Impact of pharmaceutical care for asthma patients on health-related outcomes: An umbrella review.

Recent systematic reviews suggest that pharmacists' interventions in asthma patients have a positive impact on health-related outcomes. Nevertheless, the association is not well established, and the role of clinical pharmacists is poorly represented. The aim of this overview of systematic reviews is to identify published systematic reviews assessing the impact of pharmacists' interventions on health-related outcomes measured in asthma patients. PubMed, Embase, Scopus, and Cochrane Library were searched from inception to December 2022. Systematic reviews of all study designs and settings were included. Methodological quality was assessed using AMSTAR 2. Two investigators performed study selection, quality assessment and data collection independently. Nine systematic reviews met the inclusion criteria. Methodological quality was rated as high in one, low in two, and critically low in six. Reviews included 51 primary studies reporting mainly quality of life, asthma control, lung capacity, and therapeutic adherence. Only four studies were carried out in a hospital setting and only two reviews stated the inclusion of severe asthma patients. The quality of the systematic reviews was generally low, and this was the major limitation of this overview of systematic reviews. However, solid evidence supports that pharmaceutical care improves health-related outcomes in asthma patients.

DPYD genotyping and 5-fluoropyrimidine toxicity: An overview of systematic reviews protocol / Genotipado del gen DPYD y toxicidad de 5-fluoropirimidinas: Protocolo de una revisión de revisiones sistemáticas

Introduction: The increased risk of severe and life-threatening toxicity in patients with dihydropyridine dehydrogenase (DPD) deficiency, under treatment with fluoropyrimidines, has been widely studied. An up-to-date overview of systematic reviews summarizing existing literature can add value by highlighting most relevant information and supports decision-making regarding treatment in DPD deficient patients. The main objective of this overview of systematic reviews is to identify published systematic reviews on the association between germline variations in the DPYD gene and fluoropyrimidine toxicity.Methods and analysis: This protocol was developed following the Preferred Reported Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) checklist, and the overview of systematic reviews will be reported in accordance with the PRISMA statement. PubMed, Embase, Scopus, and the Cochrane Library will be searched from inception to 2023. Systematic reviews irrespective of study designs that analyze the association between germline variations in the DPYD and fluoropyrimidine toxicity will be considered. Methodological quality will be assessed using AMSTAR2 checklist (Measurement Tool to Assess Systematic Reviews 2). Two independent investigators will perform the study selection, quality assessment, and data collection. Discrepancies will be solved by a third investigator.(AU)

Introducción: El incremento del riesgo de toxicidad grave y potencialmente mortal en pacientes con deficiencia de dihidropiridina deshidrogenasa (DPD) en tratamiento con fluoropirimidinas ha sido ampliamente estudiado. Una revisión actualizada de las revisiones sistemáticas publicadas, que agrupe la literatura existente, puede añadir valor al resaltar la información más relevante y respaldar la toma de decisiones con respecto al tratamiento en pacientes con deficiencia de DPD. El objetivo principal de esta revisión de revisiones sistemáticas es identificar revisiones sistemáticas publicadas sobre la asociación entre variaciones en el linaje germinal del gen DPYD y la toxicidad de las fluoropirimidinas. Métodos y análisis: Este protocolo se ha desarrollado siguiendo la lista de verificación de los Protocolos para Revisiones Sistemáticas y Metaanálisis Preferidos (PRISMA-P), y la revisión de las revisiones sistemáticas se comunicará de acuerdo con la declaración PRISMA. Se realizará una búsqueda en PubMed, Embase, Scopus y la Biblioteca Cochrane desde su inicio hasta 2023. Se considerarán aquellas revisiones sistemáticas, independientemente de los diseños de estudio, que analicen la asociación entre variaciones en el linaje germinal del gen DPYD y la toxicidad de las fluoropirimidinas. La calidad metodológica se evaluará utilizando la lista de verificación AMSTAR2 (Herramienta de Medición para Evaluar Revisiones Sistemáticas 2). Dos investigadores independientes realizarán la selección de estudios, la evaluación de la calidad y la recopilación de datos. Las discrepancias se resolverán mediante un tercer investigador.(AU)

Genotipado del gen DPYD y toxicidad de 5-fluoropirimidinas: Protocolo de una revisión de revisiones sistemáticas / DPYD genotyping and 5-fluoropyrimidine toxicity: An overview of systematic reviews protocol

Introduction: The increased risk of severe and life-threatening toxicity in patients with dihydropyridine dehydrogenase (DPD) deficiency, under treatment with fluoropyrimidines, has been widely studied. An up-to-date overview of systematic reviews summarizing existing literature can add value by highlighting most relevant information and supports decision-making regarding treatment in DPD deficient patients. The main objective of this overview of systematic reviews is to identify published systematic reviews on the association between germline variations in the DPYD gene and fluoropyrimidine toxicity.Methods and analysis: This protocol was developed following the Preferred Reported Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) checklist, and the overview of systematic reviews will be reported in accordance with the PRISMA statement. PubMed, Embase, Scopus, and the Cochrane Library will be searched from inception to 2023. Systematic reviews irrespective of study designs that analyze the association between germline variations in the DPYD and fluoropyrimidine toxicity will be considered. Methodological quality will be assessed using AMSTAR2 checklist (Measurement Tool to Assess Systematic Reviews 2). Two independent investigators will perform the study selection, quality assessment, and data collection. Discrepancies will be solved by a third investigator.(AU)

Introducción: El incremento del riesgo de toxicidad grave y potencialmente mortal en pacientes con deficiencia de dihidropiridina deshidrogenasa (DPD) en tratamiento con fluoropirimidinas ha sido ampliamente estudiado. Una revisión actualizada de las revisiones sistemáticas publicadas, que agrupe la literatura existente, puede añadir valor al resaltar la información más relevante y respaldar la toma de decisiones con respecto al tratamiento en pacientes con deficiencia de DPD. El objetivo principal de esta revisión de revisiones sistemáticas es identificar revisiones sistemáticas publicadas sobre la asociación entre variaciones en el linaje germinal del gen DPYD y la toxicidad de las fluoropirimidinas. Métodos y análisis: Este protocolo se ha desarrollado siguiendo la lista de verificación de los Protocolos para Revisiones Sistemáticas y Metaanálisis Preferidos (PRISMA-P), y la revisión de las revisiones sistemáticas se comunicará de acuerdo con la declaración PRISMA. Se realizará una búsqueda en PubMed, Embase, Scopus y la Biblioteca Cochrane desde su inicio hasta 2023. Se considerarán aquellas revisiones sistemáticas, independientemente de los diseños de estudio, que analicen la asociación entre variaciones en el linaje germinal del gen DPYD y la toxicidad de las fluoropirimidinas. La calidad metodológica se evaluará utilizando la lista de verificación AMSTAR2 (Herramienta de Medición para Evaluar Revisiones Sistemáticas 2). Dos investigadores independientes realizarán la selección de estudios, la evaluación de la calidad y la recopilación de datos. Las discrepancias se resolverán mediante un tercer investigador.(AU)

Clinical evaluation of antifungal de-escalation in Candida infections: A systematic review and meta-analysis.

OBJECTIVES: De-escalation (DES) from echinocandins to azoles is recommended by several medical societies in Candida infections. We summarise the evidence of DES on clinical and microbiological cure and 30-day survival and compare it with continuing the treatment with echinocandins (non-DES). METHODS: We searched MEDLINE, Embase, Web of Science and Scopus. Studies describing DES in inpatients and reporting any of the outcomes evaluated were included. Pooled estimates of the tree outcomes were calculated with a fixed or random-effects model. Heterogeneity was explored stratifying by subgroups and via meta-regression. This systematic review is registered with PROSPERO (CRD42023475486). RESULTS: Of 1853 records identified, 9 studies were included, totalling 1575 patients. Five studies stepped-down to fluconazole; one to voriconazole and three to any of azoles. The mean day of DES was 5.2 (4.6-6.5) days. The clinical cure OR was 1.29 (95% CI: 0.88-1.88); the microbiological cure 1.62 (95% CI: 0.71-3.71); and 30-day survival 2.17 (95% CI: 1.09-4.32). The 30-day survival data into subgroups showed higher effect on critically ill patients and serious-risk bias studies. Meta-regression did not identify significant effect modifiers. CONCLUSIONS: DES is a safe strategy; it showed no higher 30-day mortality and a trend towards greater clinical and microbiological cure.

DPYD genotyping and 5-fluoropyrimidine toxicity: An overview of systematic reviews protocol. / [Artículo traducido] Genotipado del gen DPYD y toxicidad de las 5-fluoropirimidinas: protocolo de un resumen de revisiones sistemáticas.

INTRODUCTION: The increased risk of severe and life-threatening toxicity in patients with dihydropyridine dehydrogenase deficiency, under treatment with fluoropyrimidines, has been widely studied. An up-to-date overview of systematic reviews summarizing existing literature can add value by highlighting most relevant information and supports decision-making regarding treatment in dihydropyridine dehydrogenase deficient patients. The main objective of this overview is to identify published systematic reviews on the association between germline variations in the DPYD gene and fluoropyrimidine toxicity. METHODS AND ANALYSIS: This protocol was developed following the Preferred Reported Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) checklist, and the overview of systematic reviews will be reported in accordance with the PRISMA statement. PubMed, Embase, Scopus and the Cochrane Library will be searched from inception to 2023. Systematic reviews irrespective of study designs that analyze the association between germline variations in the DPYD and fluoropyrimidine toxicity will be considered. Methodological quality will be assessed using AMSTAR2 checklist (Measurement Tool to Assess Systematic Reviews 2). Two independent investigators will perform the study selection, quality assessment and data collection. Discrepancies will be solved by a third investigator.

Atención farmacéutica y asma: protocolo de una revisión de revisiones sistemáticas / Pharmaceutical care and asthma: Protocol of an umbrella review of systematic reviews

Introducción las revisiones sistemáticas y metaanálisis recientes sugieren que las intervenciones por parte de farmacéuticos en pacientes asmáticos tienen un impacto positivo en resultados en salud. Sin embargo, la asociación no está bien establecida y el papel de los farmacéuticos clínicos está pobremente representado, así como el de los pacientes con asma grave. El objetivo de esta revisión de revisiones es identificar revisiones sistemáticas publicadas que evalúen el impacto de las intervenciones farmacéuticas en resultados en salud medidos en pacientes asmáticos, así como describir los componentes clave de las intervenciones, los resultados medidos y cualquier asociación entre las intervenciones farmacéuticas y los resultados en salud medidos. Métodos se hará una busqueda en PubMed, Embase, Scopus y la Cochrane Library desde el primer registro hasta diciembre de 2022. Se considerará la inclusión de revisiones sistemáticas de todo tipo de estudios primarios, severidad del asma o nivel asistencial que midan resultados en salud. La calidad metodológica se medirá usando A Measurement Tool to Assess Systematic Reviews 2. Dos investigadores independientes realizarán la selección de los estudios, la evaluación de la calidad y la extracción de datos. Cualquier discrepancia será solventada por un tercer investigador. Ambos resultados, narrativos y metaanálisis, de los estudios primarios incluidos en las revisiones sistemáticas serán sintetizados. Si los datos son apropiados para un análisis cuantitativo, las medidas de asociación se expresarán como cociente de riesgos y diferencia de medias. Discusión los primeros resultados del establecimiento de una red multidisciplinar para el manejo de los pacientes asmáticos mostraron beneficios en integrar los diferentes niveles asistenciales en el control de la enfermedad y la reducción de la morbilidad...(AU)

Introduction Recent systematic reviews and meta-analyses suggest that pharmacists' interventions in asthma patients have a positive impact on health-related outcomes. Nevertheless, the association is not well established and the role of clinical pharmacists is poorly represented, as well as severe asthma patients. The aim of this overview of systematic reviews is to identify published systematic reviews assessing the impact of pharmacists' interventions on health-related outcomes measured in asthma patients, as well as to describe key components of the interventions, the outcomes assessed and any associations between pharmacists' interventions and health-related outcomes. Methods PubMed, Embase, Scopus and the Cochrane Library will be searched from inception to December 2022. Systematic reviews of all study designs, severity of asthma and level of care that measured health-related outcomes will be considered. Methodological quality will be assessed using A Measurement Tool to Assess Systematic Reviews 2. Two independent investigators will perform the study selection, quality assessment and data collection, any discrepancy will be solved by a third investigator. Both narrative findings and meta-analysis of primary study data included in the systematic reviews will be synthesized. If data are appropriate for quantitative synthesis, the measures of association will be expressed as the risk ratio and difference in means. Discussion The first results on the establishment of a multidisciplinary network for the management of asthmatic patients have shown the benefits of integrating different levels of care in disease control and morbidity reduction. Further studies showed benefits in hospital admissions, patients' basal oral corticosteroid dose, exacerbations and quality of life of asthma patients...(AU)

Pharmaceutical care and asthma: Protocol of an umbrella review of systematic reviews. / [Artículo traducido] Atención farmacéutica y asma: protocolo de una revisión de revisiones sistemáticas.

INTRODUCTION: Recent systematic reviews and meta-analyses suggest that pharmacists' interventions in asthma patients have a positive impact on health-related outcomes. Nevertheless, the association is not well established and the role of clinical pharmacists is poorly represented, as well as severe asthma patients. The aim of this overview of systematic reviews is to identify published systematic reviews assessing the impact of pharmacists' interventions on health-related outcomes measured in asthma patients, as well as to describe key components of the interventions, the outcomes assessed and any associations between pharmacists' interventions and health-related outcomes. METHODS: PubMed, Embase, Scopus and the Cochrane Library will be searched from inception to December 2022. Systematic reviews of all study designs, severity of asthma and level of care that measured health-related outcomes will be considered. Methodological quality will be assessed using A Measurement Tool to Assess Systematic Reviews 2. Two independent investigators will perform the study selection, quality assessment and data collection, any discrepancy will be solved by a third investigator. Both narrative findings and meta-analysis of primary study data included in the systematic reviews will be synthesized. If data are appropriate for quantitative synthesis, the measures of association will be expressed as the risk ratio and difference in means. DISCUSSION: The first results on the establishment of a multidisciplinary network for the management of asthmatic patients have shown the benefits of integrating different levels of care in disease control and morbidity reduction. Further studies showed benefits in hospital admissions, patients' basal oral corticosteroid dose, exacerbations and quality of life of asthma patients. A systematic review is the most appropriate design in order to summarize the literature and identify the evidence of the benefits of interventions performed by clinical pharmacists in asthma patients, especially those with severe uncontrolled asthma, and encourage future studies to stablish the role of clinical pharmacists in asthma units. REGISTRATION DETAILS: Systematic review registration number: CRD42022372100.

Is ranitidine necessary as premedication for regimens containing paclitaxel? A non-inferiority study.

BACKGROUND: Histamine type-2-receptor antagonist drugs (H2-antagonists) have been used as standard treatment to prevent hypersensitivity reactions (HRs) in paclitaxel-containing regimens, however, their use has been strongly questioned. Ranitidine has been the most widely used H2-antagonist. Therefore, especially after its withdrawal from the market, the objective of this study is to determine the impact of its elimination from premedication on HR incidence. METHODS: A cohort, multicenter, observational, prospective, and non-inferiority study, including paclitaxel-naïve cancer patients, designed to determine the incidence of HRs of any grade associated with paclitaxel administration and analyze non-inferiority against the incidence estimated in the literature (20%), with 5% as the maximum difference (Δ). Patients with a solid neoplasm of any type/stage, who initiated treatment with paclitaxel without H2-antagonists in the premedication regimen were enrolled. RESULTS: A total of 441 patients were included, of whom 50 presented 54 HRs of any grade. The cumulative incidence was 11.3% (95%CI 8.5-14.7), thus fulfilling the hypothesis of non-inferiority. Of the overall HRs detected, 15 were grade ≥ 3 with a cumulative incidence of 3.4% (95%CI 1.9-5.5). CONCLUSIONS: This study demonstrates that the elimination of ranitidine from paclitaxel premedication schedules is non-inferior in the development of HRs of any grade compared to the administration of H2-antagonists.

Pericardial effusion with pembrolizumab.

INTRODUCTION: The treatment of non-small cell lung cancer (NSCLC) has profoundly changed on account of the arrival of new therapies, like immunotherapy. Within this group of drugs, those aimed at the programmed cell death-1 or programmed cell death ligand-1(PD1/PDL-1) are very relevant, for example, Pembrolizumab. Although its adverse reactions are generally mild and well tolerated, it has been associated with certain immune-related adverse events (IrAEs) than can be serious and affect any organ. CASE REPORT: A 62-year-old woman diagnosed with stage IV NSCLC with a single bone metastasis and PD-L1 expression of 60% started treatment with cisplatin-pemetrexed-pembrolizumab, and maintenance with pembrolizumab. MANAGEMENT AND OUTCOME: The patient attended the ER with pericardial effusion that was assumed to be a Pembrolizumab IrAE and was managed with corticosteroids. The patient fully recovered but immunotherapy was not reintroduced due to the severity of the AE. DISCUSSION: The cardiovascular system is among the least affected organs by immunotoxicity, with an incidence between 0.09-0.6%. However, some authors suspect the incidence is underestimated. Median time to onset is highly variable, ranging from 6 weeks since the first dose to 2 years after discontinuation of the treatment. There are not guidelines on the most effective management of the IrAEs, but according to the pharmaceutical reference, corticosteroids should be initiated followed by a progressive reduction. If no response is obtained, another immunosuppressive agent should be added. The determination to restart immunotherapy depends on the severity of the adverse reaction, the availability of other alternative treatments, and the cancer response.

Successful treatment of Verona integron-encoded metallo-ß-lactamase-producing Klebsiella pneumoniae infection using the combination of ceftazidime/avibactam and aztreonam.

The case of a female who had an accident that caused an open fracture is reported. During hospitalisation, Verona integron-encoded metallo-ß-lactamase (VIM)-producing Klebsiella pneumoniae was isolated. Antimicrobial susceptibility testing revealed resistance to ß-lactam antibiotics, quinolones, trimethoprim/sulfamethoxazole, and susceptibility to tigecycline, colistin, fosfomycin and aminoglycosides. Synergistic activity of ceftazidime-avibactam and aztreonam was proved in vitro and a combined therapy with tigecycline was started. Combination with aminoglycosides was ruled out as it was not described in the literature and also in order to avoid side effects. Colistin was rejected because of its nephrotoxicity profile. The antibiotic treatment was assessed by a multidisciplinary team with a pharmacist who closely monitored adverse effects and interactions with other drugs. The total duration of this combination was 25 days, without any adverse events reported. Fourteen weeks after the accident the patient was discharged. After 2 months of follow-up neither relapses nor reinfections have been reported.

Hypophysitis secondary to pembrolizumab: a case report and review of the literature.

Pembrolizumab is a mAb against the programmed cell death protein-1 (PD-1). It has been approved for the treatment of advanced melanoma (unresectable or metastatic) in adults. Side effects associated with the use of anti-PD-1 are usually considered well tolerated; nevertheless, there are immune-related adverse events that may require treatment discontinuation. A 79-year-old man diagnosed with stage IV right scapular melanoma experienced unspecific symptoms and alterations of the hypothalamus-hypophysis axis after six cycles with pembrolizumab. The case was compatible with immune-related hypophysitis. Autoimmune thyroiditis and primary hypophysitis were excluded and toxicity due to pembrolizumab was considered the cause of hypophysitis. Pembrolizumab was discontinued and toxicity was managed with corticosteroids and hormonal replacement therapy (HRT). After 7 months of follow-up, symptoms were controlled with HRT but thyrotropin and corticotropin hormones had not recovered. It was decided not to reintroduce immunotherapy. Although endocrine disorders are common with the use of anti-PD-1, hypophysitis is very rare. However, clinical signs and symptoms can be nonspecific, therefore, it has probably been underdiagnosed. Monitoring hormones before and during the treatment is important for an early diagnosis and also to replace the alterations with HRT to control the symptoms. Hormonal function does not always recover, but it does not mean immunotherapy cannot be restarted and it should be evaluated in every case.

Effectiveness and safety of mepolizumab in severe refractory eosinophilic asthma: results in clinical practice.

BACKGROUND: Asthma is an inflammatory disease of the airways with symptoms that vary over time and intensity, sometimes leading to disability or even death. Eosinophilic asthma accounts for 25% of cases of severe asthma. It is mediated by eosinophils regulated by interleukin-5 (IL-5), the target of mepolizumab, which has been recently licensed as an add-on treatment of severe refractory eosinophilic asthma. The aim of this study was to evaluate the effectiveness and safety of mepolizumab in clinical practice. METHODS: A multicentre, retrospective, and descriptive study covering a year was conducted in a province of Spain with more than 500,000 inhabitants. Every patient prescribed with mepolizumab since its introduction into the hospital was included in the study. Clinical parameters were collected from the pharmacists' counselling reports from electronic prescription software and electronic patient records. Effectiveness was assessed as a decrease in the exacerbation frequency and/or a reduction in the use of oral corticosteroids (OCS) compared to the previous year. RESULTS: A total of 25 patients were studied, but only 23 could be evaluated by the cut-off date. A decrease in the exacerbation frequency was observed in 19 (82.6%) patients, 11 of them without any exacerbation during the treatment. A relative reduction of 87% in the exacerbation rate per year was obtained. A total of 15 patients were on regular OCS - 9 patients (60%) reduced their average dose, whilst 4 (26.7%) patients completely abandoned OCS. Safety was evaluated based on reported adverse effects. Adverse events were observed in 12 patients, the most common being headache, arthralgia, and dizziness/nausea. CONCLUSION: Mepolizumab has been shown to be effective based on the high decrease in the exacerbation frequency and reduced use of OCS. Reported adverse effects were mostly mild and appeared in half of the patients; some of the adverse events had not been previously described in pivotal trials.