Therapeutic Advances in Drug Safety最新文献

Background: One in five patients admitted to the hospital treated with intravenous (IV) fluid therapy suffer complications due to inappropriate administration. Errors have been reported in 13-84% of the preparation and administration of IV medications. The safe delivery of IV fluids requires precise rate administration.

Objectives: This systematic review aims to determine the accuracy of infusion sets and devices and examine the factors that affect the flow rate accuracy of devices.

Data sources and methods: Six databases (CINAHL, MEDLINE PubMed, EMBASE, Web of Science and Cochrane Database of systematic reviews) were systematically searched. Search terms included infusion pumps, infusion devices, flow rate accuracy, fluid administration rate, gravity-led infusion set and fluid balance. Studies were included if they examined infusion devices' flow rate accuracy and drop rates for fluids or non-oncological drugs. Findings were tabulated and synthesised qualitatively. The quality of the studies was examined based on the design of the studies due to their heterogeneity.

Results: Eight studies were included: Four studies were conducted on human subjects in the hospital environment; studies recruited 182 participants between the ages of 18 and 94 years. Two studies examined flow rate accuracy in recruited patients across 509 observations and 2387 drip hours. No trials prospectively assessed the accuracy of infusion pumps in the clinical domain, and no studies were reported on patient safety outcomes. Four studies examined the impact of mechanical and physiological factors on the flow rate accuracies of infusion devices. Height and back pressure simulated vibrating conditions, the viscosity of IV fluid and the positions of patients were reported to have a significant impact on infusion volume and flow rates of infusion devices. Additionally, giving sets that vary from the manufacturer's specifications are reported to increase error percent by 10-20%.

Conclusion: Infusion devices are an important source of error in administering IV fluids. Yet, there needs to be more prospective trial data to support their clinical accuracy and the impact on patient outcomes. Future flow variability and accuracy studies should capture their impact on patient safety and clinical outcomes.

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: 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: 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: 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.

During the COVID-19 pandemic, the behavior of self-medication has increased. The dissemination of misleading information regarding the efficacy of certain drugs or substances for the prevention and treatment of COVID-19 has been the major contributing factor for this phenomenon. Alongside with the increase in self-medication behavior, the inherent risks to this act such as drug-drug interactions, adverse events, drug toxicity, and masking of symptoms have also increased. Self-medication in the context of COVID-19 has led to drug misuse leading in some cases to the development of fatal adverse drug reactions. It is important that during this ongoing pandemic drugs with potential clinical efficacy against COVID-19 are adequately analyzed regarding their efficacy, safety, and monitoring. The aim of this review is to describe the available evidence regarding the efficacy, safety, and monitoring of the drugs and substances that have been shown to be frequently used for self-medication in patients with COVID-19 (hydroxychloroquine, non-steroidal anti-inflammatory drugs, ivermectin, azithromycin, vitamins, aspirin, and chlorine dioxide) to adequately characterize their risks, safe use, monitoring strategies, and to reinforce the concept that these substances should not be used for self-medication and require a medical prescription.

Plain language summary: Drug safety of frequently used drugs and substances for self-medication in COVID-19 Dissemination of information about potential COVID-19 treatments has led individuals to self-medicate and expose themselves to risks such as drug-drug interactions, side effects, antibiotic resistance, and misdiagnosis. There is a need to review the medical literature to evaluate the safety and efficacy of the drugs and substances commonly used by the population for the treatment and prevention of SARS CoV-2 infection. In this review, we included drugs that are frequently used for self-medication and commonly advertised such as ivermectin, hydroxychloroquine, chlorine dioxide, azithromycin, and non-steroidal anti-inflammatory drugs, among others. A brief introduction of the drug and its mechanism of action, followed by a summary of the efficacy in COVID-19 and safety, will be described for each drug in order to promote their responsible use.

Purpose: Weekly gemcitabine + paclitaxel (wGT) administration is widely applied in real-world clinical practice. The 28-day and 21-day regimens of wGT are the most widely accepted regimens. We evaluated the efficacy and safety of wGT administration in patients with metastatic breast cancer (MBC) and compared the two regimens.

Methods: Patients with human epidermal growth factor receptor 2 (HER-2)-negative MBC who received wGT between October 2013 and October 2016 were identified using an electronic database. The outcome variables included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety profile. Propensity score matching was performed to minimize potential confounders.

Results: A total of 140 patients were included. The median PFS and OS was 7.8 [95% confidence interval (CI) = 7.0-8.7] months and 22.5 (95% CI = 18.8-26.1) months, respectively. The toxicity of wGT was manageable. Among the patients, 90 (64.3%) received the 21-day regimen and 50 (35.7%) received the 28-day regimen. A higher number of younger patients and patients receiving later-line therapy received the 28-day regimen. There was no significant difference between the two groups in PFS after propensity score matching, though subgroup analysis showed that patients with early relapse benefited more from the 28-day regimen. The ORR was numerically higher in 28-day regimen (37.8% versus 28.0%, p = 0.310). However, the 21-day regimen was better tolerated than the 28-day regimen.

Conclusion: wGT administration showed efficacy and safety in patients with MBC. The efficacy was comparable between the two regimens after adjustment for confounding factors while the 21-day regimen was better tolerated.

Plain language summary: 21-day regimen of wGT was well tolerated in patients with metastatic breast cancer Weekly gemcitabine + paclitaxel (wGT) administration is widely applied in real-world clinical practice. The 28-day and 21-day regimens of wGT are the most widely accepted regimens. We evaluated the efficacy and safety of wGT administration in patients with metastatic breast cancer (MBC) and compared the two regimens. Patients with human epidermal growth factor receptor 2 (HER-2)-negative MBC who received wGT between October 2013 and October 2016 were identified using an electronic database. The outcome variables included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and safety profile. Propensity score matching was performed to minimize potential confounders. We found that the efficacy was comparable between the two regimens after adjustment for confounding factors while the 21-day regimen was better tolerated.