Using Patient-Reported Outcome Measures to Evaluate Care for Patients With Inflammatory Chronic Rheumatic Disease

Objectives: Few countries integrate patient-reported outcome measures (PROMs) in routine performance assessment and those that do focus on elective surgery. This study addresses the challenges of using PROMs to evaluate care in chronic conditions. We set out a modeling strategy to assess the extent to which changes over time in self-reported health status by patients with inflammatory chronic rheumatic disease are related to their biological drug therapy and rheumatology center primarily responsible for their care. Methods: Using data from the Portuguese Register of Rheumatic Diseases, we assess health status using the Health Assessment Questionnaire-Disability Index for rheumatic patients receiving biological drugs between 2000 and 2017. We specify a fixed-effects model using the least squares dummy variables estimator. Results: Patients receiving infliximab or rituximab report lower health status than those on etanercept (the most common therapy) and patients in 4 of the 26 rheumatology centers report higher health status than those at other centers. Conclusions: PROMs can be used for those with chronic conditions to provide the patient's perspective about the impact on their health status of the choice of drug therapy and care provider. Care for chronic patients might be improved if healthcare organizations monitor PROMs and engage in performance assessment initiatives on a routine basis.info:eu-repo/semantics/publishedVersio

Using patient-reported outcome measures to evaluate care for patients with inflammatory chronic rheumatic disease

Objectives: Few countries integrate Patient-Reported Outcome Measures (PROMs) in routine performance assessment, and those that do focus on elective surgery. This study addresses the challenges of using PROMs to evaluate care in chronic conditions. We set out a modelling strategy to assess the extent to which changes over time in self-reported health status by patients with inflammatory chronic rheumatic disease are related to their biological drug therapy and Rheumatology centre primarily responsible for their care. Methods: Using data from the Portuguese Register of Rheumatic Diseases, we assess the health status using the Health Assessment Questionnaire-Disability Index (HAQ-DI) for rheumatic patients receiving biological drugs between 2000 and 2017. We employ a fixed effects model using the Least Squares Dummy Variables estimator. Results: Patients receiving infliximab or rituximab report lower health status than those on etanercept (the most common therapy) and patients in 4 of the 26 Rheumatology centres report higher health status than those at other centres. Conclusions: PROMs can be used for those with chronic conditions to provide the patient’s perspective about the impact on their health status of the choice of drug therapy and care provider. Care for chronic patients might be improved if healthcare organisations monitor PROMs and engage in performance assessment initiatives on a routine basis

Drug-Induced Anaphylaxis Survey in Portuguese Allergy Departments

Background and Objective: Drug-induced anaphylaxis is an unpredictable and potentially fatal adverse drug reaction. The aim of this study was to identify the causes of drug-induced anaphylaxis in Portugal. Methods: During a 4-year period a nationwide notification system for anaphylaxis was implemented, with voluntary reporting by allergists. Data on 313 patients with drug anaphylaxis were received and reviewed. Statistical analysis included distribution tests and multiple logistic regression analysis to investigate significance, regression coefficients, and marginal effects. Results: The mean (SD) age of the patients was 43.8 (17.4) years, and 8.3% were younger than 18 years. The female to male ratio was 2:1. The main culprits were nonsteroidal anti-inflammatory drugs (NSAIDs) (47.9% of cases), antibiotics (35.5%), and anesthetic agents (6.1%). There was a predominance of mucocutaneous symptoms (92.2%), followed by respiratory symptoms (80.4%) and cardiovascular symptoms (49.0%). Patients with NSAID-induced anaphylaxis showed a tendency towards respiratory and mucocutaneous manifestations. We found no significant associations between age, sex, or atopy and type of drug. Anaphylaxis recurrence was observed in 25.6% of cases, and the risk was higher when NSAIDs were involved. Conclusions: NSAIDs were the most common cause of anaphylaxis in this study and were also associated with a higher rate of recurrence. We stress the need for better therapeutic management and prevention of recurring episodes of drug-induced anaphylaxis

Drug-Induced Anaphylaxis: National Survey 2007-2010

Introdução: A anafilaxia a fármacos constitui uma situação potencialmente fatal e imprevisível, desconhecendo -se a real prevalência em diferentes grupos populacionais e os factores de risco relacionados. Objectivo: Contribuir para o melhor conhecimento epidemiológico da anafilaxia induzida por fármacos no nosso país. Métodos: Durante um período de 4 anos (Janeiro de 2007 a Dezembro de 2010) foi implementado um sistema de notificação nacional de anafilaxia, focalizado na notificação voluntária por clínicos com diferenciação em patologia imunoalérgica. Foram recebidas e analisadas notificações de anafilaxia a fármacos de 313 doentes. No estudo estatístico foram aplicados testes de distribuição e análise de regressão logística múltipla para obter significância e coeficientes de regressão e efeitos marginais. Resultados: A média de idade foi de 43,8 ±17,4 anos, sendo 8% de idade inferior a 18 anos. A relação género feminino/masculino foi de 2/1. A média de idade do primeiro episódio foi de 39 ±18,2 anos. Nove doentes apresentaram mais que uma causa de anafilaxia, correspondendo a um total de 322 notificações de grupos de fármacos envolvidos. As principais causas da anafilaxia a fármacos foram os anti -inflamatórios não esteróides (AINEs), os antibióticos e os agentes anestésicos, com respectivamente 48%, 36% e 6% dos casos. Outros fármacos implicados foram citostáticos, corticosteróides, inibidores da bomba de protões e meios de contraste iodados, entre outros. Houve predomínio de manifestações mucocutâneas (92%), seguido de respiratórias (81%) e de cardiovasculares (49%). Os doentes com anafilaxia a AINEs apresentaram aumento significativo da associação de manifestações mucocutâneas e respiratórias. Não foram observadas diferenças significativas em idade, género ou antecedentes de atopia entre os diferentes grupos de fármacos envolvidos. As reacções ocorreram em ambiente hospitalar em 45% dos casos. Em 53% nos 15 minutos após a administração do fármaco e 35% motivaram internamento. A recorrência da anafilaxia foi observada em 26% e o risco foi significativamente mais elevado nos casos de anafilaxia a AINEs. Apenas 48% dos doentes receberam tratamento com adrenalina e somente em 9% dos casos foi prescrito dispositivo para auto -administração de adrenalina. Conclusões: Neste estudo os AINEs foram os fármacos mais frequentes e os mais associados a recorrência de anafilaxia. Destaca -se o sub -tratamento com adrenalina e a necessidade de serem tomadas medidas no sentido do tratamento eficaz e da prevenção da recorrência de anafilaxia a fármacos

Outcomes oncológicos da colocação de próteses metáli- cas auto-expansíveis como “ponte para cirurgia” versus cirurgia emergente na oclusão intestinal por cancro colorectal: Um estudo comparativo português

Prémio Medtronic Investigação em Coloproctologia 2015, no XXV Congresso Nacional de Coloproctologia, que decorreu nos dias 26 e 27 de Novembro de 2015, no Porto.Introduction: The short-term results of colonic stenting followed by elective surgery (bridge to surgery, BTS) for malignant large- -bowel obstruction (MLBO) have been well described. However long-term oncological outcomes are still debated and interna- tional endoscopy societies have recently not recommended it as a first-line approach. Aims & Methods: A longitudinal observational cohort study was performed based on clinical data review from patients treated in our center between 2006 and 2012 (7 years). We analysed disease-free survival (DFS), overall survival (OS) and recurrence as primary end-points. We also reviewed demographic data, disease staging and peri-operatory morbility and mortality. Results: A total of 126 patients were included: 79 (62,7%) were treated with a BTS strategy (group 1) and 47 (37,3%) underwent an emergent surgery (group 2). The distribution by sex, age (70,9+/-11,4 years) and TNM stage was similiar. The median follow-up time was 49,2 +/- 3,6 months. There was no significant difference in peri-operatory complications (p=0,23) and adjuvant chemotherapy (p=0,53). The need for a definite stoma was higher in group 2 (p<0,001). The recurrence did not differ significantly between the two groups, although it was superior in group 2 (34,5% vs. 42,5%,p=0,492). DFS (22,2 vs 19,7 months; p=0,652) and OS (43,2 vs. 31,9 months, p=0,096) also did not differ signficantly between the two groups, being slightly longer in group 1. Conclusion: Results of our study on oncological outcomes, as stated in most recent meta-analysis, as well as well-described short-term outcomes, suggest that BTS could be a promising alternative strategy for MLBO. Larger prospective studies and randomized clinical trials are definetely needed in the future.Introdução: Os resultados a curto prazo da utilização de próteses metálicas do cólon seguida de cirurgia eletiva (ponte para cirurgia, PPC) na oclusão intestinal por cancro colorectal são bem conhecidos. Os resultados oncológicos a longo prazo permanecem alvo de discussão e levaram a que, recentemente, as sociedades internacionais de endoscopia não recomendassem esta estratégia como primeira linha. Objetivo e Métodos: Realizámos um estudo longitudinal obser- vacional de coorte com base nos dados clínicos dos doentes tratados na nossa instituição entre 2006 e 2012 (7 anos). Analisámos a sobrevida livre de doença (SLD), a sobrevida global (SG) e a recidiva como end-points primários. Os dados demográficos, o estádio da doença e a morbi-mortalidade peri-operatórias foram também comparados. Resultados: Incluímos 126 doentes, 79 (62,7%) foram tratados seguindo uma estratégia PPC (grupo 1) e 47 (37,3%) foram submetidos a cirurgia emergente (grupo 2). A distribuição por sexo, idade (70,9+/-11,4 anos) e estádio TNM foi semelhante. O tempo de follow-up médio foi de 49,2 +/- 3,6 meses. Não houve diferenças estatisticamente significativas em relação a complicações peri-operatórias (p=0,23) ou realização de quimioterapia adjuvante (p=0,53). A incidência de estoma definitivo foi superior no grupo 2(p<0,001). A recidiva não foi significativamente diferente, apesar de ter sido superior no grupo 2 (34,5% vs . 42,5%,p=0,492). A SLD (22,2 vs. 19,7 meses;p=0,652) e a SG (43,2 vs. 31,9 meses, p=0,096) também não foram significativamnete diferentes, embora tenham sido ligeiramente superiores no grupo 1. Conclusões: Os resultados do nosso estudo vão ao encontro das meta-análises mais recentes sugerindo que a estratégia PPC poderá ser uma alternativa promissora à cirurgia emer- gente. São necessários ensaios clínicos e estudos prospetivos que o comprovem

Validation of control of allergic rhinitis and asthma test for children (CARATKids)--a prospective multicenter study

BACKGROUND: Control of Allergic Rhinitis and Asthma Test for Children (CARATKids) is the first questionnaire that assesses simultaneously allergic rhinitis and asthma control in children. It was recently developed, but redundancy of questions and its psychometric properties were not assessed. This study aimed to (i) establish the final version of the CARATKids questionnaire and (ii) evaluate its reliability, responsiveness, cross-sectional validity, and longitudinal validity. METHODS: A prospective observational study was conducted in 11 Portuguese centers. During two visits separated by 6 wk, CARATKids, visual analog scale scales and childhood asthma control test were completed, and participant's asthma and rhinitis were evaluated by his/her physician without knowing the questionnaires' results. Data-driven item reduction was conducted, and internal consistency, responsiveness analysis, and associations with external measures of disease status were assessed. RESULTS: Of the 113 children included, 101 completed both visits. After item reduction, the final version of the questionnaire has 13 items, eight to be answered by the child and five by the caregiver. Its Cronbach's alpha was 0.80, the Guyatt's responsiveness index was -1.51, and a significant (p < 0.001) within-patient change of CARATKids score in clinical unstable patients was observed. Regarding cross-sectional validity, correlation coefficients of CARATKids with the external measures of control were between 0.45 and -0.69 and met the a priori predictions. In the longitudinal validity assessment, the correlation coefficients between the score changes of CARATKids and those of external measures of control ranged from 0.34 to 0.46

Impairment of Adenosinergic System in Rett syndrome: Novel Therapeutic Target to Boost BDNF Signalling

Rett syndrome (RTT; OMIM#312750) is mainly caused by mutations in the X-linked MECP2 gene (methyl-CpG-binding protein 2 gene; OMIM*300005), which leads to impairments in the brain-derived neurotrophic factor (BDNF) signalling. The boost of BDNF mediated effects would be a significant breakthrough but it has been hampered by the difficulty to administer BDNF to the central nervous system. Adenosine, an endogenous neuromodulator, may accomplish that role since through A2AR it potentiates BDNF synaptic actions in healthy animals. We thus characterized several hallmarks of the adenosinergic and BDNF signalling in RTT and explored whether A2AR activation could boost BDNF actions. For this study, the RTT animal model, the Mecp2 knockout (Mecp2-/y) (B6.129P2 (C)-Mecp2tm1.1Bird/J) mouse was used. Whenever possible, parallel data was also obtained from post-mortem brain samples from one RTT patient. Ex vivo extracellular recordings of field excitatory post-synaptic potentials in CA1 hippocampal area were performed to evaluate synaptic transmission and long-term potentiation (LTP). RT-PCR was used to assess mRNA levels and Western Blot or radioligand binding assays were performed to evaluate protein levels. Changes in cortical and hippocampal adenosine content were assessed by liquid chromatography with diode array detection (LC/DAD). Hippocampal ex vivo experiments revealed that the facilitatory actions of BDNF upon LTP is absent in Mecp2-/y mice and that TrkB full-length (TrkB-FL) receptor levels are significantly decreased. Extracts of the hippocampus and cortex of Mecp2-/y mice revealed less adenosine amount as well as less A2AR protein levels when compared to WT littermates, which may partially explain the deficits in adenosinergic tonus in these animals. Remarkably, the lack of BDNF effect on hippocampal LTP in Mecp2-/y mice was overcome by selective activation of A2AR with CGS21680. Overall, in Mecp2-/y mice there is an impairment on adenosinergic system and BDNF signalling. These findings set the stage for adenosine-based pharmacological therapeutic strategies for RTT, highlighting A2AR as a therapeutic target in this devastating pathology.info:eu-repo/semantics/publishedVersio

Transition of plasmodium sporozoites into liver stage-like forms is regulated by the RNA binding protein pumilio

Many eukaryotic developmental and cell fate decisions that are effected post-transcriptionally involve RNA binding proteins as regulators of translation of key mRNAs. In malaria parasites (Plasmodium spp.), the development of round, non-motile and replicating exo-erythrocytic liver stage forms from slender, motile and cell-cycle arrested sporozoites is believed to depend on environmental changes experienced during the transmission of the parasite from the mosquito vector to the vertebrate host. Here we identify a Plasmodium member of the RNA binding protein family PUF as a key regulator of this transformation. In the absence of Pumilio-2 (Puf2) sporozoites initiate EEF development inside mosquito salivary glands independently of the normal transmission-associated environmental cues. Puf2- sporozoites exhibit genome-wide transcriptional changes that result in loss of gliding motility, cell traversal ability and reduction in infectivity, and, moreover, trigger metamorphosis typical of early Plasmodium intra-hepatic development. These data demonstrate that Puf2 is a key player in regulating sporozoite developmental control, and imply that transformation of salivary gland-resident sporozoites into liver stage-like parasites is regulated by a post-transcriptional mechanism