Hepatitis B Virus Genotypes and Subgenotypes Circulating in Infected Residents in a Country with High Vaccination Rate.

Despite the availability of a vaccine against hepatitis B virus (HBV), this infection still causes public health problems, particularly in susceptible populations. In Portugal, universal free vaccination started in 1994, and most HBV infections are diagnosed in immigrants from high-prevalence countries. Our aim was to assess the pattern of HBV genotypes/subgenotypes in samples collected between 2017 and 2021 from a convenience sample of 70 infected residents in Portugal. The HBV pol/HBsAg region was amplified and sequenced, allowing the analysis of RT sequences submitted to phylogenetic analysis and mutations assessment. A total of 37.1% of samples were from native Portuguese, aged 25-53 years (mean: 36.7 years), and the remaining samples were from individuals born outside of Portugal. A high diversity of HBV was identified: subgenotypes A1-A3 in 41.0% (16/39); D1, D3, and D4 in 30.7% (12/39); E in 23.1% (9/39); and F4 in 2.6% (1/39). Besides genotypes A and D, Portuguese were also infected with genotypes E and F, which are prevalent in Africa and South America, respectively. Resistance mutations in RT sequences were not found. The findings provide valuable insights for updating the HBV molecular epidemiology in Portugal. However, successful strategies to prevent and control the infection are still needed in the country, especially among susceptible and vulnerable populations.

Diversity of Human T-Lymphotropic Virus Type 1 Cosmopolitan Subtype (HTLV-1a) Circulating in Infected Residents in Portugal.

Human T-cell lymphotropic virus type 1 (HTLV-1) prevalence in Portugal is low and mainly affects immigrants from endemic areas where human immunodeficiency virus (HIV) infection represents a public health problem. Despite the majority of HTLV-1-infected individuals remains asymptomatic, severe pathologies may develop after prolonged viral persistence, namely an aggressive form of leukemia. An increased mortality rate and faster progression to death is often related to HTLV-1/HIV coinfection. Nevertheless, studies showed that some antiretrovirals used in HIV treatment lead to a positive immune response against HTLV-1. This study aimed to analyze epidemiological and clinical data, and to assess the diversity of HTLV-1 strains circulating in infected residents diagnosed in the Portuguese national reference laboratory between 2010 and 2021. Long terminal repeat and env proviral sequences derived from 20 individuals were used to generate phylogenetic trees along with multiples reference sequences from different geographic origins retrieved from the database. Three samples belong to Portuguese natives and 17 belong to immigrants: 15 from several countries of Africa, 1 from South America, and 1 from Europe; 6 patients (30%, mean age 40.3 years) showed HTLV-1-related diseases, and 6 (30%, mean age 45.2 years) were coinfected with HIV/AIDS. The results show that the Cosmopolitan subtype is circulating in Portugal, with 10 sequences being classified as subgroup A, that include Portuguese and natives from S. Tomé and Príncipe with a mean age of 39.4 years, and 10 sequences that segregated into the Senegal cluster derived from natives born in Guinea-Bissau with a mean age of 43.5 years. A high proportion of HTLV-1-related diseases and HIV/AIDS coinfection was observed. Risk behavior practices and the absence of specific control measures, including diagnostic and treatment, may contribute to a silent dissemination of a broad diversity of HTLV-1 strains and, therefore, the increased rate of progression to debilitating diseases. In this manner, an early diagnostic and a molecular surveillance of HTLV-1 transmission remains necessary in Portugal.

Clinical, Economic, and Humanistic Impact of Short-Bowel Syndrome/Chronic Intestinal Failure in Portugal (PARENTERAL Study).

Introduction: This study aimed to assess the clinical, economic, and humanistic impact of short-bowel syndrome/chronic intestinal failure (SBS/CIF) in Portugal. Methods: This is a retrospective multicenter cohort chart review study, with a cross-sectional component for quality-of-life (QoL) evaluation. Inclusion criteria comprised patients with SBS/CIF, aged ≥1 year, with stable parenteral nutrition (PN). Data collection included patient chart review over a 12-month period and patient/caregiver self-report and SF-36/PedsQL™ questionnaires. Main endpoints comprised clinical and PN characterization, healthcare resource use (HRU), direct costs, and patient QoL. Results: Thirty-one patients were included (11 adults and 20 children). Patients' mean age (standard deviation [SD]) was 57.9 (14.3) years in adults and 7.5 (5.0) years in children, with a mean time since diagnosis of 10.2 (5.9) and 6.6 (4.2) years, respectively. PN was administered for a mean of 5.2 and 6.6 days/week in adults and children, respectively; home PN occurred in 81.8% of adults and 90.0% of children for a mean of 9.6 and 10.8 months/year, respectively. The mean annual number of hospitalizations was 1.9 and 2.0 which lasted for a mean of 34.0 and 29.4 days in adults and children, respectively. Twenty-one and forty hospitalization episodes were reported in adults and children, respectively, of which 71.4% and 85.0% were due to catheter-related complications. Mean annual direct costs per patient amounted to 47,857.53 EUR in adults and 74,734.50 EUR in children, with PN and hospitalizations as the main cost-drivers. QoL assessment showed a clinically significant impaired physical component in adults and a notable deterioration in the school functioning domain in children. Conclusion: In Portugal, SBS/CIF patient management is characterized by a substantial therapeutic burden and HRU, translating into high direct costs and a substantial impairment of the adults' physical function and children's school functioning.

Introdução: Este estudo teve como objetivo avaliar o impacto clínico, económico e social da síndrome do intestino curto/falência intestinal crónica (SIC/FIC) em Portugal. Métodos: Estudo de coorte retrospectivo e multicêntrico de revisão dos processos clínicos incluindo uma componente transversal para avaliação da qualidade de vida (QV). Os critérios de elegibilidade incluíram doentes com SIC/FIC, idade ≥1 ano, em nutrição parenteral (NP) e clinicamente estáveis. A recolha de dados incluiu a revisão dos processos clínicos ao longo de um período de 12 meses e a aplicação de questionários auto-administrados a doentes e cuidadores e de questionários de QV (SF-36/PedsQL™). Os indicadores principais foram a caracterização clínica e da NP, a utilização de recursos de saúde, custos diretos e QV dos doentes. Resultados: Foram incluídos 31 doentes (11 adultos e 20 crianças). A idade média (desvio padrão: DP) foi de 57.9 (14.3) anos nos adultos e de 7.5 (5.0) nas crianças com um tempo médio desde o diagnóstico de 10.2 (5.9) e 6.6 (4.2) anos, respetivamente. A NP foi administrada durante uma média de 5.2 e 6.6 dias por semana, em adultos e crianças respetivamente, em 81.8% e 90.0% dos adultos/crianças foi feita em casa durante uma média de 9.6 ou 10.8 meses por ano, respetivamente. O número médio anual de hospitalizações foi de 1.9 (1.6) e 2.0 (1.5) com uma duração média de 34.0 (47.4) e 29.4 (32.3) dias, em adultos e crianças, respetivamente. Foram reportados 21 e 40 episódios de hospitalização em adultos/crianças, dos quais 71.4% e 85.0% foram devido a complicações relacionadas ao uso de cateter. Os custos diretos anuais médios por doente ascenderam a 47,857.53 EUR nos adultos e a 74,734.50 EUR nas crianças, sendo que os maiores responsáveis foram a NP e as hospitalizações. A avaliação da QV mostrou um comprometimento clinicamente significativo da componente física nos adultos e uma deterioração relevante da dimensão escolar nas crianças. Conclusões: A gestão dos doentes com SIC/FIC em Portugal é caracterizada por uma sobrecarga substancial a nível terapêutico e de utilização de recursos de saúde, o que se traduz em elevados custos diretos e comprometimento substancial da componente física nos adultos e do desempenho escolar nas crianças.

Looking at the Molecular Target of NS5A Inhibitors throughout a Population Highly Affected with Hepatitis C Virus.

Hepatitis C virus (HCV) is associated with liver damage and an increased progression rate to cirrhosis and hepatocellular carcinoma. In Portugal, it is prevalent in vulnerable populations such as injection drug users (IDU). HCV is characterized by a high intra-host variability, and the selecting driving forces could select variants containing resistance-associated substitutions (RAS) that reduce treatment effectiveness. The main goal of this study was to analyze the sequence variation of NS5A in treatment-naïve IDU. The epidemiological and clinical status of hepatitis C were analyzed, and samples were sequenced by Sanger and Next-Generation sequencing (NGS) to assess RAS and confirm HCV subtypes. Phylogenetic classification was concordant: 1a, 52.4%; 1b, 10.7%; 3a, 20.2%; 4a, 8.3%; 4d, 7.1%; and one 2k/1b recombinant. A 1a/3a mixed infection was detected by NGS. RAS were found in 34.5% (29/84) of samples using Sanger sequencing, while in 42.9% (36/84) using NGS. In sequences from subtypes 1a and 1b, RAS K24R, M28V, Q30H/R, H58D/P/Q/R, and RAS L31M and P58S were detected, respectively. In subtype 3a, RAS A30S/T, Y93H and polymorphisms in position 62 were identified. Additionally, RAS P58L was detected in genotype 4. The strategy used for the molecular survey of baseline HCV resistance is of particular importance to achieve treatment effectiveness and contribute to the elimination of hepatitis C.

Value-based decision-making for orphan drugs with multiple criteria decision analysis: burosumab for the treatment of X-linked hypophosphatemia.

OBJECTIVE: Burosumab is an orphan medicinal product (OMP) approved in Europe for the treatment of X-linked hypophosphatemia (XLH). The aim of this study was to assess the value of burosumab versus conventional therapy for the treatment of paediatric XLH, through a multi-criteria decision analysis (MCDA) framework for health technology assessment (HTA) of OMPs in Portugal. METHODS: The MCDA framework considered 14 criteria related to disease burden, therapeutic value and economic burden. A multidisciplinary panel of national stakeholders participated in a two-phase exercise. In the first phase, relative weights and part-worth utilities for the criteria and their levels were elicited and a reimbursement likelihood function was calibrated through adaptive conjoint analysis. In the second phase, burosumab and conventional therapy were assessed against the criteria, providing a global value score (0-100) and reimbursement likelihood (0-100%) for both. RESULTS: Of the 14 criteria, disease burden, therapeutic value and economic burden criteria represented 27.29%, 57.17% and 15.53% of the total weight in the decision, respectively. All disease burden and some therapeutic value criteria, typically not included in traditional HTA, represented 47.88% of the total weight. Burosumab was unanimously considered superior to conventional therapy, with an average (range) global value score of 84.96 (82.48-86.54) against 48.06 (43.37-57.68), and reimbursement likelihood of 97.50% (96.78%-98.32%) against 43.66% (31.48%-68.73%), respectively. CONCLUSIONS: MCDA represents a powerful tool in HTA decision-making for OMPs. The results of this MCDA acknowledge burosumab as a disease-modifying drug, deemed superior to conventional therapy for the treatment of paediatric XLH.

Incidence of endophthalmitis after intravitreal injection with and without topical antibiotic prophylaxis.

PURPOSE: The purpose was to compare the incidence of endophthalmitis after intravitreal injection with and without topical antibiotic prophylaxis. METHODS: This is a single-center, retrospective case-control study. All patients treated with intravitreal injection of ranibizumab, bevacizumab, aflibercept, or corticosteroids for a variety of retinal vascular diseases between 1 October 2014 and 30 November 2018 were included. The total number of patients and injections were determined from a review of billing code and practice management records. Endophthalmitis cases were determined from billing records and then confirmed with chart review. A 24-month period when topical antibiotics were prescribed after intravitreal injection was compared with a 24-month period when topical antibiotics were not prescribed. RESULTS: Between 1 October 2014 and 30 November 2018, a total of 33,515 intravitreal injections were performed and 13 cases of post-intravitreal injection endophthalmitis were identified (incidence rate of 0.0388%; 95% confidence interval, 0.0217%-0.0644%) or approximately 1 case for every 2578 intravitreal injections. Between 1 October 2014 and 31 October 2016, while topical antibiotic prophylaxis was used postoperatively, 14,828 intravitreal injections were performed and 5 cases of endophthalmitis were reported (0.0337%; 95% confidence interval, 0.0129%-0.0739%). Between 1 November 2016 and 30 November 2018, while no prophylaxis was used, 18,687 intravitreal injections were performed and 8 cases of endophthalmitis were identified (0.0428%; 95% confidence interval, 0.0202%-0.0808%). There were no statistical differences in the incidence rates between the two groups (p = 0.675). CONCLUSION: The incidence rate of endophthalmitis in the group with topical antibiotic prophylaxis after intravitreal injection was similar to the group with no prophylaxis. Changing the current clinical practice to no antibiotic prophylaxis had no effect on the incidence of endophthalmitis.