Motor complications (dyskinesias and motor fluctuations) are a common and disabling problem of dopaminergic therapy in Parkinson's disease, which are often difficult to treat with the current therapeutic strategies. It has been proposed that continuous dopaminergic delivery could reduce the emergence of motor complications, which has been tried with levodopa intestinal infusion or subcutaneous apomorphine infusion. In selected refractory cases, surgical approaches such as deep brain stimulation should be considered. Ongoing clinical and preclinical research tried to lead the field into the discovery of other therapeutic targets and strategies that might prevent or reduce motor complications. These include drugs targeting non-dopaminergic systems (e.g. glutamatergic, serotonergic, noradrenergic, adenosinergic and cholinergic systems), gene therapy for delivering neurotrophic factors or critical enzymes for dopamine synthesis, and cell therapy. These studies found variable results, some of them promising, with the possibility of new therapeutic armamentarium in the management of Parkinson's disease in the near future.
Olaparib and niraparib are poly ADP-ribose polymerase inhibitors (PARPis) that have shown efficacy as maintenance treatment in platinum-sensitive relapsed ovarian cancer (PSROC). The aim of this study was to assess the effectiveness and safety of maintenance PARPis in patients with PSROC, in a comprehensive cancer centre.
Methodology
We retrospectively evaluated patients with PSROC treated with maintenance olaparib (400mg bid, capsules or 300mg bid, tablets) and niraparib (300mg id), who received ≥2 previous lines of platinum-based chemotherapy (ChT) and had a partial or complete response to the last platinum-based regimen. Patients who received olaparib were BRCA 1/2 mutated (germline and/or somatic) and those who received niraparib were BRCA 1/2 wild-type. Study endpoints were progression-free survival (PFS), overall survival (OS) and adverse events (AEs).
Result(s)*
Between May 2016 and December 2020, 35 patients received maintenance PARPis (21 received olaparib and 14 received niraparib). Median age was 55 years (43-75), and all had ECOG ≤1. The majority had an ovary primary tumour location (74.3%) with serous histology (85.7%). Most patients (65.7%) received 2 prior platinum regimens; 22 (62.9%) had partial response and 13 (37.1%) had complete response to last platinum-based ChT. Median follow-up was 15.1 months (1.8-60.1), with 26 patients alive (61.9% olaparib and 92.8% niraparib patients alive). Median PFS was 7.0 months (95%CI 4.3-9.7) [median PFS for BRCA 1/2 mutated and BRCA 1/2 wild-type patients was 8.3 (95%CI 6.0-10.6) and 5.9 (95%CI 2.3-9.4) months, respectively]. There were no differences in PFS by number of prior platinum regimens, response to last platinum-based ChT or time-to-progression after penultimate platinum-based ChT (>6-12 vs >12 months). Median OS was not reached. Grade ≥3 AEs (anaemia, thrombocytopaenia, neutropaenia and nausea) occurred in 11 (31.4%) patients (17.1% with olaparib and 14.3% with niraparib). Treatment was suspended in 24 (68.6%) patients: 20 (57.2%) due to progression (34.3% with olaparib and 22.9% with niraparib) and 3 (8.6%) due to toxicity to niraparib (none due to olaparib). Eighteen (51.4%) patients required dose reduction due to AEs (28.6% with olaparib and 22.8% with niraparib).
Conclusion*
Maintenance PARPis in real-world setting is effective and has a safe toxicity profile.
A introdução da vacina antipertussis nos programas de vacinação originou uma diminuição drástica da incidência de tosse convulsa no mundo. No entanto, nos últimos anos tem-se observado um aumento gradual do número de notificações, facto que já levou vários países a reformularem estratégias vacinais para esta doença. Foi efectuada uma revisão epidemiológica da tosse convulsa, realçando estudos baseados em modelos matemáticos que tentam prever o impacto de novas estratégias vacinais e novas recomendações internacionais. Tendo em conta a realidade portuguesa, alerta-se para a necessidade de um reforço vacinal na idade da adolescência e sugerem-se outras recomendações para um melhor controlo da tosse convulsa no nosso país. Rev Port Pneumol 2010; XVI (4): 573-588 The introduction of routine vaccination against Bordetella pertussis led to a drastic decline in the number of reported cases of pertussis. Nevertheless, a gradual increase in pertussis notifications has been observed in the last years, and political vaccination changes have been conducted in some countries. Pertussis epidemiology is reviewed, taking into account mathematical models studies concerning new vaccinal strategies for pertussis prevention and new international recommendations. Regarding Portugal, the need for a “booster” in adolescence is emphasized, and other recommendations for pertussis control are suggested. Rev Port Pneumol 2010; XVI (4): 573-588
rEsumo A melhoria da qualidade dos cuidados pre-natais e dos cuidados intensivos neonatais resultaram, nas ultimas decadas, numa continuada diminuicao da morbilidade e da mortalidade perinatais e infantis, particularmente de recem-nascidos muito pre-termo. No entanto, ha uma grande variabilidade entre unidades de saude na decisao sobre procedimentos e intervencoes, quer a nivel nacional quer internacional, que se pode refletir em desigualdades nos resultados em saude e que importa aBstract In the last decades, the improvement of antenatal and neonatal care led to a continued decrease in perinatal and infant morbidity and mortality, particularly for very preterm infants. However, there is a great variability in medical procedures and interventions across health units, both at national and international levels, which can result in avoidable inequalities in health outcomes. This study intends to describe (1) the European project Effective Perinatal Intensive Care in Europe (EPICE), designed to identify and understand such variation; (2) the pilot study conducted in the Northern Region of Portugal to test the protocol and the questionnaire for data collection and (3) the recruitment and final sample of the EPICE-Portugal cohort. The EPICE project includes 19 regions from 11 EU Member states and aims to explore how scientific knowledge is effectively applied to monitor very preterm infants, using both quantitative and qualitative methodologies. In Portugal, this study involves all the public maternity and neonatal intensive care units from Northern and Lisbon and Tagus Valley
Low-grade serous ovarian cancer (LGSOC) is now considered a different entity from high-grade serous ovarian cancer. The chemoresistance inherent to this type of ovarian cancer narrows the therapeutic options, especially in the recurrent setting. It is thought that the mitogen-activated protein kinase (MAPK) pathway plays a significant role in the pathogenesis of these tumours, and about 2 to 20% of LGSOC harbour a BRAF mutation. Here we present a case report of two patients with a BRAF V600E mutation that achieved sustained clinical responses with combination treatment with dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor).
e13017 Background: Activation of the mammalian target of rapamycin intracellular signaling pathway is one of the mechanisms of endocrine resistance in breast cancer. The addition of everolimus to exemestane improves progression-free survival (PFS) in patients with hormone receptor positive (HR+) advanced breast cancer (ABC) previously treated with nonsteroidal aromatase inhibitors (NSAIs). The aim of this study was to assess the effectiveness and safety of everolimus plus exemestane in patients with HR+ ABC. Methods: We retrospectively evaluated patients with HR+, HER2 negative ABC treated with everolimus/exemestane that recurred or progressed during/after treatment with NSAIs in a portuguese comprehensive cancer center. Study endpoints were PFS, overall survival (OS), overall response rate and adverse events. Results: Between April 2014 and September 2020, 63 female patients were treated with everolimus/exemestane. Median age was 59 years (36-79), and all had performance status ECOG ≤2. Seventeen (27.0%) patients had bone metastasis alone, 39 (61.9%) had bone and visceral metastasis, 25 (39.7%) had metastasis in 3 or more sites and 87.3% had previous hormone-sensitive disease. Before everolimus/exemestane, 61 (96.8%) patients were being treated with palliative endocrine therapy (alone or in combination with CDK4/6 inhibitors) or chemotherapy (ChT) and 2 (3.2%) patients were under adjuvant endocrine therapy. Median follow-up time was 12.8 months (1.4-74.6), with 39 patients alive. Overall response rate was 14.3% (1 complete response and 8 partial responses) and 45 patients had stable disease. Median PFS was 5.6 months (CI95% 2.4-8.8) and median OS was 25.4 months (CI95% 10.3-40.5). Subgroup analysis regarding PFS was statistically significant for previous treatment with CDK4/6 inhibitors (p = 0.026) and for site of metastasis (p = 0.025). In the subgroup of patients that previously underwent palliative ChT, median PFS was 4.0 months (CI95% 0.2-9.6) and median OS was 18.6 months (CI95% 8.2-29.0). For patients that did not receive previous palliative ChT, median PFS was 5.8 months (CI95% 3.8-7.8) and median OS was 43.5 months (CI95% 2.0-85.0). Grade 3 and 4 adverse events occurred in 21 (33.3%) patients, and were: nausea, anorexia, rash, headache, haematologic toxicity, hepatic cytolysis, hyperglycaemia, pneumonitis, oral mucositis and acute kidney failure with need for haemodialysis. Fifty-five (87.3%) patients suspended everolimus, 34 (54.0%) due to disease progression and 21 (33.3%) due to toxicity. Conclusions: Our results confirm the effectiveness and safety of everolimus/exemestane in real-world setting and support its use mainly before palliative ChT. Everolimus/exemestane in HR+ ABC is feasible in the clinic, with toxicity manageable under close surveillance.
Background: The increased focus on quality indicators (QIs) and the use of clinical registries in real-world cancer studies have increased compliance with therapeutic standards and patient survival. The European Society of Breast Cancer Specialists (EUSOMA) established QIs to assess compliance with current standards in breast cancer care. Methods: This retrospective study is part of H360 Health Analysis and aims to describe compliance with EUSOMA QIs in breast cancer management in different hospital settings (public vs. private; general hospitals vs. oncology centers). A set of key performance indicators (KPIs) was selected based on EUSOMA and previously identified QIs. Secondary data were retrieved from patients’ clinical records. Compliance with target KPIs in different disease stages was compared with minimum and target EUSOMA standards. Results: A total of 259 patient records were assessed. In stages I, II, and III, 18 KPIs met target EUSOMA standards, 5 met minimum standards, and 8 failed to meet minimum standards. Compliance with KPIs varied according to the type of hospital (particularly regarding diagnosis) and disease stage. Although small differences were found in KPI compliance among institutions, several statistical differences were found among treatment KPIs according to disease stage, particularly in stage III. Conclusions: This study represents the first assessment of the quality of breast cancer care in different hospital settings in Portugal and shows that, although most QIs meet EUSOMA standards, there is room for improvement. Differences have been found across institutions, particularly between oncology centers and general hospitals, in diagnosis and compliance with KPIs among disease stages. Stage III showed the greatest variability in compliance with treatment KPIs, probably related to the lower specificity of the guidelines in this disease stage.
As infeccoes agudas das vias aereas representam as infeccoes mais frequentes da infância, na sua maioria de etiologia virica. O virus sincicial respiratorio (VSR), em particular, e um importante patogeneo em lactentes e criancas, provocando epidemias anuais de bronquiolites e pneumonias. A gravidade da infeccao por VSR e a associacao com a existencia previa de factores de risco (prematuridade, doenca de membrana hialina, displasia broncopulmonar, cardiopatia congenita e imunodeficiencia) motivou os autores a efectuar uma analise dos internamentos em que tivesse sido efectuada a pesquisa de virus nas secrecoes respiratorias, em criancas com menos de 2 anos. O intervalo abrangido (1/3/97 a 28/2/98) correspondeu ao ano em que se iniciou a deteccao de virus respiratorios por imunofluorescencia, no HGSA. Foram efectuadas 128 pesquisas, tendo 47% sido positivas para os virus respiratorios, 87% correspondendo ao isolamento do VSR. Neste subgrupo, avaliaram-se as complicacoes registadas e a relacao com o padrao de gravidade. Foi possivel estabelecer-se uma associacao estatisticamente significativa entre a maior gravidade clinica das infeccoes por VSR, a presenca de factores de risco e o tempo de internamento mais prolongado.
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