RESUMO
BACKGROUND: The Bullous Pemphigoid Disease Area Index (BPDAI) score has been proposed to provide an objective measure of bullous pemphigoid (BP) activity. OBJECTIVES: The objective of this study was to calculate BPDAI cut-off values defining mild, moderate and severe BP. We also aimed to assess the interrater reliability and correlation with the number of daily new blisters, and anti-BP180 and anti-BP230 antibodies. METHODS: Severity scores were recorded by two blinded investigators. Anti-BP180 and anti-BP230 antibodies were measured using an enzyme-linked immunosorbent assay (ELISA). Cut-off values defining mild, moderate and severe subgroups were calculated based on the 25th and 75th percentiles of the BPDAI score. RESULTS: In total, 285 patients with BP were enrolled from 50 dermatology departments in Europe. Median BPDAI activity was 37·5 points (range 0-164). Cut-off values corresponding to the first and third quartiles of the BPDAI score were 20 and 57, respectively; thus, these values were used to define mild (≤ 19), moderate (≥ 20 and ≤ 56) and severe (≥ 57) BP. The median BPDAI score for patients with ≤ 10 daily new blisters was 26 [interquartile range (IQR) 17-45], and for patients with > 10 daily new blisters the median score was 55 (IQR 39-82). The BPDAI intraclass correlation coefficient measured at baseline was 0·97 and remained higher than 0·90 up to month 6. The improvement in the BPDAI score was correlated with the absolute decrease in anti-BP180 ELISA value (Spearman's rank r = 0·34, P < 0·004), but not with anti-BP230 antibodies (r = 0·17, P = 0·15). CONCLUSIONS: This study suggests cut-off values of 20-57 for BPDAI to distinguish mild, moderate and severe BP, and confirms that it is a robust tool to assess BP severity precisely.
Assuntos
Penfigoide Bolhoso , Autoanticorpos , Autoantígenos , Distonina , Ensaio de Imunoadsorção Enzimática , Europa (Continente) , Humanos , Colágenos não Fibrilares , Penfigoide Bolhoso/diagnóstico , Reprodutibilidade dos Testes , Índice de Gravidade de DoençaRESUMO
In studies investigating the effects of endocrine disruptors (ED) such as phthalates, bisphenols and some pesticides on human health, exposure is usually characterized with urinary metabolites. The variability of biomarkers concentration, due to rapid elimination from the body combined with frequent exposure is however pointed out as a major limitation to exposure assessment. This study was conducted to assess variability of urinary metabolites of ED, and to investigate how sampling time and number of samples analyzed impacts exposure assessment. Urine samples were collected over 6â¯months from 16 volunteers according to a random sampling design, and analyzed for 16 phthalate metabolites, 9 pesticide metabolites and 4 bisphenols. The amount of biomarkers excreted in urine at different times of the day were compared. In parallel, 2 algorithms were developed to investigate the effect of the number of urine samples analyzed per subject on exposure assessment reliability. In the 805 urine samples collected from the participants, all the biomarkers tested were detected, and 18 were present in >90% of the samples. Biomarkers variability was highlighted by the low intraclass correlation coefficients (ICC) ranging from 0.09 to 0.51. Comparing the amount of biomarkers excreted in urine at different time did not allow to identify a preferred moment for urine collection between first day urine, morning, afternoon and evening. Algorithms demonstrated that between 10 (for monobenzyl (MBzP) phthalate) and 31 (for bisphenol S) samples were necessary to correctly classify 87.5% of the subjects into quartiles according to their level of exposure. The results illustrate the high variability of urinary biomarkers of ED over time and the impossibility to reliably classify subjects based on a single urine sample (or a limited number). Results showed that classifying individuals based on urinary biomarkers requires several samples per subject, and this number is highly different for different biomarkers.
Assuntos
Disruptores Endócrinos , Praguicidas , Ácidos Ftálicos , Biomarcadores , Exposição Ambiental/análise , Humanos , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Corticosteroids (CS) with or without adjuvant immunosuppressant agents are standard treatment for pemphigus vulgaris (PV). The efficacy of adjuvant therapies in minimizing steroid-related adverse events (AEs) is unproven. OBJECTIVES: To utilize data collected in a French investigator-initiated, phase III, open-label, randomized controlled trial to demonstrate the efficacy and safety of rituximab and seek approval for its use in PV. METHODS: This was an independently conducted post hoc analysis of the moderate-to-severe PV subset enrolled in the Ritux 3 study. Patients were randomized to rituximab plus 0·5 or 1·0 mg kg-1 per day prednisone tapered over 3 or 6 months, or 1·0 or 1·5 mg kg-1 per day prednisone alone tapered over 12 or 18 months, respectively (according to disease severity). The primary end point was complete remission at month 24 without CS (CRoff) for ≥ 2 months, and 24-month efficacy and safety results were also reported. RESULTS: At month 24, 34 of 38 patients (90%) on rituximab plus prednisone achieved CRoff ≥ 2 months vs. 10 of 36 patients (28%) on prednisone alone. Median total cumulative prednisone dose was 5800 mg in the rituximab plus prednisone arm vs. 20 520 mg for prednisone alone. Eight of 36 patients (22%) who received prednisone alone withdrew from treatment owing to AEs; one rituximab-plus-prednisone patient withdrew due to pregnancy. Overall, 24 of 36 patients (67%) on prednisone alone experienced a grade 3/4 CS-related AE vs. 13 of 38 patients (34%) on rituximab plus prednisone. CONCLUSIONS: In patients with moderate-to-severe PV, rituximab plus short-term prednisone was more effective than prednisone alone. Patients treated with rituximab had less CS exposure and were less likely to experience severe or life-threatening CS-related AEs. What's already known about this topic? Pemphigus vulgaris (PV) is the most common type of pemphigus. Corticosteroids, a standard first-line treatment for PV, have significant side-effects. Although their effects are unproven, adjuvant corticosteroid-sparing agents are routinely used to minimize steroid exposure and corticosteroid-related side-effects. There is evidence that the anti-CD20 antibody rituximab is effective in the treatment of patients with severe recalcitrant pemphigus and in patients with newly diagnosed pemphigus. What does this study add? This study provides a more detailed analysis of patients with PV enrolled in an investigator-initiated trial. Rituximab plus prednisone had a steroid-sparing effect and more patients achieved complete remission off prednisone. Fewer patients experienced grade 3 or grade 4 steroid-related adverse events than those on prednisone alone. This collaboration between academia and industry, utilizing independent post hoc analyses, led to regulatory authority approvals of rituximab in moderate-to-severe PV.
Assuntos
Pênfigo , Humanos , Fatores Imunológicos/efeitos adversos , Imunossupressores/efeitos adversos , Pênfigo/tratamento farmacológico , Prednisona , Rituximab/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: The efficiency of traditional anthropometric measurements such as body mass index (BMI) or waist circumference (Waist C) used to replace biomedical imaging for assessing visceral adipose tissue (VAT) is still highly controversial in youth. HYPOTHESIS AND OBJECTIVES: We evaluated the most accurate model predicting VAT in overweight/obese youth, using various anthropometric measurements and their correlation with different body fat compartments, especially by testing, for the first time in youth, the hypothesis that subtracting the anthropometric measurement the most highly correlated with subcutaneous abdominal adipose tissue (SAAT) and less correlated possible with VAT from an anthropometric abdominal measurement highly correlated with visceral and total abdominal adipose tissue (TAAT), predicts VAT with higher accuracy. SUBJECTS AND METHODS: VAT and SAAT data resulted from magnetic resonance imaging (MRI) analysis performed on 181 boys and girls (7-17 y) from Diabetes & Endocrinology Care Paediatrics Clinic in Luxembourg. Height, weight, abdominal diameters, waist, hip, and thigh circumferences were measured with a view to developing the anthropometric VAT predictive algorithms. RESULTS: In girls, subtracting proximal thigh circumference (Proximal Thigh C), the most closely correlated anthropometric measurement with SAAT, from Waist C, the most closely correlated anthropometric measurement with VAT was instrumental in improving VAT prediction, in comparison with the most accurate single VAT anthropometric surrogate. [Formula: see text] Residual analysis showed a negligible estimation error (5 cm2 ). In boys, Waist C was the best VAT predictor. CONCLUSIONS: Subtraction of abdominal subcutaneous fat is important to predict VAT in overweight/obese girls.
Assuntos
Adiposidade , Gordura Intra-Abdominal/diagnóstico por imagem , Modelos Biológicos , Sobrepeso/diagnóstico por imagem , Obesidade Infantil/diagnóstico por imagem , Gordura Subcutânea Abdominal/diagnóstico por imagem , Adolescente , Algoritmos , Índice de Massa Corporal , Tamanho Corporal , Criança , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Luxemburgo , Imageamento por Ressonância Magnética , Masculino , Reprodutibilidade dos Testes , Caracteres Sexuais , Coxa da Perna , Circunferência da CinturaRESUMO
PURPOSE: Second cancers and cardiovascular toxicities are long term radiation toxicity in locally advanced Hodgkin's lymphomas. In this study, we evaluate the potential reduction of dose to normal tissue with helical tomotherapy and proton therapy for Hodgkin's lymphoma involved-field or involved-site irradiation compared to standard 3D conformal radiation therapy. PATIENTS AND METHODS: Fourteen female patients with supradiaphragmatic Hodgkin's lymphoma were treated at our institution with 3D conformal radiation therapy or helical tomotherapy to a dose of 30Gy in 15 fractions. A planning comparison was achieved including proton therapy with anterior/posterior passive scattered beams weighted 20Gy/10Gy. RESULTS: Mean doses to breasts, lung tissue and heart with proton therapy were significantly lower compared to helical tomotherapy and to 3D conformal radiation therapy. Helical tomotherapy assured the best protection of lungs from doses above 15Gy with the V20Gy equal to 16.4%, compared to 19.7% for proton therapy (P=0.01) or 22.4% with 3D conformal radiation therapy (P<0.01). Volumes of lung receiving doses below 15Gy were significantly larger for helical tomotherapy than for proton therapy or 3D conformal radiation therapy, with respective lung doses V10Gy=37.2%, 24.6% and 27.4%. Also, in the domain of low doses, the volumes of breast that received more than 10Gy or more than 4Gy with helical tomotherapy were double the corresponding volumes for proton therapy, with V4Gy representing more than a third of one breast volume with helical tomotherapy. CONCLUSIONS: Helical tomotherapy achieved a better protection to the lungs for doses above 15Gy than passive proton therapy or 3D conformal radiation therapy. However, dose distributions could generally be improved by using protons even with our current passive-beam technology, especially allowing less low dose spreading and better breast tissue sparing, which is an important factor to consider when treating Hodgkin's lymphomas in female patients. Prospective clinical study is needed to evaluate the tolerance and confirm these findings.
Assuntos
Doença de Hodgkin/radioterapia , Neoplasias do Mediastino/radioterapia , Órgãos em Risco , Terapia com Prótons , Radioterapia Conformacional , Radioterapia de Intensidade Modulada , Adulto , Mama/efeitos da radiação , Feminino , Coração/efeitos da radiação , Humanos , Pulmão/efeitos da radiação , Tratamentos com Preservação do Órgão , Planejamento da Radioterapia Assistida por Computador , Adulto JovemRESUMO
The neighbourhood is recognized as an important unit of analysis in research on the relation between obesogenic environments and development of obesity. One important challenge is to define the limits of the residential neighbourhood, as perceived by study participants themselves, in order to improve our understanding of the interaction between contextual features and patterns of obesity. An innovative tool was developed in the framework of the SPOTLIGHT project to identify the boundaries of neighbourhoods as defined by participants in five European urban regions. The aims of this study were (i) to describe self-defined neighbourhood (size and overlap with predefined residential area) according to the characteristics of the sampling administrative neighbourhoods (residential density and socioeconomic status) within the five study regions and (ii) to determine which individual or/and environmental factors are associated with variations in size of self-defined neighbourhoods. Self-defined neighbourhood size varies according to both individual factors (age, educational level, length of residence and attachment to neighbourhood) and contextual factors. These findings have consequences for how residential neighbourhoods are defined and operationalized and can inform how self-defined neighbourhoods may be used in research on associations between contextual characteristics and health outcomes such as obesity.
Assuntos
Obesidade , Características de Residência , População Urbana , Adulto , Idoso , Bélgica , Feminino , França , Humanos , Hungria , Masculino , Pessoa de Meia-Idade , Países Baixos , Fatores Socioeconômicos , Inquéritos e Questionários , Reino UnidoRESUMO
Heart murmurs are common in children and adolescents. Although most are innocent, an isolated heart murmur in asymptomatic children may be the sole finding indicating serious heart disease. Historical elements of familial heart disease, cardiovascular symptoms and a well-conducted medical examination can identify children with an increased risk of heart disease. The distinction between an innocent heart murmur and a pathologic heart murmur is not always easy for primary care physicians because most of them have little experience with auscultation searching for congenital heart malformation. Echocardiography provides a definitive diagnosis of heart disease but is not required in case of innocent murmur. Inappropriate pediatric cardiologist and echocardiographic referral leads to useless and expensive examinations, resulting in a work overload for pediatric cardiologists. The objective of this review is to provide the keys to differentiate innocent and pathologic murmurs, and to help physicians decide on the optimal diagnostic strategy.
Assuntos
Doenças Assintomáticas , Sopros Cardíacos/diagnóstico , Encaminhamento e Consulta , Criança , Competência Clínica , Ecocardiografia , Auscultação Cardíaca , HumanosAssuntos
Alginatos/efeitos adversos , Hidróxido de Alumínio/efeitos adversos , Amiodarona/efeitos adversos , Antiácidos/efeitos adversos , Antiarrítmicos/efeitos adversos , Ácido Silícico/efeitos adversos , Bicarbonato de Sódio/efeitos adversos , Taquicardia Supraventricular/tratamento farmacológico , Alginatos/administração & dosagem , Hidróxido de Alumínio/administração & dosagem , Amiodarona/administração & dosagem , Antiácidos/administração & dosagem , Antiarrítmicos/administração & dosagem , Combinação de Medicamentos , Interações Medicamentosas , Refluxo Gastroesofágico/tratamento farmacológico , Humanos , Lactente , Masculino , Ácido Silícico/administração & dosagem , Bicarbonato de Sódio/administração & dosagem , Falha de TratamentoRESUMO
Hepatitis E (HEV) is an emerging disease in our developed countries, but is not routinely tested for in case of liver cytolysis. However, a growing number of extra-hepatic manifestations of HEV infection associated with acute hepatitis are reported. In this article, we discuss two cases of HEV with neurological symptoms, one with encephalitis, and the other with Parsonage Turner syndrome. All these disorders appeared concomitantly with liver cytolysis and disappeared quickly, following the viral kinetics. Only twenty cases of neurological manifestation of HEV have been described before. The use of HEV serology in patients with concurrent liver cytolysis and neurological symptoms has to be improved.
Assuntos
Neurite do Plexo Braquial/diagnóstico , Neurite do Plexo Braquial/etiologia , Encefalite Viral/diagnóstico , Encefalite Viral/etiologia , Hepatite E/complicações , Hepatite E/diagnóstico , Adulto , Neurite do Plexo Braquial/patologia , Encefalite Viral/patologia , Hepatite E/patologia , Vírus da Hepatite E/isolamento & purificação , Humanos , Masculino , ViremiaRESUMO
BACKGROUND: Healthy diet and physical activity improve risk factors for cerebrovascular disease. It is unclear whether patients with carotid artery disease from Luxemburg meet common guideline criteria and whether systematic counseling has a sustained effect. METHODS: We assessed anthropometric data, eating habits and physical activity habits in 53 patients with carotid atherosclerosis at baseline, after 4 and 20 weeks, and advised them five times for 30 min to follow a modified Mediterranean diet and to perform moderate physical exercise at least during 30 min/day. RESULTS: The patients had a mildly increased BMI (mean 27.6, recommended below 25), they already ate enough vegetables and fruits (mean 485 g daily, recommended at least 400 g), they ate too much sugar (mean 74 g daily) and sodium (mean 2710 mg daily, recommended less than 1500), they consumed 13% of calories from saturated fatty acids (recommended less than 10%), and they already moved sufficiently (62 min daily of moderate and intense physical activity, recommended at least 30 min of moderate physical activity). Lifestyle counseling had a sustained effect on weight, reduction of global caloric intake, carbohydrate and cholesterol intake and on an increase in consumption of poly-unsaturated fatty acids, vegetables and fibres. There was no sustained effect on the consumption of sugar, sodium, and saturated fat. CONCLUSIONS: The reduction of sugar, sodium and saturated fat consumption should be stressed more in counselling of this patient group.
Assuntos
Doenças das Artérias Carótidas/dietoterapia , Aconselhamento , Dieta com Restrição de Carboidratos , Dieta com Restrição de Gorduras , Dieta Hipossódica , Estilo de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Dieta , Ingestão de Energia , Exercício Físico , Feminino , Frutas , Humanos , Luxemburgo , Masculino , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Verduras , Redução de PesoAssuntos
Colonoscopia/efeitos adversos , Endocardite Bacteriana/etiologia , Infecções por Bactérias Gram-Positivas/etiologia , Lactobacillus/isolamento & purificação , Probióticos/efeitos adversos , Idoso , Amoxicilina/administração & dosagem , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Antimaníacos/efeitos adversos , Antimaníacos/sangue , Antimaníacos/uso terapêutico , Artroplastia de Quadril/efeitos adversos , Bacteriemia/tratamento farmacológico , Bacteriemia/etiologia , Bacteriemia/microbiologia , Translocação Bacteriana , Transtorno Bipolar/complicações , Transtorno Bipolar/tratamento farmacológico , Calafrios/induzido quimicamente , Calafrios/etiologia , Diagnóstico Tardio , Suscetibilidade a Doenças , Quimioterapia Combinada , Endocardite Bacteriana/diagnóstico por imagem , Endocardite Bacteriana/tratamento farmacológico , Endocardite Bacteriana/microbiologia , Gentamicinas/administração & dosagem , Gentamicinas/uso terapêutico , Infecções por Bactérias Gram-Positivas/diagnóstico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Lactobacillus/efeitos dos fármacos , Lactobacillus/patogenicidade , Carbonato de Lítio/efeitos adversos , Carbonato de Lítio/sangue , Carbonato de Lítio/uso terapêutico , Masculino , Insuficiência da Valva Mitral/complicações , Neoplasias da Próstata/complicações , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Relacionadas à Prótese/microbiologia , Fatores de Tempo , Ultrassonografia , Iogurte/microbiologiaRESUMO
A retrospective study of 155 cases (114 dogs). The breed, sex and age at the time of the first and opposite onset of nictitans gland prolapse were recorded. Long-term follow-up with a minimum of one-year duration was performed by telephone conversations. One hundred and fourteen dogs representing 155 nictitans gland prolapses were included. 75.4 per cent of the first prolapse occur before one year of age. Unilateral nictitans gland prolapse was observed in 64 per cent of cases. When the condition was bilateral, it occurred simultaneously in 41.4 per cent. When it was bilateral but not simultaneous (24/41), the opposite gland prolapse occurred within three months in 70.8 per cent of the cases. Five breeds were most commonly affected by the bilateral condition: French bulldog, shar pei, great dane, English bulldog and cane corso.
Assuntos
Doenças do Cão/patologia , Glândulas Exócrinas/patologia , Doenças Palpebrais/veterinária , Membrana Nictitante/patologia , Idade de Início , Animais , Cruzamento , Doenças do Cão/epidemiologia , Cães , Doenças Palpebrais/epidemiologia , Doenças Palpebrais/patologia , Feminino , Masculino , Prevalência , Prolapso , Estudos RetrospectivosRESUMO
OBJECTIVE: Excessive food intake has been linked to many factors including taste preference and the presence of psychopathology. The purpose of this study was to investigate the association between sweet and salty taste preference and psychopathology in patients with severe obesity. METHODS: A consecutive series of patients applying for bariatric surgery was recruited for the study. Taste preference was self-reported. Psychopathology was assessed using the revised version of the Minnesota Multiphasic Personality Inventory-2 (MMPI-2). 190 patients were included in the study. RESULTS: In comparison with patients who had salty taste preference, patients with sweet taste preference had significantly higher elevations on the depression (OD: 4.090, p = 0.010) and the hysteria (OD: 2.951, p = 0.026) clinical scales of the MMPI-2. CONCLUSION: The results suggest the presence of an association between taste preference and psychopathology. The findings may be of interest for clinicians who are involved in the treatment of obesity. In particular, they may wish to pay increased attention to patients with sweet taste preference or who have a strong attraction for both sweet and salty foods, in order to detect psychopathology and to adapt the treatment.
Assuntos
Preferências Alimentares/fisiologia , Obesidade Mórbida/fisiopatologia , Obesidade Mórbida/psicologia , Paladar , Adolescente , Adulto , Fatores Etários , Índice de Massa Corporal , Depressão/fisiopatologia , Carboidratos da Dieta , Feminino , Humanos , Hiperfagia/fisiopatologia , Hiperfagia/psicologia , Histeria/fisiopatologia , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Fatores Sexuais , Cloreto de Sódio na DietaRESUMO
Artemisinin derivatives, the current cornerstone of malaria treatment, possess also anti-angiogenic and anti-tumor activity. Hypoxia plays a crucial role both in severe malaria (as a consequence of the cytoadherence of infected erythrocytes to the microvasculature) and in cancer (due to the restricted blood supply in the growing tumor mass). However, the consequences of hypoxia onto the effects of artemisinins is under-researched. This study aimed at assessing how the inhibition of microvascular endothelial cell (HMEC-1) growth induced by dihydroartemisinin (DHA, an antimalarial drug and the active metabolite of currently in-use artemisinins) is affected by oxygen tension. Low doses of DHA (achieved in the patients' plasma when treating malaria) were more inhibitory in hypoxia, whereas high doses (required for anti-angiogenic or anti-tumor activity) were more effective in normoxia. The peroxide bridge is essential for cellular toxicity (deoxyDHA was inactive). High doses of DHA caused HMEC-1 apoptosis and G2 cell cycle arrest. Effects were mediated by the generation of oxidative stress as demonstrated by DCF-DA fluorescence and membrane lipid peroxidation analysis. Overall, these results suggest that DHA inhibition of endothelial cell growth is related to the level of tissue oxygenation and drug concentration. This should be considered when studying both the effects of artemisinin derivatives as antimalarials and the potential therapeutic applications of these drugs as anti-tumor agents.
Assuntos
Antimaláricos/farmacologia , Artemisininas/farmacologia , Hipóxia Celular , Células Endoteliais/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Ácido Ascórbico/farmacologia , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Células Endoteliais/metabolismo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismoRESUMO
UNLABELLED: The value of prenatal diagnosis of major congenital heart diseases (CHDs) has already been proved. In this study, we observed the evolution of the detection rate of CHDs and the quality of the diagnoses over a 15-year period in the Indre-et-Loire department of France. METHOD: Retrospective analysis of the quantitative and qualitative data of prenatal diagnosis between 2000 and 2005 (period 3) and comparison with studies conducted from 1991 to 1994 (period 1) and from 1995 to 1999 (period 2). The CHDs considered to be detectable are the major CHDs with neonatal symptoms. In order to analyze the quality of prenatal diagnosis, each diagnosis was classified as correct, false, or incomplete during period 3. RESULTS: Period 3: 65.7% detectable CHDs were screened. Using period 1 criteria for prenatal diagnosis, the percentage of CHDs detected for periods 1, 2, and 3 was 43.2, 66.7, and 78%, respectively. Between periods 2 and 3, the detection rate increased from 52 to 74% for CHDs diagnosed with the visualization of the outflow tract. It increased from 63 to 71% for CHDs diagnosed with a four-chamber view. During period 3, diagnoses made by a pediatric cardiologist were correct and complete in 80% of cases. It was less than 25% otherwise. CONCLUSION: The improvement of prenatal diagnosis over time results from technological progress, the greater experience of ultrasonographers, and the systematic visualization of the outflow tract in addition to the four-chamber view. Despite the improvement in prenatal diagnosis, one-third of major CHDs were not screened before birth. Pediatricians still need to diagnose CHDs after birth.
Assuntos
Cardiopatias Congênitas/diagnóstico , Diagnóstico Pré-Natal/tendências , Feminino , França , Humanos , Gravidez , Estudos Retrospectivos , Fatores de Tempo , Ultrassonografia Pré-NatalRESUMO
OBJECTIVE: To ascertain whether mefloquine (MQ) produces electrocardiogram (ECG) changes that could be a risk for Torsades de Pointe (TdP), a potentially malignant, ventricular tachyarrhythmia. METHODS: We measured the Fridericia corrected QT (QTcF) intervals on 12 lead ECGs on days (D) 0, 3, 7 in Plasmodium falciparum infected adults, treated with oral artesunate (AS) and MQ as a new fixed dose (n = 25) combination or loose tablets (n = 25) over 3 days. Target total doses were 12 mg/kg of AS and 24-25 mg/kg of MQ. MQ concentrations ([MQ]) were measured by HPLC. RESULTS: All ECG intervals were similar between drug arms and were combined for analysis. Mean QTcF values were 389 (D0), 407 (D3) and 399 (D7) ms (Ps < 0.003 vs. D0); corresponding heart rates and [MQ]s were 83, 67 and 73 beats/minute (Ps ≤ 0.0003 vs. D0) and 0, 3095 and 1721 ng/ml. One male patient (loose arm) had a D3 QTcF 504 ms (D0 406 ms, D7 433 ms). In the modelling of QTcF and JTcF from D0 to D7, significant effects were observed individually for [MQ], temperature and heart rate (HR). The MQ AUC(0-∞) was not a significant factor. Using a manual descending, model building approach to select variables, the HR was the only significant variable (P = 0.001) over time in the model that best explained the changes in the QTcF and JTcF intervals. CONCLUSIONS: In this small group of patients, slowing heart rates due to malaria resolution best explained the observed increases in the QTcF intervals.
Assuntos
Antimaláricos/efeitos adversos , Artemisininas/efeitos adversos , Malária Falciparum/tratamento farmacológico , Mefloquina/efeitos adversos , Torsades de Pointes/induzido quimicamente , Adolescente , Adulto , Antimaláricos/administração & dosagem , Antimaláricos/uso terapêutico , Artemisininas/administração & dosagem , Artemisininas/uso terapêutico , Artesunato , Combinação de Medicamentos , Quimioterapia Combinada/métodos , Eletrocardiografia/efeitos dos fármacos , Feminino , Humanos , Masculino , Mefloquina/administração & dosagem , Mefloquina/uso terapêutico , Pessoa de Meia-Idade , Adulto JovemRESUMO
A new fixed-dose artesunate (AS)-mefloquine (MQ) was assessed in adults hospitalized for 28 days with uncomplicated drug-resistant falciparum malaria. The patients (n = 25/arm) were treated with (i) two fixed-dose tablets (AS-MQ arm; 100 mg AS-200 mg MQ/tablet) daily for 3 days (days 0, 1, and 2) or (ii) nonfixed AS (AS-plus-MQ arm; 4 mg/kg of body weight/day for 3 days) plus MQ (15 mg/kg on day 1 and 10 mg/kg on day 2), dosed by weight. Clinical laboratory electrocardiogram (ECG), adverse events (AEs), efficacy, and pharmacokinetic parameters were assessed over 28 days. Both regimens were well tolerated. No AEs were drug related. Two serious AEs of malaria-induced hypotension occurring in the AS-MQ arm necessitated rescue treatment. There were no significant changes in hematology, biochemistry, or PR and QRS intervals. For all patients, mean Fridericia-corrected QT intervals were significantly (P < or = 0.0027) prolonged on day 3 (407 ms) and day 7 (399 ms) versus day 0 (389 ms), in parallel with significant (P < or = 0.0003) falls in heart rates (67 [day 3], 73 [day 7], and 83 [day 0] beats/minute). Fixed-nonfixed formulations were bioequivalent for MQ, but not for AS and dihydroartemisinin (DHA). One AS-MQ patient developed a new infection on day 28; his day 28 plasma MQ concentration was 503.8 ng/ml. Fixed-dose AS-MQ was well tolerated, had pharmacokinetic (PK) profiles broadly similar to those of nonfixed AS plus MQ, and is a suitable replacement.
Assuntos
Antimaláricos/farmacocinética , Antimaláricos/uso terapêutico , Artemisininas/farmacocinética , Artemisininas/uso terapêutico , Malária Falciparum/tratamento farmacológico , Mefloquina/farmacocinética , Mefloquina/uso terapêutico , Adolescente , Adulto , Idoso , Antimaláricos/administração & dosagem , Antimaláricos/efeitos adversos , Antimaláricos/farmacologia , Artemisininas/administração & dosagem , Artemisininas/efeitos adversos , Artemisininas/farmacologia , Artesunato , Resistência a Múltiplos Medicamentos , Feminino , Humanos , Malária Falciparum/metabolismo , Malária Falciparum/patologia , Masculino , Mefloquina/administração & dosagem , Mefloquina/efeitos adversos , Mefloquina/farmacologia , Pessoa de Meia-Idade , Plasmodium falciparum/efeitos dos fármacos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: In Parkinson's disease (PD), there is entanglement of disease-inherent and treatment-induced sleep abnormalities. So far, there has been no study specifically investigating the influence of diurnal dopaminergic medication (DM) on nocturnal slow wave sleep (SWS). METHODS: Polysomnographic analysis in 62 PD patients. RESULTS: PD patients had a sleep efficiency of 70 +/- 17% and an SWS amount of 16 +/- 11%. Linear regression analysis showed no significant correlation between the amounts of SWS and DM. However, patients with a medium DM dosage (300-600 mg of levodopa equivalents) preserved a SWS percentage >25% (p = 0.035, chi(2) test) more frequently than patients with higher or smaller DM. The DM dosage had no effect on other main sleep parameters. Psychotropic comedication had no effect on SWS percentage. In contrast, SWS amount was inversely correlated with both disease duration and age. It was independent of rapid eye movement sleep amount. The natural female bonus effect on SWS amount was absent in women with PD. CONCLUSION: Diurnal dopaminergic treatment has no major impact on SWS in PD, which, however, decreases with disease duration. Disease-dependent, but treatment-independent decrease in SWS suggests primary degeneration of sleep-regulating systems in PD.
Assuntos
Dopaminérgicos/efeitos adversos , Doença de Parkinson/tratamento farmacológico , Sono/efeitos dos fármacos , Idoso , Relação Dose-Resposta a Droga , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/fisiopatologia , Polissonografia , Fatores Sexuais , Sono REM , Estatísticas não ParamétricasRESUMO
Obesity is an important public health issue with an epidemic spread in adolescents and children, which needs to be tackled. This systematic review of primary care physicians' knowledge, attitudes, beliefs and practices (KABP) regarding childhood obesity will help to implement or adjust the actions necessary to counteract obesity. Eligible studies were identified through a systematic database search for all available years to 2007. Articles were selected if they included data on primary care physicians' KABP regarding childhood obesity: 130 articles were assessed and eventually 11 articles covering the period 1987-2007 and responding to the inclusion criteria were analyzed. The included studies showed that almost all physicians agreed on the necessity to treat childhood obesity but they believed to have a low self-efficacy in the treatment and experienced a negative feeling regarding obesity management. There was a large heterogeneity in the assessment of childhood obesity between the different studies but the awareness of the importance of using body mass index increased over the years among physicians. Almost all studies noted that physicians recommended dietary advice, exercise or referral to a dietician. From this review, it is obvious that there is a need for education of primary care physicians to increase the uniformity of the assessment and to improve physicians' self-efficacy in managing childhood obesity. Multidisciplinary treatment including general practitioners, paediatricians and specialized dieticians appears to be the way to counteract the growing obesity epidemic and thus, primary care physicians have to initiate, coordinate and obviously participate in obesity prevention initiatives.