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  • Medication Reconciliation in Primary Care: Practices, Knowledge and Attitudes in the Lisbon and Tagus Valley Health Region
    Publication . Ascenção, Raquel; Almeida, Mariana; Ribeiro, Cristina; Broeiro, Paula; Costa, João; Ordem dos Médicos
    Despite the importance of medication reconciliation for the continuity of care, there is currently no information on the practices, knowledge, and attitudes of Portuguese family doctors on this subject. This study aimed to characterize the formal medication reconciliation procedures in the Lisbon and Tagus Valley Health Region, as well as the perception of family doctors in this region about what they know, how they think and how they practice medication reconciliation.
  • Prescrição de Benzodiazepinas e Outros Sedativos na Administração Regional de Saúde de Lisboa e Vale do Tejo de 2013 a 2020: um Estudo Retrospetivo
    Publication . Gomes, S; Broeiro-Gonçalves, P; Meireles, C; Caldeira, D; Costa, J; Guerreiro, M; Ribeiro, N; Afonso, R
    Introduction: Among the Organization for Economic Co-operation and Development members, Portugal has the highest reported consumption of anxiolytics, hypnotics, and sedatives, of which a large proportion are benzodiazepines or related drugs. These are known to cause tolerance and dependence. Other drugs with hypnotic effect, such as antidepressants, antihistamines, antipsychotics, or anticonvulsants have been identified by some reports as alternatives to benzodiazepines for the treatment of insomnia. In this regard, the aim of this study was to characterize the consumption of benzodiazepines, non-benzodiazepine anxiolytic, hypnotic or sedative effect drugs and other drugs with the potential to be used off-label to treat insomnia, and the results concerning benzodiazepine consumption related indicators in the primary health care setting in the Lisbon and Tagus Valley region. Material and methods: From 2013 to 2020, a census, descriptive and retrospective study was conducted. The evolution of the variables total defined daily doses, defined daily doses per 1000 inhabitants per day (DHD) and relevant indicators were characterized. Data were extracted from the SIARS platform used in the Lisbon and Tagus Valley regional Health Administration. Results: There was a decrease in the consumption of benzodiazepines (from 57.44 to 63.11 DHD) and an increase of non-benzodiazepines and of drugs with potential off-label use (from 6.56 to 8.56 DHD and from 14.70 to 25.95 DHD, respectively). Among non-benzodiazepines, zolpidem was the most consumed drug, also showing an increasing trend (from 4.86 to 6.96 DHD). For the group of drugs with off-label use potential, there was an increased consumption of trazodone (from 3.81 to 7.92 DHD), mirtazapine (from 3.52 to 6.48 DHD), pregabalin (from 3.15 to 4.87 DHD), quetiapine (from 2.68 to 4.59 DHD) and gabapentin (from 1.32 to 1.90 DHD), which was only the case (or, at least, more significantly) for the lower dose formulations. The median of results of the Primary Health Care setting indicator "proportion of elderly patients without prescription of sedatives, anxiolytics, and hypnotics", was 81.0 in 2015 and increased to 84.9 in 2020. For the indicator "proportion of patients without prolonged prescription of sedatives, anxiolytics, and hypnotics", the median was 93.6 in 2019 and 94.3 in 2020. Conclusion: There was, overall, a decreasing trend in the dispensing of benzodiazepines in the Lisbon and Tagus Valley Region. Even though this data suggests a change in the therapeutic pattern for insomnia, more robust studies are needed to confirm this observation.
  • A Cross‐Sectional Assessment of Frailty, Falls and Perceptions of Ageing in People Living with HIV Using an mHealth Platform
    Publication . Levett, TJ; Vera, JH; Jones, CI; Bremner, S; Leon, A; Begovac, J; Apers, L; Borges, M; Zekan, S; Teofilo, E; Garcia, F; Whetham, J
    Objective: To evaluate frailty, falls and perceptions of ageing among clinically stable individuals with HIV, engaged with remote healthcare delivered via a novel smartphone application. Methods: This was a multi-centre European cross-sectional, questionnaire-based sub-study of EmERGE participants. Frailty was assessed using the five-item FRAIL scale. Present criteria were summed and categorized as follows: 0, robust; 1-2, pre-frail; 3-5, frail. Falls history and EQ-5D-5L quality of life measure were completed. Participants were asked their felt age and personal satisfaction with ageing. Results: A total of 1373 participated, with a mean age of 45 (± 9.8) years. Frailty was uncommon at 2%; 12.4% fell in the previous year, 58.8% of these recurrently. Mood symptoms and pain were prevalent, at 43.3% and 31.8%, respectively. Ageing satisfaction was high at 76.4%, with 74.6% feeling younger than their chronological age; the mean felt age was 39.3 years. In multivariable analysis, mood symptoms and pain were positively associated with frailty, falls and ageing dissatisfaction. An increase in pain severity and mood symptoms were respectively associated with 34% and 63% increased odds of pre-frailty/frailty. An increment in pain symptoms was associated with a 71% increase in odds of falling. Pain was associated with ageing poorly, as were mood symptoms, with odds of dissatisfaction increasing by 34% per increment in severity. Conclusions: Although uncommon, frailty, falls and ageing dissatisfaction were seen in a younger cohort with medically stable HIV infection using a remote care model, promoting screening as advocated by European guidelines. These were more common in those with pain or mood symptoms, which should be proactively managed in clinical care and explored further in future research.
  • Atherosclerosis in the Primary Health Care Setting: A Real-Word Data Study
    Publication . Ascenção, R; Alarcão, J; Araújo, F; Costa, J; Fiorentino, F; Gil, V; Gouveia, M; Lourenço, F; Mello e Silva, A; Vaz Carneiro, A; Borges, M
    Introduction and objectives: To characterize patients with atherosclerosis, a disease with a high socioeconomic impact, in the Lisbon and Tagus Valley Health Region. Methods: A cross-sectional observational study was carried out through the Lisbon and Tagus Valley Regional Health Administration primary health care database, extracting data on the clinical and demographic characteristics and resource use of adult primary health care users with atherosclerosis during 2016. Different criteria were used to define atherosclerosis (presence of clinical manifestations, atherothrombotic risk factors and/or consumption of drugs related to atherosclerosis). Comparisons between different subpopulations were performed using parametric tests. Results: A total of 318 692 users were identified, most of whom (n=224 845 users; 71%) had no recorded clinical manifestations. The subpopulation with clinical manifestations were older (72.0±11.5 vs. 71.3±11.0 years), with a higher proportion of men (58.0% vs. 45.9%), recorded hypertension (78.3% vs. 73.5%) and dyslipidemia (55.8% vs. 53.5%), and a lower proportion of recorded obesity (18.2% vs. 20.8%), compared to those without clinical manifestations (p<0.001). Mean blood pressure, LDL-C and glycated hemoglobin values were lower in the subpopulation with manifestations (142/74 vs. 146/76 mmHg, 101 vs. 108 mg/dl, and 6.80 vs. 6.84%, respectively; p<0.001). Each user with atherosclerosis attended 4.1±2.9 face-to-face medical consultations and underwent 8.6±10.0 laboratory test panels, with differences in subpopulations with and without clinical manifestations (4.4±3.2 vs. 4.0±2.8 and 8.3±10.3 vs. 8.7±9.8, respectively; p<0.001). Conclusions: About one in three adult primary health care users with atherosclerosis have clinical manifestations. The results suggest that control of cardiovascular risk factors is suboptimal in patients with atherosclerosis.
  • The Kidney Genetics Clinic: Delivering Precision Medicine for Kidney Patients
    Publication . Calado, J; Barata, R; Lucas, R; Francisco, T; Gonçalves, R; Carrilho Ribeiro, N; Nolasco, F
    Molecular genetic testing in human traits has traditionally relied on affiliated academic facilities, been focused on specific phenotypes and supported by research funding. We report the experience of the Kidney Genetics Clinic (“consulta de Doenças Renais Hereditárias”) for the past 5 years, a period during which we have outsourced genetic testing. We evaluated the impact of molecular testing in patients’ care, but we also assessed disease‑specific imaging procedures and medicines provided. During the study period, 293 individuals were evaluated. Autosomal Dominant Polycystic Kidney Disease was the most frequent diagnosis (61.8%). In 125 patients, a genetic test was available, and for 76 of these (60.8%) a pathogenic/likely pathogenic variant was identified. Depending on the phenotype, the mutation detection rate ranged from 100% (Tuberous Sclerosis Complex) to 15.4% (Autosomal Dominant Tubulointerstitial Kidney Disease). The impact of genetic testing on patients’ diagnosis and treatments is discussed. Total kidney volume was calculated in 6 patients with Autosomal Dominant Polycystic Kidney Disease and the combined volume for selected angiomyolipoma monitored in 3 individuals with the Tuberous Sclerosis Complex. Currently, 4 patients are being treated with Everolimus/Votubia™, 3 with Eculizumab/Soliris™ and 2 with Tolvaptan/Jinarc™. Our results demonstrate the feasibility of genetic molecular testing in a clinical setting while relying on outsourced sites for gene testing. We emphasize that it was only because the Kidney Genetics Clinic was given the opportunity to look after several patients affected by the same specific orphan or rare diseases (cohort enrichment) that we were able to improve diagnostic skills and deliver personalized medicines.
  • Cost-Effectiveness of the 13-Valent Pneumococcal Conjugate Vaccine in Adults in Portugal Versus "No Vaccination" and Versus Vaccination with the 23-Valent Pneumococcal Polysaccharide Vaccine
    Publication . Gouveia, M; Jesus, G; Inês, M; Costa, J; Borges, M
    The burden of pneumococcal disease in adults is substantial from a social and economic point of view. This study assessed the cost-effectiveness of the 13-valent pneumococcal conjugate vaccine (PCV13) for the prevention of invasive pneumococcal disease and pneumococcal pneumonia in adults versus "no vaccination" and versus vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPSV23). A Markov model was used to simulate three strategies: no vaccination, complete vaccination with PPSV23 and complete vaccination with PCV13. The comparison between strategies allowed the estimation of clinical and economic outcomes including incremental cost-effectiveness ratios (ICER) and incremental cost-utility ratios (ICUR). The model took into account the distributions of age, risk profile, vaccination status, type of immunization and time since vaccination in the population. A societal perspective was adopted and a lifetime horizon was considered. Different sources of data and assumptions were used to calibrate PPSV23 and PCV13 effectiveness. Inpatient costs were based on the 2013 diagnosis-related group (DRG) database for National Health Service (NHS) hospitals and expert opinion; NHS official tariffs were the main source for unitary costs. PCV13 shows ICURs of €17,746/QALY and €13,146/QALY versus "no vaccination" and vaccination with PPSV23, respectively. Results proved to be robust in univariate sensitivity analyses, where all ratios were below a €20,000 threshold, with the exception of the scenario with PCV13 effectiveness halved. In a probabilistic sensitivity analysis, 94% of simulations showed cost-effectiveness ratios lower than €20,000/QALY, in both strategies. It was found that PCV13 is a cost-effective strategy to prevent pneumococcal disease in adults in Portugal.
  • Cost-Effectiveness of the 13-Valent Pneumococcal Conjugate Vaccine in Children in Portugal
    Publication . Gouveia, M; Fiorentino, F; Jesus, G; Costa, J; Borges, M
    Pneumococcal infections are the leading cause of vaccine-preventable death in children. In June 2015, the 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the Portuguese Immunization Program. We evaluated the cost-effectiveness of children vaccinated with PCV13 versus no vaccination for preventing pneumococcal diseases.
  • Parenteral Nutrition-Associated Cholestasis and Triglyceridemia in Surgical Term and Near-Term Neonates: A Pilot Randomized Controlled Trial of Two Mixed Intravenous Lipid Emulsions
    Publication . Pereira-da-Silva, L; Nóbrega, S; Rosa, ML; Alves, M; Pita, A; Virella, D; Papoila, AL; Serelha, M; Cordeiro-Ferreira, G; Koletzko, B
    BACKGROUND: Cholestasis is a common complication in infants receiving prolonged parenteral nutrition (PN). We studied the effects of two intravenous lipid emulsions composed with either 30% soybean oil, 30% medium-chain triglycerides (MCT), 25% olive oil, and 15% fish oil (SMOF) or with 50% MCT and 50% soybean oil n-6 (MCT/SOY) on the incidence of cholestasis in surgical term and near-term neonates. METHODS: A single-center, double-blinded, randomized controlled trial compared the incidence of cholestasis using either SMOF or MCT/SOY in neonates born at gestational age ≥34 weeks undergoing major surgery. The primary outcome was the incidence of conjugated serum bilirubin >1 mg/dL. Other liver enzymes were assessed as secondary outcomes. A post-hoc analysis assessed serum triglycerides levels. Odds ratios were estimated by mixed-effects regression models. RESULTS: Enrollment was prematurely interrupted because the MCT/SOY became unavailable, thus 49 infants (SMOF 22, MCT/SOY 27) completed the study. The exposure (time on PN, cumulative dose of lipids) was similar in both groups. Similar cumulative incidence rates were found for elevated conjugated bilirubinemia and other liver enzymes. Hypertriglyceridemia >250 mg/dL (12/49) was more frequent in MCT/SOY (37.0%, 95% CI 21.53-55.77) than in SMOF (9.1%, 95% CI 2.53-27.81, p = 0.024). Triglyceridemia at the first assessment (median 8 postnatal days) was significantly higher with MCT/SOY than with SMOF (181 vs. 134 mg/dL, p = 0.006). Over the whole study period, mean triglyceride concentration was 36.5 mg/dL higher with MCT/SOY compared with SMOF (p = 0.013). CONCLUSION: Both emulsions had similar effects on the incidence of cholestasis and markers of liver integrity, but MCT/SOY induced higher serum triglyceride concentrations.
  • Cost-Effectiveness of Non-Vitamin K Antagonist Oral Anticoagulants for Atrial Fibrillation in Portugal
    Publication . Costa, J; Fiorentino, F; Caldeira, D; Inês, M; Lopes Pereira, C; Pinheiro, L; Vaz-Carneiro, A; Borges, M; Gouveia, M
    INTRODUCTION AND OBJECTIVES:Recently, three novel non-vitamin K antagonist oral anticoagulants received approval for reimbursement in Portugal for patients with non-valvular atrial fibrillation (AF). It is therefore important to evaluate the relative cost-effectiveness of these new oral anticoagulants in Portuguese AF patients. METHODS: A Markov model was used to analyze disease progression over a lifetime horizon. Relative efficacy data for stroke (ischemic and hemorrhagic), bleeding (intracranial, other major bleeding and clinically relevant non-major bleeding), myocardial infarction and treatment discontinuation were obtained by pairwise indirect comparisons between apixaban, dabigatran and rivaroxaban using warfarin as a common comparator. Data on resource use were obtained from the database of diagnosis-related groups and an expert panel. Model outputs included life years gained, quality-adjusted life years (QALYs), direct healthcare costs and incremental cost-effectiveness ratios (ICERs). RESULTS:Apixaban provided the most life years gained and QALYs. The ICERs of apixaban compared to warfarin and dabigatran were €5529/QALY and €9163/QALY, respectively. Apixaban was dominant over rivaroxaban (greater health gains and lower costs). The results were robust over a wide range of inputs in sensitivity analyses. Apixaban had a 70% probability of being cost-effective (at a threshold of €20 000/QALY) compared to all the other therapeutic options. CONCLUSIONS:Apixaban is a cost-effective alternative to warfarin and dabigatran and is dominant over rivaroxaban in AF patients from the perspective of the Portuguese national healthcare system. These conclusions are based on indirect comparisons, but despite this limitation, the information is useful for healthcare decision-makers.
  • Economic Evaluation of Ticagrelor for Secondary Prevention Following Acute Coronary Syndromes
    Publication . Gouveia, M; Borges, M; Trindade, R; Rikner, K
    INTRODUCTION AND OBJECTIVES: To estimate the cost-effectiveness and cost-utility of ticagrelor in the treatment of patients with acute coronary syndromes (unstable angina or myocardial infarction with or without ST-segment elevation), including patients treated medically and those undergoing percutaneous coronary intervention or coronary artery bypass grafting. METHODS: A short-term decision tree and a long-term Markov model were used to simulate the evolution of patients' life-cycles. Clinical effectiveness data were collected from the PLATO trial and resource use data were obtained from the Hospital de Santa Marta database, disease-related group legislation and the literature. RESULTS: Ticagrelor provides increases of 0.1276 life years and 0.1106 quality-adjusted life years (QALYs) per patient. From a societal perspective these clinical gains entail an increase in expenditure of €610. Thus the incremental cost per life year saved is €4780 and the incremental cost per QALY is €5517. CONCLUSIONS: The simulation results show that ticagrelor reduces events compared to clopidogrel. The costs of ticagrelor are partially offset by lower costs arising from events prevented. The use of ticagrelor in clinical practice is therefore cost-effective compared to generic clopidogrel.