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.

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.

Systematic review of cost-effectiveness analyses of novel oral anticoagulants for stroke prevention in atrial fibrillation.

INTRODUCTION AND OBJECTIVES: Novel oral anticoagulants are emerging options for the prevention and treatment of thromboembolic diseases. They are increasingly used in clinical practice due to their simplicity of use and clinical benefits, but an important step is to evaluate their cost-effectiveness. The aim of the AFFORD study (A Review of Cost EFFectiveness of Novel ORal Anticoagulant Drugs) was to perform a systematic review of cost-effectiveness studies of novel oral anticoagulants for stroke prevention in non-valvular atrial fibrillation (AF). METHODS: A systematic review of the literature was conducted by searching the PubMed, Embase, Scopus, Cochrane and Web of Knowledge databases to identify all cost-effectiveness studies of novel oral anticoagulants for stroke prevention in AF. RESULTS: The search identified 27 studies, 18 with dabigatran, three with apixaban, two with rivaroxaban and four with at least two of these drugs. The incremental cost-effectiveness ratios were 30 405 ± 16 101 euros per quality-adjusted life-year (QALY) for dabigatran 110 mg, 17 566 ± 16 902 euros/QALY for dabigatran 150 mg, 8102 ± 3252 euros/QALY for age-adjusted dabigatran, 11 897 ± 3341 euros/QALY for apixaban and 17 960 ± 12 005 euros/QALY for rivaroxaban. CONCLUSION: The present systematic review demonstrates that novel oral anticoagulants are cost-effective for stroke prevention in AF.

Medication errors in an internal medicine department. Evaluation of a computerized prescription system.

OBJECTIVE: Evaluation of a computerized physician order entry in an Internal Medicine Department, with a unit-dose distribution system. SETTING: Pharmacy Department, Internal Medicine Department. S. Francisco Xavier Hospital, Lisbon, Portugal. METHOD: This study was carried out in December 2001 and January 2002. After two years experience of the CPOE system, medication errors were evaluated prospectively, in an internal medical department of a 360-bed academic hospital. Data were collected once a week. Pharmacists reviewed all medical prescriptions as part of their routine work. Medication errors detected were recorded on a data collection form with a design based on the types of errors as defined by the American Society of Hospital Pharmacists (ASHP). Completed forms were reviewed and medication errors were classed according to ASHP guidelines. RESULTS: A total of 2268 orders were monitored (162 patients). In these orders, 73 medication errors (22.4% of the patients) were detected and documented (59 prescribing errors and 14 monitoring errors). The most common prescribing errors were deficiencies related to the right class but wrong drug (28.3%): omeprazole vs. ranitidine/sucralfate in stress ulcer prophylaxis; incorrect dose (30%) and unclear orders (13.3%). Errors related to incorrect frequency of administration (5%); maintenance of IV route (5%); duplicated drug therapy (11.7%); drug interactions (1.7%) and length of therapy (3.3%) were also detected. The 14 monitoring errors detected were failures to review a prescribed regimen for appropriateness and detection of problems. CONCLUSIONS: Computerized prescription order entry has demonstrated effectiveness in eliminating medication errors related to transcribing and patient identification. Nevertheless, medication errors related to prescription and monitoring still occur. The use of clinical decision support systems and pharmacist involvement is vital to achieve maximum medication safety and reduce medication error rates.