Drugs - Real World Outcomes最新文献

Introduction: Numerous investigations on herbal medicine that have been undertaken in the past several years demonstrate the general acceptance of its safety. The Saudi Food and Drug Authority (SFDA) established the Herb-Drug Interaction (HDI) project to detect and assess potential HDIs to ensure safety. The aim is to detect safety signals and assess them based on available evidence.

Methods: First, SFDA-registered herbal products (n = 30) were selected and prioritized based on commonly used herbs. Second, reported potential HDIs were retrieved from the World Health Organization global database of individual case safety reports (VigiBase), AdisInsight^®, and the Natural Medicines database. We excluded drugs non-registered by SFDA and labeled interactions in the product information of SFDA, the US Food and Drug Administration (FDA), and the European Medicines Agency (EMA). Finally, a comprehensive evaluation of potential HDIs was carried out using several evidence sources: literature, global cases, local cases, and other relevant documents. The Drug Interaction Probability Scale (DIPS) scale was used to assess the probability of a causal relationship between the interacting herb and drug and the event.

Results: The search yielded 566 potential signals, and 41 had published evidence and were referred for assessment. The assessment results using DIPS were: 22 possible (53.6 %), 7 probable (17%), and 12 doubtful (29.2%) interactions. The recommendation was to include probable HDIs in the product information, including turmeric-tacrolimus, etoposide-Echinacea, Ginkgo biloba-ibuprofen, green tea-warfarin, and licorice-thiazides interactions.

Conclusion: The HDI project assessed the screening and identification of potential HDIs. The action plan of this project can be used in post-marketing activities to identify potential drug interactions.

Introduction: A 6-month course of isoniazid, 300 mg daily, was programmatically introduced in Eritrea in 2014 as tuberculosis preventive therapy in people living with human immunodeficiency virus (PLHIV). The rollout of isoniazid preventive therapy (IPT) in PLHIV was successful in the first 2-3 years. After 2016, rumours based on rare but real incidents of liver injuries following use of IPT spread widely across the country and created concerns amongst healthcare professionals and consumers, that ultimately caused dramatic decline in the rollout of the intervention. Decision makers have been demanding better evidence as previously conducted local studies had inherent methodological limitations. This real-world observational study was conducted to evaluate the risk of liver injury associated with IPT among PLHIV attending Halibet national referral hospital, Asmara, Eritrea.

Methods: A prospective cohort study, that consecutively enrolled PLHIV attending Halibet hospital, was conducted between 1 March and 30 October 2021. Those exposed to anti-retroviral therapy (ART) plus IPT were considered as exposed and those taking only ART were considered as unexposed. Both groups were prospectively followed up for 4-5 months with monthly liver function tests (LFTs). A Cox proportional hazard model was used to explore whether there was increased risk of drug-induced liver injury (DILI) associated with IPT. Probability of survival without DILI was also estimated using Kaplan-Meier curves.

Results: A total of 552 patients, 284 exposed and 268 unexposed, completed the study, with a mean follow-up time of 3.97 (SD 0.675) months for the exposed and 4.06 (SD 0.675) months for the unexposed. Twelve patients developed drug-induced liver injury (DILI), with a median time-to-onset of 35 days (interquartile range: 26.8, 60 days). All cases were from the exposed group and all except two cases were asymptomatic. The incidence rate of DILI in the exposed group was 10.6 cases per 1000 person-months and zero for the unexposed group (p = 0.002).

Conclusion: DILI in PLHIV taking IPT was common; therefore, liver function should be closely monitored to safely administer the product. Despite high levels of deranged liver enzymes, the majority had no symptoms of DILI, emphasising the importance of close laboratory monitoring, especially during the first 3 months of treatment.

Background: Antimicrobials are drugs that are more likely to trigger the development of resistance naturally. Thus, they need to be prescribed, dispensed, and administered with greater caution. To underline the significance of their proper usage, antibiotics are divided as AWaRe: Access, Watch, and Reserve. Timely evidence on medicine use, prescribing patterns, and the factors affecting prescribing of antibiotic and their use percentage from AWaRe classification would help decision-makers to draft guidelines that can enable more rational use of medicines.

Methods: Prospective and cross-sectional study was conducted among seven community pharmacies in Dire Dawa to assess current prescribing practices related World Health Organization (WHO) indicators and AWaRe classification including antibiotic use and associated factors. Using stratified random sampling techniques, 1200 encounters were reviewed between 1 October and 31 October 2022, and SPSS version 27 was used for the analysis.

Results: The average of medications per prescription was 1.96. Antibiotics were included in 47.8% of encounters, while 43.1% were prescribed from the Watch groups. In 13.5% of the encounters, injections were administered. In multivariate models, patient age, gender, and the number of medications prescribed were significantly associated to prescription of antibiotics. Antibiotics were about 2.5 times more likely to be prescribed to patients under the age of 18 years than to subjects 65 years and older [adjusted odds ratio (AOR): 2.51, 95% confidence interval (CI): 1.88-5.42; P < 0.001]. Men were also more likely than women to receive an antibiotic prescription (AOR: 1.74, 95% CI: 1.18-2.33; P = 0.011). Subjects who received more than two drugs were 2.96 times more likely to receive an antibiotic drug (AOR: 2.96, 95% CI: 1.77-6.55; P < 0.003). The probability of prescribing antibiotics was increased by 2.57 for every one-unit increase in the number of medications [crude odds ratio (OR): 2.57; 95% CI: 2.16-3.47; P < 0.002].

Conclusion: According to the present study, the amount of prescriptions with antibiotics at community pharmacies is much higher than the WHO standard (20-26.2%). The antibiotics prescribed from Access group were 55.3%, which is slightly lower than WHO recommended level (60%). The prescribing of antibiotics was significantly correlated to the patient's age, gender, and number of medications. The preprint version of the present study is available on Research Square with the following link: https://doi.org/10.21203/rs.3.rs-2547932/v1 .

Introduction: Polypharmacy, defined as the concurrent use of multiple (commonly five or more) prescription drugs, is widely prevalent among the elderly. It is a preventable and significant contributor to morbidity and mortality among older people. It is linked to prescribing potentially inappropriate medications (PIMs), which have been shown to be associated with an increased risk of adverse drug interactions and reduced compliance, and in some cases result in prescribing cascades where more drugs are prescribed to manage adverse outcomes. This study aimed to examine risk factors associated with polypharmacy and PIMs among elderly patients in outpatient settings in the US.

Methods: We conducted a cross-sectional analysis using the nationally representative National Ambulatory Medical Care Survey, between 2010 and 2016. We extracted data from all people aged 65 years or older and evaluated factors associated with polypharmacy and PIMs using multivariable logistic regression. Weights were applied to obtain national estimates.

Results: During the study period, there were a total of 81,295 ambulatory visits among adults 65 years and older. Being a woman (compared with a man) was more likely to be associated with greater prevalence of PIMs (OR: 1.31, 95% CI 1.23-1.40), and living in rural areas were more likely to be associated with both polypharmacy (OR: 1.15, 95% CI 1.07-1.23) and PIMs (OR: 1.19, 95% CI 1.09-1.29), compared with living in urban areas. Older age was positively associated with polypharmacy (OR: 1.08, 95% CI 1.06-1.10), but negatively associated with PIMs (OR: 0.97, 95% CI 0.95-0.99).

Conclusions: Our study suggests age, being a woman, and living in rural areas are risk factors for both polypharmacy and PIMs usage. Aside from primary care providers' roles in managing polypharmacy, collaborative care with other specialty providers, such as clinical pharmacists, should also be considered as an approach to improving the quality of prescribing in geriatric patients. Future research should further explore reasons for polypharmacy and focus on deprescribing and quality improvement initiatives in primary care to lower polypharmacy among the elderly.

Background: Inappropriate prescribing is associated with negative patient outcomes. In hospitalized patients, the use of Clinical Decision Support Systems (CDSSs) may reduce inappropriate prescribing and thereby improve patient-related outcomes. However, recently published large clinical trials (OPERAM and SENATOR) have shown negative results on the use of CDSSs and patient outcomes and strikingly low acceptance of recommendations.

Objective: The purpose of the present study was to investigate the use of a CDSS in a real-life clinical setting of hospitalized older patients. As such, we report on the real-life pattern of this in-hospital implemented CDSS, including (i) whether generated alerts were resolved; (ii) whether a recorded action by the pharmacist led to an improved number of resolved alerts; and (iii) the natural course of generated alerts, in particular of those in the non-intervention group; as these data are largely lacking in current studies.

Methods: Hospitalized patients, aged 60 years and older, admitted to Zuyderland Medical Centre, the Netherlands, in 2018 were included. The evaluation of the CDSS was investigated using a database used for standard care. Alongside demographic and clinical data, we also collected the total numbers of CDSS alerts, the number of alerts 'handled' by the pharmacist, those that resulted in an action by the pharmacist, and finally the outcome of the alerts at day 1 and day 3 after the alert was generated.

Results: A total of 3574 unique hospitalized patients, mean age 76.7 (SD 8.3) years and 53% female, were included. From these patients, 8073 alerts were generated, of which 7907 (97.9% of total) were handled by the pharmacist (day 1). In 51.6% of the alerts handled by the pharmacist, an action was initiated, resulting in 36.1% of the alerts resolved after day 1, compared with 27.3% if the pharmacist did not perform an action (p < 0.001). On day 3, in 52.6% of the alerts an action by the pharmacist was initiated, resulting in 62.4% resolved alerts, compared with 48.0% when no action was performed (p < 0.001). In the category renal function, the percentages differed significantly between an action versus no action of the pharmacist at day 1 and at day 3 (16.6% vs 10.6%, p < 0.001 [day 1]; 29.8% vs 19.4%, p < 0.001 [day 3]).

Conclusion: This study demonstrates the pattern and natural course of clinical alerts of an in-hospital implemented CDSS in a real-life clinical setting of hospitalized older patients. Besides the already known beneficial effect of actions by pharmacists, we have also shown that many alerts become resolved without any specific intervention. As such, our study provides an important insight into the spontaneous course of resolved alerts, since these data are currently lacking in the literature.

Background: Brexanolone is currently the only medication approved by the US FDA for the treatment of postpartum depression (PPD) in patients ≥15 years. Brexanolone is available commercially only through a restricted program (ZULRESSO^® Risk Evaluation and Mitigation Strategy; REMS) due to risk of excessive sedation or sudden loss of consciousness during administration.

Objective: The aim of this analysis was to assess the postmarketing safety of brexanolone in adults with PPD.

Methods: The cumulative postmarketing adverse event (AE) listing from spontaneous and solicited individual case safety reports (ICSRs) received from March 19, 2019, through December 18, 2021, was analyzed. Clinical trial ICSRs were excluded. Reported AEs were classified as serious or nonserious as defined by FDA seriousness criteria and as listed or unlisted based on Table 2.0 within section 6 "Adverse Reactions" of the current brexanolone FDA-approved US Prescribing Information (PI).

Results: Overall, 499 patients received brexanolone in this postmarketing surveillance analysis between June 2019 and December 2021 (postmarketing setting). There were 137 ICSRs with 396 total AEs: 15 serious unlisted, 2 serious listed, 346 nonserious unlisted, and 33 nonserious listed. In total, two serious and one nonserious listed excessive sedation AEs were reported-all resolved by stopping infusion and did not require any treatment; no loss of consciousness AEs were received.

Conclusion: Results from postmarketing surveillance data analysis are consistent with the safety profile of brexanolone for the treatment of PPD as described in the FDA-approved PI. No new safety concerns or new aspects of known risks requiring an update to the FDA-approved PI were identified.

Background and objective: Clozapine use is associated with development of neutropenia, and lithium carbonate may be co-administered to reduce this risk; however, this has not yet been adequately investigated. The present study examined whether lithium administration is associated with the risks of clozapine side effects, including neutropenia.

Methods: Data on patients taking clozapine, extracted from the Japanese Adverse Drug Event Report (JADER) database, were analyzed. Patients who developed clozapine side effects were identified by the Standardized Medical Dictionary for Regulatory Activities Queries. The relationship between the use of lithium and risk of clozapine side effects was examined using logistic regression analysis.

Results: The use of lithium was reported in 530 out of 2,453 clozapine users. Hematopoietic leukopenia, convulsion, and noninfectious myocarditis/pericarditis developed in 109, 87, and seven lithium-treated patients, and in 335, 173, and 62 untreated patients, respectively. Univariate analysis showed no relationship between lithium administration and the risks of hematopoietic leukopenia (adjusted odds ratio (aOR) 1.11; 95% confidence interval (CI) 0.98-1.25), and the association with the risks of convulsion (aOR 1.41; 95% CI 1.23-1.62) and noninfectious myocarditis/pericarditis (aOR 0.63; 95% CI 0.43-0.94). Multivariate analysis revealed that lithium use was independently associated with the risks of convulsion (aOR 1.40; 95% CI 1.21-1.60) and noninfectious myocarditis/pericarditis (aOR 0.62; 95% CI 0.41-0.91).

Conclusion: The risks of seizure and myocarditis, but not of neutropenia, in clozapine-treated patients may be altered by lithium. Although the JADER database is based on spontaneous reporting, the present results warrant further study.

Background: Cardiovascular diseases are responsible for a significant proportion of mortalities worldwide. Elderly patients are the most affected by cardiovascular diseases, and because of factors such as polypharmacy, multimorbidity, and age-related changes in drug availability and metabolism, they are highly susceptible to the occurrence of drug-drug interactions. Drug-drug interactions are among the many drug-related problems leading to negative outcomes among inpatients and outpatients. Thus, it is important to investigate the prevalence, involved drugs, and factors related to potential drug-drug interactions (pDDIs) to properly optimize pharmacotherapy regimens for these patients.

Objective: We aimed to determine the prevalence of pDDIs, drugs most frequently implicated, and significant predictors associated with these interactions among hospitalized patients in the Cardiology Unit at Sultan Qaboos University Hospital in Muscat, Oman.

Methods: This retrospective cross-sectional study included 215 patients. Micromedex Drug-Reax^® was used to identify pDDIs. Data extracted from patients' medical records were collected and analyzed. Univariable and multivariable linear regression was applied to determine the predictors associated with the observed pDDIs.

Results: A total of 2057 pDDIs were identified, with a median of nine (5-12) pDDIs per patient. Patients with at least one pDDI accounted for 97.2% of all the included patients. The majority of pDDIs were of major severity (52.6%), fair level of documentation (45.5%), and pharmacodynamic basis (55.9%). Potential drug-drug interactions between atorvastatin and clopidogrel were the most frequently observed (9%). Of all the detected pDDIs, around 79.6% of them included at least one antiplatelet drug. Having diabetes mellitus as a comorbidity (B = 2.564, p < 0.001) and the number of drugs taken during the hospitalization period (B = 0.562, p < 0.001) were factors positively associated with the frequency of pDDIs.

Conclusions: Potential drug-drug interactions were highly prevalent among hospitalized cardiac patients at Sultan Qaboos University Hospital, Muscat, Oman. Patients having diabetes as a comorbidity and with a high number of administered drugs were at a higher risk of an increased number of pDDIs.

Background: Type 2 diabetes mellitus is a chronic disease affecting millions of people worldwide. Achieving and maintaining glycemic control is essential to prevent or delay complications and different strategies are available as second-line treatment options for patients with type 2 diabetes who do not achieve glycemic control with metformin monotherapy.

Objective: The aim of this work is to describe the impact of initiating a combination treatment to reduce glycated hemoglobin in patients with type 2 diabetes with insufficient glycemic control.

Methods: We included patients with a type 2 diabetes diagnosis between 2015 and 2020 at the Information System for Research in Primary Care (SIDIAP) database in Catalonia, Spain. The primary outcome was the time to glycated hemoglobin control (≤ 7%) during the first 720 days, expressed as the restricted mean survival time. Adjusted differences of the restricted mean survival time were compared to analyze the performance of each treatment versus the combination with a sulfonylurea. Adherence was calculated as the medication possession ratio using an algorithm to model treatment exposure.

Results: A total of 28,425 patients were analyzed. The most frequent combinations were those with sulfonylureas and dipeptidyl peptidase-4 inhibitors. All treatments reduced glycated hemoglobin and the restricted mean survival time for the sulfonylurea treatment was 455 (451-459) days although combinations with glucagon-like peptide-1 and insulin reached glycemic control earlier, - 126 days (- 152 to - 100, p < 0.001) and - 69 days (- 88 to - 50, p < 0.001), respectively. Adherence was high in all groups apart from the insulin combination and had a significant effect in reducing glycated hemoglobin except in sodium-glucose cotransporter type 2 inhibitors and insulin. Glucagon-like peptide-1 and sodium-glucose cotransporter type 2 inhibitors showed significant reductions in weight.

Conclusions: Patients achieved the glycated hemoglobin goal with second-line treatments. Glucagon-like peptide-1 and insulin combinations achieved the goal earlier than sulfonylurea combinations. Adherence significantly reduced the time to glycated hemoglobin control except for the combination with sodium-glucose cotransporter type 2 inhibitors.