Abstract The leading cause of death and disability worldwide are due to atherosclerotic cardiovascular disease (ASCVD), entailing a heavy economic impact, in Portugal corresponding to 1% of the gross domestic product. The development and progression of ASCVD are closely related to hypercholesterolaemia, with high LDL-C levels being its most important and easily modifiable risk factor. Reducing LDL-C has been shown to decrease the incidence of cardiovascular events and European recommendations advocate LDL-C target values according to the patient's cardiovascular risk. The risk of hypercholesterolaemia is cumulative, making it relevant to reduce LDL-C as early as possible. Despite the efficacy and safety demonstrated by several existing lipid-lowering therapies, in the real world most patients do not achieve the recommended lipid values. Several limita-tions to adequate lipid control have been pointed out, namely the low adherence of patients to treatment. Inclisiran is the first drug to inhibit PCSK9 synthesis through RNA small interference mechanism. With a subcutaneous administration every six months after initial and 3-month dose, it allows a LDL-C reduction higher than 50%, with a good safety profile. The advantage of its long duration of action will potentially overcome the low compliance of patients to treat-ment and increase the effectiveness in reducing LDL-C, which may translate into a reduction in morbidity and mortality from ASCVD and its high economic impact.

Resumo A doença cardiovascular aterosclerótica (DCVA) lidera as principais causas de morte e incapacidade a nível mundial, acarretando um pesado impacto económico, correspondente a 1% do produto interno bruto em Portugal. O desenvolvimento e progressão da DCVA encontra-se em estreita relação com a hipercolesterolemia, sendo que níveis elevados de C-LDL são o seu fator de risco mais importante e facilmente modificável. A redução do C-LDL provou diminuir a incidência de eventos cardiovasculares e as recomendações europeias advogam valores alvo de C-LDL de acordo com o risco cardiovascular do doente. O risco da hipercolesterolemia é cumulativo, tornando-se relevante a redução do C-LDL o mais precocemente possível. Apesar da eficácia e segurança demonstrada pelas diversas terapêuticas hipolipemiantes existentes, no mundo real a maioria dos doentes não atinge os valores lipídicos recomendados. Várias limitações ao adequado controlo lipídico foram apontadas, nomeadamente a baixa adesão dos doentes ao tratamento. Inclisiran é o primeiro fármaco que permite inibir a síntese de PCSK9 através do mecanismo de RNA de interferência. Com uma administração subcutânea semestral, após administração nos dias 1 e 90, possibilita uma redução do C-LDL superior a 50%, com bom perfil de segurança. A vantagem da sua longa duração de ação permitirá potencialmente contornar a baixa adesão dos doentes ao tratamento e aumentar a efetividade na redução do C-LDL, que se poderá traduzir na redução da morbi-mortalidade por DCVA e do seu elevado impacto económico.

Objetivo: Rever a evidência sobre a eficácia da suplementação oral de magnésio na prevenção de cãibras musculares, sem patologia evidente associada, em indivíduos adultos. Fontes de dados: National Guideline Clearinghouse, Canadian Medical Association Practice Guidelines Infobase, Guidelines Finder, The Cochrane Library, DARE, Bandolier, Evidence-Based Medicine Online e PubMed. Métodos: Pesquisa realizada no dia 4 de julho de 2018 com os termos MeSH muscle cramp, magnesium e magnesium compounds de meta-análises, revisões sistemáticas, ensaios clínicos aleatorizados e controlados (ECAC), estudos de coorte e caso-controlo e normas de orientação clínica publicados desde 1 de janeiro de 2008 nas línguas portuguesa, inglesa e espanhola. Para atribuir níveis de evidência (NE) e forças de recomendação foi utilizada a Strength of Recommendation Taxonomy (SORT), da American Academy of Family Physicians. Resultados: Dos 47 artigos encontrados, cinco cumpriram os critérios de inclusão: uma meta-análise (NE 2), três revisões sistemáticas (NE 2) e um ECAC (NE 2). Não foram identificados estudos relativos a cãibras associadas ao exercício. Os estudos são consensuais na aparente ausência de eficácia do magnésio na prevenção de cãibras idiopáticas. Quanto às cãibras associadas à gravidez, a evidência é inconsistente. Contudo, o uso de amostras pequenas, períodos de follow-up curtos e a heterogeneidade das metodologias (população, tipo de suplemento, posologia, outcomes) comprometem a extrapolação e reduzem a força das conclusões obtidas. Conclusão: Perante a evidência encontrada, a suplementação oral de magnésio na população geral parece não ser eficaz na prevenção de cãibras idiopáticas (SORT B), não havendo evidência que suporte a sua prescrição por rotina na prática clínica. Nas cãibras associadas à gravidez a evidência da suplementação oral de magnésio não é clara (SORT B). Para obter conclusões mais robustas são necessários ECAC de melhor qualidade e com metodologias mais homogéneas.

Aim: Evidence review on the efficacy of oral magnesium supplementation in the prevention of muscle cramps without associated pathology, in adults. Data sources: National Guideline Clearinghouse, Canadian Medical Association Practice Guidelines Infobase, Guidelines Finder, The Cochrane Library, DARE, Bandolier, Evidence-Based Medicine Online, and PubMed. Methods: On 4th July 2018, using the MeSH terms ‘Muscle Cramp’, ‘Magnesium’ and ‘Magnesium Compounds’, we searched for meta-analyses, systematic reviews, randomized controlled trials (RCT), observational studies and clinical guidelines published in Portuguese, Spanish, and English. To assign levels of evidence (LE) and strength of recommendations, the Strength of Recommendation Taxonomy (SORT) scale of the American Academy of Family Physicians was used. Results: We found 47 articles, of which five met the inclusion criteria: one meta-analysis (LE 2), three systematic reviews (LE 2) and one RCT (LE 2). No studies related to exercise-associated cramps were found. Studies are consensual in the apparent lack of efficacy of the magnesium in the prevention of idiopathic muscle cramps. As for the pregnancy-associated cramps, the evidence is inconsistent. However, the use of small samples, short follow-up periods and the heterogeneity of methodologies (population, supplement type, posology, and outcomes) compromise the extrapolation and reduce the strength of the conclusions obtained. Conclusion: According to the evidence found, oral magnesium supplementation in the general population seems to be ineffective in preventing idiopathic muscle cramps (SORT B), therefore, with no evidence to support its routine prescription in clinical practice. In pregnancy-associated cramps, the evidence of oral magnesium supplementation is unclear (SORT B). To achieve more robust conclusions, higher quality RCT is needed, with more homogeneous methodologies.

Abstract The reconstruction of facial surgical defects is usually challenging for the dermatologic surgeon. Three different cases of facial defects in which tunneled island flaps were used are reported. In 2 cases, wide defects involving the nasal dorsum and ala were repaired using a nasolabial island flap tunneled through the lateral side of the nose. A tunneled island glabellar flap was used for medial canthus reconstruction in the third case. Despite complex pedicle dissection and frequent trapdoor deformation, tunneled island flaps allow reconstruction of wide defects in a single-staged procedure, camouflaging the scar of the donor area in boundaries of cosmetic units and preserving the facial central symmetry.

Abstract Dyspigmentation along the Blaschko lines is strongly suggestive of a mosaic skin disorder. We report a 9-year-old male patient who presented with swirls and streaks of both hypo and hyperpigmentation involving the entire body. Additionally, he had hypertrichosis, musculoskeletal and minor neurodevelopment abnormalities but no intellectual disability. Cultured fibroblast displayed trisomy 7 mosaicism, which can explain this pigmentary phenotype. Widespread dyspigmentation associated with involvement of other organs should prompt systemic examination to detect additional anomalies and genetic evaluation should be considered, even with normal fetal karyotype.

Abstract: Non-steroidal, anti-inflammatory drugs, followed by antibiotics, are the main causes of fixed drug eruption. They provoke one or several round erythematous or bullous lesions that recur in the same place after taking the causative medication. A positive patch test on residual, lesional skin can replace satisfactorily oral reintroduction. We describe the case of a 74-year-old woman with numerous, rounded, erythematous lesions on the trunk and recurrent blistering on the fifth right-hand finger, which developed a few hours after taking etoricoxib. Lesional patch testing with etoricoxib was positive and reproduced the typical pattern of a fixed drug eruption upon histopathology. We emphasize the specific reactivity of the etoricoxib patch test, and the capacity to reproduce the histologic pattern of the reaction.

Abstract: Rosai-Dorfman disease is a benign histiocytic proliferative disorder of unknown etiology. The disease mainly affects lymph node tissue, although it is rarely confined to the skin. Here, we describe a 53-year-old woman with purely cutaneous Rosai-Dorfman disease. The patient presented with a large pigmented plaque on her left leg, and sparse erythematous papules on her face and arms. A complete clinical response was achieved with thalidomide, followed by recurrence at the initial site one year later. The histological examination displayed the typical features of Rosai-Dorfman disease in the recent lesions but not in the older lesions. In the setting of no lymphadenopathy, the histopathological features of Rosai-Dorfman disease are commonly misinterpreted. Therefore, awareness of the histological aspects present at different stages, not always featuring the hallmark microscopic signs of Rosai-Dorfman disease, is particularly important for a correct diagnosis of this rare disorder.

Abstract: Background: Cancer is currently among the three leading causes of death after solid organ transplantation and its incidence is increasing. Non-melanoma skin cancer - squamous cell carcinoma and basal cell carcinoma - is the most common malignancy found in kidney transplant recipients (KTRs). The incidence of non-melanoma skin cancer in KTRs has not been extensively studied in Portugal. Objectives: To determine the incidence of non-melanoma skin cancer in KTRs from the largest Portuguese kidney transplant unit; and to study risk factors for non-melanoma skin cancer. Methods: Retrospective analysis of clinical records of KTRs referred for the first time for a dermatology consultation between 2004 and 2013. A case-control study was performed on KTRs with and without non-melanoma skin cancer. Results: We included 288 KTRs with a median age at transplantation of 47 years, a male gender predominance (66%) and a median transplant duration of 3.67 years. One fourth (n=71) of KTRs developed 131 non-melanoma skin cancers, including 69 (53%) squamous cell carcinomas and 62 (47%) basal cell carcinomas (ratio squamous cell carcinoma: basal cell carcinoma 1.11), with a mean of 1.85 neoplasms per patient. Forty percent of invasive squamous cell carcinomas involved at least two clinical or histological high-risk features. The following factors were associated with a higher risk of non-melanoma skin cancer: an older age at transplantation and at the first consultation, a longer transplant duration and the presence of actinic keratosis. KTRs treated with azathioprine were 2.85 times more likely to develop non-melanoma skin cancer (p=0.01). Conclusion: Non-melanoma skin cancer was a common reason for dermatology consultation in Portuguese KTRs. It is imperative for KTRs to have access to specialized dermatology consultation for early referral and treatment of skin malignancies.

Abstract Multiple minute digitate hyperkeratosis is a rare, non-follicular dermatosis, with fewer than 30 cases described worldwide. It can be either acquired or inherited in an autosomal dominant pattern. We describe the case of an 83-year old patient with life-long, multiple, digitate, milimetric lesions, and a positive family history for the same dermatosis.

Introdução: As análises económicas aplicadas à saúde são fontes úteis de informação à alocação de recursos escassos. Este estudo compara a qualidade de vida e os custos em subgrupos de doentes em hemodiálise e transplantados renais. Métodos: No âmbito dum estudo prospectivo com follow-up de 1-3 anos, realizou-se uma análise custo-utilidade do transplante renal vs hemodiálise, na perspectiva da sociedade. O horizonte temporal escolhido foi o ciclo de vida dos doentes. Incluíram-se os custos da colheita de órgãos, seleção dos candidatos a transplante, cirurgia do transplante e follow-up dos dadores vivos. Registaram-se os eventos clínicos. Utilizou-se o EuroQol-5D na avaliação da qualidade de vida. Resultados: Não se observou variação da QVRS nos doentes em hemodiálise. Observou-se melhoria do índice de utilidade ao 3º mês de transplante e os valores na escala EQ-VAS melhoraram em todos os tempos de observação. O custo médio por doente em hemodiálise foi 32.567,57€. O custo médio no 1º ano de transplante foi de 60.210,09€ e nos anos seguintes 12.956,77€. O custo médio do internamento inicial foi de 18.740.74€. Cada incompatibilidade-HLA aumentou em 75% o custo do internamento inicial (p < 0.001) e em 41% o custo no 1º ano (p < 0.05), e duplicou o risco de internamento no 1º ano (p < 0.05). O rácio custo-utilidade incremental foi 5.534,46€/QALY; a inclusão dos custos da colheita de órgãos para transplante agravou esse rácio em 35%. O transplante gera um acréscimo de 41.541,63€ e um ganho adicional de 7,51 QALY. Conclusões: O transplante renal é custo-efetivo comparado com a hemodiálise; consequentemente, o financiamento deve refletir o valor criado pela intervenção e adequar-se à sua procura

Background: Economic evaluations help health authorities facing budget constraints. This study compares the health-related quality of life (HRQOL) and costs in patient subgroups on haemodialysis (HD) and renal transplantation (KT). Methods: In a prospective study with follow-up of 1-3 years, we performed a costutility analysis of KT vs. HD, adopting a lifetime horizon. A societal perspective was taken. Costs for organ procurement, KT eligibility, transplant surgery and follow-up of living donors were included. Key clinical events were recorded. HRQOL was assessed using the EuroQol instrument. Results: The HRQOL remained stable on HD patients. After KT, mean utility score improved at 3 months while mean EQ-VAS scores showed a sustained improvement. Mean annual cost for HD was 32,567.57€. Mean annual costs for KT in the year-1 and in subsequent years were, 60,210.09€ and 12,956.77€ respectively. Cost for initial hospitalization averaged 18,740.74€. HLA-mismatches increased costs by 75% for initial hospitalization (p < 0.001) and 41% in the year-1 (p < 0.05), and duplicate the risk of readmission in the year-1 (p < 0.05). The incremental costutility ratio was 5,534.46€/QALY, increasing 35% when costs for organ procurement were added. KT costs were 41,541.63€ more but provided additional 7.51 QALY. Conclusions: The KT is cost-effective compared with HD. Public funding should reflect the value created by the intervention and adapt to the organ demand.

O programa "Via verde do AVC" foi implementado em Portugal desde 2005, com o objetivo de reduzir a mortalidade por AVC. As taxas de mortalidade por AVC têm vindo a diminuir, mas nenhum estudo tentou medir a ligação entre esta tendência e a "Via verde do AVC". Este estudo pretendeu avaliar se o programa conseguiu ganhos significativos de saúde. Contámos com 2 fontes de dados: dados hospitalares a nível individual de internamentos por AVC isquémico e taxas regionais de mortalidade por AVC. Para ambos os tipos de dados não encontrámos qualquer evidência de a "Via verde do AVC" ter um impacto estatisticamente significativo sobre a mortalidade do AVC isquémico.

The program ‘Via verde do AVC’ has been implemented in Portugal since 2005, with the objective of reducing mortality by stroke. Mortality rates from stroke have been decreasing, but no studies have been done measuring the link between this trend and ‘Via verde do AVC’. This study aims to assess whether the program has achieved significant health gains. We rely on two data sources: individual level hospital data on ischemic stroke admissions and regional level stroke mortality rates. For both types of data we find no evidence that ‘Via verde do AVC’ had a statistically significant impact on ischemic stroke mortality.

Neste trabalho estimam-se os custos indirectos da dor crónica nas costas (lombalgia) e articulações seguindo a metodologia do capital humano. Mais especificamente são estimadas as perdas de produção por redução do emprego e acréscimo do absentismo devidos à dor crónica em Portugal Continental. A análise é feita do ponto de vista da sociedade, considerando a prevalência da dor crónica, numa abordagem bottom-up. Os dados sociodemográficos utilizados provêm do 4º Inquérito Nacional de Saúde, de 2005/2006, e para estimar a produtividade recorreu-se à base de dados salariais "Quadros do Pessoal", usando-se estimativas dos custos salariais médios por sexo e grupos etários para 2010. O conhecimento dos custos indirectos da dor crónica é um passo relevante no desenvolvimento e consolidação de estratégias de prevenção e tratamento eficientes para mitigar as consequências da dor crónica na saúde e bem-estar dos portugueses. Os custos indirectos da dor crónica nas costas e articulações estimados para Portugal Continental, usando custos salariais de 2010, ascendem aos € 738,85 milhões, sendo € 280,95 milhões devidos ao absentismo gerado pela incapacidade de curto prazo e € 458,90 milhões devidos à redução do volume de emprego por reformas antecipadas e outras formas de não participação no mercado de trabalho.

In this study we estimate the indirect costs of chronic pain in the lower back and joints, following the human capital methodology. The analysis is conducted from the society's point of view and it is based on the prevalence of chronic pain using a bottom-up approach. We took demographic and social data from the 4th National Health Survey 2005/2006, whilst the database "Quadros do Pessoal" was used to calculate average wages by gender and age group. Knowledge of the indirect costs of chronic pain is important for the development and consolidation of efficient prevention and treatment strategies and to mitigate the consequences of chronic pain in the health and wellbeing of the Portuguese population. The indirect costs of chronic pain in the lower back and joints, estimated using the wage costs of 2010, were €739,85 million in mainland Portugal, where €280,95 million is attributable to the absenteeism generated by short term disability and €458,90 million is the result of the reduction of employment, owing to early retirement and other forms of non-participation in the labor market.

A Organização Mundial de Saúde (OMS) estimou no seu relatório de 2002 que cerca de 14% da larga da doença nos países mais ricos seja atribuível ao consumo de produtos de tabaco. As doenças mais relacionadas com o consumo de tabaco incluem um conjunto de doenças cardiovasculares, neoplasias e doenças respiratórias. Este artigo estima a carga da doença atribuível ao tabaco em Portugal, tomando como base os dados das estatísticas demográficas e de saúde disponíveis para Portugal em 2005. A conclusão final da analise e que 11,7% das mortes em Portugal se podem atribuir ao consumo de tabaco. Se medirmos a carga da doença através dos anos de vida ajustados por incapacidade - disability adjusted life years (DALY) gerados pela mortalidade, as proporção da carga da doença atribuível ao tabaco e 11,2%. A divisão entre sexos e muito desigual, já que 15,4% da carga da doença masculina e 17,7% das mortes são atribuíveis ao tabaco, mas apenas 4,9% da carga da doença feminina e 5,2% das mortes. Estes números para a mortalidade atribuível são mais elevados do que as estimativas anteriormente disponíveis para Portugal (Peto et al. 2006), as quais apontavam para 14% das mortes masculinas e apenas 0,9% das femininas. O artigo apresenta estimativas sobre a carga da doença redutível, ou seja, as reduções de mortalidade e DALY que ocorreriam se os fumadores abandonassem o tabagismo e passassem a experimentar o risco médio das populações de ex-fumadores, o qual e superior ao dos nunca fumadores mas inferior ao dos fumadores. As estimativas são que a carga da doença medida pelos DALY se reduziria em 5,8% (7,8% dos homens e 2,8% das mulheres) e que as mortes se reduziriam em 5,8% (8,5% homens e 2,9% mulheres). O artigo inclui igualmente estimativas dos DALY perdidos por incapacidade. As doenças relacionadas com o tabagismo geraram 121 643 DALY, dos quais 72 126 (59%) são atribuíveis ao tabagismo e 12 417 (10%) são redutíveis.

The World Health Organization’s (WHO) 2002 Annual Report estimated that about 14% of the burden of disease in wealthier countries is attributable to smoking. Smoking related diseases include cardiovascular diseases, cancer and respiratory diseases. This paper presents an estimate of the burden of disease attributable to smoking in Portugal. The estimates are based on the Portuguese demographic and health statistics available for 2005. The most important conclusion of the analysis is that 11.7% of deaths in Portugal are attributable to smoking. If we use disability adjusted life years (DALYs) to measure the burden of disease, we find that 11.2% of death DALYs in Portugal is attributable to smoking. The gender distribution of this amount is very unequal; 15.4% of the male burden of disease and 17.7% of all male deaths can be attributed to smoking, but only 4.9% of the female burden of disease and 5.2% of all female deaths. These estimates are higher than death estimates previously available (Peto et al. 2006); 14% in men and only 0.9% in women. This paper also presents estimates of the burden of reducible disease, that is, the reduction in mortality and DALYs that would occur if all current smokers quit and thus experienced the mean risk of ex-smo kers, which is lower than for current smokers but typically not as low as for never-smokers. Our estimates are that the burden of disease would decrease by 5.8% (7.8% in men and 2.8% in women), and that deaths would decrease by 5.8% as well (with an 8.5% and 2.9% decrease in men and women, respectively). The paper also includes estimates of the burden of disease generated by smoking related disability. Smoking related illnesses generated 121,643 DALYs, 72,126 (59%) of which are attributable to smoking and 12,417 would be reducible if all smokers were to quit.