Efficacy and safety of onasemnogene abeparvovec for the treatment of patients with spinal muscular atrophy type 1: A systematic review with meta-analysis.

BACKGROUND: Onasemnogene abeparvovec has been approved for the treatment of spinal muscular atrophy 5q type 1 in several countries, which calls for an independent assessment of the evidence regarding efficacy and safety. OBJECTIVE: Conduct a meta-analysis to assess the efficacy and safety of onasemnogene abeparvovec in patients diagnosed with SMA type 1, based on the available evidence. METHODS: This article results from searches conducted on databases up to November 2022. Outcomes of interest were global survival and event-free survival, improvement in motor function and treatment-related adverse events. Risk of bias assessment and certainty of evidence were performed for each outcome. Proportional meta-analysis models were performed when applicable. RESULTS: Four reports of three open-label, non-comparative clinical trials covering 67 patients were included. Meta-analyses of data available in a 12-month follow-up estimate a global survival of 97.56% (95%CI: 92.55 to 99.86, I2 = 0%, n = 67), an event-free survival of 96.5% (95%CI: 90.76 to 99.54, I2 = 32%, n = 66) and a CHOP-INTEND score ≥ 40 points proportion of 87.28% (95%CI: 69.81 to 97.83, I2 = 69%, n = 67). Proportion of 52.64% (95%CI: 27.11 to 77.45, I2 = 78%, n = 67) of treatment-related adverse events was estimated. CONCLUSION: The results indicate a potential change in the natural history of type 1 SMA, but the methodological limitations of the studies make the real extent of the technology's long-term benefits uncertain.

Key performance indicators for pharmaceutical services: A systematic review.

Background: Key performance indicators (KPIs) are a set of indicators that improve the quality of services provided by pharmacists. They enable the monitoring and evaluation of result progress and optimize decision-making for stakeholders. Currently, there is no systematic review regarding KPIs for pharmaceutical services. Objectives: To identify and assess the quality of KPIs developed for pharmaceutical services. Methods: A systematic review was conducted in PubMed, Scopus, EMBASE, and LILACS from the inception of the database until February 5th, 2024. Studies that developed a set of KPIs for pharmaceutical services were included. The indicators were evaluated using the Appraisal of Indicators through Research and Evaluation (AIRE) instrument. Two independent reviewers performed the study selection, data extraction, and quality assessment. Results: Fifteen studies were included. The studies were conducted in different regions, most of which were developed for clinical services in hospitals or ambulatory settings, and used similar domains for the development of KPIs such as medication review, patient safety, and patient counseling. Literature review combined with the Delphi technique was the method most used by the studies, with content validity by inter-rater agreement. Regarding methodological quality, most studies described information on the purpose, definition, and stakeholders' involvement in the set of KPIs. However, little information was observed on the strategy for risk adjustment, instructions for presenting and interpreting the indicator results, the detailed description of the numerator and denominator, evidence scientific, and the feasibility of the set of KPIs. Only one study achieved a high methodological quality in all domains of the AIRE tool. Conclusion: Our findings showed the potential of KPIs to monitor and assess pharmacy practice quality. Future studies should expand KPIs for other settings, explore validity evidence of the existing KPIs, provide detailed descriptions of evidence, formulation, and usage, and test their feasibility in daily practice.

Cost-Effectiveness of Onasemnogene Abeparvovec Compared With Nusinersen and Risdiplam in Patients With Spinal Muscular Atrophy Type 1 in Brazil: Custo-Efetividade do Onasemnogeno Abeparvoveque (AVXS-101) em Comparação ao Nusinersena e Risdiplam em Pacientes com Atrofia Muscular Espinhal Tipo 1 no Brasil.

OBJECTIVES: This study aimed to evaluate the cost-effectiveness of the onasemnogene abeparvovec in relation to nusinersen and risdiplam in the treatment of spinal muscular atrophy type 1 from the perspective of the Brazilian Unified Health System. METHODS: A Markov model was built on a lifetime horizon. Short-term data were obtained from clinical trials of the technologies and from published cohort survival curves (long term). Costs were measured in current 2022 local currency (R$) values and benefits in quality-adjusted life-years (QALYs). Utility values were derived from type 1 spinal muscular atrophy literature, whereas costs related to technologies and maintenance care in each health state were obtained from official sources of reimbursement in Brazil. Deterministic and probabilistic, as well as scenario, sensitivity analyses were performed. RESULTS: Compared with the less costly strategy (nusinersen), the use of onasemnogene abeparvovec resulted in an incremental cost of R$2.468.448,06 ($975 671.169 - purchasing power parity [PPP]) and a 3-QALY increment and incremental cost-effectiveness ratio of R$742.890,92 ($293 632.774 - PPP)/QALY. Risdiplam had an extended dominance from other strategies, resulting in an incremental cost-effectiveness ratio of R$926.586,22 ($366 239.612 - PPP)/QALY compared with nusinersen. Sensitivity analysis showed a significant impact of the follow-up time of the cohort and the cost of acquiring onasemnogene abeparvovec. CONCLUSIONS: Over a lifetime horizon, onasemnogene abeparvovec seems to be a potentially more effective option than nusinersen and risdiplam, albeit with an incremental cost. Such a trade-off should be weighed in efficiency criteria during decision making and outcome monitoring from the perspective of the Brazilian Unified Health System.

Pharmacists' contribution to benzodiazepine deprescribing in older outpatients: a systematic review and meta-analysis.

BACKGROUND: Consolidated and reliable evidence regarding the effectiveness of pharmacist interventions for deprescribing benzodiazepines in older outpatients is lacking. AIM: This study evaluated and summarized the impact of pharmacist interventions on benzodiazepine deprescribing among older outpatients. METHOD: A literature search was conducted until August 2022 in PubMed, PsycINFO, and the Cochrane Central Register of Controlled Trials databases. The review included randomized controlled trials that assessed the impact of pharmacist interventions on deprescribing benzodiazepine in older outpatients. Two independent investigators conducted the study selection, data extraction, and risk of bias assessment. Meta-analyses were conducted using random-effect models in the RStudio software. RESULTS: A total of 893 records were identified. Five studies, including 3,879 patients, met the inclusion criteria and were included in the systematic review. All five studies used health education as an intervention strategy, and three also conducted medication reviews. There was no evidence of the pharmacist's authority to modify prescriptions during benzodiazepine deprescribing. One study was classified as having a low risk of bias, whereas the other had some concerns or a high risk of bias. Three studies were included in the meta-analysis and a significant impact of pharmacist interventions on benzodiazepines deprescribing rates in older outpatients was observed (RR = 2.75 [95%CI 1.29; 5.89]; p = 0.04; I2 = 69%; low certainty of evidence). CONCLUSION: Pharmacists may contribute to deprescribing benzodiazepines in older outpatients. Further studies are needed to increase the reliability of these findings. PROSPERO registration number: CRD42022358563.

Implementation of Medication Reconciliation conducted by hospital pharmacists: A case study guided by the Consolidated Framework for Implementation Research.

BACKGROUND: Medication reconciliation (MR) implementation in hospital care transitions has proved to be a challenge for health professionals and managers. It points to the need to conduct Implementation Research with a view to understanding the tasks of the real world and knowing how they impact this process. Guided by the Consolidated Framework for Implementation Research (CFIR), this study aims to analyze the factors that influenced the MR implementation process conducted by pharmacists at a hospital setting. METHODS: A qualitative case study was carried out in the cardiology and gastroenterology units of a teaching hospital in Brazil, involving participant observation and semi-structured interviews with physicians, pharmacists, nurses, nutritionists and a social worker. The CFIR was used to guide data collection and thematic analysis. The constructs were classified according to their influence and strength. RESULTS: Sixteen health professionals involved directly or indirectly with MR implementation participated in the study. Based on the analysis of the participants' quotes and of the field diary, 18 constructs of the CFIR were identified as influencing MR implementation. The constructs that most strongly influenced MR implementation concerned "Inner Setting", "Characteristics of Individuals" and "Characteristics of Intervention". The participating professionals showed little knowledge of MR and had different points of view on its scope, weakly relating MR to patient safety. The tools used to conduct MR were adapted according to the hospital's needs, thus facilitating its implementation. However, MR proved to be complex and require clinical knowledge and aligned teamwork to identify and resolve undocumented medication discrepancies, being as well intertwined with culture and organizational communication. CONCLUSIONS: The results point to implementation failures and highlight that MR is a complex intervention, requiring specific knowledge from the multidisciplinary team and alignment with other existing workflows. The barriers and facilitators identified may serve to design and test implementation improvement strategies.

Application and utility of geographic information systems in pharmacy specific health research: A scoping review.

BACKGROUND: Geographic Information Systems (GIS) are considered essential tools to analyze spatially referenced health data. OBJECTIVES: The purpose of this scoping review is to describe how GIS is used in pharmacy specific health research. METHODS: During July 2020, the following databases were searched: EMBASE, MEDLINE (PubMed), Web of Science and Scopus. The search strategy included terms relating to spatial analysis and pharmacy. Studies were considered eligible if they involved the use of GIS and focused on pharmacies. A narrative and tabular synthesis of the results was carried out, structured around the spatial analysis methods utilized across studies, as well as the characteristics of pharmacies evaluated in studies. RESULTS: After a review of 6967 sources, 48 studies were included in this review. Twenty-nine studies were conducted in the United States (60.4%) and thirty-six focused on accessibility (75.0%; n = 36). Twenty-two studies investigated the relationship between sociodemographic aspects of the population and the accessibility and availability of pharmacies (45.8%). Twelve studies (25.0%) performed distance analysis and six studies (12.5%) performed geostatistical analysis. Community pharmacies were the setting evaluated most frequently, with over-the-counter selling products being the most evaluated pharmacy variable (13.3%; n = 6). Population density (58.3%; n = 28), income indicators (43.8%; n = 21) and minority community composition rates (41.7%; n = 20) were the most used population variables. CONCLUSIONS: GIS have been increasingly used in pharmacy specific health research. Generally, research has sought to identify potential barriers to access and their effects on the population. Future research may benefit by utilizing robust spatial methods and applications across countries outside of the United States. Doing so could help to confirm the impact of sociodemographic characteristics on the availability and/or accessibility of pharmacies globally.

Tools to prioritize outpatients for pharmaceutical service: A scoping review.

BACKGROUND: The performance of pharmacists in clinical services contributes to improving outcomes in patient drug therapy. In the context of streamlined resources and high health services' demand, the use of patient selection tools can screen those who would benefit more from a pharmaceutical service. OBJECTIVE: This review aims to map and describe tools developed for patient selection for pharmaceutical services delivered in primary health care and outpatient settings. METHODS: The search was conducted in MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and the Latin American and Caribbean Health Sciences. The search strategy included terms relating to patient selection and outpatient pharmaceutical service. We included papers on outpatient settings, and which described the tool developed for the selection of a patient for pharmaceutical service. Two reviewers extracted data of each study concerning the types and items making up the tool. The items composing the tools were grouped into categories. RESULTS: Twelve studies were included in the literature. Most of the studies were developed in the United States (53.8%), followed by Canada (30.8%). Approximately half of the studies developed tools for selecting patients for a medication review (46.2%), and only 15.4% for drug therapy management. Identification of patients at risk of drug-related problems, the need for pharmaceutical service follow-up, and patients at risk of hospital readmission were the main objective to develop the tools. In total, 92.3% of the developed tools had items related to drug therapy complexity, 76.9% to comorbidities and 61.5% to adherence/subjective aspects. Statistical methods were employed to evaluate the validation parameters, such as the ROC curve and internal consistency. CONCLUSIONS: Few studies that developed tools to select outpatients for pharmaceutical services were found. However, many tools showed unsatisfactory validation parameters. Thus, it is necessary to improve the development of instruments that can identify patients who would benefit from the pharmaceutical service accurately.

Pharmacist-led medication reconciliation at patient discharge: A scoping review.

BACKGROUND: One of the strategies to promote patient safety in care transitions is medication reconciliation (MR), which is conducted by the pharmacist at the patient's discharge from hospital. However, there are divergences about this process and about the pharmacist's role in conducting such intervention. OBJECTIVE: To systematically review the literature that reports the MR process led by pharmacists at patient discharge and map the different methods, strategies and tools used in the process. METHODS: Relevant studies were searched in the following databases: EMBASE, MEDLINE (PubMed), The Cochrane Library, and LILACS. No language restriction or publication date was applied. The studies considered eligible were those involving and describing pharmacist-led MR processes at acute patient discharge from hospital, with an experimental, quasi-experimental, or observational design. The characteristics of the studies and the MR processes were identified and then a qualitative synthesis was performed. RESULTS: Fifty studies were included. The majority of them were observational ones (82%), and the main outcome was medication discrepancies (42%). The studies were mostly conducted in university hospitals (70%) and in internal medicine wards (54%). Pharmacists were responsible mainly for gathering medication histories (72%), and identifying (96%) and solving (98%) pharmacotherapeutic problems. The main sources of information on pre-admission medications were patient/caregiver interviews (66%) and records from other care providers (40%). Only 30% of the studies described a patient discharge plan, and 14% shared information of the patient's pharmacotherapy with community pharmacists. CONCLUSION: The concept of MR and the pharmacist-led activities in the process varied in the literature, as well as the pharmacotherapy assessment focus and the communication strategies towards patients and other care providers, showing that standardization of the process and concepts is necessary.