Epidemiology of Asthma and Allergic Diseases in Portuguese Speaking Regions

The application of the same epidemiological methods in different countries allows important comparisons between different races and cultures. During the last decade, two large multi-centres epidemiological studies, the Portuguese Study of Allergic Diseases in Childhood (PAC study) and the International Study of Asthma and Allergies in Childhood (ISAAC study), were implemented in Portuguese speaking regions. The main objectives were to assess and compare allergic diseases prevalence. The authors stress out the significant differences observed in schoolchildren from the three continents, with different genetic and environmental background. It was found an increase trend in the prevalence of all allergic diseases, mainly rhinitis, in last decade. Rhinitis has been identified as an independent risk factor for asthma in Caucasian population.

O Pé Diabético com Infecção Aguda: Tratamento no Serviço de Urgência em Portugal

O pé diabético é uma complicação major comum da Diabetes mellitus sendo o cirurgião geral o responsável pelo seu diagnóstico e tratamento. A infecção aguda é uma urgência médico-cirúrgica. Este artigo tem como objectivos orientar o cirurgião no diagnóstico e tratamento do pé diabético infectado no serviço de urgência. Antibioterapia de largo espectro, drenagem/ desbridamento cirúrgico no serviço de urgência, internamento, repouso do membro e apósitos adequados são medidas essenciais para o correcto tratamento do pé diabético com infecção moderada-grave. Os desbridamentos devem, sempre que possível, preservar a estrutura e funcionalidade do pé. A intervenção atempada é essencial para reduzir o número de amputações major, a mortalidade e custo social associados.

Optimal Cut-Off Value for Homeostasis Model Assessment (HOMA) Index of Insulin-Resistance in a Population of Patients Admitted Electively in a Portuguese Cardiology Ward

INTRODUCTION: Insulin resistance is the pathophysiological key to explain metabolic syndrome. Although clearly useful, the Homeostasis Model Assessment index (an insulin resistance measurement) hasn't been systematically applied in clinical practice. One of the main reasons is the discrepancy in cut-off values reported in different populations. We sought to evaluate in a Portuguese population the ideal cut-off for Homeostasis Model Assessment index and assess its relationship with metabolic syndrome. MATERIAL AND METHODS: We selected a cohort of individuals admitted electively in a Cardiology ward with a BMI < 25 Kg/m2 and no abnormalities in glucose metabolism (fasting plasma glucose < 100 mg/dL and no diabetes). The 90th percentile of the Homeostasis Model Assessment index distribution was used to obtain the ideal cut-off for insulin resistance. We also selected a validation cohort of 300 individuals (no exclusion criteria applied). RESULTS: From 7 000 individuals, and after the exclusion criteria, there were left 1 784 individuals. The 90th percentile for Homeostasis Model Assessment index was 2.33. In the validation cohort, applying that cut-off, we have 49.3% of individuals with insulin resistance. However, only 69.9% of the metabolic syndrome patients had insulin resistance according to that cut-off. By ROC curve analysis, the ideal cut-off for metabolic syndrome is 2.41. Homeostasis Model Assessment index correlated with BMI (r = 0.371, p < 0.001) and is an independent predictor of the presence of metabolic syndrome (OR 19.4, 95% CI 6.6 - 57.2, p < 0.001). DISCUSSION: Our study showed that in a Portuguese population of patients admitted electively in a Cardiology ward, 2.33 is the Homeostasis Model Assessment index cut-off for insulin resistance and 2.41 for metabolic syndrome. CONCLUSION: Homeostasis Model Assessment index is directly correlated with BMI and is an independent predictor of metabolic syndrome.

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.

Improving Influenza Surveillance in Portuguese Preschool Children by Parents' Report

Influenza surveillance is usually based on nationally organized sentinel networks of physicians and on hospital reports. This study aimed to test a different report system, based on parents' phone contact to the research team and in home collection of samples by a dedicated team. The identification of influenza and other respiratory viruses in children who attended a Hospital Emergency Department was also recorded. Real-time PCR and reverse transcription PCR were performed for influenza A and B, parainfluenza 1-4, adenovirus, human metapneumovirus, respiratory syncytial virus A and B, rhinovirus, enterovirus, group 1 coronaviruses, group 2 coronaviruses, and human bocavirus. One hundred children were included, 64 from the day care centers and 36 from the Hospital. Overall, 79 samples were positive for at least one respiratory virus. Influenza A (H3) was the virus most frequently detected: 25 cases, 20 of these in children under 5 years of age (ten from day care centers and ten who went to the hospital) which was higher than those reported by the National Influenza Surveillance Programme for this age. CONCLUSION: The results obtained in this study suggest that a surveillance system based on parents' reports could complement the implanted system of the National Influenza Surveillance Programme.

Variation in Haemodynamic Monitoring for Major Surgery in European Nations: Secondary Analysis of the EuSOS Dataset

BACKGROUND: The use of cardiac output monitoring may improve patient outcomes after major surgery. However, little is known about the use of this technology across nations. METHODS: This is a secondary analysis of a previously published observational study. Patients aged 16 years and over undergoing major non-cardiac surgery in a 7-day period in April 2011 were included into this analysis. The objective is to describe prevalence and type of cardiac output monitoring used in major surgery in Europe. RESULTS: Included in the analysis were 12,170 patients from the surgical services of 426 hospitals in 28 European nations. One thousand four hundred and sixteen patients (11.6 %) were exposed to cardiac output monitoring, and 2343 patients (19.3 %) received a central venous catheter. Patients with higher American Society of Anesthesiologists (ASA) scores were more frequently exposed to cardiac output monitoring (ASA I and II, 643 patients [8.6 %]; ASA III-V, 768 patients [16.2 %]; p < 0.01) and central venous catheter (ASA I and II, 874 patients [11.8 %]; ASA III-V, 1463 patients [30.9 %]; p < 0.01). In elective surgery, 990 patients (10.8 %) were exposed to cardiac output monitoring, in urgent surgery 252 patients (11.7 %) and in emergency surgery 173 patients (19.8 %). A central venous catheter was used in 1514 patients (16.6 %) undergoing elective, in 480 patients (22.2 %) undergoing urgent and in 349 patients (39.9 %) undergoing emergency surgery. Nine hundred sixty patients (7.9 %) were monitored using arterial waveform analysis, 238 patients (2.0 %) using oesophageal Doppler ultrasound, 55 patients (0.5 %) using a pulmonary artery catheter and 44 patients (2.0 %) using other technologies. Across nations, cardiac output monitoring use varied from 0.0 % (0/249 patients) to 27.5 % (19/69 patients), whilst central venous catheter use varied from 5.6 % (7/125 patients) to 43.2 % (16/37 patients). CONCLUSIONS: One in ten patients undergoing major surgery is exposed to cardiac output monitoring whilst one in five receives a central venous catheter. The use of both technologies varies widely across Europe.

Cost-Effectiveness of Non-Vitamin K Antagonist Oral Anticoagulants for Atrial Fibrillation in Portugal

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.

Renal Transplantation in HIV-Infected Patients: The First Portuguese Review

INTRODUCTION: With the introduction of combination antiretroviral therapy (cART), prognosis of human immunodeficiency virus (HIV) infection has been improved and kidney transplantation (KT) in HIV-positive patients became possible. METHODS: We reviewed the demographic, clinical, laboratory, and therapeutic data of all the HIV-infected patients who underwent KT between 2009 (first KT in Portugal in a HIV-infected patient) and May 2014. Case accrual was through all Portuguese KT centers where a KT in an HIV-infected patient was performed. Patients were transplanted following the American and Spanish guideline recommendations that included maintenance on cART, undetectable plasma HIV RNA copies, and absolute CD4 counts of ≥ 200 cells/μL in the last 6 months. RESULTS: Fourteen KT were performed on men and 3 on women. The mean age of patients at the time of transplantation was 49.9 ± 11.7 years. HIV status was known for 12 ± 5 years. Eight patients had AIDS in the past and all patients received grafts from deceased donors. Twelve patients (64.7%) underwent induction therapy with basiliximab and 2 patients experienced early graft loss. In 2 patients, humoral rejection was diagnosed and in 3 patients, cellular rejection. Two patients died and an additional patient had early graft loss. CONCLUSION: KT is a possible, but challenging, renal replacement therapy in selected HIV-positive patients. Even in those with AIDS criteria in the past, when the disease is controlled, and after the reconstitution of the immune system with cART, KT can be performed. Nevertheless, the risk-benefit ratio for each patient needs to be taken in consideration.

Multiple Sclerosis and Motherhood Choice: an Observational Study in Portuguese Women Patients

INTRODUCTION. Multiple sclerosis (MS) is a disabling disease occurring mainly in women of childbearing age. MS may interfere with family planning and motherhood decision. AIM. To study the influence of MS diagnosis and course of the disease on motherhood decision. PATIENTS AND METHODS. The cohort of 35 to 45-year-old female patients diagnosed with MS for at least ten years was selected from six Portuguese MS centers. A structured questionnaire was applied to all patients in consecutive consultation days. Clinical records were reviewed to characterize and collect information about the disease and pregnancies. RESULTS. One hundred women were included; mean age at MS diagnosis was 26.3 ± 5.0 years; 90% of the participants presented with a relapsing-remitting MS; 57% had no pregnancies after the diagnosis. MS type and number of relapses were not significantly different between women with or without pregnancies after the diagnosis (p = 0.39 and p = 0.50, respectively). Seventy-seven percent of the patients did not have the intended number of pregnancies. Main reasons given were fear of future disability and the possibility of having relapses. Forty-three women considered that pregnancy might worsen MS. CONCLUSION. In our population, motherhood choice was unrelated to the MS type and the number of relapses. However, a relevant number of women had fewer pregnancies than those intended before MS diagnosis and believed that pregnancy could worsen the disease. An effort to better inform the patients should be made to minimize the impact of MS diagnosis on motherhood decision.

Validation of Two US Risk Scores for Percutaneous Coronary Intervention in a Single-Center Portuguese Population of Patients with Acute Coronary Syndrome

INTRODUCTION: New scores have been developed and validated in the US for in-hospital mortality risk stratification in patients undergoing coronary angioplasty: the National Cardiovascular Data Registry (NCDR) risk score and the Mayo Clinic Risk Score (MCRS). We sought to validate these scores in a European population with acute coronary syndrome (ACS) and to compare their predictive accuracy with that of the GRACE risk score. METHODS: In a single-center ACS registry of patients undergoing coronary angioplasty, we used the area under the receiver operating characteristic curve (AUC), a graphical representation of observed vs. expected mortality, and net reclassification improvement (NRI)/integrated discrimination improvement (IDI) analysis to compare the scores. RESULTS: A total of 2148 consecutive patients were included, mean age 63 years (SD 13), 74% male and 71% with ST-segment elevation ACS. In-hospital mortality was 4.5%. The GRACE score showed the best AUC (0.94, 95% CI 0.91-0.96) compared with NCDR (0.87, 95% CI 0.83-0.91, p=0.0003) and MCRS (0.85, 95% CI 0.81-0.90, p=0.0003). In model calibration analysis, GRACE showed the best predictive power. With GRACE, patients were more often correctly classified than with MCRS (NRI 78.7, 95% CI 59.6-97.7; IDI 0.136, 95% CI 0.073-0.199) or NCDR (NRI 79.2, 95% CI 60.2-98.2; IDI 0.148, 95% CI 0.087-0.209). CONCLUSION: The NCDR and Mayo Clinic risk scores are useful for risk stratification of in-hospital mortality in a European population of patients with ACS undergoing coronary angioplasty. However, the GRACE score is still to be preferred.

Bronchial Asthma in Children: Clinical and Epidemiologic Approach in Different Portuguese Speaking Countries

BACKGROUND: Geographical differences in asthma prevalence are currently accepted, but evidence is sparse due to the lack of multicentre studies using the same protocol. OBJECTIVES: To compare the prevalence of asthma and atopy among schoolchildren from Portuguese speaking countries (ISAAC and Portuguese Study) and evaluate some environmental variables, such as house dust mite exposure. MATERIAL AND METHODS: Significant random samples of schoolchildren studied with standard validated methods--questionnaires, skin prick tests, methacholine bronchial challenge tests; dust bed sampling for analysis of mite antigens. RESULTS: In the ISAAC study, in the 13-14 year-old age group, statistical significant differences were found, with higher wheezing prevalence in Brazil than in Portugal (two-fold). In the Portuguese Study, atopy prevalence ranged between 6.0 and 11.9% in Sal and S. Vicente (Cape Verde), up to 48.6 and 54.1% in Macau and Madeira. Active asthma had the higher values in Madeira (14.6%), and the lower in Macau (1.3%). Cape Verde had intermediate asthma prevalence (10.6 and 7.0%). The bronchial challenge test was positive in 25, 66 and 70% of asthmatic children from Sal, S. Vicente and Madeira respectively. Significant HDM antigen concentrations (Der p1) were found in Cape Verde and Madeira. CONCLUSIONS: There are significant variations in asthma and atopy prevalence between these pediatric populations. The reasons remain under discussion, but genetics linked to race, seem to play a central role, modulated by environmental and lifestyle variables.

Clinical and Genetic Characterization of Portuguese Patients with Pseudohypoparathyroidism Type Ib

Patients with pseudohypoparathyroidism type Ib (PHP-Ib) present hypocalcemia and hyperphosphatemia, as a consequence of a resistance to PTH action, through its G-protein-coupled receptor, in the renal tubules. This resistance results from tissue-specific silencing of the G-protein alpha-subunit (G(s)α), due to imprinting disruption of its encoding locus--GNAS. In familial PHP-Ib, maternally inherited deletions at the STX16 gene are associated to a regional GNAS methylation defect. In sporadic PHP-Ib, broad methylation changes at GNAS arise from unknown genetic causes. In this study, we describe the clinical presentation of PHP-Ib in four Portuguese patients (two of whom were siblings), and provide further insight for the management of patients with this disease. The diagnosis of PHP-Ib was made after detection of GNAS imprinting defects in each of the cases. In the siblings, a regional GNAS methylation change resulted from a known 3.0 kb STX16 deletion. In the other two patients, the broad methylation defects at GNAS, which were absent in their relatives, resulted from genetic alterations that remain to be identified. We report the first clinical and genetic study of Portuguese patients with PHP-Ib. The genetic identification of a hereditary form of this rare disease allowed an early diagnosis, and may prevent hypocalcemia-related complications.

PROP1 Gene Analysis in Portuguese Patients with Combined Pituitary Hormone Deficiency

OBJECTIVE: Mutations of the PROP1 gene lead to combined pituitary hormone deficiency (CPHD), which is characterized by a deficiency of GH, TSH, LH/FSH, PRL and, less frequently, ACTH. This study was undertaken to investigate the molecular defect in a cohort of patients with CPHD. DESIGN, PATIENTS AND MEASUREMENTS: A multicentric study involving 46 cases of CPHD (17 familial cases belonging to seven kindreds and 29 sporadic cases) selected on the basis of clinical and hormonal evidence of GH deficiency, central hypothyroidism and hypogonadotrophic hypogonadism, in the absence of an identified cause of hypopituitarism. Mutations of PROP1 were investigated by DNA sequencing. Clinical, hormonal and neuroradiological data were collected at each centre. RESULTS: PROP1 mutations were identified in all familial cases: five kindreds presented a c. 301-302delAG mutation, one kindred presented a c. 358C --> T (R120C) mutation and one presented a previously unreported initiation codon mutation, c. 2T --> C. Of the 29 sporadic cases, only two (6.9%) presented PROP1 germline mutations (c. 301-302delAG, in both). Phenotypic variability was observed among patients with the same mutations, particularly the presence and age of onset of hypocortisolism, the levels of PRL and the results of pituitary imaging. One patient presented a sellar mass that persisted into adulthood. CONCLUSIONS: This is the first report of a mutation in the initiation codon of the PROP1 gene and this further expands the spectrum of known mutations responsible for CPHD. The low mutation frequency observed in sporadic cases may be due to the involvement of other unidentified acquired or genetic causes.

Mutational Analysis of Portuguese Families with Multiple Endocrine Neoplasia Type 1 Reveals Large Germline Deletions

OBJECTIVE: To determine the spectrum of MEN1 mutations in Portuguese kindreds, and identify mutation-carriers. PATIENTS, DESIGN AND RESULTS: Six unrelated MEN1 families were studied for MEN1 gene mutations by single-strand conformational polymorphism (SSCP) and DNA sequence analysis of the coding region and exon-intron boundaries of the MEN1 gene. These methods identified 4 different heterozygous mutations in four families: two mutations are novel (mt 1539 delG and mt 655 ims 11 bp) and two have been previously observed (mt 735 del 46p and mt 1656 del C) all resulting in a premature stop codon. In the remaining two families, in whom no mutations or abnormal MEN1 transcripts were detected, segregation studies of the 5' intragenic marker D11S4946 and codon 418 polymorphism in exon 9 revealed two large germline deletions of the MEN1 gene. Southern blot and tumour loss of heterozygosity analysis confirmed and refined the limits of these deletions, which spanned the MEN1 gene at least from: exon 7 to the 3' untranslated region, in one family, and the 5' polymorphic site D11S4946 to exon 9 (obliterating the initiation codon), in the other family. Twenty-six mutant-gene carriers were identified, 6 of which were asymptomatic. CONCLUSIONS: These results emphasize the importance of the detection of MEN1 germline deletions in patients who do not have mutations of the coding region. Important clues indicating the presence of such deletions may be obtained by segregation studies using the intragenic polymorphisms D11S4946 and at codon 418. The detection of these mutations will help in the genetic counselling of clinical management of the MEN1 families in Portugal.