Remdesivir and corticosteroids in the treatment of hospitalized COVID-19 patients.

Coronavirus disease 2019 (COVID-19) is a pandemic infection caused by the newly discovered severe acute respiratory syndrome coronavirus 2. Remdesivir (RDV) and corticosteroids are used mainly in COVID-19 patients with acute respiratory failure. The main objective of the study was to assess the effectiveness of remdesivir with and without corticosteroids in the treatment of COVID-19 patients. We conducted a prospective observational study, including adult patients consecutively hospitalized with confirmed COVID-19 and acute respiratory failure. Patients were divided according to treatment strategy: RDV alone versus RDV with corticosteroids. The primary outcome was the time to recovery in both treatment groups. We included 374 COVID-19 adult patients, 184 were treated with RDV, and 190 were treated with RDV and corticosteroid. Patients in the RDV group had a shorter time to recovery in comparison with patients in the RDV plus corticosteroids group at 28 days after admission [11 vs. 16 days (95% confidence Interval 9.7-12.8; 14.9-17.1; p = .016)]. Patients treated with RDV alone had a shorter length of hospital stay. The use of corticosteroids as adjunctive therapy of RDV was not associated with improvement in mortality of COVID-19 patients.

Development of the HIV360 international core set of outcome measures for adults living with HIV: A consensus process.

OBJECTIVES: HIV outcomes centre primarily around clinical markers with limited focus on patient-reported outcomes. With a global trend towards capturing the outcomes that matter most to patients, there is agreement that standardizing the definition of value in HIV care is key to their incorporation. This study aims to address the lack of routine, standardized data in HIV care. METHODS: An international working group (WG) of 37 experts and patients, and a steering group (SG) of 18 experts were convened from 14 countries. The project team (PT) identified outcomes by conducting a literature review, screening 1979 articles and reviewing the full texts of 547 of these articles. Semi-structured interviews and advisory groups were performed with the WG, SG and people living with HIV to add to the list of potentially relevant outcomes. The WG voted via a modified Delphi process - informed by six Zoom calls - to establish a core set of outcomes for use in clinical practice. RESULTS: From 156 identified outcomes, consensus was reached to include three patient-reported outcomes, four clinician-reported measures and one administratively reported outcome; standardized measures were included. The WG also reached agreement to measure 22 risk-adjustment variables. This outcome set can be applied to any person living with HIV aged > 18 years. CONCLUSIONS: Adoption of the HIV360 outcome set will enable healthcare providers to record, compare and integrate standardized metrics across treatment sites to drive quality improvement in HIV care.

Defining clinical pharmacy and support activities indicators for hospital practice using a combined nominal and focus group technique.

Background Although clinical pharmacy is a crucial part of hospital pharmacist's day-to-day activity, its performance is not usually subject to a holistic assessment. Objective To define a set of relevant and measurable clinical pharmacy and support activities key performance indicators (cpKPI and saKPI, respectively). Setting Portuguese Hospital Pharmacies. Method After a comprehensive literature review focusing on the metrics already in use in other countries, several meetings with directors of hospital pharmacies were conducted to obtain their perspectives on hospital pharmacy practices and existing metrics. Finally, five rounds with a panel of 8 experts were performed to define the final set of KPIs, where experts were asked to score each indicator' relevance and measurability, and encouraged to suggest new metrics. Main outcome measure The first Portuguese list of KPIs to assess pharmacists' clinical and support activities performance and quality in hospital pharmacies. Results A total of 136 KPIs were assessed during this study, of which 57 were included in the original list and 79 were later added by the expert panel. By the end of the study, a total of 85 indicators were included in the final list, of which 40 are considered to be saKPI, 39 cpKPI and 6 neither. Conclusion A set of measurable KPIs was established to allow for benchmarking within and between Portuguese hospital Pharmacies and to elevate professional accountability and transparency. Future perspectives include the use of both cpKPIs and saKPIs on a national scale to identify the most efficient performances and areas of possible improvement.

A prospective, observational study to evaluate adverse drug reactions in patients with COVID-19 treated with remdesivir or hydroxychloroquine: a preliminary report.

OBJECTIVES: Since the outbreak of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the pressure to minimise its impact on public health has led to the implementation of different therapeutic strategies, the efficacy of which for the treatment of coronavirus disease 2019 (COVID-19) was unknown at the time. Remdesivir (REM) was granted its first conditional marketing authorisation in the EU in June 2020. The European Medicines Agency (EMA) and local health authorities all across the EU have since strongly recommended the implementation of pharmacovigilance activities aimed at further evaluating the safety of this new drug. The objective of this study was to evaluate adverse drug reactions (ADRs) attributed to either REM or hydroxychloroquine (HCQ) in patients hospitalised for COVID-19 in Centro Hospitalar de Lisboa Ocidental, a Portuguese hospital centre based in Lisbon. We present the preliminary results reporting plausible adverse effects of either HCQ or REM. METHODS: An observational cohort study was carried out between 16 March and 15 August 2020. Participants were divided into two cohorts: those prescribed an HCQ regimen, and those prescribed REM. Suspected ADRs were identified using an active monitoring model and reported to the Portuguese Pharmacovigilance System through its online notification tool. The ADR cumulative incidence was compared between the two cohorts. RESULTS: The study included 149 patients, of whom 101 were treated with HCQ and the remaining 48 with REM. The baseline characteristics were similar between the two cohorts. A total of 102 ADRs were identified during the study period, with a greater incidence in the HCQ cohort compared with the REM cohort (47.5% vs 12.5%; p<0.001). Causality was assessed in 81 ADRs, all of which were considered possible. CONCLUSIONS: Real-world data are crucial to further establish the safety profile for REM. HCQ is no longer recommended for the treatment of COVID-19.

Experience of a Portuguese Center: Effectiveness of Direct-Acting Antiviral Therapy for Hepatitis C.

INTRODUCTION: In late 2014, Portugal implemented a national program for the treatment of patients with chronic hepatitis C with directacting antiviral agents. This program has made Portugal one of the first European countries to implement a structured measure of treatment to eliminate this serious public health problem. The aim of this study was to assess the effectiveness of direct-acting antiviral therapy in the treatment of patients with chronic hepatitis C virus infection. MATERIAL AND METHODS: A retrospective observational study was conducted at Centro Hospitalar de Lisboa Ocidental on the national online platform from December 2014 until February 2017 and included patients with hepatitis C virus infection who underwent treatment. The primary endpoint was sustained virologic response at least 12 weeks post treatment. Data was analyzed with the SPSS 17.0 program. RESULTS: During the study period, 820 patients completed therapy and achieved sufficient follow-up time to assess sustained virologic response with an overall response rate of 97.2% (n = 797) and a response rate of 98.0%, 99.5%, 90.9%, 95.1% and 94.2% for genotypes 1a, 1b, 2, 3 and 4, respectively. Data suggested that advanced fibrosis (F3/F4), human immunodeficiency virus co-infection and treatment failure with interferon and ribavirin were not negatively related with sustained virologic response in our population. Most patients (80.1%) completed treatment with ledipasvir/sofosbuvir ± ribavirin. The most common adverse events were fatigue and insomnia followed by headache and weight loss. DISCUSSION: Patients predominantly had genotype 1 infection which correlates with HCV distribution in Europe, but we found a major proportion in genotype 4 which can be explained by immigration from African countries. Our patients' ages ranging from 22 to 90 years, reflected a new approach with no upper age limit. Direct-acting antivirals regimens resulted in remarkably high SVR rates compared to interferon-based regimens, which were consistent with clinical trials data. CONCLUSION: Our data showed that direct-acting antiviral-based regimens are safe and have a high success rate in the treatment of patients with hepatitis C virus infection in a real-world setting.

Introdução: No final de 2014 foi implementado em Portugal um programa nacional para o tratamento de doentes com infecção crónica por vírus da hepatite C com recurso a antivíricos de acção directa. Este programa fez com que Portugal fosse um dos primeiros países europeus a implementar uma medida estruturante para a eliminação da hepatite C. Este estudo tem como objectivo a avaliação da efectividade dos antivíricos de acção directa no tratamento da hepatite C crónica. Material e Métodos: Estudo retrospectivo observacional dos doentes seguidos no Centro Hospitalar de Lisboa Ocidental, entre dezembro de 2014 e fevereiro de 2017. O objectivo primário do estudo é avaliar a resposta virológica sustentada a partir das 12 semanas pós tratamento. Analisámos os dados com o programa SPSS 17.0. Resultados: Durante o período do estudo 820 doentes completaram o tratamento e o tempo necessário para avaliação da resposta virológica sustentada. A resposta virológica sustentada global foi de 97.2% (n = 797), com taxas de resposta de 97,2%, 98,5%, 90,9%, 95,1% e 94,2% para os genótipos 1a, 1b, 2, 3 e 4, respectivamente. Os dados sugerem não haver relação entre a fibrose avançada (F3 / F4), a coinfecção pelo vírus da imunodeficiência humana e a falência do tratamento com interferão e ribavirina e uma menor resposta ao tratamento. A maioria dos doentes (80,1%) concluiu o tratamento com ledipasvir/sofosbuvir ± ribavirina. Os eventos adversos mais frequentes foram a fadiga e a insónia, seguida de dor de cabeça e perda de peso. Discussão: A população em estudo apresentou maior prevalência de infecção pelo genótipo 1, à semelhança dos restantes países Europeus, contudo a prevalência do genótipo 4 foi superior, reflectindo a imigração africana. A faixa etária (22 - 90 anos) dos doentes tratados reflecte uma nova abordagem sem limite superior de idade. A taxa de RVS obtida, muito superior à obtida com regimes baseados em interferão, foi consistente com os dados dos ensaios clínicos. Conclusão: Os dados encontrados demonstram que os regimes baseados em antivirais de acção directa, em contexto de vida real, são seguros e eficazes no tratamento de doentes com infecção por vírus da hepatite C.

Analysis of riluzole's profile of use in a Central Hospital in Lisbon.

PURPOSE: Riluzole is indicated to prolong life or delay the institution of mechanical ventilation in patients with amyotrophic lateral sclerosis (ALS). Clinical studies have shown that this drug prolongs survival, defined as living patients who are not intubated for mechanical ventilation and without tracheotomy. The purpose of this study is to characterize riluzole's use as well as the user population in order to contribute to a rational and safe use. PATIENTS AND METHODS: Descriptive, observational, retrospective study describing and characterizing the use of riluzole in ALS patients between July 2006 and December 2016 conducted in a Lisbon's Central Hospital. RESULTS: Over the course of the study period, 77 patients with different phenotypes of ALS received riluzole. The majority of patients (63%, n=49) were male. The median survival was 10.1 months, but 12 patients (16%) remained on therapy for more than 3 years; 65% of patients were lost to follow-up. The mean adherence rate was 91.2%, and the median adherence rate was 99.3%. One patient discontinued therapy due to gastrointestinal intolerance. Dyspnea and cough were the most common side effects, with roughly one third of patients experiencing each, followed by asthenia and hepatic effects. CONCLUSION: Despite the extended enrollment period, only 77 patients met the criteria for study inclusion. Nonetheless, statistical data regarding our population is in accordance with reported international data. High adherence rates were observed, but 14% of patients discontinued riluzole. In such cases, assessment by a multidisciplinary team is warranted.

A retrospective observational study of low-level viraemia and its immunological and virological significance: which outcome to expect.

INTRODUCTION: Low-level viraemia (LLV) is observed in some patients with HIV-1 infection on stable antiretroviral therapy (ART). The significance of these findings remains controversial as it conflicts with traditional optimal clinic outcome. This study aims to evaluate the effect of LLV on the establishment of virological failure (VF) and immune deterioration. METHODS: Retrospective observational study of a cohort of HIV-1 infected patients of an Infectious Diseases Clinic, who presented an HIV-1 viral load of 20 to 200 cp/mL, during the year 2012. Patients who were not on ART or non-adherent in the previous 6 months were excluded. Compliance was quantified by clinical and pharmaceutical records. Adherence was defined as ≥95% compliance rate. Demographic, clinical, immunological and therapeutic data were collected from clinical records. LLV was defined as a range of 20-200 cp/mL and stratified as transient (T-LLV): only one measurement, persistent (P-LLV): 2 consecutive measurements with an interval ≥3 months and recurrent (R-LLV): ≥1 T-LLV during an 18-month follow-up. Statistical analysis was performed with Microsoft Office® - Excel 2012. Kolmogorov-Smirnov test, t-test and chi-square test were performed for a significant p value <0.05. RESULTS: During 2012, 2161 HIV-1 infected patients were evaluated at our Clinic, 93% of which were on ART. LLV was documented in 378 (19%), adherence was verified in 151 (52%). The analysis of this cohort (n=151) revealed: 77 (51%) T-LLV, 13 (8.6%) R-LLV and 61 (40%) P-LLV. Mean viral load was 46 cp/mL. Mean TCD4 count was 665 cells/µL with a variation of +63 cells/µL during the study period. There was no VF documented. ART regimens were switched in 16 (11%) patients. Gastrointestinal disturbance was found in 13 (9%). Analysis showed no statistical differences between the analyzed variables (CD4 variation, time of diagnosis and treatment, duration of LLV persistence (less than or more than one year), number of ART regimens, ART regimen and type of NRTI backbone) for all groups (T-LLV, R-LLV, P-LLV), except for mean viral load that showed significant superiority in the T-LLV(38 cp/mL) and R-LLV(36 cp/mL) vs P-LLV(58 cp/mL) (p=0.01 and p<0.01, respectively). CONCLUSIONS: The absence of significant differences in immunological and virological outcomes in this cohort and the absence of VF in all groups, suggests a scarce impact of LLV in patient's prognosis. Prospective studies, with longer follow-up could bring more accurate information.

Manual de boas práticas de farmácia hospitalar

O Manual foi elaborado por um grupo de trabalho criado em 2007, constituído por farmacêuticos hospitalares, e um representante da sociedade civil. É um instrumento de trabalho que permite homogeneizar e normalizar procedimentos, além de garantir a qualidade do serviço assistencial prestado, uniformizar protocolos de atuação e padronizar processos.