Digit Ratio (2D:4D) in Newborns: Influences of Prenatal Testosterone and Maternal Environment

Introduction: The 2D:4D digit ratio is sexually-dimorphic, probably due to testosterone action through the perinatal period. We characterize the 2D:4D ratio in newborn (NB) infants, in between the pre- and postnatal surges of testosterone, and relate it to the mother's 2D:4D and to testosterone levels in the amniotic fluid (AF). Subjects and methods: Testosterone was assayed in samples of maternal plasma and AF collected at amniocentesis. Shortly after birth, 106 NBs and their mothers were measured for 2D:4D ratio. Results: NB males had lower mean 2D:4D ratios than females but this dimorphism was significant only for the left hand (males: 0.927; females: 0.950; p=0.004). Mothers who had sons had lower 2D:4D ratios than those who had daughters and the mother's 2D:4D were higher than those of NBs regardless of sex. Both hands of NB females were negatively correlated with AF testosterone and positively correlated with the mother's 2D:4D, but males showed no significant associations. Maternal plasma testosterone also showed a negative weak correlation with NB's digit ratio in both sexes. Conclusions: Sexual dimorphism at birth was only significant for the left hand, in contrast with reports of greater right hand dimorphism, suggesting that postnatal testosterone is determinant for 2D:4D stabilization. The lower 2D:4D ratios in mothers who had sons support claims that hormone levels in parents are influential for determining their children's sex. NB female's digit ratio, but not males', was associated to the level of AF testosterone. The mother's 2D:4D ratios were positively correlated with their daughters' 2D:4D, but the same was not observed for male NBs, suggesting that prenatal testosterone levels in male fetus lead their 2D:4D ratios to stray from their mothers' with high individual variability.

Complicações Hemorrágicas e/ou Tromboembólicas em Doentes sob Anticoagulação Oral Regularmente Seguidos em Consulta Diferenciada

A consulta de hipocoagulação de um hospital central contempla uma população bastante diversificada, pelo que uma melhor compreensão das características da mesma, poderá levar à melhoria da prestação de cuidados de saúde e à diminuição do número de complicações tromboembólicas (resultantes da patologia base) e hemorrágicas [resultantes da própria terapêutica anticoagulante (ACO)]. Objectivos: Avaliar as características da população que frequenta a consulta de hipocoagulação e analisar quais podem predizer um maior risco de complicações. Métodos: Utilizaram-se os dados colhidos por um médico através de um questionário colocado a doentes durante a consulta de hipocoagulação. Foram efectuados 101 questionários e avaliaram-se as características demográficas (sexo, idade, escolaridade, grau de analfabetismo), os factores de risco clássicos para doença coronária, o diagnóstico que levou ao início da ACO, a duração da ACO, a periodicidade da determinação e valores mínimos, máximos e à data do questionário de INR e as complicações desta terapêutica. Consideraram-se como complicações o aparecimento de fenómenos hemorrágicos e/ou tromboembólicos, no decurso da terapêutica hipocoagulante. Resultados: Foram estudados 101 doentes, 74 do sexo feminino (73,3%), com idade média de 6410 anos (21-85). A população analisada tinha 4,5 ± 3,5 anos de escolaridade, com 15% de analfabetismo. A maioria dos doentes iniciou ACO após colocação de prótese valvular mecânica (56,4%). Em cada doente existia em média 1 factor de risco para doença coronária. O número de meses de ACO era de 99,489 (1-360). Sessenta e seis doentes (65,3%) conheciam o motivo pelo qual iniciaram esta terapêutica. Cada doente tinha efectuado 1,20,6 determinações de INR por mês e tinha, em média, um tempo máximo sem verificação do mesmo de 6,210,4 semanas. Quarenta e cinco doentes sofreram alguma complicação tromboembólica e/ou hemorrágica no decurso da terapêutica ACO. Ocorreram 50 complicações hemorrágicas, em 41 doentes, das quais 7 motivaram internamento. Detectaram-se 7 episódios de tromboembolismo central ou periférico, em 7 doentes. Posteriormente, dividiu-se a população em dois grupos: grupo I – com complicações (GI) e grupo II – sem complicações (GII). GI – 45 doentes, idade média 63,59,1 anos (39-80) e GII – 56 doentes, idade média 64,711,3 anos (21-85). Nos doentes que iniciaram ACO por prótese mitral detectou-se um maior número de complicações (60,6% no GI e 39,4% no GII, p=0,024). Também nos doentes com INR máximo recomendado > 3 (55,2% no GI e 44,8% no GII, p=0,013) e nos que tinham sido sujeitos a terapêutica estomatológica (68,3% no GI e 31,7% no GII, p<0,001) se verificou um maior número de complicações. A duração da ACO foi o factor mais significativo para o aparecimento de complicações (GI – 138,196,5 meses, GII – 67,868,2 meses, p <0,00005). Na análise multivariada apenas a duração da ACO se manteve como factor preditivo independente. Conclusões: Na população existe uma percentagem importante de doentes com baixa escolaridade, que se poderá repercutir sobre a compreensão desta terapêutica específica, não tendo contudo, neste estudo, revelado influência significativa na taxa de complicações. O aparecimento de complicações durante a terapêutica anticoagulante é dependente da duração desta, do valor do INR máximo recomendado e da realização ou não de procedimentos estomatológicos, sendo o primeiro factor o mais significativo.

Misoprostol na Indução do Trabalho de Parto: Oral ou Vaginal?

Algumas complicações maternas ou fetais no decorrer da gravidez tornam necessária a indução do trabalho de parto. O misoprostol é um análogo sintético da prostaglandina Eı que mimetiza a acção endógena destas substâncias na maturação do colo do útero. A dose ideal, via e frequência de administração continuam sob investigação. O objectivo deste trabalho foi avaliar a eficácia do misoprostol na indução do trabalho de parto e a morbilidade associada à sua administração oral e vaginal. Foi efectuada uma avaliação retrospectiva das grávidas internadas para indução do trabalho de parto durante o ano de 2002, no serviço de Medicina Materno Fetal da Maternidade Dr. Alfredo da Costa. Foram seleccionadas as grávidas que efectuaram misoprostol oral (100 mg) e vaginal (50 mg). Foi avaliado o intervalo de tempo até à fase activa, ao parto, a necessidade de perfusão com occitocina, a via de parto e a morbilidade materna e fetal. Consideraram-se 238 grávidas, 194 efectuaram misoprostol oral e 44 vaginal. O intervalo da indução ao parto vaginal foi 24,3 horas na via oral e 16,9 horas na via vaginal (p=0.01), a dose total administrada foi significativamente inferior na via vaginal (p=0.00), a paridade foi um factor importante na via de parto (p=0.01). Não se verificaram diferenças entre os dois grupos em relação às complicações maternas e fetais. A administração vaginal de misoprostol, quando comparada com a oral, mostrou-se mais eficaz.

Oral Contraceptive Use and Clinical Outcomes in Patients with Multiple Sclerosis

Experimental and clinical data suggest a role of sex steroids in the pathogenesis of multiple sclerosis (MS). Scant information is available about the potential effect of oral contraceptive (OC) use on the prognosis of the disease. We aimed to evaluate this. The study population consisted of 132 women with relapsing-remitting MS before receiving disease modifying treatment and a mean disease duration 6.2 (SD 5.1) years. Three groups of patients were distinguished according to their OC behavior: [1] never-users, patients who never used OC [2] past-users, patients who stopped OC use before disease onset, and [3] after-users, those who used these drugs after disease onset. Multiple linear and logistic regression models were used to analyze the association between oral contraceptive use and annualized relapse rates, disability accumulation and severity of the disease. After-user patients had lower Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Severity Score (MSSS) values than never users (p<0.001 and p=0.002, respectively) and past users (p=0.010 and p=0.002, respectively). These patients were also more likely to have a benign disease course (MSSS<2.5) than never and past users together (OR: 4.52, 95%CI: 2.13-9.56, p<0.001). This effect remained significant after adjustment for confounders, including smoking and childbirths (OR: 2.97, 95%CI: 1.24, 6.54, p=0.011 and for MSSS β: -1.04; 95% C.I. -1.78, -0.30, p=0.006). These results suggest that OC use in women with relapsing-remitting MS is possible associated with a milder disabling disease course.

Environment and Health in Children Day Care Centres (ENVIRH) - Study Rationale and Protocol

Background: Indoor air quality (IAQ) is considered an important determinant of human health. The association between exposure to volatile organic compounds, particulate matter, house dust mite, molds and bacteria in day care centers (DCC) is not completely clear. The aim of this project was to study these effects. Methods --- study design: This study comprised two phases. Phase I included an evaluation of 45 DCCs (25 from Lisbon and 20 from Oporto, targeting 5161 children). In this phase, building characteristics, indoor CO2 and air temperature/relative humidity, were assessed. A children’s respiratory health questionnaire derived from the ISAAC (International Study on Asthma and Allergies in Children) was also distributed. Phase II encompassed two evaluations and included 20 DCCs selected from phase I after a cluster analysis (11 from Lisbon and 9 from Oporto, targeting 2287 children). In this phase, data on ventilation, IAQ, thermal comfort parameters, respiratory and allergic health, airway inflammation biomarkers, respiratory virus infection patterns and parental and child stress were collected. Results: In Phase I, building characteristics, occupant behavior and ventilation surrogates were collected from all DCCs. The response rate of the questionnaire was 61.7% (3186 children). Phase II included 1221 children. Association results between DCC characteristics, IAQ and health outcomes will be provided in order to support recommendations on IAQ and children’s health. A building ventilation model will also be developed. Discussion: This paper outlines methods that might be implemented by other investigators conducting studies on the association between respiratory health and indoor air quality at DCC.

Unilateral Oral Mucous Membrane Pemphigoid: Refractory Atypical Presentation Successfully Treated with Intravenous Immunoglobulins

A 57-year-old male presented with a 6-month history of blisters and painful erosions on the right buccal mucosa. No skin or other mucosal involvement was seen. The findings of histopathological and direct immunofluorescence examinations were sufficient for the diagnosis of oral mucous membrane pemphigoid in the context of adequate clinical correlation. No response was seen after topical therapies and oral corticosteroids or dapsone. Intravenous immunoglobulin was started and repeated every three weeks. Complete remission was achieved after three cycles and no recurrence was seen after two years of follow-up. The authors report a rare unilateral presentation of oral mucous membrane pemphigoid on the right buccal and hard palate mucosa, without additional involvement during a period of five years. Local trauma or autoimmune factors are possible etiologic factors for this rare disorder, here with unique presentation.

Diagnosis of Eosinophilic Esophagitis in an Infant Undergoing Milk Oral Immunotherapy - A Case Report

Although the standard of care for cow’s milk (CM) allergy is strict food avoidance, oral immunotherapy (OIT) is being widely investigated as an alternative management option in certain cases. Immediate adverse reactions to OIT have been described, but its long-term effects are much less often reported. We present the case of a girl diagnosed with IgE-mediated CM allergy that was proposed for our CM OIT protocol at the age of 3 years. The first sessions (dose escalation up to 5 ml) were well tolerated, however eight hours after her daily morning dose of 5ml CM the child developed late episodes of vomiting. No other symptoms, particularly immediately after CM ingestion, were reported. These episodes became progressively worse and on the third day she presented mild dehydration and blood eosinophilia. After OIT interruption, a progressive clinical improvement was observed. An esophageal endoscopy was performed, showing signs of eosinophilic esophagitis (EoE) with peak 20 eosinophils/hpf. After treatment with topical swallowed fluticasone (500 mcg bid) and a CM-free diet for 4 months, the child was asymptomatic and endoscopy and biopsy findings were normal. The long-term effects of milk OIT are still in part unknown. We hypothesize that eosinophilic esophagitis may have been a consequence of OIT in this case. The findings seem to indicate that food allergy may play a role in the pathogenesis of esophageal eosinophilia and stress the importance of a well programmed long-term follow-up of patients that have undergone milk OIT.

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.