Risco Cardiovascular em Doentes com Infecção por Vírus da Imunodeficiência Humana

O aumento do risco cardiovascular é considerada uma importante complicação da infecção Infecção por Vírus da Imunodeficiência Humana (VIH) e da terapêutica anti-retroviral (TARV). À disfunção endotelial característica do processo inflamatório crónico desencadeado pela infecção retroviral, associa-se a disfunção metabólica induzida pela terapêutica, predispondo, em conjunto, para a aterogénese precoce. O reconhecimento deste aumento de risco cardiovascular permite-nos elaborar estratégias de prevenção e optimização terapêutica que passam pelo uso criterioso de hipolipemiantes e modificação da TARV, consoante a avaliação do risco cardiovascular global de cada doente

Impact of the economic crisis in the approval of new oncological drugs:the Portuguese paradigm

Background: The European crisis lead to funding restrains in healthcare, already under pressure due to the ageing of the population and the increase of demands from innovation. Portugal is the paradigm of the European crisis since has both an economic and demographic crisis. The researchers aimed to evaluate the impact of economic restrains in Portugal for access and reimbursement of new oncological drugs. Methodology: A qualitative approach was used, supported by 27 formal, tape recorded, semi-structured interviews to representatives of the different healthcare stakeholders and policymakers. The content analysis with semantic associations through co-occurrence analysis were done with the support of Tropes® software. Results: The results of the content analysis showed that economic restrains are leading to a policy of cost control with lower prices and reduced access to innovation; an excessive delay in the approval of new drugs; lack of transparency; serious limitations and inequity between hospitals. Contractual boundaries to national prescription was established and agreements with pharmaceuticals were made. Changes in the reimbursement process are being implemented with an increase of risk sharing mechanisms and implementation of a new system of health technological evaluation (SINATS). Treatment protocols are also being revised and public hospitals are trying to increase the number of clinical trials but there is still much bureaucracy. In this qualitative approach, the following factors with impact on survival were identified: Innovation and technological development, government funding, the price of drugs and type of oncological diseases. Conclusions: The economic crisis is leading to a very serious problem of inequity. However, it is also an opportunity for a structural reform. In Portugal, an attempt of reform is being made with the implementation of SINATS since it is important to distinguish molecules that effectively bring added value. In order to consider the strategic vision in which the patient is the center of all efforts, the process of reimbursement approval for new medicines should be faster, more transparent and interdisciplinary. Moreover, the decisions must be done triangulating evidence based medicine, economics, health policy and ethical and legal issues. For National Health Service sustainability, efficiency and efficacy, clinical and economic reassessments must be done after market introduction of new medicines, with subsequent renegotiations.info:eu-repo/semantics/publishedVersio

Characterization of NS5A and NS5B Resistance-Associated Substitutions from Genotype 1 Hepatitis C Virus Infected Patients in a Portuguese Cohort

This study is focused on the prevalent NS5 coding region resistance-associated substitutions (RASs) in DAA-naive genotype (GT)1 HCV-infected patients and their potential impact on success rates. Plasma RNA from 81 GT1 HCV-infected patients was extracted prior to an in-house nested RT-PCR of the NS5 coding region, which is followed by Sanger population sequencing. NS5A RASs were present in 28.4% (23/81) of all GT1-infected patients with 9.9% (8/81) having the Y93C/H mutation. NS5B RASs showed a prevalence of 14.8% (12/81) and were only detected in GT1b. Overall 38.3% (31/81) of all GT1 HCV-infected patients presented baseline RASs. The obtained data supports the usefulness of resistance testing prior to treatment since a statistically significant association was found between treatment failure and the baseline presence of specific NS5 RASs known as Y93C/H (p = 0.04).publishersversionpublishe

Routine HIV Screening in Portugal: Clinical Impact and Cost-Effectiveness

Objective: To compare the clinical outcomes and cost-effectiveness of routine HIV screening in Portugal to the current practice of targeted and on-demand screening. Design: We used Portuguese national clinical and economic data to conduct a model-based assessment. Methods: We compared current HIV detection practices to strategies of increasingly frequent routine HIV screening in Portuguese adults aged 18-69. We considered several subpopulations and geographic regions with varying levels of undetected HIV prevalence and incidence. Baseline inputs for the national case included undiagnosed HIV prevalence 0.16%, annual incidence 0.03%, mean population age 43 years, mean CD4 count at care initiation 292 cells/μL, 63% HIV test acceptance, 78% linkage to care, and HIV rapid test cost €6 under the proposed routine screening program. Outcomes included quality-adjusted survival, secondary HIV transmission, cost, and incremental cost-effectiveness. Results: One-time national HIV screening increased HIV-infected survival from 164.09 quality-adjusted life months (QALMs) to 166.83 QALMs compared to current practice and had an incremental cost-effectiveness ratio (ICER) of €28,000 per quality-adjusted life year (QALY). Screening more frequently in higher-risk groups was cost-effective: for example screening annually in men who have sex with men or screening every three years in regions with higher incidence and prevalence produced ICERs of €21,000/QALY and €34,000/QALY, respectively. Conclusions: One-time HIV screening in the Portuguese national population will increase survival and is cost-effective by international standards. More frequent screening in higher-risk regions and subpopulations is also justified. Given Portugal’s challenging economic priorities, we recommend prioritizing screening in higher-risk populations and geographic settings

Non-AIDS-related comorbidities in people living with HIV-1 aged 50 years and older: The AGING POSITIVE study

Objective: To characterize the profile of non-AIDS-related comorbidities (NARC) in the older HIV-1-infected population and to explore the factors associated with multiple NARC. Methods: This was a multicentre, cross-sectional study including HIV-1-infected patients aged ≥50 years, who were virologically suppressed and had been on a stable antiretroviral therapy (ART) regimen for at least 6 months. A multiple regression model explored the association between demographic and clinical variables and the number of NARC. Results: Overall, 401 patients were enrolled. The mean age of the patients was 59.3 years and 72.6% were male. The mean duration of HIV-1 infection was 12.0 years and the median exposure to ART was 10.0 years. The mean number of NARC was 2.1, and 34.7% of patients had three or more NARC. Hypercholesterolemia was the most frequent NARC (60.8%), followed by arterial hypertension (39.7%) and chronic depression/anxiety (23.9%). Arterial hypertension and diabetes mellitus were the most frequently treated NARC (95.6% and 92.6% of cases, respectively). The linear regression analysis showed a positive relationship between age and NARC (B=0.032, 95% confidence interval 0.015-0.049; p=0.0003) and between the duration of HIV-1 infection and NARC (B=0.039, 95% confidence interval 0.017-0.059; p=0.0005). Conclusions: A high prevalence of NARC was found, the most common being metabolic, cardiovascular, and psychological conditions. NARC rates were similar to those reported for the general population, suggesting a larger societal problem beyond HIV infection. A multidisciplinary approach is essential to reduce the burden of complex multi-morbid conditions in the HIV-1-infected population.Merck Sharp & Dohme, Lda, Portugal provided financial support for the non-interventional study (Protocol Nr. MK0518-826 ).info:eu-repo/semantics/publishedVersio

Recomendações para Análise Mutacional em Tumores do Estroma Gastrointestinal (GISTs)

GIST Portuguese Working Group – Condeixa ProposalThe authors outline recommendations for the mutational analysis of GISTs unanimously approved by a multidisciplinary group on July 20th, 2062. The mutational status of KIT and PDGFRA allows identifying therapeutic targets to tyrosine kinase inhibitors (TKIs), and therefore, the safe clinical practice in the biotherapy decisions for patients with GISTs should include the analysis of the mutational status. The mutational analysis of the primary disease is not recommended in the diagnostic routine of most GISTs; ne- vertheless may have prognostic value and be useful in the selection for adjuvant treatment after complete resection of primary GIST, and is considered experimental in the progressive disease under treatment with TKIs. The mutational analysis should be considered in selected cases as described herewith and performed in laboratories in compliance with high standards of quality assurance, considering the strong impact on clinical decisions.Keywords: gastrointestinal stromal tumor (GIST); mutational analysisGrupo de Trabalho Português GIST – Proposta de Condeixa Os autores apresentam as recomendações para a análise mutacional de GISTs, aprovadas por unanimidade por um grupo multidisciplinar em 20 de Julho de 2062. O estado mutacional de genes como o KIT e o PDGFRA permite identificar alvos terapêuticos para inibidores da tirosinacínase (ITKs) e, por isso, a boa prática clínica nas decisões bioterapêuticas de doentes com GISTs deve incluir a análise do estado mutacional. A análise mutacional da doença primária não é recomendada na rotina diagnóstica da generalidade dos GISTs; no entanto, pode ter valor prognóstico e ser útil na seleção de doentes, após ressecção completa de GIST primário e é considerada experimental na doença progressiva sob tratamento com ITKs. A análise mutacional deve considerar-se nos casos selecionados descritos neste texto e ser realizada em laboratórios em conformidade com padrões elevados de garantia de qualidade, atendendo ao seu elevado impacto sobre as decisões clínicas. Palavras chave: Tumores do estroma gastrointestinal (GIST); Análise mutacional

Ongoing monkeypox virus outbreak, Portugal, 29 April to 23 May 2022

Up to 27 May 2022, Portugal has detected 96 confirmed cases of monkeypox. We describe 27 confirmed cases (median age: 33 years (range: 22–51); all males), with an earliest symptom onset date of 29 April. Almost all cases (n = 25) live in the Lisbon and Tagus Valley health region. Most cases were neither part of identified transmission chains, nor linked to travel or had contact with symptomatic persons or with animals, suggesting the possible previously undetected spread of monkeypox.info:eu-repo/semantics/publishedVersio

Incidence of cancer and overall risk of mortality in individuals treated with raltegravir-based and non-raltegravir-based combination antiretroviral therapy regimens

Objectives: There are currently few data on the long-term risk of cancer and death in individuals taking raltegravir (RAL). The aim of this analysis was to evaluate whether there is evidence for an association. Methods: The EuroSIDA cohort was divided into three groups: those starting RAL-based combination antiretroviral therapy (cART) on or after 21 December 2007 (RAL); a historical cohort (HIST) of individuals adding a new antiretroviral (ARV) drug (not RAL) to their cART between 1 January 2005 and 20 December 2007, and a concurrent cohort (CONC) of individuals adding a new ARV drug (not RAL) to their cART on or after 21 December 2007. Baseline characteristics were compared using logistic regression. The incidences of newly diagnosed malignancies and death were compared using Poisson regression. Results: The RAL cohort included 1470 individuals [with 4058 person-years of follow-up (PYFU)] compared with 3787 (4472 PYFU) and 4467 (10 691 PYFU) in the HIST and CONC cohorts, respectively. The prevalence of non-AIDS-related malignancies prior to baseline tended to be higher in the RAL cohort vs. the HIST cohort [adjusted odds ratio (aOR) 1.31; 95% confidence interval (CI) 0.95–1.80] and vs. the CONC cohort (aOR 1.89; 95% CI 1.37–2.61). In intention-to-treat (ITT) analysis (events: RAL, 50; HIST, 45; CONC, 127), the incidence of all new malignancies was 1.11 (95% CI 0.84–1.46) per 100 PYFU in the RAL cohort vs. 1.20 (95% CI 0.90–1.61) and 0.83 (95% CI 0.70–0.99) in the HIST and CONC cohorts, respectively. After adjustment, there was no evidence for a difference in the risk of malignancies [adjusted rate ratio (RR) 0.73; 95% CI 0.47–1.14 for RALvs. HIST; RR 0.95; 95% CI 0.65–1.39 for RALvs. CONC] or mortality (adjusted RR 0.87; 95% CI 0.53–1.43 for RALvs. HIST; RR 1.14; 95% CI 0.76–1.72 for RALvs. CONC). Conclusions: We found no evidence for an oncogenic risk or poorer survival associated with using RAL compared with control groups.Peer reviewe