SummaryObjective To evaluate the efficacy, safety and tolerability of octreotide LAR ® (long-acting repeatable octreotide) in the primary therapy of acromegaly. Design and patients Ninety-eight previously untreated acromegalics were recruited into this prospective multicentre study. A total of 68 patients successfully completed 48 weeks of the study period, received 12 doses of octreotide LAR 10 -30 mg every 4 weeks, and constituted the population used for this analysis.Measurements and results A clinically relevant reduction (i.e. to ≤ 5 µ g/l) in mean GH (mGH) was recorded in 72% of patients after 24 weeks of treatment, and 42% reached a 'safe' GH value ( ≤ 2·5 µ g/l). At week 48, 16 more patients were considered partial GH responders (GH > 2·5 µ g/l and ≤ 5 µ g/l) and 44% had reached a GH level ≤ 2·5 µ g/l. IGF-1 levels normalized in 38% and 34% of patients after 24 and 48 weeks of treatment, respectively. At study completion, 10 patients (14·7%) who had not normalized their IGF-1 levels had achieved at least a 50% decrement in this marker. In eight microadenoma patients, tumour volume decreased from a mean baseline level of 298 ± 145 mm 3 to 139 ± 94 mm 3 after 24 weeks and to 99 ± 70 mm 3 after 48 weeks of therapy. In 60 patients with macroadenoma, the corresponding values were 3885 ± 5077 mm 3 at baseline and 2723 ± 3435 and 2406 ± 3207 mm 3 after 24 and 48 weeks, respectively. At weeks 24 and 48, a significant ( > 20%) tumour volume reduction was reported in 63% and 75% of patients, respectively. A reduction in the severity of symptoms of acromegaly was observed early in treatment and was maintained throughout the study period. Conclusion Octreotide LAR represents a viable alternative to surgery for primary treatment of acromegaly leading to a progressive regression of tumour volume, a sustained control of biochemical abnormalities and an adequate relief of symptoms of the disease.

Background: Iodine is the key element for thyroid hormone synthesis, and its deficiency, even moderate, is harmful in pregnancy, when needs are increased, because of its potential deleterious effects on fetal brain development. In Portugal, no recent data on iodine intake exists. The objective of this countrywide study was to analyze iodine status in pregnant Portuguese women in order to propose adequate measures to the health authorities. Subjects and methods: Using a fast colorimetric method, urine iodine concentration (UIC) was evaluated in 3631 pregnant women followed in 17 maternity hospitals from hinterland and coastal areas in Continental Portugal and the Portuguese islands of Açores and Madeira. Results: Median UIC value was 84.9 mg/l (range 67.6-124.1) in Continental Portugal, 69.5 mg/l in Madeira, and 50.0 mg/l in Açores. The percentage of satisfactory values (O150 mg/l) was 16.8, ranging from 8.8 to 34.1 in the Continent, and being 8.2 in Madeira and 2.3 in Açores. The percentage of values below 50 mg/l was 23.7, ranging from 14.0 to 37.4 in the Continent, 33.7 in Madeira, and 50.0 in Açores. Conclusions: Our results point to an inadequate iodine intake in pregnant women assisted in most Portuguese maternity hospitals. Considering the potential deleterious effects of inadequate iodine supply in pregnancy, iodine supplementation is strongly recommended in this period of life.

Rheumatic carditis was the most common manifestation of rheumatic fever, predominant in the group with a racial mixture of Caucasian and Indian (60.6%). Low compliance with antibiotic therapy contributed to the recurrence of the disease and to cardiac sequelae.

Background Toxicity of oncology treatments in real-life patients is frequently disregarded and hence underreported. Objective To characterize adverse events (AEs) of immunotherapy and targeted therapy reported in patients with locally advanced or metastatic melanoma. Setting District Hospital for Cancer treatment (Instituto Português de Oncologia de Lisboa Francisco Gentil). Method A retrospective cohort of melanoma patients was established, comprising adult patients diagnosed with malignant melanoma treated with immunotherapy or targeted therapy. Exposure was characterized by nature, time and intensity of exposure. To account for different exposure periods, person-time was used as unit of analysis. Main outcomes measure Occurrence of AEs. Results Data from 111 patients included in the cohort indicates the majority received immunotherapy regimens (CTLA-4, anti-PD-1 and combination therapy; (n = 70; 63.1%), among which anti-PD-1 were the predominant treatment. Pembrolizumab was the most frequently prescribed drug (n = 30; 45.7%). Three hundred and seventy-one AEs were extracted. The incidence of AEs was lower in the anti-PD-1 mAc group (54 AEs per 1000 person.months) and the number of AEs/patient was also lower (3.1 ± 2.0). Grade 3 to 4 AEs occurred in 15.3% (n = 17) of the cohort, being more common in the targeted therapy group. Forty-two (11.6%) of the extracted AEs were not described in the Summary of Product Characteristics of the drugs under study. Conclusion This study suggests various known and unknown AEs of immunotherapy and targeted therapy may be identified using the Cancer Registry database. These events should be considered as signals worth further investigation for assessment of causality as the underreporting of AEs in cancer may have potential implications for the patient's quality of life.

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Summary Selecting the most appropriate chronic lymphocytic leukaemia (CLL) treatment is challenging. Patient‐reported health‐related quality of life (HRQoL) is therefore a critical aspect to consider. This international study by the European Organization for Research and Treatment of Cancer (EORTC) tested the psychometric properties of a newly developed measure for CLL patients: the EORTC QLQ‐CLL17 to supplement the core questionnaire (EORTC QLQ‐C30). Patients with CLL (n = 341) from 12 countries completed the QLQ‐C30, QLQ‐CLL17 and a debriefing questionnaire. Sociodemographic and clinical data were recorded from medical records. A high percentage (30%–66%) reported symptoms and/or worries (e.g. aches/pains in muscles, lack of energy and worry/fears about health). Confirmatory factor analysis showed an acceptable to good fit of the 17 items on the three scales (i.e. symptom burden, physical condition/fatigue and worries/fears about health and functioning). Completion took on average 8 min. Test–retest and convergent validity was demonstrated. The QLQ‐CLL17 differentiated between patients with an Eastern Cooperative Oncology group (ECOG) performance of 0 versus 1–3 (p's < 0.01 and clinically relevant). The newly developed EORTC QLQ‐CLL17 will increase sensitivity of HRQoL assessment in patients with CLL. Implementation of this questionnaire both in clinical research and practice will help to generate unique clinically relevant data to better inform CLL treatment decision‐making.

Objectives To evaluate the effectiveness and safety of pembrolizumab use in advanced melanoma in a real‐life context; and to explore the existence of an efficacy‐effectiveness gap, comparing registry data with the reference clinical trial. Methods This study followed the guidelines for good pharmacoepidemology practice. An ambispective cohort was constituted, initiating the observation upon drug approval (17/07/2015) and following exposed patients until death or cut‐off date (15/11/2019). The primary outcome was overall survival (OS); secondary outcomes comprised progression‐free survival (PFS), overall response rate (ORR) and the occurrence of adverse events (AE). For all survival analyses, the Kaplan‐Meier estimator was used, considering a 95% confidence interval (CI), aside with one‐year survival rates. Results A total of 125 patients constituted the cohort, originating from 16 hospitals in Portugal. Median OS was estimated to be 16.9 months (CI95% 11.3‐25.5) and the probability of survival after 1 year was 57.5% (CI95% 48.4%‐65.6%). Median PFS was estimated to be 4.8 months (CI95% 3.9‐6.7) and the probability of remaining progression‐free after 1 year was 32.8% (CI95% 24.8‐41.1). ORR was 30.4% (CI95% 22.5%‐39.3%). AEs were experienced by 82% of patients, and 27% experienced AE≥ grade 3. Conclusions Our data suggest lower effectiveness in a real‐life context than the efficacy reported in the clinical trial. Safety data seems, however, quite comparable to KEYNOTE‐006.

Purpose: Immunotherapy is promising for lung cancer treatment, although at significant financial impact. The aim of this study was to evaluate the effectiveness and the efficacy-effectiveness gap of pembrolizumab in previously treated non-small cell lung cancer (NSCLC). Methods: A population-based ambispective cohort study was conducted. Cases of interest were identified through the National Cancer Registry database and additional data sources. Patients aged ≥18 years, diagnosed with NSCLC and exposed to pembrolizumab, between 23 June 2016 and 31 October 2018, as second or later lines of treatment for advanced disease were included. Patients were followed-up until death or cutoff date (30 April 2019). Primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS), event-free survival (EFS), and adverse events (AEs) leading to treatment discontinuation. The efficacyeffectiveness gap was evaluated comparing results with clinical trial data. Results: A total of 181 patients were included. Median age was 63 years (range 33-94); 74.6% were male. Median treatment duration was 5.6 months (interquartile range: 1.4-10.4) and, at cutoff date, treatment had been discontinued in 141 patients, mainly due to disease progression. Median OS was 13.0 months (95% confidence interval [CI] 9.3-15.9) and 1-year OS was 53.1% (95% CI 45.2%-60.3%). Median PFS was 5.6 months (95% CI 4.6-7.2), median EFS was 4.7 months (95% CI 3.2-6.0), and treatment was discontinued due to AE in 8.3% of cases (n = 15). The efficacy-effectiveness gap seems to favor pembrolizumab use in clinical practice. Conclusion: Real-world data suggest the performance of pembrolizumab to reflect the clinical trial outcomes in previously treated NSCLC.