is utilized in observational studies on glucose-lowering and antiarrhythmic drugs. Method: A systematic literature search of MEDLINE, Embase, and Web of Science was conducted from January 2010 to 21 February 2020. To calculate the utilization of PK/PD modeling in observational studies, we followed two search strategies. In the first strategy, we screened a 1% random set from 95,672 studies on glucose-lowering and antiarrhythmic drugs on inclusion criteria. In the second strategy, we evaluated the percentage of studies in which PK/PD modeling techniques were utilized. Subsequently, we divided the total number of included studies in the second search strategy by the total number of eligible studies in the first search strategy. Results: The comprehensive search of databases and the manual search of included references yielded a total of 29 studies included in the qualitative synthesis of our systematic review. Nearly all 29 studies had utilized a PK model, whereas only two studies developed a PD model to evaluate the effectiveness of medications. In total, 16 out of 29 studies (55.1%) used a PK/PD model in the observational setting to study effect modification. The utilization of PK/PD modeling in observational studies was calculated as 0.42%. Conclusion: PK/PD modeling techniques were substantially underutilized in observational studies of antiarrhythmic and glucose-lowering drugs during the past decade.

Trends of Utilization of Antiseizure Medications Among Pregnant Women in Manitoba, Canada: A 20-Year Population-Based Study.

Background: Evidence from developed countries demonstrates that the use of antiseizure medications (ASMs) has been increasing in the last decade. Pregnant women have a very challenging risk benefit trade-off in terms of ASM utilization, and it is crucial to know if increased utilization is seen among pregnant women. Objective: To examine time-trends of utilization of ASM therapies among pregnant women in Manitoba, Canada. Methods: We conducted a population-based cohort study using de-identified, linked administrative databases from Manitoba. Pregnancies between 1995 and 2018 were included. Four groups of pregnant people were created based on ASM exposure and epilepsy diagnosis. Results: Of 273,492 pregnancies, 812 (3/1000) had epilepsy diagnosis and were exposed to ASMs, 963 (3.5/1000) had epilepsy diagnosis and were unexposed, and 2742 (10/1000) were exposed to ASMs and did not have epilepsy diagnosis. Overall, the number of pregnancies exposed to ASMs increased significantly from 0.56% in 1997 to 2.21% in 2018 (p < 0.0001). Subgroup analysis by epilepsy diagnosis showed no significant change in ASMs exposure among pregnant women with epilepsy [the proportion of women exposed to ASM from all pregnancies was 0.37% (in 1997) and 0.36% (in 2018), p = 0.24]. A drop in carbamazepine use was observed, while the number of lamotrigine prescriptions increased from 6.45% in 1997 to 52% by 2018. ASM use among pregnant women without epilepsy increased significantly from 0.19% in 1997 to 1.85% in 2018 (p < 0.0001). In the total cohort of pregnancies, 1439 (0.53%) were exposed during their entire pregnancy, and 1369 (0.5%) were exposed only in their first trimester. Clonazepam was the most used ASM during the study period (1953 users, 0.71%), followed by gabapentin (785 users, 0.29%) and carbamazepine (449 users, 0.16%). Conclusion: No major shifts in the quantity of ASM use over the study period were observed among pregnant women with epilepsy. However, there was a significant increase in ASM use among pregnant women without epilepsy. The study results warrant further investigation into the implications of ASM use in pregnancy for indications other than epilepsy.

The Effects of Probiotic Supplementation on Clinical Symptom, Weight Loss, Glycemic Control, Lipid and Hormonal Profiles, Biomarkers of Inflammation, and Oxidative Stress in Women with Polycystic Ovary Syndrome: a Systematic Review and Meta-analysis of Randomized Controlled Trials.

The purpose of this systematic review and meta-analysis of randomized controlled trials (RCTs) is to determine the effectiveness of probiotic supplementation on clinical symptoms, weight loss, glycemic control, lipid and hormonal profiles, and biomarkers of inflammation and oxidative stress in women with polycystic ovary syndrome (PCOS). Eligible studies were systematically searched from Cochrane Library, Embase, Medline, and Web of Science databases until January 2019. Cochran (Q) and I-square statistics were used to measure heterogeneity among included studies. Data were pooled by using random-effect model and expressed as standardized mean difference (SMD) with 95% confidence interval (CI). Eleven articles were included in this meta-analysis. Probiotic supplementation significantly decreased weight (SMD - 0.30; 95% CI, - 0.53, - 0.07; P = 0.01), body mass index (BMI) (SMD - 0.29; 95% CI, - 0.54, - 0.03; P = 0.02), fasting plasma glucose (FPG) (SMD - 0.26; 95% CI, - 0.45, - 0.07; P < 0.001), insulin (SMD - 0.52; 95% CI, - 0.81, - 0.24; P < 0.001), homeostatic model assessment for insulin resistance (HOMA-IR) (SMD - 0.53; 95% CI, - 0.79, - 0.26; P < 0.001), triglycerides (SMD - 0.69; 95% CI, - 0.99, - 0.39; P < 0.001), VLDL-cholesterol (SMD - 0.69; 95% CI, - 0.99, - 0.39; P < 0.001), C-reactive protein (CRP) (SMD - 1.26; 95% CI, - 2.14, - 0.37; P < 0.001), malondialdehyde (MDA) (SMD - 0.90; 95% CI, - 1.16, - 0.63; P < 0.001), hirsutism (SMD - 0.58; 95% CI, - 1.01, - 0.16; P < 0.001), and total testosterone levels (SMD - 0.58; 95% CI, - 0.82, - 0.34; P < 0.001), and also increased the quantitative insulin sensitivity check index (QUICKI) (SMD 0.41; 95% CI, 0.11, 0.70; P < 0.01), nitric oxide (NO) (SMD 0.33; 95% CI 0.08, 0.59; P = 0.01), total antioxidant capacity (TAC) (SMD 0.64; 95% CI, 0.38, 0.90; P < 0.001), glutathione (GSH) (SMD 0.26; 95% CI, 0.01, 0.52; P = 0.04), and sex hormone binding globulin (SHBG) levels (SMD 0.46; 95% CI, 0.08, 0.85; P = 0.01). Probiotic supplementation may result in an improvement in weight, BMI, FPG, insulin, HOMA-IR, triglycerides, VLDL-cholesterol, CRP, MDA, hirsutism, total testosterone, QUICKI, NO, TAC, GSH, and SHBG but did not affect dehydroepiandrosterone sulfate levels, and total, LDL, and HDL cholesterol levels in patients with PCOS.

Affordability of Medication Therapy in Diabetic Patients: A Scenario-Based Assessment in Iran's Health System Context.

BACKGROUND: Diabetes imposes an enormous burden on patients, families, societies, and healthcare systems. Determining the affordability of medications is an important complicated and vague task, especially in low- and middle-income countries (LMICs). This study aimed to assess the affordability of diabetes medication therapy in Iran's health system. METHODS: This paper presents a scenario-based assessment of the affordability of all registered anti-diabetes medications in Iran in 2017. To this end, 4 medication therapy scenarios were defined as mono, dual, triple, and insulin therapy in accordance with the existing guidelines and clinicians' opinions. Then the affordability ratio of each treatment scenario was determined for type 1 and type 2 diabetes drawing on the World Health Organization (WHO)/Health Action International (HAI) Methodology. If the affordability ratio for treatment schedules was more than 1, the patients' out-of-pocket (OOP) expenses exceeded the lowest-paid unskilled government worker (LPGW)' wage per day, and the treatment was labelled as non-affordable. RESULTS: The results revealed that the mono, dual, and triple (non-insulin) medication therapies in type 2 diabetes were affordable, despite an increase in the dosage or a switch from the monotherapy to the combination therapy of oral medications. However, some treatment scenarios in the triple therapy, including oral plus insulin and some insulin only therapies, were proved to be non-affordable. In type 1 diabetes, only insulin glulisine, detemir, and lispro were non-affordable in monotherapy. Regarding the combination therapy, only isophane insulin with aspart or regular insulin were affordable treatments. CONCLUSION: Although oral medication therapies were documented to be affordable, insulin therapy, with current coverage conditions, for patients with lowest paid wages and those receiving even less is unaffordable and a major barrier to treatment; hence, policy-maker should consider targeting and more financial protection policies to improve the affordability of insulin therapies among this group of patients.

Assessing the Performance of Community Pharmacies in Iran by Measuring Responsiveness to Non-Medical Needs: An Application of WHO Responsiveness Framework.

OBJECTIVE: Despite growing debates about the health systems' nonmedical performance, there has not been any empirical research on nonmedical performance and patients' rights consideration as a driver of human rights in the pharmaceutical sector. This study's main objective was to assess the nonmedical performance of community pharmacies of Shiraz, Iran. METHODS: A cross-sectional study was conducted using two self-administrated Likert-based questionnaires based on the World Health Organization (WHO) responsiveness framework and the legal charter communicated by the Ministry of Health and Medical Education of Iran. The population was patients older than 18 years who took a prescription from community pharmacies located in Shiraz and willing to answer the questions voluntarily, from 2018 to 2019. Considering the weights of subdimensions of responsiveness provided by the WHO framework, the total score of responsiveness was calculated ranging from 0 to 100. FINDINGS: The response rate was 80.5%. The mean (standard deviation) overall score of responsiveness was 57.18 (21.61), with a median of 56.71. The mean score of client orientation was lower in respondents with a high education level than those with a diploma and under diploma (P = 0.028). CONCLUSION: Nonmedical pharmacy performance was considered either medium or high in more than half of the cases based on the participants' views. Regarding client, orientation was seen less often in patients with high education level compared to those with a lower education level.

The Pattern of Medication Usage in the Southern Region of Iran: A population-based Pharmacoepidemiological Study.

OBJECTIVE: The purpose of this study was to document the demographic data, to assess the proportion of consumed medicines and the amounts and types of drugs available to households, and to to estimate the probable prevalence of certain diseases in the southern region of Iran. METHODS: In this cross-sectional population-based study carried out in Shiraz (the central city in the Southern part of Iran), we documented and evaluated the drug usage details in a random sample of 1000 households during 2018-2020. We analyzed the usage of drug categories based on the anatomical therapeutic chemical classification, which the World Health Organization recommends. FINDINGS: In the studied population, the average age (± standard deviation) was 45.54 ± 15.82, ranged 18-91 years. More than 90% had medical insurance coverage. About 81.8% of the participants had individual family medicine practitioners, and most of them (93.8%) received medications with a physician's prescription. The most frequently used medications were cough and cold preparations (12.9%), nervous system drugs (12.6%), and cardiovascular system drugs (11.6%). CONCLUSION: Despite the easy access to medications for most participants, few individuals (about 6%) received their medications without a prescription. The most frequently prescribed medicines were the common cold, acetaminophen, and metformin. Common cold, gastrointestinal (GI) disorder, and diabetes were the most commonly used medication classes. Furthermore, we have found a probably higher than average prevalence of cardiovascular, GI, and endocrine disorders. This information could be used by the local policymakers as a basis for the estimation and allotment of health-care resources.

Factors Facilitating and Hindering Development of a Medication Use Review Service in Eastern Europe and Iran-Cross-Sectional Exploratory Study.

Polypharmacy is a common issue in patients with chronic diseases. Eastern-European countries and Iran are exploring possibilities for implementing the Medication Use Review (MUR) as a measure for optimizing medication use and ensuring medication safety in polypharmacy patients. The aim of this study was to gain insights into the development of the community pharmacy sector and map facilitators and barriers of MUR in Eastern Europe and Iran. The representatives of the framework countries received a questionnaire on community pharmacy sector indicators, current and future developments of pharmacies, and factors encouraging and hindering MUR. To answer the questionnaire, all representatives performed document analysis, literature review, and qualitative interviews with key stakeholders. The socio-ecological model was used for inductive thematic analysis of the identified factors. Current community pharmacist competencies in framework countries were more related to traditional pharmacy services. Main facilitators of MUR were increase in polypharmacy and pharmaceutical waste, and access to patients' electronic list of medications by pharmacists. Main barriers included the service being unfamiliar, lack of funding and private consultation areas. Pharmacists in the framework countries are well-placed to provide MUR, however, the service needs more introduction and barriers mostly on organizational and public policy levels must be addressed.

Drug-induced liver injury in Switzerland: an analysis of drug-related hepatic disorders in the WHO pharmacovigilance database VigiBase from 2010 to 2020.

AIMS OF THE STUDY: Our aim was to explore drug-induced liver injury (DILI) in Switzerland using the real-world data of the global pharmacovigilance database VigiBaseÔ, with a special focus on the new drug class of checkpoint inhibitors. This is the first study investigating drug-related hepatic disorders in Switzerland in a global pharmacovigilance database. METHODS: This was a retrospective study analysing the ICSRs (individual case safety reports) of the global pharmacovigilance database VigiBaseÔ. We explored all ICSRs submitted in Switzerland within the last 10 years (1 July 2010 to 30 June 2020). For data extraction, the standardised MedDRA query (SMQ) “narrow drug-related hepatic disorders – severe events only” was applied. The ICSRs, drug-reaction pairs and adverse drug reactions were analysed descriptively, including a special focus on checkpoint inhibitors. For comparing the hepatic adverse drug reactions of pembrolizumab, nivolumab and ipilimumab, the reporting odds ratios (RORs) were calculated in a disproportionality analysis. RESULTS: In total, 2042 ICSRs could be investigated, comprising 10,646 drugs and 6436 adverse drug reactions. Gender was equally distributed between male and female. Patients were on average 57 years old. The mortality rate was high, with fatal adverse reactions in over 10% of cases. On average, patients used five drugs including two suspected drugs. Paracetamol, amoxicillin/clavulanic acid, esomeprazole and atorvastatin ranked among the most frequently suspected drugs for severe drug-related hepatic disorders. However, VigibaseÔ data are not appropriate for judging causality and these results should be interpreted with caution owing to the possible influences of comedication or comorbidity. An average of three adverse drug reactions per ICSR were reported, most frequently including hepatocellular injury, cholestatic liver injury, and liver injury. For checkpoint inhibitors, hepatitis was the most frequently reported hepatic adverse drug reaction. In comparison with nivolumab and ipilimumab, pembrolizumab had a significantly higher ROR for hepatitis (2.41, p = 0.016), but also a lower ROR for autoimmune hepatitis (0.11, p = 0.009). CONCLUSION: Our findings highlight the importance for healthcare providers in Switzerland to pay special attention to possible drug-induced liver injuries because of their high mortality rate. The analysis of real-world data confirms the previous assumption that hepatitis is the most frequent hepatic adverse event for checkpoint inhibitors. Further clinical studies are warranted to directly compare hepatic adverse drug reactions to different checkpoint inhibitors.

Statins in patients with COVID-19: a retrospective cohort study in Iranian COVID-19 patients.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has profoundly affected the lives of millions of people. To date, there is no approved vaccine or specific drug to prevent or treat COVID-19, while the infection is globally spreading at an alarming rate. Because the development of effective vaccines or novel drugs could take several months (if not years), repurposing existing drugs is considered a more efficient strategy that could save lives now. Statins constitute a class of lipid-lowering drugs with proven safety profiles and various known beneficial pleiotropic effects. Our previous investigations showed that statins have antiviral effects and are involved in the process of wound healing in the lung. This triggered us to evaluate if statin use reduces mortality in COVID-19 patients. RESULTS: After initial recruitment of 459 patients with COVID-19 (Shiraz province, Iran) and careful consideration of the exclusion criteria, a total of 150 patients, of which 75 received statins, were included in our retrospective study. Cox proportional-hazards regression models were used to estimate the association between statin use and rate of death. After propensity score matching, we found that statin use appeared to be associated with a lower risk of morbidity [HR = 0.85, 95% CI = (0.02, 3.93), P = 0.762] and lower risk of death [(HR = 0.76; 95% CI = (0.16, 3.72), P = 0.735)]; however, these associations did not reach statistical significance. Furthermore, statin use reduced the chance of being subjected to mechanical ventilation [OR = 0.96, 95% CI = (0.61-2.99), P = 0.942] and patients on statins showed a more normal computed tomography (CT) scan result [OR = 0.41, 95% CI = (0.07-2.33), P = 0.312]. CONCLUSIONS: Although we could not demonstrate a significant association between statin use and a reduction in mortality in patients with COVID19, we do feel that our results are promising and of clinical relevance and warrant the need for prospective randomized controlled trials and extensive retrospective studies to further evaluate and validate the potential beneficial effects of statin treatment on clinical symptoms and mortality rates associated with COVID-19.