Therapeutic Advances in Drug Safety最新文献

Amid the coronavirus disease 2019 (COVID-19) pandemic, massive immunization campaigns became the most promising public health measure. During clinical trials, certain neurological adverse effects following immunization (AEFIs) were observed; however, acceptable safety profiles lead to emergency authorization for the distribution and use of the vaccines. To contribute to pharmacovigilance and lessen the potential negative impact that vaccine hesitancy would have on immunization programs, we conducted a review of the scientific literature concerning the epidemiological data, clinical presentation, and potential mechanisms of these neurological AEFIs. There is some epidemiological evidence linking COVID-19 vaccines to cerebral venous sinus thrombosis, arterial ischemic stroke, convulsive disorder, Guillain-Barré syndrome, facial nerve palsy, and other neurological conditions. Cerebral venous sinus thrombosis has been associated with a thrombotic thrombocytopenia induced by the vaccine, similar to that induced by heparin, which suggests similar pathogenic mechanisms (likely involving antibodies against platelet factor 4, a chemokine released from activated platelets). Arterial ischemic stroke is another thrombotic condition observed among some COVID-19 vaccine recipients. Vaccine-induced convulsive disorder might be the result of structural abnormalities potentially caused by the vaccine or autoimmune mechanisms. Guillain-Barré syndrome and facial nerve palsy may also be linked to the immunization event, possibly due to immune mechanisms such as uncontrolled cytokine release, autoantibody production, or bystander effect. However, these events are mostly uncommon and the evidence for the association with the vaccine is not conclusive. Furthermore, the potential pathophysiological mechanisms remain largely unknown. Nevertheless, neurological AEFIs can be serious, life-threatening or even fatal. In sum, COVID-19 vaccines are generally safe and the risk of neurological AEFIs does not outweigh the benefits of immunization. However, early diagnosis and treatment of neurological AEFIs are of utmost importance, and both health professionals and the public should be aware of these conditions.

Background: This research aims to explore and compare the signals of rhabdomyolysis from the use of Proton pump inhibitors (PPIs) using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Methods: Rhabdomyolysis and related terms submitted between 2013 and 2021 were retrieved from the FAERS database. The data were analyzed using the reporting odds ratio (ROR), proportional reporting ratio (PRR), Empirical Bayes Geometric Mean (EBGM) and the information component (IC). The signals of rhabdomyolysis associated with PPIs use were detected in both 3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) utilizers and non-utilizers.

Results: A total of 7,963,090 reports were retrieved and analyzed. Fifty-seven reports linked PPIs to rhabdomyolysis out of 3670 reports from other drugs (non-statin included). The association of rhabdomyolysis and PPIs was significant in both statins included, and non-statin-included reports, although with varying degrees of association. The ROR was 2.5 (95% confidence interval [CI] 1.9-3.2) for PPIs in non-statin-included reports and 2 (95% CI: 1.5-2.6) for PPIs in statin-included reports.

Conclusion: Significant signals of rhabdomyolysis were associated with PPIs. However, its signals were higher in non-statin-included reports compared to statin-included reports.

Plain language summary: Plain language summaryProton Pump Inhibitors and rhabdomyolysis risk Background: The FDA created the FDA Adverse Event Reporting System (FAERS) database to support post-marketing surveillance programs. The FAERS is a computerized database with more than nine million adverse event reports, including all reports from 1969 to the present. This research aims to explore and compare the signals of rhabdomyolysis from the use of proton pump inhibitors (PPIs) using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) database.Research design and methods: We retrieved rhabdomyolysis and related terms submitted between 2013 and 2021 from the FAERS database. Then, we analyzed the data that we found. We detected the signals of rhabdomyolysis associated with PPIs use in both statins utilizers and non-utilizers.Results: We retrieved and analyzed a total of 7,963,090 reports. We found 57 reports linked PPIs to rhabdomyolysis out of 3670 reports from other drugs (non-statin included). The association of rhabdomyolysis and PPIs was significant in both statins included, and non-statin-included reports, although with varying degrees of association.Conclusion: Significant signals of rhabdomyolysis were associated with PPIs. However, its signals were higher in non-statin-included reports than in statin-included reports.

Background: An important factor hindering the growth of pharmacovigilance (PV) in resource-limited settings is the lack of adequate funds to establish a functional National Pharmacovigilance System. Consequently, the crucial function of monitoring and ensuring the availability of safe medicines in these settings cannot be guaranteed considering the peculiarities of diseases and medicines used.

Objectives: The objective of this paper is to provide an overview as to the availability of potential sources of funds, which could be explored to ensure Medicine Safety and to proffer a potential framework likely to ensure sustainable funding of PV in Africa.

Methods/processes: The process of developing this framework entailed a review of PV financing in some developed economies, a landscape study of funding of PV in some African countries, an in-depth understanding of the PV system and the organisational structure and nexus between the regulatory agencies and National Pharmacovigilance Centre. Critical points for consideration included the sources of funds, revenue pool, the disbursement of funds, budgeting and expenditure profile and the legal framework. Consultative meetings, webinars and interviews with experts were carried out.

Results: The findings showed that most of the PV systems were mainly integrated into the regulatory agencies regarding operational and fiscal governance with few facilities being independent of the regulatory agencies. The main source of funding was from the government with significant donor funding which is ad hoc and non-sustainable. Several potential sources were identified but yet to be exploited. There were no legal provisions for PV financing. A framework likely to ensure sustainable PV financing is suggested to capture all available sources of funding, mine the potential sources providing a sizeable pool of revenue to address its activities and enabling legal framework which will engender autonomy. Furthermore, it will address the nexus between the regulatory agencies and the PV outfits, thus enabling appropriate share of resources and blockage of diversions.

Conclusion: In all, addressing the various elements identified in this study and providing the legal provisions which guarantees some degree of autonomy will provide a sustainable mechanism for PV funding in the resource-limited setting of Africa.

Background: Healthcare is challenged by a rapidly growing group of patients with multi-morbidity and polypharmacy. Increasing activity and specialization puts pressure on healthcare sectors. Medication errors in cross-sectoral transition of patients are often seen. The aim of the study was to explore drug-related problems (DRPs) in the transition of patients between sectors and to develop and pilot-test a cross-sectoral hospital pharmacist intervention to overcome some of these problems.

Methods: DRPs in cross-sectoral transitions were explored from four perspectives; the literature, the primary and secondary healthcare sector and the patients. An intervention was developed from the findings through co-creation between pharmacists, doctors and a nurse. The intervention was piloted and evaluated from data on the included patients and the activities performed.

Results: DRPs in transitions from general practice (GP) to hospital were caused by inadequate focus on updating the Shared Medication Record (SMR). For patients being discharged, DRPs were described with multiple facets; for example, missing information on medication changes, lacking patient involvement and problems with dose-dispensed medicine or electronic prescriptions. An intervention with a pharmacist in a shared employment between Hospital Pharmacy and GP was developed and piloted. The intervention included medication reconciliation and updating SMR for patients referred to hospital; and medication review, overview of medication changes and follow-up telephone calls for patients discharged from hospital. The intervention identified and solved several DRPs; in this way, medication errors were avoided. Access to health records in both sectors was important in the identification and resolution of DRPs.

Conclusion: DRPs in cross-sectoral transitions are multifaceted and the experiences depend on the point of view. The cross-sectoral hospital pharmacist intervention identified and solved several DRPs and medication errors were avoided. The intervention made sense to both healthcare sectors and patients. Shared employment and unique access to health records in both sectors showed to be of importance in the identification and resolution of DRPs.

Plain language summary: Development and pilot-test of a pharmacist intervention for patients in transition between hospital and general practice Background: Healthcare is challenged by a rapidly growing group of patients with multiple chronic diseases treated with several drugs at the same time. The aim of the study was to explore drug-related problems in the transition of patients between the hospital and patients' general practitioner and to develop and pilot-test a pharmacist intervention to overcome some of these problems.Methods: Drug-related problems in patient transitions were explored from the perspectives of the

More than 2 years has passed since the pandemic was declared in 2019 due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was later declared to be the pathogen causing coronavirus disease 2019 (COVID-19). During this time, many healthcare systems faced numerous challenges to control the high morbidity and mortality of the disease. Unlike previous pandemics, the actions against this pandemic started quickly on both the global and country levels. These actions were, scientifically, to study the virus as well as transmission process and to develop medications and vaccines against it. Also, we had to protect people from transmission by knowing how best to apply precautionary methods. However, there were some unexpected negative consequences of the pandemic and one of those the World Health Organization (WHO) called 'infodemic'. This term infodemic refers to the manipulation of a population's behavior in the assessment of information (or, more accurately, lack of assessment) related to the use of medications, particularly vaccines. Unfortunately, even with positive development in science, there was limited and often contradictory amount of information on the safety and efficacy profile of drugs and vaccines. Therefore, this made it harder for public health agencies to determine the impact of the incidence of adverse reactions and events associated with interventions such as vaccines. Hence, risk communication needs to be emphasized during any pandemic, as ignoring risk communications to different stakeholders could undermine all well-intended therapeutic interventions. Given this, it is important that the different stakeholders involved (health authorities, societies, healthcare professionals, etc.) assess the different behavioral patterns within their respective populations and propose appropriate strategies to act. Such an approach complement having risk management and communication plans for this and future pandemics. The aim of this article is to explore how information management, risk management, and risk communication during the pandemic can provide valuable lessons for the future.

Plain language summary: Impact of risk communication on patient's safety during the pandemic More than 2 years have gone by since the pandemic was declared in 2019 due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Many challenges have been confronted by the healthcare system during this time to control the high impact of this disease. This pandemic, unlike others that humanity has faced, is characterized by a special feature: today, we have an enormous amount of information only a click away. This situation has been of great benefit to humanity and has allowed the development of science; nevertheless, misinformation (infodemics) has been a major problem, which has revealed the behavior of the population regarding the evaluation of information (or better, lack of assessment) related to th

Background: Clinical trials investigating the effects of beta-blockers (BBs) on cancer are underway. Evidence from preclinical research suggests that BBs could serve as anticancer agents and immune boosters. There is conflicting evidence regarding the effect of BB use on clinical outcomes in patients with breast cancer.

Objectives: The study aimed to determine whether BB use is associated with progression-free survival (PFS) and overall survival (OS) in patients receiving anti-human epidermal growth factor receptor 2 (HER2) treatment for advanced breast cancer.

Design: Retrospective hospital-based study.

Methods: The participants enrolled were breast cancer patients with advanced HER2-positive status who initiated trastuzumab monotherapy or concomitant therapy with trastuzumab and any dose of BB. The patients were enrolled between January 2012 and May 2021 and divided into three groups based on whether they received a BB or not in the therapeutic regimen: BB-/trastuzumab+, BB+ (non-selective)/trastuzumab+, and BB+ (selective)/trastuzumab+. PFS and OS were the primary and secondary endpoints, respectively.

Results: The estimated median PFS in the BB-/trastuzumab+, BB+ (non-selective)/trastuzumab+, and BB+ (selective)/trastuzumab+ groups was 51.93, 21.50, and 20.77 months, respectively. The corresponding OS was 56.70, 29.10, and 27.17 months. The intergroup differences in these durations were significant. Both PFS [adjusted hazard ratio (HR): 2.21, 95% confidence interval (CI): 1.56-3.12; p < 0.001]) and OS (adjusted HR: 2.46, 95% CI: 1.69-3.57; p < 0.001) were worse when BBs were used.

Conclusion: Our study provides important evidence that BB use potentially has a negative effect on patients with HER2-positive advanced breast cancer. Nevertheless, despite the study's results, cardiovascular disease (CVD) should be appropriately treated in patients with HER2-positive advanced breast cancer. Other types of drugs can be used to treat CVD, but BB use should be avoided. Large real-world database and prospective studies should be conducted to validate the results of this study.

Introduction: The primary aim of this study was to compare the incidence of venous thromboembolism (VTE) among women initiating ospemifene vs other selective estrogen receptor modulator (SERM) therapies for estrogen-deficiency conditions or breast cancer prevention, and vs women with untreated vulvar and vaginal atrophy (VVA). The secondary objective examined numerous additional safety outcomes.

Methods: This was a retrospective cohort study using the IBM Watson MarketScan claims database. Women receiving ospemifene, another SERM, or with a new diagnosis of VVA with no treatment from 1 May 2013 to 2 October 2018 were followed through the claims for incident adverse outcomes. The primary outcome was the first occurrence of VTE following cohort entry; secondary outcomes included cerebrovascular events and other adverse events potentially associated with SERM use. Cox models compared the risk of VTE between ospemifene and comparators, using a variety of approaches to control for confounding.

Results: The incidence of VTE during the first continuous treatment episode was 3.39 (95% confidence interval [CI]: 1.55-6.43) events per 1,000 person-years (PY) for ospemifene (N = 8977), 11.30 (95% CI: 8.81-14.28) events per 1,000 PY for comparator SERM (N = 12,621), and 10.92 (95% CI: 10.49-11.37) events per 1,000 PY for untreated VVA (N = 242,488). Cox models indicated no increase in risk of VTE for ospemifene vs other SERMs (hazard ratio [HR]: 0.40, 95% CI: 0.19-0.82), and vs untreated VVA (HR: 0.47, 95% CI: 0.24-0.91).

Conclusion: This real-world safety analysis found no increase in risk of VTE or other adverse events with use of ospemifene in postmenopausal women.

Plain language summary: Introduction: This study assessed the risk of venous thromboembolism (VTE) among women treated with ospemifene or another selective estrogen receptor modulator (SERM) therapy and women with untreated vulvar and vaginal atrophy (VVA). Numerous additional safety outcomes were examined.Methods: This study was conducted in the IBM Watson MarketScan claims database. Women receiving ospemifene, another SERM, or with a new diagnosis of VVA with no treatment from 1 May 2013 to 2 October 2018 were followed through the claims for adverse outcomes, including VTE, cerebrovascular events (such as stroke), and other outcomes that might occur with use of a SERM. The analyses compared the risk of VTE between ospemifene and the other two groups, using methods that accounted for differences in patient characteristics between the groups. Because few women over 72 years old used ospemifene, the main analyses examined women aged 54-72 years.Results: The analyses included 8,977 ospemifene users, 12,621 other SERM users, and 242,488 women with untreated VVA. Among women aged 54-72 years, only 9 experienced a VTE during ospemifene treatment, wh

Introduction: Debate on the association between the use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) and the risk of developing cancer has been ongoing for decades. This study aimed to generate reliable results by analysing observational studies published in the decade after our last meta-analysis was conducted.

Methods: We searched Embase and Medline databases on 21 January 2021 for cohort and case-control studies. Two researchers independently reviewed the literature and assessed the title and abstract of each publication. The I2 statistic used to evaluate the heterogeneity of the effect measures. Risk of bias was qualitatively assessed using the Newcastle-Ottawa scale.

Results and discussion: We included an additional 16 cohort, 6 nested case-control, and 9 conventional case-control studies in the updated analysis. Overall HRs decreased, while overall relative risks increased.

Conclusion: Our results show some protective effects through the hazard ratio and some detrimental effects through the relative risk. Large-scale investigations of cohorts followed up for decades are needed to clarify association.

Plain language summary: Introduction: Two types of drug, angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), have been linked to the risk of developing cancer. We performed a meta-analysis by aggregating individual studies looking into the cancer risk of ACEIs and ARBs.Methods: We searched for articles on Embase and Medline databases until 21 January, 2021. Two researchers independently reviewed the literature and assessed the title and abstract of each publication.Results: Overall, the hazard ratio showed less than 1, while the relative risks showed higher than 1.Conclusion: Our results show some protective effects through the hazard ratio and some detrimental effects through the relative risk. Evidence supporting the risk of developing cancer is insufficient to prevent prescribing ACEIs or ARBs for patients with high blood pressure.

Aims: The gene polymorphism of voriconazole metabolism-related liver enzyme is notable in East Asia population. It casts a significant influence on the rational use of voriconazole. We conducted this study to investigate the relationship between steady-state voriconazole trough concentration (C_trough) and adverse effects (AEs), especially hepatotoxicity.

Methods: We conducted a real-world study in the Jinling Hospital from January 2015 to June 2020. A total of 140 patients receiving voriconazole were enrolled in this study. The determination and scoring of voriconazole-associated hepatotoxicity were performed according to the Roussel Uclaf Causality Assessment Method scoring scale and the severity of hepatotoxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE).

Results: Elevated steady-state voriconazole C_trough with concomitant AEs are the most common reason for dose adjustments during treatment. Compared with the group without any AEs, voriconazole C_trough was significantly higher in the hepatotoxicity and neurotoxicity groups, and the incidence of both events showed an overall increasing trend with increasing voriconazole C_trough. Hepatotoxicity occurred in 66.7% of patients within 7 days of the first dose of voriconazole and 94.4% within 15 days of the dose. Steady-state voriconazole C_trough >3.61 mg/l was associated with an increased incidence of hepatotoxicity (area under the curve = 0.645, p = 0.047). Logistic regression analysis showed that timely voriconazole dose adjustment was a predictor of attenuated hepatotoxicity after adjustment for confounders, but hepatotoxicity was not associated with voriconazole C_trough measured at a single time point.

Conclusion: Hepatotoxicity and neurotoxicity correlate with voriconazole C_trough, and dose reduction in patients with elevated steady-state voriconazole C_trough may prevent hepatotoxicity. In patients with early occurrence of hepatotoxicity, initial therapeutic drug monitoring (TDM) might predict the risk of hepatotoxicity. Follow-up TDM may be necessary to predict late onset hepatotoxicity.

Plain language summary: Safety of voriconazole for the treatment of pulmonary fungal diseases Introduction: Several studies have suggested an association between the concentration of voriconazole in the blood and liver damage, but the evidence is weak. This study aimed to investigate relationships between voriconazole drug concentration and side effects and to analyze the factors affecting liver damage caused by voriconazole.Methods: We conducted a study at the Jinling Hospital from January 2015 to June 2020, in which a total of 140 patients were finally enrolled.Results: Voriconazole doses were adjusted in 44 patients due to abnormal voric