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This cross-sectional study aims to describe and compare energy, nutrient intake and food consumption according to eating location and by age groups using data from the National Food, Nutrition and Physical Activity Survey (IAN-AF 2015/2016). Dietary intake was estimated by two non-consecutive days of food diaries (children)/24-h recalls (other age groups), and four eating location categories were defined according to the proportion of meals consumed at out-of-home locations: Home (at least 80 % of meals at home), Other Homes, School or Work and Restaurants and Other Places. The majority of meals (69·1 %) were consumed at home. Meals were also often taken at school by children and adolescents and in restaurants and similar outlets by adults and elderly. Children and adolescents in the School or Work category ate more fruit, vegetables and pulses and cereals and starchy tubers, whereas adults in this category ate more red and processed meats, sugar-sweetened beverages and sweets. Compared with Home category, Restaurants and Other Places was associated with worse diet adequacies among children (ß = -1·0; 95 % CI = -2·0, -0·04), adolescents: (ß = -2·4; 95 % CI = -3·2, -1·5) and adults (ß = -1·3; 95 % CI = -1·6, -1·0) reflecting higher intakes of energy, fat, trans-fatty acids and SFA, and Na. The elderly consumed more free sugars and fat when eating out of home in general. Overall, findings reflect important variation in nutrient profiles by eating location, with meals taken at school or work contributing to higher consumption of nutrient-dense foods and those taken in restaurants and other similar settings implying higher consumption of energy-dense foods.
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Dieta , Ingestión de Energía , Conducta Alimentaria , Comidas , Restaurantes , Humanos , Portugal , Adolescente , Niño , Estudios Transversales , Adulto , Femenino , Masculino , Adulto Joven , Persona de Mediana Edad , Anciano , Encuestas Nutricionales , Registros de Dieta , Instituciones Académicas , Preescolar , Ingestión de AlimentosRESUMEN
OBJECTIVES: As epilepsy management medical devices emerge as potential technological solutions for prediction and prevention of sudden death in epilepsy (SUDEP), there is a gap in understanding the features and priorities that should be included in the design of these devices. This study aims to bridge the gap between current technology and emerging needs by leveraging insights from persons with epilepsy (PWE) and caregivers (CG) on current epilepsy management devices and understanding how SUDEP awareness influences preferences and design considerations for potential future solutions. METHODS: Two cross-sectional surveys were designed to survey PWE and CG on medical device design features, SUDEP awareness, and participation in medical device research. Data analysis included both qualitative thematic analysis and quantitative statistical analysis. RESULTS: The survey revealed that among 284 responses, CG were more aware of SUDEP than PWE. Comfort was identified as the primary concern regarding wearable medical devices for epilepsy management with significant differences between PWE and CG regarding acceptance and continuous use preferences. The thematic analysis identified integration with daily life, aesthetic and emotional resonance, adaptability to seizure characteristics, and user-centric design specifications as crucial factors to be considered for enhanced medical device adoption. The integration of a companion app is seen as an important tool to enhance communication and data sharing. DISCUSSION: This study reveals that while SUDEP awareness can promote the development of future SUDEP predictive and preventive medical devices, these should be designed to mitigate its impact on daily life and anxiety of both PWE and CG. Comfort and acceptance are seen as key priorities to support continuous use and are seen as a technical requirement of future medical devices for SUDEP prediction and prevention. Widespread adoption requires these technologies to be customizable to adapt to different lifestyles and social situations. A holistic approach should be used in the design of future medical devices to capture several dimensions of PWE and CG epilepsy management journey and uphold communication between healthcare professionals, PWE and CG. CONCLUSION: Data from this study highlight the importance of considering user preferences and experiences in the design of epilepsy management medical devices with potential applicability for SUDEP prediction and prevention. By employing user-centered design methods this research provides valuable insights to inform the development of future SUDEP prediction and prevention devices.
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Ovarian cancer (OC) and venous thromboembolism (VTE) have a close relationship, in which tumour cells surpass the haemostatic system to drive cancer progression. Long non-coding RNAs (lncRNAs) have been implicated in VTE pathogenesis, yet their roles in cancer-associated thrombosis (CAT) and their prognostic value are unexplored. Understanding how these lncRNAs influence venous thrombogenesis and ovarian tumorigenesis may lead to the identification of valuable biomarkers for VTE and OC management. Thus, this study evaluated the impact of five lncRNAs, namely MALAT1, TUG1, NEAT1, XIST and MEG8, on a cohort of 40 OC patients. Patients who developed VTE after OC diagnosis had worse overall survival compared to their counterparts (log-rank test, p = 0.028). Elevated pre-chemotherapy MEG8 levels in peripheral blood cells (PBCs) predicted VTE after OC diagnosis (Mann-Whitney U test, p = 0.037; Χ2 test, p = 0.033). In opposition, its low levels were linked to a higher risk of OC progression (adjusted hazard ratio (aHR) = 3.00; p = 0.039). Furthermore, low pre-chemotherapy NEAT1 levels in PBCs were associated with a higher risk of death (aHR = 6.25; p = 0.008). As for the remaining lncRNAs, no significant association with VTE incidence, OC progression or related mortality was observed. Future investigation with external validation in larger cohorts is needed to dissect the implications of the evaluated lncRNAs in OC patients.
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Neoplasias Ováricas , ARN Largo no Codificante , Tromboembolia Venosa , Humanos , Femenino , ARN Largo no Codificante/genética , Tromboembolia Venosa/genética , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/genética , CarcinogénesisRESUMEN
The Mediterranean Diet Quality Index (KIDMED Index) is frequently used to evaluate adherence to the Mediterranean Dietary Pattern among children and adolescents, through sixteen questions with the associated total score ranging from -4 to 12. However, in the authors' best knowledge, the psychometric properties of this index had not yet been investigated in Portugal. Thus, the main purpose of the present study was to investigate the reproducibility and the validity of the KIDMED Index in a sample of 185 Portuguese adolescents. The reproducibility was tested by comparing the application of the KIDMED Index at two different times (2-week interval), using McNemar test and Kappa statistics. There was moderate agreement (κw = 0·591; 95 % CI 0·485, 0·696) and no significant change (P-value = 0·201) in the KIDMED Index classification, between the two applications. The validity was explored by comparing the results obtained by the KIDMED Index and by the average of 3-d Dietary-Record (DR), using Spearman's correlation coefficient and Kappa statistics. There was weak correlation (ρ = 0·317; P-value < 0·001) and slight agreement (κw = 0·167; 95 % CI 0·071, 0·262) between the KIDMED Index classification and the 3-d DR-derived KIDMED score, and moderate correlation (ρ = 0·423; P-value < 0·001) and fair agreement (κw = 0·344; 95 % CI 0·202, 0·486) between the terciles of the KIDMED Index and the Mediterranean Adequacy Index scores. The results suggested an acceptable reproducibility and validity of the Portuguese version of the KIDMED Index, in alignment with the few studies investigating psychometric properties of this index in other countries.
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Dieta Mediterránea , Adolescente , Niño , Registros de Dieta , Conducta Alimentaria , Humanos , Portugal , Psicometría , Reproducibilidad de los Resultados , Encuestas y CuestionariosRESUMEN
OBJECTIVE: Recurrence of termination of pregnancy (TOP) due to fetal or maternal pathology is an uncommon event, and not always related to the same pathology. We aimed to evaluate the indications leading to recurrent TOP and associated risk factors. MATERIALS AND METHODS: Retrospective study of the recurrent cases of TOP conducted between January 2002 and December 2018. RESULTS: A recurrence rate of 2.5% was found in a cohort of 693 women submitted to TOP (17/693). Among the paired cases of recurrent TOP, 65% (11/17) were consequent to a different indication, whereas 35% (6/17) were due to the same cause, mainly related to monogenic diseases. TOP related to chromosomopathy was significantly associated with higher maternal and gestational age. CONCLUSIONS: Most of recurrent cases of TOP do not seem related to the same cause. The occurrence of a monogenic disease or polymalformative syndrome should raise the suspicion of recurrence due to the same pathology.
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Feto , Estudios de Cohortes , Femenino , Edad Gestacional , Humanos , Embarazo , Estudios RetrospectivosRESUMEN
CONTEXT: Assessing the overall sustainability of a diet is a challenging undertaking requiring a holistic approach capable of addressing the multicriteria nature of this concept. OBJECTIVE: The aim was to identify and summarize the multicriteria measures used to assess the sustainability characteristics of diets reported at the individual level by healthy adults. DATA SOURCES: Articles were identified via PubMed, Scopus, and Web of Science. The search strategy consisted of key words and MeSH terms, and was concluded in September 2022, covering references in English, Spanish, and Portuguese. DATA EXTRACTION: This systematic review followed the PRISMA guidelines. The search identified 5663 references, from which 1794 were duplicates. Two reviewers independently screened the titles and abstracts of each of the 3869 records and the full-text of the 144 references selected. Of these, 7 studies met the inclusion criteria. DATA ANALYSIS: A total of 6 multicriteria measures were identified: 3 different Sustainable Diet Indices, the Quality Environmental Costs of Diet, the Quality Financial Costs of Diet, and the Environmental Impact of Diet. All of these incorporated a health/nutrition dimension, while the environmental and economic dimensions were the second and the third most integrated, respectively. A sociocultural sustainability dimension was included in only 1 of the measures. CONCLUSION: Despite some methodological concerns in the development and validation process of the identified measures, their inclusion is considered indispensable in assessing the transition towards sustainable diets in future studies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42022358824.
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Ovarian cancer (OC) is the deadliest gynaecological malignancy. Identifying new prognostic biomarkers is an important research field. Haemostatic components together with leukocytes can drive cancer progression while increasing the susceptibility to venous thromboembolism (VTE) through immunothrombosis. Unravelling the underlying complex interactions offers the prospect of uncovering relevant OC prognostic biomarkers, predictors of cancer-associated thrombosis (CAT), and even potential targets for cancer therapy. Thus, this study evaluated the expression of F3, F5, F8, F13A1, TFPI1, and THBD in peripheral blood cells (PBCs) of 52 OC patients. Those with VTE after tumour diagnosis had a worse overall survival (OS) compared to their counterparts (mean OS of 13.8 ± 4.1 months and 47.9 ± 5.7 months, respectively; log-rank test, p = 0.001). Low pre-chemotherapy F3 and F8 expression levels were associated with a higher susceptibility for OC-related VTE after tumour diagnosis (χ2, p < 0.05). Regardless of thrombogenesis, patients with low baseline F8 expression had a shorter progression-free survival (PFS) than their counterparts (adjusted hazard ratio (aHR) = 2.54; p = 0.021). Among those who were not under platelet anti-aggregation therapy, low F8 levels were also associated with a shorter OS (aHR = 6.16; p = 0.006). Moving forward, efforts should focus on external validation in larger cohorts.
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Ovarian cancer (OC) is a leading cause of death among gynaecological malignancies. The haemostatic system, which controls blood flow and prevents clotting disorders, paradoxically drives OC progression while increasing the risk of venous thromboembolism (VTE). MicroRNAs (miRNAs) have emerged as crucial in understanding VTE pathogenesis. Exploring the connection between cancer and thrombosis through these RNAs could lead to novel biomarkers of cancer-associated thrombosis (CAT) and OC, as well as potential therapeutic targets for tumour management. Thus, this study examined the impact of eight plasma miRNAs targeting the tissue factor (TF) coagulation pathway-miR-18a-5p, -19a-3p, -20a-5p, -23a-3p, -27a-3p, -103a-3p, -126-5p and -616-3p-in 55 OC patients. Briefly, VTE occurrence post-OC diagnosis was linked to shorter disease progression time (log-rank test, p = 0.024) and poorer overall survival (OS) (log-rank test, p < 0.001). High pre-chemotherapy levels of miR-20a-5p (targeting coagulation factor 3 (F3) and tissue factor pathway inhibitor 2 (TFPI2)) and miR-616-3p (targeting TFPI2) predicted VTE after OC diagnosis (χ2, p < 0.05). Regarding patients' prognosis regardless of VTE, miR-20a-5p independently predicted OC progression (adjusted hazard ratio (aHR) = 6.13, p = 0.005), while miR-616-3p significantly impacted patients' survival (aHR = 3.72, p = 0.020). Further investigation is warranted for their translation into clinical practice.
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MicroARNs , Neoplasias Ováricas , Tromboplastina , Humanos , Femenino , Neoplasias Ováricas/sangre , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/genética , MicroARNs/sangre , MicroARNs/genética , Tromboplastina/metabolismo , Tromboplastina/genética , Persona de Mediana Edad , Pronóstico , Anciano , Trombosis/sangre , Trombosis/etiología , Tromboembolia Venosa/sangre , Tromboembolia Venosa/etiología , Tromboembolia Venosa/genética , Adulto , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión GénicaRESUMEN
Introduction: Preoperative staging of uterine cancer has recently been implied as an important contribution to an accurate selection of low-risk cases, ultimately avoiding unnecessary lymph node debulking. The aim of this study was to evaluate the validity of transvaginal ultrasonography (TVS) in preoperative staging of uterine cancer in comparison to pelvic magnetic resonance imaging (MRI) and permanent section. Methods: We conducted a prospective longitudinal multicenter trial between 2017 and 2018. Inclusion criteria comprised cases of endometrial neoplasia histologically confirmed or strong imaging suspicion, candidates for elective surgery as primary treatment. Proportions of Agreement (PA), kappa statistic (K), sensitivity, specificity and accuracy were calculated with 95% confidence intervals (95%CI). Results: Eighty-two patients were eligible for the study, presenting a mean age of 68 years (standard deviation 11). In what concerns the TVS evaluation of myometrial invasion, the subjective and objective methods of Gordon and Karlsson presented a sensitivity of 79%, 79% and 67% [95%CI 63-91; 63-91; 50-81], a specificity of 65%, 58% and 79% [95%CI 49-79; 42-73; 64-89] and an overall accuracy of 72%, 68% and 73% [95%CI 61-81; 57-78; 63-82]. MRI presented respectively a sensitivity, specificity and overall accuracy of 92%, 70% and 82% [95%CI 77-98; 52-85; 71-90]. Regarding cervical involvement, the sensitivity was respectively 31%, 50% and 67% [95%CI 9-61; 21-79; 35-90] for the subjective method, objective TVS and MRI, and the specificity was 98%, 90% and 100% [95%CI 92-100; 77-97; 94;100]. Agreement between TVS and MRI was superior in the assessment of cervical invasion, with PA ranging from 0.82 to 0.93 and K from 0.45 to 0.58, in comparison to myometrial invasion with PA ranging from 0.68 to 0.73 and K from 0.31 to 0.50. Considering the assessment of cervical involvement, as MRI showed a specificity of 100% it is not possible to increase the specificity. However, it was possible to increase the sensitivity, considering the combination of TVS with objective approach and MRI. Conclusion: TVS may have a promising role as a tool for preoperative staging of endometrial carcinoma, presenting a performance that approximates to MRI, with a higher agreement in the assessment of cervical invasion.
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Ovarian borderline serous tumors present with peritoneal involvement in 20% of cases, either as non-invasive or invasive implants, also known as extraovarian low-grade serous carcinoma. The coexistence of high-grade serous carcinoma is rare, suggesting a synchronous neoplasia with a distinct and independent tumor biology and behavior. We aim to describe a case of a synchronous ovary-peritoneum neoplasia: serous borderline tumor and primary peritoneal high-grade serous carcinoma. A discussion and literature review concerning the optimal diagnostic and therapeutic approach is provided.
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Cistadenocarcinoma Seroso , Neoplasias Ováricas , Neoplasias Peritoneales , Cistadenocarcinoma Seroso/diagnóstico , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/diagnóstico , Neoplasias Peritoneales/diagnósticoRESUMEN
PURPOSE: To determine the accuracy of transvaginal ultrasonography (TVS) and pelvic magnetic resonance imaging (MRI) in preoperative staging of endometrial cancer in comparison to frozen section (FS) for the assessment of myometrial invasion, considering permanent section as the gold standard. METHODS: A retrospective longitudinal study of all endometrial carcinomas diagnosed in our institution between March 2012 and October 2018 was conducted. Women with histologically confirmed endometrial malignancy, planned for surgery as primary treatment and submitted either to TVS, MRI and/or intraoperative FS followed by comprehensive surgical staging were eligible. RESULTS: From a total of 187 endometrial carcinomas, 156 were eligible for the study. The most frequent histology was endometrioid carcinoma (n=115), followed by serous carcinoma (n=25); the majority presented a FIGO stage IA (n=85) or IB (n=21). TVS, MRI and FS presented a sensitivity 56 %, 71 % and 67 % [95 %CI 0.35-0.75; 0.49-0.87; 0.45-0.84] and a specificity of 90 %, 78 % and 94 % [95 %CI 0.79-0.97; 0.58-0.91; 0.84-0.98], respectively. FS was the method with the lowest overestimation rate (6.5 %, 95 %CI 0.02-0.16), whereas MRI showed the lowest underestimation rate (29.2 %, 95 %CI 0.13-0.51). Agreement was superior between MRI and FS (Pa=0.79, K=0.56) and secondly between MRI and TVS (Pa=0.78, K=0.47). CONCLUSIONS: Intraoperative FS presents the higher specificity and the lowest overestimation rate, while MRI seems to be the exam with the highest sensitivity in the evaluation of myometrial invasion. Agreement between the different methods is reasonable, suggesting that the best alternative will be highly dependent on the availability and experience of each institution.
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SisPorto 4.0 is the most recent version of a program for the computer analysis of cardiotocographic (CTG) signals and ST events, which has been adapted to the 2015 International Federation of Gynaecology and Obstetrics (FIGO) guidelines for intrapartum foetal monitoring. This paper provides a detailed description of the analysis performed by the system, including the signal-processing algorithms involved in identification of basic CTG features and the resulting real-time alerts.
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Cardiotocografía/métodos , Atención Perinatal/métodos , Procesamiento de Señales Asistido por Computador , Algoritmos , Cardiotocografía/instrumentación , Cardiotocografía/normas , Sistemas de Computación , Parto Obstétrico , Femenino , Humanos , Atención Perinatal/normas , Guías de Práctica Clínica como Asunto , Embarazo , Programas InformáticosRESUMEN
BACKGROUND: Visual analysis of cardiotocographic (CTG) tracings has been shown to be prone to poor intra- and interobserver agreement when several interpretation guidelines are used, and this may have an important impact on the technology's performance. OBJECTIVES: The aim of this study was to evaluate agreement in CTG interpretation using the new 2015 FIGO guidelines on intrapartum fetal monitoring. STUDY DESIGN: A pre-existing database of intrapartum CTG tracings was used to sequentially select 151 cases acquired with a fetal electrode, with duration exceeding 60minutes, and signal loss less than 15%. These tracings were presented to six clinicians, three with more than 5 years' experience in the labor ward, and three with 5 or less years' experience. Observers were asked to evaluate tracings independently, to assess basic CTG features: baseline, variability, accelerations, decelerations, sinusoidal pattern, tachysystole, and to classify each tracing as normal, suspicious or pathologic, according to the 2015 FIGO guidelines on intrapartum fetal monitoring. Agreement between observers was evaluated using the proportions of agreement (Pa), with 95% confidence intervals (95%CI). RESULTS: A good interobserver agreement was found in the evaluation of most CTG features, but not bradycardia, reduced variability, saltatory pattern, absence of accelerations and absence of decelerations. For baseline classification Pa was 0.85 [0.82-0.90], for variability 0.82 [0.78-0.85], for accelerations 0.72 [0.68-0.75], for tachysystole 0.77 [0.74-0.81], for decelerations 0.92 [0.90-0.95], for variable decelerations 0.62 [0.58-0.65], for late decelerations 0.63 [0.59-0.66], for repetitive decelerations 0.73 [0.69-0.78], and for prolonged decelerations 0.81 [0.77-0.85]. For overall CTG classification, Pa were 0.60 [0.56-0.64], for classification as normal 0.67 [0.61-0.72], for suspicious 0.54 [0.48-0.60] and for pathologic 0.59 [0.51-0.66]. No differences in agreement according to the level of expertise were observed, except in the identification of accelerations, where it was better in the more experienced group. CONCLUSIONS: A good interobserver agreement was found in evaluation of most CTG features and in overall tracing classification. Results were better than those reported in previous studies evaluating agreement in overall tracing classification. Observer experience did not appear to play a role in agreement.
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Cardiotocografía/métodos , Monitoreo Fetal/métodos , Frecuencia Cardíaca Fetal/fisiología , Femenino , Humanos , Variaciones Dependientes del Observador , Guías de Práctica Clínica como Asunto , EmbarazoRESUMEN
INTRODUCTION: The satisfaction with the medical profession has been identified as an essential factor for the quality of care, the wellbeing of patients and the healthcare systems' stability. Recent studies have emphasized a growing discontent of physicians, mainly as a result of changes in labor relations. OBJECTIVES: To assess the perception of Portuguese medical residents about: correspondence of residency with previous expectations; degree of satisfaction with the specialty, profession and place of training; reasons for dissatisfaction; opinion regarding clinical practice in Portugal and emigration intents. MATERIAL AND METHODS: Cross-sectional study. Data collection was conducted through the "Satisfaction with Specialization Survey", created in an online platform, designed for this purpose, between May and August 2014. RESULTS: From a total population of 5788 medical residents, 804 (12.25 %) responses were obtained. From this sample, 77% of the responses were from residents in the first three years. Results showed that 90% of the residents are satisfied with their specialty, 85% with the medical profession and 86% with their place of training. Nevertheless, results showed a decrease in satisfaction over the final years of residency. The overall assessment of the clinical practice scenario in Portugal was negative and 65% of residents have plans to emigrate after completing their residency. CONCLUSION: Portuguese residents revealed high satisfaction levels regarding their profession. However, their views on Portuguese clinical practice and the results concerning the intent to emigrate highlight the need to take steps to reverse this scenario.
Introdução: A satisfação com a profissão médica tem sido apontada como um fator essencial para a qualidade assistencial, o bemestar dos doentes e a estabilidade dos sistemas de saúde. Estudos recentes têm vindo a enfatizar um crescente descontentamento dos médicos, principalmente como consequência das alterações das relações laborais.Objetivos: Avaliar a perceção dos médicos de formação específica em Portugal, sobre as expectativas e grau de satisfação com a profissão, especialidade e local de formação; razões da insatisfação e intenção de emigrar.Material e Métodos: Estudo transversal. A colheita de dados foi efetuada entre Maio e Agosto de 2014 através de um Inquérito online sobre a âÄúSatisfação com a EspecialidadeâÄù.Resultados: De uma população total de 5788 médicos, foram obtidas 804 respostas (12,25% do total de médicos internos). Desta amostra, 77% das respostas correspondem a internos dos três primeiros anos de formação. Verificou-se que 90% dos médicos se encontram satisfeitos com a especialidade, tendo-se encontrado também níveis elevados de satisfação com a profissão (85%) e local de formação (86%). Por outro lado, constatou-se que estes diminuíam com a progressão ao longo dos anos de internato. A avaliação global sobre o panorama da prática médica foi negativa e 65% dos médicos responderam que consideram emigrar após conclusão do internato.Conclusão: Os médicos internos em Portugal apresentam níveis positivos de satisfação com a sua profissão. No entanto, a sua opinião sobre o panorama da Medicina e os resultados relativos à intenção de emigrar alertam para a necessidade de tomada de medidas para inverter este cenário.
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Internado y Residencia , Satisfacción en el Trabajo , Medicina , Estudios Transversales , Humanos , Portugal , AutoinformeRESUMEN
Objective. To evaluate the impact of preeclampsia in the modification of lifestyle habits and decreasing cardiovascular risk factors in a population of women at least 6 months after having the diagnosis of preeclampsia. Methods. Cross-sectional observational study. Data included 141 cases of preeclampsia and chronic hypertension with superimposed preeclampsia on singleton births diagnosed in our institution between January 2010 and December 2013. From the cases diagnosed over 6 months a standardized questionnaire evaluating lifestyle changes was applied. Results. We reviewed 141 cases, of which 120 were diagnosed for more than 6 months. An overall participation rate in the questionnaire of 65% was yielded. A slight increase from the mean BMI before pregnancy was found. No statistical significant association was established between postpregnancy mean BMI, weight variation, and the frequency of aerobic exercise with the severity of preeclampsia. Only 28% of our cases were practising aerobic exercise at least weekly. The majority of women assessed blood pressure at least monthly (45/78), but only 25 assessed glycaemia at least once/year. Conclusion. This study shows that the majority of our patients and general practitioners do not take into consideration a previous pregnancy affected by preeclampsia as a risk factor for future cardiovascular disease.