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1.
PLoS Negl Trop Dis ; 14(1): e0008028, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31986140

RESUMO

BACKGROUND: Nifurtimox eflornithine combination therapy (NECT) to treat human African trypanosomiasis (HAT), commonly called sleeping sickness, was added to the World Health Organisation's (WHO) Essential Medicines List in 2009 and to the Paediatric List in 2012. NECT was further tested and documented in a phase IIIb clinical trial in the Democratic Republic of Congo (DRC) assessing the safety, effectiveness, and feasibility of implementation under field conditions (NECT-FIELD study). This trial brought a unique possibility to examine concomitant drug management. METHODOLOGY/PRINCIPAL FINDINGS: This is a secondary analysis of the NECT-FIELD study where 629 second stage gambiense HAT patients were treated with NECT, including children and pregnant and breastfeeding women in six general reference hospitals located in two provinces. Concomitant drugs were prescribed by the local investigators as needed. Patients underwent daily evaluations, including vital signs, physical examination, and adverse event monitoring. Concomitant medication was documented from admission to discharge. Patients' clinical profiles on admission and safety profile during specific HAT treatment were similar to previously published reports. Prescribed concomitant medications administered during the hospitalization period, before, during, and immediately after NECT treatment, were mainly analgesics/antipyretics, anthelmintics, antimalarials, antiemetics, and sedatives. Use of antibiotics was reasonable and antibiotics were often prescribed to treat cellulitis and respiratory tract infections. Prevention and treatment of neurological conditions such as convulsions, loss of consciousness, and coma was used in approximately 5% of patients. CONCLUSIONS/SIGNIFICANCE: The prescription of concomitant treatments was coherent with the clinical and safety profile of the patients. However, some prescription habits would need to be adapted in the future to the evolving available pharmacopoeia. A list of minimal essential medication that should be available at no cost to patients in treatment wards is proposed to help the different actors to plan, manage, and adequately fund drug supplies for advanced HAT infected patients. TRIAL REGISTRATION NUMBER: The initial study was registered at ClinicalTrials.gov, number NCT00906880.


Assuntos
Eflornitina/uso terapêutico , Nifurtimox/uso terapêutico , Tripanossomicidas/uso terapêutico , Trypanosoma brucei gambiense , Tripanossomíase Africana/tratamento farmacológico , República Democrática do Congo/epidemiologia , Quimioterapia Combinada , Eflornitina/administração & dosagem , Humanos , Nifurtimox/administração & dosagem , Resultado do Tratamento , Tripanossomíase Africana/epidemiologia
2.
Front Pharmacol ; 10: 1326, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31780942

RESUMO

Introduction: Use of herbal medicines (HMs) is widespread across the world, with many people relying on HMs for their primary healthcare or using HMs in the context of a healthy life style. HMs originate from plant material and, as such, are often seen as "natural" and believed to be (relatively) safe by patients. Hepatobiliary disorders have been associated with numerous HMs. Aim: This paper aims to analyze reporting patterns for hepatobiliary disorders associated with HMs use from reports submitted to the WHO global database of individual case safety reports (ICSRs) VigiBase. Methods: A data extraction in VigiBase, the WHO international database of ICSR reports, was performed by the Uppsala Monitoring Centre on 2019-01-16. The dataset contained all ICSRs where an HM was identified with the UMC-assigned ATC code "V90: unspecified herbal and traditional medicine" and where the HM was classified as being either the suspected drug or an interacting drug, and containing at least one adverse reaction in the MedDRA® System Organ Class (SOC) Hepatobiliary Disorders (HBD). Descriptive analyses in Excel 2013® were used to determine general characteristics of the reports in the broad data set, including total number of reports, reporting country and patient characteristics. For single suspect herbal reports, reports categorized as "serious" according to CIOMS criteria (CIOMS), 2001) were extracted. Results: In total, 2,483 reports describing with at least one ADR in the SOC HBD were extracted from VigiBase. In total, 780 (31.4%) reports concern only one suspect HM. However, for 188 reports of these reports (24.1%), the single suspect herbal preparation contains more than one herbal ingredient. The 592 reports for single suspect herbal preparations described a total of 764 ADRs in the SOC HBD. Jaundice was the most reported ADR for these reports. Conclusion: Almost 2,500 reports for HMs and with at least one ADR coded to the MedDRA® SOC HBD were retrieved from VigiBase. Of the HBD SOC HM reports, around 25% concerned a single herbal species as the suspect "drug." Substantial issues with coding of the suspect herbal drugs were found. In-depth causality assessment of the cases is needed to draw conclusions on the strength of the relationships.

3.
Ther Adv Drug Saf ; 10: 2042098619864853, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31360433

RESUMO

Implementation of pharmacovigilance (PV) systems in resource-limited countries is a real endeavor. Despite country- and continent-specific challenges, the Democratic Republic of the Congo (DRC) has been able to develop one of the most active PV systems in the sub-Saharan Africa. The World Health Organization (WHO) regional Office identified the DRC experience to set up a PV system for antimalarial drugs safety monitoring as a 'best practice' that needed to be documented in order to help DRC improve its PV system and to be scaled up in other African countries. In response to the WHO request, a best practices and bottlenecks analysis was conducted in 2015. This analysis was updated in 2018 in the light of the minimum requirements of the WHO to set up a PV system taking into account other guidance for PV systems. The following themes were retained for analysis: (1) creation of the national PV center; (2) implementation of PV in the health system; (3) data collection and analysis; (4) collaboration with public health programs; (5) collaboration with the National Regulatory Authority. Lessons learnt from the DRC experience show that it is possible to implement PV systems in order to promote patients' safety in resource limited sub-Saharan African countries with no guaranteed funding. The ability of national PV centers to collaborate with Public health stakeholders, including public health authorities at all levels as well as public health programs, and to use existing health information systems are considered the main key to success and may substantially reduce the cost of PV activities.

4.
BMJ Open ; 9(1): e022206, 2019 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-30670502

RESUMO

OBJECTIVE: The aim of this study was to determine the burden and risk factors of prediabetes and diabetes in the general adult population of Luxembourg. DESIGN: Cross-sectional survey between 2013 and 2015. SETTING: Data were collected as part of the European Health Examination Survey in Luxembourg (EHES-LUX). PARTICIPANTS: 1451 individuals were recruited in a random sample of the 25-64-year-old population of Luxembourg. OUTCOMES: Diabetes was defined by a glycaemic biomarker (fasting plasma glucose (FPG) ≥7.0 mmol/L), self-reported medication and medical diagnosis; prediabetes by a glycaemic biomarker (FPG 5.6-6.9 mmol/L), no self-reported medication and no medical diagnosis. Undiagnosed diabetes was defined only from the glycaemic biomarker; the difference between total and undiagnosed diabetes was defined as diagnosed diabetes. Odds of diabetes and prediabetes as well as associated risk factors were estimated. RESULTS: The weighted prevalence of prediabetes and diabetes was 25.6% and 6.5%, respectively. Nearly 4.8% (men: 5.8%; women: 3.8%) were diagnosed diabetes and 1.7% (men: 2.6%; women: 0.7%) were undiagnosed diabetes. The multivariable-adjusted OR (MVOR) for diabetes risk were: age 1.05 (95% CI 1.01 to 1.09), family history of diabetes 3.24 (1.95-5.38), abdominal obesity 2.63 (1.53-4.52), hypertension 3.18 (1.76-5.72), one-unit increase of triglycerides 1.16 (1.10-1.22) and total cholesterol 0.74 (0.64-0.86). The MVOR for prediabetes risk were: age 1.04 (95% CI 1.02 to 1.06), male sex 1.84 (1.30-2.60), moderate alcohol consumption 1.38 (1.01-1.89), family history of diabetes 1.52 (1.13-2.05), abdominal obesity 1.44 (1.06-1.97), second-generation immigrants 0.61 (0.39-0.95) and a one-unit increase of serum high-density lipoprotein cholesterol 0.70 (0.54-0.90). CONCLUSIONS: In Luxembourg, an unexpectedly high number of adults may be affected by prediabetes and diabetes. Therefore, these conditions should be addressed as a public health priority for the country, requiring measures for enhanced detection and surveillance, which are currently lacking, especially in primary care settings.


Assuntos
Efeitos Psicossociais da Doença , Diabetes Mellitus/epidemiologia , Emigrantes e Imigrantes/estatística & dados numéricos , Estado Pré-Diabético/epidemiologia , Saúde Pública , Adulto , Distribuição por Idade , Glicemia/análise , Estudos Transversais , Diabetes Mellitus/diagnóstico , Feminino , Inquéritos Epidemiológicos , Humanos , Hipertensão/epidemiologia , Modelos Logísticos , Luxemburgo/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Estado Pré-Diabético/diagnóstico , Fatores de Risco , Distribuição por Sexo
5.
BMC Public Health ; 18(1): 1169, 2018 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-30309333

RESUMO

BACKGROUND: The European Health Examination Survey in Luxembourg (EHES-LUX) is a population based survey performed from 2013 to 2015 with the aim to establish baseline information on the general health status of the Luxembourg population aged 25 to 64 years. The paper introduces the study design, recruitment method and representativeness of the sample, and summarizes the sociodemographic characteristics of participants and the prevalence of major health outcomes. METHODS: EHES-LUX is based on a random sample representative of the population of Luxembourg based on gender, age and district of residence. The sample size of the study was determined to provide accurate prevalence estimates for major chronic conditions. During two visits, data were collected from participants through a questionnaire (personal data, health status and health care), medical examinations (anthropometric measures, electrocardiogram and spirometry) and biological analysis (blood, urine and hair). Means and frequencies were used to describe the general characteristics of the population and a one-way ANOVA to test the representativeness of the sample and the comparability of participants and non-participants. RESULTS: A total of 1529 individuals participated in this study (participation rate of 24.1%). Differences between participants and non-participants based on gender, age and district of residence were corrected by sampling weights. The mean age (±SD) of participants was 44.9 (±10.1) years, of which 52.8% were women. Based on clinical measurements, nearly 20% of participants were obese and more than one in three participants were overweight. From measurements (respectively from self-report), 22.0% (respectively 12.2%) were hypertensive, 49.3% (respectively 22.5%) had hypercholesterolemia, 3.5% (respectively 3.7%) had diabetes and 7.6% (respectively 6.0%) had depressive symptoms. CONCLUSIONS: This nationwide epidemiological study on the general health status of Luxembourg residents provides updated prevalence estimates on a range of major health conditions. This information can be used by health authorities to evaluate policies and public health initiatives. At European level, prevalence data obtained by this study following the EHES-Reference Committee (EHES-RC) recommendations, will be comparable between European countries participating in this program.


Assuntos
Nível de Saúde , Inquéritos Epidemiológicos , Projetos de Pesquisa , Adulto , Depressão/epidemiologia , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Hipercolesterolemia/epidemiologia , Hipertensão/epidemiologia , Luxemburgo/epidemiologia , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Prevalência
6.
Vaccine ; 36(41): 6170-6182, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30190119

RESUMO

BACKGROUND: In early 2016, there was a Yellow Fever (YF) outbreak in Central Africa with several deaths reported from Angola and the Democratic Republic of Congo. Due to a shortage in vaccine supply, fractional dosing (0.1 ml) of 17DD Yellow Fever Vaccine (YFV) was proposed in preventive vaccination campaign in Kinshasa in August 2016. A Pharmacovigilance surveillance at community level was implemented to track Adverse Events Following Immunization (AEFIs). The objective of this study was to describe AEFIs as captured from community-based pharmacovigilance and to compare the safety profile of the fractional dosing of YFV between gender. METHODS: PV information sessions were organized in churches, academic institutions, and pediatrician, obstetrician and friend networks. Prior to data collection, education about AEFI was provided through face-to-face discussions, phone calls, SMS and WhatsApp messages. Individuals reported AEFIs though the above communication channels to assigned individuals. Reported AEFIs were entered into VigiFlow and extracted for statistical analysis using Stata 12. Only vaccinees who received fractional dose (subjects from the age of 2-year-old and non-pregnant women) were included in analysis. Proportional t-test was used to compare AEFI preferred terms among males and females. RESULTS: A total of 4020 subjects reported 5409 AEFIs. Reporters were mostly males (54.9%) with an average age of 26 ±â€¯10.7 years. Fever and injection site pain were the most reported systemic and local AEFI respectively. The safety profile was similar between gender although females reported more diarrhea and dizziness whilst males reported more asthenia (P < 0.001). Five individuals reported serious AEFIs. Among them, 4 were less-immunocompetent. CONCLUSION: Fractional dosing of 17DD YFV has a good safety profile, which is similar between gender. These findings complement the documented immunogenicity profile to support recommendation of fractional dose of YFV for outbreak control.


Assuntos
Vacina contra Febre Amarela/administração & dosagem , Vacina contra Febre Amarela/efeitos adversos , Adolescente , Adulto , República Democrática do Congo , Feminino , Humanos , Masculino , Vacinação/efeitos adversos , Febre Amarela/prevenção & controle , Adulto Jovem
7.
PLoS One ; 13(6): e0197021, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29902172

RESUMO

The analyses of geographic variations in the prevalence of major chronic conditions, such as overweight and obesity, are an important public health tool to identify "hot spots" and inform allocation of funding for policy and health promotion campaigns, yet rarely performed. Here we aimed at exploring, for the first time in Luxembourg, potential geographic patterns in overweight/obesity prevalence in the country, adjusted for several demographic, socioeconomic, behavioural and health status characteristics. Data came from 720 men and 764 women, 25-64 years old, who participated in the European Health Examination Survey in Luxembourg (2013-2015). To investigate the geographical variation, geo-additive semi-parametric mixed model and Bayesian modelisations based on Markov Chain Monte Carlo techniques for inference were performed. Large disparities in the prevalence of overweight and obesity were found between municipalities, with the highest rates of obesity found in 3 municipalities located in the South-West of the country. Bayesian approach also underlined a nonlinear effect of age on overweight and obesity in both genders (significant in men) and highlighted the following risk factors: 1. country of birth for overweight in men born in a non-European country (Posterior Odds Ratio (POR): 3.24 [1.61-8.69]) and women born in Portugal (POR: 2.44 [1.25-4.43]), 2. low educational level (secondary or below) for overweight (POR: 1.66 (1.06-2.72)] and obesity (POR:2.09 [1.05-3.65]) in men, 3. single marital status for obesity in women (POR: 2.20 [1.24-3.91]), 4.fair (men: POR: 3.19 [1.58-6.79], women: POR: 2.24 [1.33-3.73]) to very bad health perception (men: POR: 15.01 [2.16-98.09]) for obesity, 5. sleeping more than 6 hours for obesity in unemployed men (POR: 3.66 [2.02-8.03]). Protective factors highlighted were: 1. single marital status against overweight (POR: [0.60 (0.38-0.96)]) and obesity (POR: 0.39 [0.16-0.84]) in men, 2. the fact to be widowed against overweight in women (POR: [0.30 (0.07-0.86)], as well as a non European country of birth (POR: 0.49 [0.19-0.98]), tertiary level of education (POR: 0.34 [0.18-0.64]), moderate alcohol consumption (POR: 0.54 [0.36-0.90]) and aerobic physical activity practice (POR: 0.44 [0.27-0.77]) against obesity in women. A double burden of environmental exposure due to historic mining and industrial activities and past economic vulnaribility in the South-West of the country may have participated to the higher prevalence of obesity found in this region. Other demographic, socioeconomic, behavioural and health status covariates could have been involved as well.


Assuntos
Comportamentos Relacionados com a Saúde , Inquéritos Epidemiológicos , Obesidade/epidemiologia , Adulto , Feminino , Humanos , Luxemburgo/epidemiologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Sexuais , Fatores Socioeconômicos
8.
J Affect Disord ; 222: 41-48, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28668715

RESUMO

BACKGROUND: Depression is a complex mental disorder that affects an increasing proportion of the worldwide population. This study aims to estimate the prevalence of depressive symptoms in Luxembourg, associated risk factors and geographic variations. Additionally, it aims to assess whether first and second generation immigrants are at higher risk for depressive symptoms compared to non-immigrants. METHODS: Representative cross-sectional data from 1499 residents of Luxembourg, aged 25-64 years, were collected from the Luxembourg European Health Survey (EHES-LUX). Depressive symptoms were defined as a score of ≥5 on the Patient Health Questionnaire for depression (PHQ-9) (i.e. mild, moderate or severe). Standard and Bayesian regression models were used to examine associations between depressive symptoms, immigration status and geographic distribution across Luxembourg. RESULTS: The prevalence of depressive symptoms was 21.55% (15.54% mild, 3.54% moderate, and 2.49% moderately severe to severe). The odds of having depressive symptoms was higher among second generation immigrants compared to non-immigrants (OR: 1.58, 95% CI: 1.04, 2.41), independent of socioeconomic and behavioral characteristics. Healthier diet, higher social support and good health perception were protective towards experiencing depressive symptoms. One of the highest likelihoods of reporting depressive symptoms was observed in the South-West of the country with a positive effect at 80% credible region [CR] (1.42 [0.92, 2.73]). LIMITATIONS: The participation rate was low (26.7%). The cross-sectional nature of the study does not allow us to establish causality. CONCLUSIONS: Depression constitutes an important public health challenge in Luxembourg due to the impact on the overall health of the population. Social programs of health promotion should be developed to improve mental wellbeing in immigrants, especially those of second generation.


Assuntos
Transtorno Depressivo/epidemiologia , Emigração e Imigração , Adulto , Teorema de Bayes , Estudos Transversais , Grupo com Ancestrais do Continente Europeu , União Europeia , Feminino , Geografia , Inquéritos Epidemiológicos , Humanos , Luxemburgo/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto Jovem
9.
Medicine (Baltimore) ; 95(36): e4758, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27603374

RESUMO

Hypertension is a modifiable risk factor for cardiovascular disease, but it remains the main cause of death in Luxembourg. We aimed to estimate the current prevalence of hypertension, associated risk factors, and its geographic variation in Luxembourg.Cross-sectional, population-based data on 1497 randomly selected Luxembourg residents aged 25 to 64 years were collected as part of the European Health Examination Survey from 2013 to 2015. Hypertension was defined as systolic/diastolic blood pressure ≥140/90 mm Hg, self-report of a physician diagnosis or on antihypertensive medication. Standard and Bayesian regressions were used to examine associations between hypertension and covariates, and also geographic distribution of hypertension across the country.Nearly 31% of Luxembourg residents were hypertensive, and over 70% of those were either unaware of their condition or not adequately controlled. The likelihood of hypertension was lower in men more physically active (odds ratio [95% credible region] 0.6 [0.4, 0.9]) and consuming alcohol daily (0.3 [0.1, 0.8]), and higher in men with a poor health perception (1.6 [1.0, 2.7]) and in women experiencing depressive symptoms (1.8 [1.3, 2.7]). There were geographic variations in hypertension prevalence across cantons and municipalities. The highest odds ratio was observed in the most industrialized region (South-West) (1.2 [0.9, 1.6]) with a positive effect at 90% credible region.In Luxembourg, the vast majority of people with hypertension are either unaware of their condition or not adequately controlled, which constitutes a major, neglected public health challenge. There are geographic variations in hypertension prevalence in Luxembourg, hence the role of individual and regional risk factors along with public health initiatives to reduce disease burden should be considered.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Hipertensão/epidemiologia , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Exercício Físico , Feminino , Nível de Saúde , Inquéritos Epidemiológicos , Humanos , Hipertensão/tratamento farmacológico , Luxemburgo/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Proteção , Fatores de Risco
10.
Cerebrovasc Dis ; 37(5): 368-75, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24970377

RESUMO

BACKGROUND: A Mediterranean diet, with and without small daily amounts of red wine, and physical activity reduce the risk of cerebrovascular disease and improve cognition. An increase in cerebral blood flow may be the underlying mechanism. Under normal conditions, cerebral blood flow velocity changes in the internal carotid arteries and in large basal cerebral arteries correlate closely with cerebral blood flow changes, as the diameter of these vessels hardly changes and only the smaller vessels downstream change their diameter. METHODS: A prospective randomized controlled trial was performed in 108 patients with carotid atherosclerosis (mean age 64 years, 67% men, 66% on statin therapy). Half of them were advised to follow a polyphenol-rich modified Mediterranean diet including 1-2 tomatoes, 3-5 walnuts and a bar of dark chocolate (25 g) a day and to perform moderate physical exercise for 30 min/day (lifestyle changes). Within these two groups, half of the patients were randomized either to avoid any alcohol or to drink 100 ml of red wine (women) or 200 ml of red wine (men) daily. Bilateral middle cerebral and internal carotid blood flow velocity (peak systolic, peak end-diastolic and mean) was measured at baseline and after 4 and 20 weeks using colour-coded duplex ultrasound. Insonation depth and insonation angle were used to identically place the sample volume during follow-up investigations. A general linear model with Tukey-Kramer adjustment for multiple comparisons was used to assess the primary end points. For the analysis we used the mean values of the right and left artery. RESULTS: Neither lifestyle changes nor red wine had an effect on peak systolic, peak end-diastolic or mean cerebral blood flow velocity. CONCLUSIONS: Advice on lifestyle changes, including a modified polyphenol-rich Mediterranean diet, a glass of red wine daily and physical exercise, did not affect middle cerebral and internal carotid blood flow velocity in our patient group with carotid atherosclerosis. An increase in cerebral blood flow is thus unlikely to be the cause of the reduced risk of cerebrovascular disease and improved cognitive functioning described in the literature. One possible explanation for the fact that blood flow velocity was not affected by red wine, diet and physical activity advice is that two thirds of our patients were already on statin therapy. Statins increase cerebral blood flow and vasomotor reactivity via nitric oxide.


Assuntos
Arteriosclerose/sangue , Velocidade do Fluxo Sanguíneo/fisiologia , Artéria Carótida Interna/diagnóstico por imagem , Circulação Cerebrovascular/fisiologia , Estilo de Vida , Artéria Cerebral Média/diagnóstico por imagem , Atividade Motora/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Arteriosclerose/fisiopatologia , Dieta , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ultrassonografia Doppler Dupla/métodos , Ultrassonografia Doppler Transcraniana , Vinho
11.
Nutr J ; 12(1): 147, 2013 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-24228901

RESUMO

BACKGROUND: Physical exercise and a Mediterranean diet improve serum lipid profile. The present work studied whether red wine has an effect on top of a lipid-lowering lifestyle in patients with carotid atherosclerosis. METHODS: A prospective randomised unblinded trial was performed from 2009 to 2011 in 108 patients with carotid atherosclerosis, 65% of whom were already on statin therapy with a low mean LDL of 104.9 mg/dl. Half of them were advised to follow a modified Mediterranean diet and to perform moderate physical exercise during 30 min/day (lifestyle changes) for 20 weeks. Within these two groups half of the patients were randomised either to avoid any alcohol or to drink 100 ml of red wine (women) or 200 ml of red wine (men) daily. RESULTS: LDL was significantly lowered by 7% in the lifestyle-changes group compared to the no-lifestyle-changes group (p = 0.0296) after 20 weeks. Lifestyle changes lowered the LDL/HDL ratio after 20 weeks by 8% (p = 0.0242) and red wine independently by 13% (p = 0.0049). The effect on LDL/HDL ratio after 20 weeks was, however, more pronounced in the non-LC group. Total cholesterol (-6%; p = 0.0238) and triglycerides (-13%; p = 0.0361) were lowered significantly by lifestyle changes after 20 weeks compared to the no-lifestyle-changes group. Lipoprotein (a) was not significantly affected by any intervention. The given results are per ITT analysis. CONCLUSIONS: Lifestyle changes including a modified Mediterranean diet and physical exercise as well as a glass of red wine daily improve independently the LDL/HDL ratio in patients with carotid arteriosclerosis even though the vast majority of them was already on statin therapy.


Assuntos
Arteriosclerose/sangue , Estilo de Vida , Vinho , Adulto , Idoso , Idoso de 80 Anos ou mais , Arteriosclerose/tratamento farmacológico , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dieta Mediterrânea , Determinação de Ponto Final , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Masculino , Pessoa de Meia-Idade , Atividade Motora , Estudos Prospectivos , Triglicerídeos/sangue , Vinho/classificação
12.
Cerebrovasc Dis Extra ; 3(1): 121-9, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24403903

RESUMO

BACKGROUND: Regular consumption of small amounts of red wine improves blood lipids. However, there is concern whether this beneficial effect might be counterbalanced by an increase in blood pressure (BP) and heart rate (HR), which are risk factors for cerebro-cardiovascular disease. In particular, we studied whether regular consumption of red wine with and without lifestyle changes (LC; healthy diet and physical activity advice) results in an increase in BP and HR. METHODS: A prospective, unblinded randomized trial was performed in 108 patients (67% men) with carotid atherosclerosis documented by ultrasound, a mean BP of 122/79 mm Hg and a mean HR of 71 bpm at inclusion in the study. Sixty-eight percent were known and treated hypertensives. The mean 24-hour BP at baseline was 122/79 mm Hg. Half of the study participants, the control group, was seen by a nurse at baseline, after 4 and after 20 weeks, and was instructed not to change their eating and physical activity habits. In the other half, a dietician performed five sessions of 30 min each (at baseline, after 1 week and after 2, 3 and 4 weeks) giving advice on healthy eating based on a Mediterranean diet and physical exercise. The recommendations given were the following: 5 portions of fruit/vegetables per day, a diet low in absolute fat, a preference of vegetable oil (olive or rapeseed oil), whole-grain products, poultry, low-fat dairy products, 1 fat and 1 lean fish meal per week, reduced consumption of red meat, and avoidance of pork, ready-made meals, sugar and excessive salt intake. In addition, regular consumption of 1 bar of dark chocolate (25 g, >70% of cacao), 1-2 tomatoes, and 3-5 walnuts as well as at least 30 min of moderate daily physical activity were recommended. Within these two groups, half of the patients were randomized either to avoid alcohol completely or to drink 100 ml (women) or 200 ml of red wine (men) daily. RESULTS: Neither LC nor red wine had an effect on the mean systolic and diastolic 24-hour BP and HR after 4 and 20 weeks, as analyzed by general linear modeling. No difference was found for diurnal and nocturnal values. CONCLUSIONS: The possible beneficial effect of regular consumption of small amounts of red wine is not counterbalanced in the long term by an increase in the mean BP or HR in mainly normotensive and well-treated hypertensive patients with carotid atherosclerosis, neither in the patients given healthy lifestyle advice nor in those with a standard lifestyle. Yet, we remain cautious about actively advice patients to drink alcohol regularly given the well-known risks.

13.
PLoS Negl Trop Dis ; 6(11): e1920, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23209861

RESUMO

BACKGROUND: Trypanosoma brucei (T.b.) gambiense Human African trypanosomiasis (HAT; sleeping sickness) is a fatal disease. Until 2009, available treatments for 2(nd) stage HAT were complicated to use, expensive (eflornithine monotherapy), or toxic, and insufficiently effective in certain areas (melarsoprol). Recently, nifurtimox-eflornithine combination therapy (NECT) demonstrated good safety and efficacy in a randomised controlled trial (RCT) and was added to the World Health Organisation (WHO) essential medicines list (EML). Documentation of its safety profile in field conditions will support its wider use. METHODOLOGY: In a multicentre, open label, single arm, phase IIIb study of the use of NECT for 2(nd) stage T.b. gambiense HAT, all patients admitted to the trial centres who fulfilled inclusion criteria were treated with NECT. The primary outcome was the proportion of patients discharged alive from hospital. Safety was further assessed based on treatment emergent adverse events (AEs) occurring during hospitalisation. PRINCIPAL FINDINGS: 629 patients were treated in six HAT treatment facilities in the Democratic Republic of the Congo (DRC), including 100 children under 12, 14 pregnant and 33 breastfeeding women. The proportion of patients discharged alive after treatment completion was 98.4% (619/629; 95%CI [97.1%; 99.1%]). Of the 10 patients who died during hospitalisation, 8 presented in a bad or very bad health condition at baseline; one death was assessed as unlikely related to treatment. No major or unexpected safety concerns arose in any patient group. Most common AEs were gastro-intestinal (61%), general (46%), nervous system (mostly central; 34%) and metabolic disorders (26%). The overall safety profile was similar to previously published findings. CONCLUSIONS/SIGNIFICANCE: In field conditions and in a wider population, including children, NECT displayed a similar tolerability profile to that described in more stringent clinical trial conditions. The in-hospital safety was comparable to published results, and long term efficacy will be confirmed after 24 months follow-up. REGISTRATION: The trial is registered at ClinicalTrials.gov, number NCT00906880.


Assuntos
Quimioterapia Combinada/métodos , Eflornitina/administração & dosagem , Nifurtimox/administração & dosagem , Tripanossomicidas/administração & dosagem , Trypanosoma brucei gambiense/isolamento & purificação , Tripanossomíase Africana/tratamento farmacológico , Adolescente , Adulto , Criança , Pré-Escolar , República Democrática do Congo , Quimioterapia Combinada/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Eflornitina/efeitos adversos , Feminino , Hospitais , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Nifurtimox/efeitos adversos , Gravidez , Análise de Sobrevida , Resultado do Tratamento , Tripanossomicidas/efeitos adversos , Adulto Jovem
14.
Anticancer Res ; 31(6): 2121-8, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21737631

RESUMO

BACKGROUND: Isolated lung perfusion (ILP) with doxorubicin allows a regional increase in drug exposure while sparing unaffected tissues, but clinical results have so far been disappointing, presumably in part because of the limited tumor penetration of doxorubicin. The aim of this study was to assess whether tumor uptake of doxorubicin, administered locoregionally by ILP, would be increased by the administration of P-glycoprotein (P-gp) modulators. MATERIALS AND METHODS: Single-pass antegrade ILP (A-ILP) was performed with doxorubicin in rats bearing a pulmonary sarcoma nodule which were either untreated or received P-gp inhibitors cyclosporin, valspodar or the vehicle, Cremophor®, only. Doxorubicin concentrations in tumor, lung and effluent were measured by high performance liquid chromatography (HPLC) coupled to spectrofluorimetric detection and the expression of P-gp was examined by Western blot in tumors and lungs. RESULTS: Doxorubicin concentrations in tumors were 5- to 10-fold lower than those measured in lungs tissues. Doxorubicin penetration in tumors, expressed as tumor retention ratios (TR60min), were not different between the groups. Western blot analysis did not show any evidence of baseline or doxorubicin-induced P-gp expression in the tumor model. CONCLUSION: P-gp modulation with cyclosporin or valspodar fails to increase the tumor uptake of doxorubin administered by A-ILP. Other reasons for low doxorubicin penetration in tumor, such as high interstitial fluid pressure or tumor vasculature barrier, or alternate cell membrane drug transporters, need to be examined for a better understanding of impaired doxorubicin delivery to tumor.


Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Ciclosporina/farmacologia , Ciclosporinas/farmacologia , Doxorrubicina/farmacocinética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Sarcoma/tratamento farmacológico , Sarcoma/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/biossíntese , Animais , Antibióticos Antineoplásicos/farmacocinética , Quimioterapia do Câncer por Perfusão Regional , Ciclosporina/sangue , Doxorrubicina/administração & dosagem , Interações Medicamentosas , Neoplasias Pulmonares/secundário , Masculino , Ratos , Ratos Endogâmicos F344 , Sarcoma/secundário
15.
Malar J ; 10: 57, 2011 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-21388536

RESUMO

BACKGROUND: In spite of enhanced control efforts, malaria remains a major public health problem causing close to a million deaths annually. With support from several donors, large amounts of artemisinin-based combination therapy (ACT) are being deployed in endemic countries raising safety concerns as little is known about the use of ACT in several of the settings where they are deployed. This project was undertaken to profile the provenance of the pharmacovigilance reporting of all anti-malarials, including ACT to the WHO adverse drug reaction (ADR) database (Vigibase™) over the past 40 years. METHODS: The WHO Programme for International Drug Monitoring, the Uppsala Monitoring Centre (UMC) provided anonymized extracts of Vigibase™ covering the period 1968-2008. All countries in the programme were clustered according to their malaria control phase and income status. The number of individual case safety reports (ICSRs) of anti-malarials was analyzed according to those clusters. RESULTS: From 1968 to 2008, 21,312 ICSRs suspecting anti-malarials were received from 64 countries. Low-income countries, that are also malaria-endemic (categorized as priority 1 countries) submitted only 1.2% of the ICSRs. Only 60 out of 21,312 ICSRs were related to ACT, 51 of which were coming from four sub-Saharan African countries. Although very few ICSRs involved artemisinin-based compounds, many of the adverse events reported were potentially serious. CONCLUSIONS: This paper illustrates the low reporting of ADRs to anti-malarials in general and ACT in particular. Most reports were submitted by non-endemic and/or high-income countries. Given the current mix of large donor funding, the insufficient information on safety of these drugs, increasing availability of ACT and artemisinin-based monotherapies in public and private sector channels, associated potential for inappropriate use and finally a pipeline of more than 10 new novel anti-malarials in various stages of development, the presence of well functioning national pharmacovigilance systems is vital to ensure safe and responsible scale up of ACT deployment. Bringing together the competencies of national pharmacovigilance centres and various types of organizations in the NGO, academic and private sectors with global coordination to create short- and long-term solutions may help address the lag between rapidly growing ACT use and poor ADR reporting.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Antimaláricos/efeitos adversos , Artemisininas/efeitos adversos , Malária/tratamento farmacológico , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Saúde Global , Humanos , Organização Mundial da Saúde
16.
Cancer Chemother Pharmacol ; 63(2): 331-41, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18587581

RESUMO

PURPOSE: As no curative treatment for advanced pancreatic and biliary cancer with malignant ascites exists, new modalities possibly improving the response to available chemotherapies must be explored. This phase I study assesses the feasibility, tolerability and pharmacokinetics of a regional treatment of gemcitabine administered in escalating doses by the stop-flow approach to patients with advanced abdominal malignancies (adenocarcinoma of the pancreas, n = 8, and cholangiocarcinoma of the liver, n = 1). EXPERIMENTAL DESIGN: Gemcitabine at 500, 750 and 1,125 mg/m(2) was administered to three patients at each dose level by loco-regional chemotherapy, using hypoxic abdominal stop-flow perfusion. This was achieved by an aorto-caval occlusion by balloon catheters connected to an extracorporeal circuit. Gemcitabine and its main metabolite 2',2'-difluorodeoxyuridine (dFdU) concentrations were measured by high performance liquid chromatography with UV detection in the extracorporeal circuit during the 20 min of stop-flow perfusion, and in peripheral plasma for 420 min. Blood gases were monitored during the stop-flow perfusion and hypoxia was considered stringent if two of the following endpoints were met: pH /=1.35. The tolerability of this procedure was also assessed. RESULTS: Stringent hypoxia was achieved in four patients. Very high levels of gemcitabine were rapidly reached in the extracorporeal circuit during the 20 min of stop-flow perfusion, with C (max) levels in the abdominal circuit of 246 (+/-37%), 2,039 (+/-77%) and 4,780 (+/-7.3%) mug/ml for the three dose levels 500, 750 and 1,125 mg/m(2), respectively. These C (max) were between 13 (+/-51%) and 290 (+/-12%) times higher than those measured in the peripheral plasma. Similarly, the abdominal exposure to gemcitabine, calculated as AUC(t0-20), was between 5.5 (+/-43%) and 200 (+/-66%)-fold higher than the systemic exposure. Loco-regional exposure to gemcitabine was statistically higher in presence of stringent hypoxia (P < 0.01 for C (max) and AUC(t0-20), both normalised to the gemcitabine dose). Toxicities were acceptable considering the complexity of the procedure and were mostly hepatic; it was not possible to differentiate the respective contributions of systemic and regional exposures. A significant correlation (P < 0.05) was found between systemic C (max) of gemcitabine and the nadir of both leucocytes and neutrophils. CONCLUSIONS: Regional exposure to gemcitabine-the current standard drug for advanced adenocarcinoma of the pancreas-can be markedly enhanced using an optimised hypoxic stop-flow perfusion technique, with acceptable toxicities up to a dose of 1,125 mg/m(2). However, the activity of gemcitabine under hypoxic conditions is not as firmly established as that of other drugs such as mitomycin C, melphalan or tirapazamine. Further studies of this investigational modality, but with bioreductive drugs, are therefore warranted first to evaluate the tolerance in a phase I study and later on to assess whether it does improve the response to chemotherapy.


Assuntos
Antimetabólitos Antineoplásicos/farmacocinética , Ascite/tratamento farmacológico , Desoxicitidina/análogos & derivados , Sistemas de Liberação de Medicamentos/métodos , Hipóxia , Neoplasias Pancreáticas/tratamento farmacológico , Cavidade Abdominal , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Ascite/etiologia , Ascite/metabolismo , Gasometria , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/farmacocinética , Desoxicitidina/uso terapêutico , Esquema de Medicação , Circulação Extracorpórea , Feminino , Humanos , Hipóxia/sangue , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Perfusão
17.
Ann Thorac Surg ; 82(6): 2024-30, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17126104

RESUMO

BACKGROUND: Antegrade and retrograde doxorubicin-based isolated lung perfusions were compared in rodents bearing a sarcomatous tumor in the perfused lung. Inasmuch as these tumors derive their vascularization from the bronchial artery system, we hypothesized that retrograde isolated lung perfusion through the pulmonary vein might result in an improved tumor drug uptake. METHODS: Single-pass antegrade (n = 9) and retrograde (n = 9) isolated left lung perfusions were performed with 100 microg of doxorubicin in Fischer rats 10 days after subpleural tumor cell injection. The perfusion, washout, and recirculation times were 20, 10, and 60 minutes, respectively, followed by harvesting of the lung. The doxorubicin concentration and compartmental distribution in the tumor and in normal parenchyma of each perfused lung were measured by high-pressure liquid chromatography (6 animals of each group) and fluorescence microscopy (3 animals of each group). RESULTS: Doxorubicin concentration and pattern of doxorubicin-based fluorescence signaling were comparable for both perfusion techniques in normal lung tissue. Antegrade and retrograde isolated lung perfusion resulted in similar tumor drug uptake, which was lower than in normal lung parenchyma, and in weak and sporadic fluorescence signaling emerging from the tumor periphery and from blood vessels situated within the tumor tissue. CONCLUSIONS: Retrograde isolated lung perfusion did not confer a better doxorubicin uptake in the tumor as compared with antegrade lung perfusion despite the fact that the tumor vascularization in this model is based on the bronchial artery circulation.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Quimioterapia do Câncer por Perfusão Regional/métodos , Doxorrubicina/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Sarcoma/tratamento farmacológico , Animais , Antibióticos Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Doxorrubicina/farmacocinética , Masculino , Ratos , Ratos Endogâmicos F344 , Ensaios Antitumorais Modelo de Xenoenxerto
18.
J Thorac Cardiovasc Surg ; 132(2): 304-11, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16872954

RESUMO

OBJECTIVES: Comparison of doxorubicin uptake, leakage and spatial regional blood flow, and drug distribution was made for antegrade, retrograde, combined antegrade and retrograde isolated lung perfusion, and pulmonary artery infusion by endovascular inflow occlusion (blood flow occlusion), as opposed to intravenous administration in a porcine model. METHODS: White pigs underwent single-pass lung perfusion with doxorubicin (320 mug/mL), labeled 99mTc-microspheres, and Indian ink. Visual assessment of the ink distribution and perfusion scintigraphy of the perfused lung was performed. 99mTc activity and doxorubicin levels were measured by gamma counting and high-performance liquid chromatography on 15 tissue samples from each perfused lung at predetermined localizations. RESULTS: Overall doxorubicin uptake in the perfused lung was significantly higher (P = .001) and the plasma concentration was significantly lower (P < .0001) after all isolated lung perfusion techniques, compared with intravenous administration, without differences between them. Pulmonary artery infusion (blood flow occlusion) showed an equally high doxorubicin uptake in the perfused lung but a higher systemic leakage than surgical isolated lung perfusion (P < .0001). The geometric coefficients of variation of the doxorubicin lung tissue levels were 175%, 279%, 226%, and 151% for antegrade, retrograde, combined antegrade and retrograde isolated lung perfusion, and pulmonary artery infusion by endovascular inflow occlusion (blood flow occlusion), respectively, compared with 51% for intravenous administration (P = .09). 99mTc activity measurements of the samples paralleled the doxorubicin level measurements, indicating a trend to a more heterogeneous spatial regional blood flow and drug distribution after isolated lung perfusion and blood flow occlusion compared with intravenous administration. CONCLUSIONS: Cytostatic lung perfusion results in a high overall doxorubicin uptake, which is, however, heterogeneously distributed within the perfused lung.


Assuntos
Antibióticos Antineoplásicos/farmacocinética , Quimioterapia do Câncer por Perfusão Regional/métodos , Doxorrubicina/farmacocinética , Pulmão/metabolismo , Animais , Cateterismo de Swan-Ganz , Infusões Intravenosas , Pulmão/irrigação sanguínea , Pulmão/diagnóstico por imagem , Microesferas , Modelos Animais , Compostos de Organotecnécio , Artéria Pulmonar , Cintilografia , Fluxo Sanguíneo Regional , Suínos , Distribuição Tecidual
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