Centro Hospitalar de Lisboa Central

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    Impact of Poverty and Inequality in Children and Youth Health: A Permanent Challenge

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    Prescribing Trends of Benzodiazepine and other Sedatives in the Lisbon and Tagus Valley Regional Health Administration between 2013 and 2020: A Retrospective Study

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    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.Introdução: Portugal é o país da Organização para a Cooperação e Desenvolvimento Económico com maior consumo de ansiolíticos, hipnóticos e sedativos, sendo uma proporção significativa constituída por benzodiazepinas ou análogos, associados a efeitos de tolerância e dependência. Por este motivo, em alternativa às benzodiazepinas para tratamento da insónia, algumas publicações identificam outros fármacos com efeito hipnótico, como antidepressivos, anti-histamínicos, antipsicóticos ou anticonvulsivantes. Assim, torna-se necessário compreender a evolução do consumo destes medicamentos, pelo que foi objetivo deste estudo avaliar a evolução da dispensa de benzodiazepinas, outros fármacos ansiolíticos, hipnóticos ou sedativos não benzodiazepínicos, fármacos com potencial uso off-label na insónia e os resultados de indicadores dos Cuidados de Saúde Primários neste âmbito na região de Lisboa e Vale do Tejo. Material e Métodos: Realizou-se um estudo em base de dados, censitário e retrospetivo, no período de 2013 até 2020, avaliando-se a evolução das variáveis total de doses diárias definidas, doses diárias definidas por 1000 habitantes por dia (DHD) e dos indicadores relevantes. Os dados foram extraídos da plataforma SIARS da Administração Regional de Saúde de Lisboa e Vale do Tejo. Resultados: Verificou-se uma diminuição da dispensa de benzodiazepinas (de 57,44 para 51,77 DHD) mas o aumento da dispensa de não benzodiazepinas e de fármacos com potencial uso off-label (de 6,56 para 8,56 DHD e de 14,70 para 25,92 DHD, respetivamente). O zolpidem foi o mais dispensado entre os fármacos não benzodiazepínicos, acompanhando a tendência crescente de dispensa (de 4,86 para 6,96 DHD). Do conjunto de fármacos com potencial para uso off-label verificaram-se aumentos da dispensa para a trazodona (de 3,81 para 7,92 DHD), mirtazapina (de 3,52 para 6,48 DHD), pregabalina (de 3,15 para 4,87 DHD), quetiapina (de 2,68 para 4,59 DHD) e gabapentina (de 1,32 para 1,90 DHD), mas mais significativo ou apenas verificado nas formulações com dosagem mais baixa. A mediana dos resultados do indicador “proporção de idosos sem prescrição de sedativos, ansiolíticos e hipnóticos” em 2015 foi de 81,0, tendo em 2020 aumentado para 84,9. A mediana do indicador “proporção de utentes sem prescrição prolongada de ansiolíticos, sedativos e hipnóticos” em 2019 foi de 93,6 e aumentou para 94,3 em 2020. Conclusão: Globalmente, verificou-se uma redução da dispensa de benzodiazepinas prescritas na Região de Lisboa e Vale do Tejo. Parece existir uma alteração do padrão de prescrição no tratamento da insónia. São necessários estudos mais robustos para confirmar esta observação.info:eu-repo/semantics/publishedVersio

    Albumin-Bilirubin Grade and Tumor Burden Score Predict Outcomes Among Patients with Intrahepatic Cholangiocarcinoma After Hepatic Resection: a Multi-Institutional Analysis.

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    Background: The prognostic role of tumor burden score (TBS) relative to albumin-bilirubin (ALBI) grade among patients undergoing curative-intent resection of ICC has not been examined. Methods: We identified patients who underwent curative-intent resection for ICC between 1990 and 2017 from a multi-institutional database. Multivariable analysis was performed to assess the effect of TBS relative to ALBI grade on both short- and long-term outcomes. Results: Among 724 patients, 360 (49.7%) patients had low TBS and low ALBI grade, 142 (19.6%) patients had low TBS and high ALBI grade, 138 (19.1%) patients had high TBS and low ALBI grade, and 84 patients (11.6%) had high TBS and high ALBI grade. Decreased tumor burden was associated with better long-term outcomes among patients with both low (5-year OS; low TBS vs. high TBS: 52.4% vs 21.4%; p 10 days) (OR 2.80, 95%CI 1.62-4.82; p < 0.001), perioperative transfusion (OR 2.04, 95%CI 1.25-3.36; p = 0.005), 90-day mortality (OR 2.56, 95%CI 1.12-5.81; p = 0.025), as well as a major complication (OR 1.99, 95%CI 1.13-3.49; p = 0.016) among patients with similar tumor burden. Of note, patients with high TBS and high ALBI grade had markedly worse overall survival compared with patients who had low TBS and low ALBI grade disease (HR 2.27; 95%CI 1.44-3.59; p < 0.001). Importantly, high TBS and high ALBI grade were strongly associated with both early recurrence (88.1%%) and 5-year risk of death (96.4%). Conclusion: Both TBS (i.e., tumor morphology) and ALBI grade (i.e., hepatic function reserve) were strong predictors of outcomes among patients undergoing ICC resection. There was an interplay between TBS and ALBI grade relative to patient prognosis after hepatic resection of ICC with high ALBI grade predicting worse outcomes among ICC patients with different TBS

    The Rare DRB1*04:08-DQ8 Haplotype is the Main HLA Class II Genetic Driver and Discriminative Factor of Early-Onset Type 1 Diabetes in the Portuguese Population

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    Introduction: Early-onset Type 1 diabetes (EOT1D) is considered a disease subtype with distinctive immunological and clinical features. While both Human Leukocyte Antigen (HLA) and non-HLA variants contribute to age at T1D diagnosis, detailed analyses of EOT1D-specific genetic determinants are still lacking. This study scrutinized the involvement of the HLA class II locus in EOT1D genetic control. Methods: We conducted genetic association and regularized logistic regression analyses to evaluate genotypic, haplotypic and allelic variants in DRB1, DQA1 and DQB1 genes in children with EOT1D (diagnosed at ≤5 years of age; n=97), individuals with later-onset disease (LaOT1D; diagnosed 8-30 years of age; n=96) and nondiabetic control subjects (n=169), in the Portuguese population. Results: Allelic association analysis of EOT1D and LaOT1D unrelated patients in comparison with controls, revealed that the rare DRB1*04:08 allele is a distinctive EOT1D susceptibility factor (corrected p-value=7.0x10-7). Conversely, the classical T1D risk allele DRB1*04:05 was absent in EOT1D children while was associated with LaOT1D (corrected p-value=1.4x10-2). In corroboration, HLA class II haplotype analysis showed that the rare DRB1*04:08-DQ8 haplotype is specifically associated with EOT1D (corrected p-value=1.4x10-5) and represents the major HLA class II genetic driver and discriminative factor in the development of early onset disease. Discussion: This study uncovered that EOT1D holds a distinctive spectrum of HLA class II susceptibility loci, which includes risk factors overlapping with LaOT1D and discriminative genetic configurations. These findings warrant replication studies in larger multicentric settings encompassing other ethnicities and may impact target screening strategies and follow-up of young children with high T1D genetic risk as well as personalized therapeutic approaches

    High Incidence of Early Thalamic Lesions in the Continuous Spike-Wave Related with Slow Sleep (CSWS)

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    Objective: Continuous Spike-Wave during slow Sleep (CSWS) syndrome associates a clinically important neurocognitive regression with strong activation of non-REM sleep spikes. Its mechanisms remain unknown, but a contribution of rare perinatal thalamic injuries has been highlighted. We determine the incidence of such lesions in a cohort of CSWS patients. Methods: N = 65 patients with CSWS and a control group (N = 51) were studied. Spikes were quantified in long-term ambulatory EEGs, brain Magnetic Ressonance Imaging (MRI) structural lesions were assessed and thalamic volumetry was performed. A neurocognitive scale was used to assess dysfunction. Results: The most common etiologies in the control patients were not represented in the CSWS group. Structural lesions were detected in a minority of CSWS patients (25/53) but included a thalamic injury in the large majority (24/25). This ratio was 4/40 in controls. Lesions belonged to one of five types: 1. Circumscribed to the thalamus (N = 11); 2. Extending beyond the thalamus (N = 3); 3. Hypothalamic-Hamartomas (N = 4); 4. Periventricular-Leukomalacia (N = 4); 5. Hypoplasia-Polymicrogyria (N = 1). Most lesions were lateralized to one hemisphere, which in all cases corresponded to the lateralization of the CSWS. Significance: Thalamic lesions are present in most CSWS patients with abnormal MRIs, supporting an important role in its genesis.info:eu-repo/semantics/publishedVersio

    Consistent Trajectories of Rhinitis Control and Treatment in 16,177 Weeks: The MASK‐air® Longitudinal Study

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    Introduction: Data from mHealth apps can provide valuable information on rhinitis control and treatment patterns. However, in MASK-air®, these data have only been analyzed cross-sectionally, without considering the changes of symptoms over time. We analyzed data from MASK-air® longitudinally, clustering weeks according to reported rhinitis symptoms. Methods: We analyzed MASK-air® data, assessing the weeks for which patients had answered a rhinitis daily questionnaire on all 7 days. We firstly used k-means clustering algorithms for longitudinal data to define clusters of weeks according to the trajectories of reported daily rhinitis symptoms. Clustering was applied separately for weeks when medication was reported or not. We compared obtained clusters on symptoms and rhinitis medication patterns. We then used the latent class mixture model to assess the robustness of results. Results: We analyzed 113,239 days (16,177 complete weeks) from 2590 patients (mean age ± SD = 39.1 ± 13.7 years). The first clustering algorithm identified ten clusters among weeks with medication use: seven with low variability in rhinitis control during the week and three with highly-variable control. Clusters with poorly-controlled rhinitis displayed a higher frequency of rhinitis co-medication, a more frequent change of medication schemes and more pronounced seasonal patterns. Six clusters were identified in weeks when no rhinitis medication was used, displaying similar control patterns. The second clustering method provided similar results. Moreover, patients displayed consistent levels of rhinitis control, reporting several weeks with similar levels of control. Conclusions: We identified 16 patterns of weekly rhinitis control. Co-medication and medication change schemes were common in uncontrolled weeks, reinforcing the hypothesis that patients treat themselves according to their symptoms.info:eu-repo/semantics/publishedVersio

    Resultados Clínicos de Procedimento Único com Balão de CrioEnergia para o Tratamento da Fibrilhação Auricular: uma Experiência Multicêntrica em Portugal

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    Background: Cryoballoon ablation (CBA) for pulmonary vein isolation (PVI) has been growing as an alternative technique, not only in patients with paroxysmal atrial fibrillation (PAF) but also in persistent atrial fibrillation (AF). Cryoballoon ablation has demonstrated encouraging acute and mid-term results. However, data on long-term follow-up of CB-based PVI are scarce. Objective: We sought to examine efficacy, safety, and long-term outcomes of CBA in PAF and persistent AF in four Portuguese centers. Methods: All patients that were treated with the cryoballoon catheter according to routine practices with a second-generation 28-mm CB in four centers were included. This was a retrospective, non-randomized analysis. Patients were followed-up for >12 months and freedom from atrial arrhythmias (AA) was evaluated at the end of follow-up. Results: Four hundred and six patients (57.7±12.4 years, 66% men) participated. AF was paroxysmal in 326 patients (80.2%) and persistent in 80 (19.7%). The mean procedure time duration was 107.7±50.9 min, and the fluoroscopy time was 19.5±9.7 min. Procedural/periprocedural complications occurred in 30 cases (7.3%), being transient phrenic nerve palsy the most frequent incident (2 out of 3 complications). Anatomic variations of the PV were present in 16.1% of cases. At a mean follow-up of 22.0±15.0 months, 310 patients (76.3%) remained in stable sinus rhythm, with at least one AF episode recurrence documented in 98 cases (24.1%). The recurrence rate was 20.5% in the PAF group and 37.8% in the persistent AF group. Conclusion: In this multicenter experience, a single CBA procedure resulted in 75.9% freedom from AF at a 22-month follow-up. This technique was demonstrated to be a safe and effective option in experienced centers for the treatment of PAF and PersAF.Introdução: Observa-se um crescimento progressivo na utilização do cateter de balão de CrioEnergia (CBC) para isolamento das veias pulmonares (IVP), não apenas em doentes com fibrilhação auricular paroxística (FAParox), mas também com fibrilhação auricular persistente (FAPers). Esta tecnologia tem apresentado resultados --- a curto e a médio prazo --- encorajadores. No entanto, ainda há escassez de dados sobre o acompanhamento de longo prazo do IVP baseado em CBC. Objetivo: Procurámos examinar a eficácia, segurança e os resultados clínicos a longo prazo da ablação com CBC em doentes com FAParox e FAPers nos procedimentos realizados em quatro centros portugueses. Métodos: Foram incluídos todos os doentes submetidos a ablação com CBC de 28 mm de segunda geração, em quatro centros de eletrofisiologia. Esta foi uma análise retrospetiva e não randomizada. Os doentes foram acompanhados por um período >12 meses, tendo sido avaliada a presença de taquiarritmias auriculares (TA) nesse período, bem como a ocorrência de complicações do procedimento. Resultados: Nesta análise, foram incluídos 406 (57,7 ± 12,4 anos, 66% homens). Nestes, observou-se que a FA era paroxística em 326 doentes (80,2%) e persistente em 80 (19,7%). O tempo médio de procedimento foi de 107,7 ± 50,9 minutos e o tempo de fluoroscopia de 19,5 ± 9,7 minutos. Ocorreram complicações no procedimento/periprocedimento em 30 casos (7,3%), sendo a paralisia do nervo frénico o incidente mais frequente (2 de 3 complicações). Observaram-se variações anatómicas das VPs em 16,1% dos casos. Em um seguimento médio de 22,0 ± 15,0 meses, 310 doentes (76,3%) permaneceram em ritmo sinusal estável, sendo documentado, pelo menos um episódio de FA em 98 casos (24,1%). A taxa de recorrência foi de 20,5% no grupo FAParox e 37,8% no grupo FAPers. Conclusão: Nesta experiência multicêntrica, um único procedimento com CBC resultou em 75,9% de ausência de FA em 22 meses de acompanhamento. Essa técnica demonstrou ser uma opção segura e eficaz em centros experientes no tratamento da FAParox e FAPers.info:eu-repo/semantics/publishedVersio

    Hábitos Alimentares Durante a Gravidez em Mulheres com Parto Muito Pré-Termo: Uma Análise Exploradora

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    Introduction: Preterm birth is increasing worldwide, representing a major cause of death and long-term loss of human potential among survivors. Some morbidities during pregnancy are well-known risk factors for preterm labor, but it is not yet known whether deviations from adequate dietary patterns are associated with preterm delivery. Diet may be an important modulator of chronic inflammation, and pro-inflammatory diets during pregnancy were reported to be associated with preterm birth. The aim of this study was to assess the food consumption during pregnancy of Portuguese women giving birth very prematurely and the association between the food consumption and the major maternal morbidities during pregnancy related with preterm delivery. Material and methods: A single-center cross-sectional observational study including consecutive Portuguese women giving birth before 33 weeks of gestation was conducted. Recall of eating habits during pregnancy was obtained within the first week after delivery, using a semi quantitative food frequency questionnaire validated for Portuguese pregnant women. Results: Sixty women with a median age of 36.0 years were included. Of these, 35% were obese or overweight at the beginning of pregnancy, 41.7% and 25.0% gained excessive or insufficient weight during pregnancy, respectively. Pregnancy-induced hypertension was present in 21.7% of cases, gestational diabetes in 18.3%, chronic hypertension in 6.7%, and type 2 diabetes mellitus in 5.0%. Pregnancy-induced hypertension was significantly associated with increased daily consumption of pastry products (31.2 vs 10.0 g, p = 0.022), fast food (39.6 vs 29.7 g, p = 0.028), bread (90.0 vs 50.0 g, p = 0.005), pasta, rice and potatoes (225.7 vs 154.3 g, p = 0.012). In a multivariate analysis, only bread consumption maintained a significant, albeit weak, association (OR = 1.021; 1.003 - 1.038, p = 0.022). Conclusion: Pregnancy-induced hypertension was associated with increased consumption of pastry products, fast food, bread, pasta, rice, and potatoes, although only bread consumption had a weak but statistically significant association with pregnancy-induced hypertension in a multivariate analysis.info:eu-repo/semantics/publishedVersio

    Hypophosphatemia As a Possible Biomarker for Epileptic Seizures at the Emergency Department

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    Introduction: Hypophosphatemia seems to be temporally associated with seizures, despite not being considered a trigger. We aimed to evaluate hypophosphatemia as a biomarker for seizures. Methods: Retrospective study, including all consecutive patients admitted at our central hospital's emergency department from 01/01-31/03/2021, screened as "altered consciousness/syncope" or "seizures", with available phosphate levels. Results: 277 patients included, mostly male (61.7%), mean age 64.3 years. Final diagnosis was "seizure" in 34.7% and "other diagnosis" in 65.3%. Patients with seizures were younger (p200U/L) was more frequent in the seizure group (p=0.04). Odds ratio (OR) of hypophosphatemia for seizures was 4.330 (CI 95% 2.170-8.640, p<0.001), persisting after correction for confounders. OR of hyperCK was 1.890 (CI 95% 1.060-3.371, p=0.03), losing significance when adjusted. Sensitivity was low for both. Hypophosphatemia was more specific (91.2% vs 79.9%). Conclusions: Our findings support hypophosphatemia as a seizure biomarker. More studies are needed.info:eu-repo/semantics/publishedVersio

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