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1.
Am J Transplant ; 20(6): 1659-1667, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31912961

RESUMO

Fluid overload has been associated with a high prevalence of sleep apnea (SA) in patients with end-stage kidney disease (ESKD). In this prospective study, we hypothesized that improvement in kidney function and hydration status after kidney transplantation (Tx) may result in an improvement in SA severity. A total of 196 patients on the kidney Tx waiting list were screened for SA using home nocturnal polysomnography (PSG) to measure the apnea-hypopnea index (AHI) and underwent bioimpedance to assess body composition. Of 88 participants (44.9%) with SA (AHI ≥ 15/h), 42 were reassessed 6 months post-Tx and were compared with 27 control patients. There was a significant, but small, post-Tx improvement in AHI (from 44.2 ± 24.3 to 34.7 ± 20.9/h, P = .02) that significantly correlated with a reduction in fluid overload (from 1.8 ± 2.0 to 1.2 ± 1.2 L, P = .02) and body water (from 54.9% to 51.6%, P = .003). A post-Tx increase in body fat mass (from 26% to 30%, P = .003) possibly blunted the beneficial impact of kidney Tx on SA. All parameters remained unchanged in the control group. In conclusion, SA is a frequent condition in ESKD patients and partially improved by kidney Tx. We suggest that SA should be systematically assessed before and after kidney Tx. ClinicalTrials.gov Identifier: NCT02020642.


Assuntos
Falência Renal Crônica , Transplante de Rim , Síndromes da Apneia do Sono , Humanos , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Polissonografia , Estudos Prospectivos , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/epidemiologia , Síndromes da Apneia do Sono/etiologia
2.
Crit Care ; 24(1): 610, 2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33066801

RESUMO

BACKGROUND: Data on SARS-CoV-2 load in lower respiratory tract (LRT) are scarce. Our objectives were to describe the viral shedding and the viral load in LRT and to determine their association with mortality in critically ill COVID-19 patients. METHODS: We conducted a binational study merging prospectively collected data from two COVID-19 reference centers in France and Switzerland. First, we described the viral shedding duration (i.e., time to negativity) in LRT samples. Second, we analyzed viral load in LRT samples. Third, we assessed the association between viral presence in LRT and mortality using mixed-effect logistic models for clustered data adjusting for the time between symptoms' onset and date of sampling. RESULTS: From March to May 2020, 267 LRT samples were performed in 90 patients from both centers. The median time to negativity was 29 (IQR 23; 34) days. Prolonged viral shedding was not associated with age, gender, cardiac comorbidities, diabetes, immunosuppression, corticosteroids use, or antiviral therapy. The LRT viral load tended to be higher in non-survivors. This difference was statistically significant after adjusting for the time interval between onset of symptoms and date of sampling (OR 3.78, 95% CI 1.13-12.64, p = 0.03). CONCLUSIONS: The viral shedding in LRT lasted almost 30 days in median in critically ill patients, and the viral load in the LRT was associated with the 6-week mortality.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Síndrome do Desconforto Respiratório/terapia , Síndrome do Desconforto Respiratório/virologia , Sistema Respiratório/virologia , Idoso , COVID-19 , Infecções por Coronavirus/mortalidade , Estado Terminal/mortalidade , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/mortalidade , Estudos Prospectivos , Respiração Artificial , SARS-CoV-2 , Suíça/epidemiologia , Carga Viral , Eliminação de Partículas Virais
3.
Rev Med Suisse ; 15(662): 1620-1624, 2019 Sep 11.
Artigo em Francês | MEDLINE | ID: mdl-31508913

RESUMO

Obstructive sleep apnea syndrome (OSAS) and arterial hypertension (HT) are two frequent, often concomitant diseases, who are both associated with an increased cardiovascular risk. In the last years, an association between these two entities has been established. The purpose of this article is to review the current knowledge about the link between HT and OSAS, the pathophysiological mechanisms involved in the common genesis of the two conditions and the characteristics suggesting an underlying OSAS in a hypertensive subject. We will also update readers about the current screening of OSAS in which primary care physicians are directly involved, and review the pros and cons of different treatment options for HT in OSAS.


Le syndrome des apnées obstructives du sommeil (SAOS) et l'hypertension artérielle (HTA) sont deux pathologies fréquentes, souvent concomitantes, qui sont toutes deux associées à un risque cardiovasculaire augmenté. Le but de cet article est de revoir l'état actuel des connaissances sur l'association entre HTA et SAOS, en se basant sur les mécanismes physiopathologiques impliqués dans la genèse commune aux deux conditions. L'article passe en revue les caractéristiques qui devraient faire suspecter un SAOS chez un sujet hypertendu et fait le point sur la démarche de dépistage du SAOS par le médecin traitant et sur les différentes options thérapeutiques à disposition pour le traitement de l'HTA associée au SAOS.


Assuntos
Hipertensão/complicações , Hipertensão/terapia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnóstico , Humanos , Hipertensão/fisiopatologia , Apneia Obstrutiva do Sono/fisiopatologia
4.
Rev Med Suisse ; 13(574): 1558-1564, 2017 Sep 13.
Artigo em Francês | MEDLINE | ID: mdl-28905543

RESUMO

Considering the high prevalence of hypertension among general population, the general practitioner is frequently challenged to start an antihypertensive therapy, which aims to lower blood pressure and to reduce the cardiovascular risk. At the initial stage, several critical questions must be asked : « Is a pharmacological treatment necessary ? ¼, « Which are the target blood pressures ? ¼ and « Which antihypertensive drug should be chosen to start therapy ? ¼The aim of this article is to give general practicioners some practical tools to guide them in the initial management of hypertensive patients.


En raison de la forte prévalence de l'hypertension artérielle dans la population générale, le praticien est fréquemment amené à proposer un traitement antihypertenseur dont l'objectif est de normaliser la pression artérielle et réduire le risque cardiovasculaire. Au stade initial, plusieurs questions doivent être posées : « Un traitement pharmacologique est-il nécessaire ? ¼, « Quelles sont les pressions cibles ? ¼ et « Avec quel médicament antihypertenseur faut-il commencer ? ¼Le but de cet article est de donner aux praticiens quelques outils pour les guider dans la prise en charge initiale des patients hypertendus.


Assuntos
Anti-Hipertensivos , Hipertensão , Anti-Hipertensivos/administração & dosagem , Pressão Sanguínea , Determinação da Pressão Arterial , Humanos , Hipertensão/tratamento farmacológico , Prevalência
5.
Br J Clin Pharmacol ; 82(6): 1486-1497, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27447737

RESUMO

AIMS: The biological response to clopidogrel is highly variable and a poor responsiveness is associated with major adverse cardiac events. Adherence to therapy is a major cause of poor responsiveness but its impact on long-term platelet inhibition is unknown. The objective of the present study was to evaluate the effect of different programmes monitoring adherence to clopidogrel on platelet reactivity. METHODS: The study took the form of a monocentric, parallel group, randomized controlled trial. Adults treated with clopidogrel 75 mg after elective coronary stenting were randomized into one of three groups: (i) a standard of care group; (ii) a standard of care + adherence electronic monitoring group, in which drug intake was recorded but kept blinded until the study end; or (iii) an integrated care group, with regular feedback on recorded adherence. Clopidogrel response was assessed with the vasodilator-stimulated phosphoprotein-platelet reactivity index (VASP-PRI) at randomization, 3 months and 6 months. RESULTS: A total of 123 adults were enrolled and randomized. Baseline VASP-PRI was highly variable, with a mean of 48 ± 18.8%. No difference between groups in VASP-PRI was found at 6 months (P = 0.761), despite better adherence to clopidogrel in the integrated care group. However, adherence (P = 0.035) and baseline VASP-PRI (P = 0.015) were associated with VASP-PRI at 3 months and 6 months. The association between adherence and VASP-PRI was lost in patients with baseline VASP-PRI > 50%. Diabetes, CYP2C19*2 carrier status and body mass index were significant predictors of VASP-PRI. CONCLUSIONS: The platelet response to clopidogrel during chronic therapy remained highly variable, despite high adherence. Different adherence monitoring programmes did not affect VASP-PRI at 6 months. Poor adherence is associated with lower VASP-PRI only in initial good responders to clopidogrel.


Assuntos
Moléculas de Adesão Celular/sangue , Adesão à Medicação/estatística & dados numéricos , Proteínas dos Microfilamentos/sangue , Intervenção Coronária Percutânea , Fosfoproteínas/sangue , Inibidores da Agregação Plaquetária/uso terapêutico , Agregação Plaquetária/efeitos dos fármacos , Ticlopidina/análogos & derivados , Idoso , Clopidogrel , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/administração & dosagem , Ticlopidina/administração & dosagem , Ticlopidina/uso terapêutico , Fatores de Tempo , Resultado do Tratamento
6.
Eur J Nutr ; 55(3): 1089-97, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25971845

RESUMO

PURPOSE: Glomerular hyperfiltration has been suggested as a possible mechanism linking obesity and chronic kidney disease (CKD), independently of classical risk factors. We explored the association of overweight and obesity with glomerular hyperfiltration in a large sample of the Swiss adult population, accounting for several confounders including dietary factors. METHODS: Data from a 2010 to 2012 cross-sectional population-based survey in Switzerland were used. Creatinine clearance (CrCl) was determined from 24-h urine collection; CrCl > 140 ml/min was used to define glomerular hyperfiltration. Participants were categorized into lean (<25 kg/m(2)), overweight (25-29.9 kg/m(2)) and obese (≥30 kg/m(2)) according to body mass index (BMI). RESULTS: A total of 1339 participants were included in the analysis [median (IQR) age 49.4 (34.3-63.5) years, 48.9 % men]. The prevalences of overweight and obesity were 32.2 and 14.2 %, respectively. Median CrCl was 102[84-121] ml/min in lean, 110 [87-136] ml/min in overweight and 124 [97-150] ml/min in obese participants (p < 0.001). The prevalence of glomerular hyperfiltration increased across BMI categories (10.4, 20.8 and 34.7 %, respectively; p < 0.001). This positive association remained significant after adjusting for age, sex, hypertension, diabetes, smoking and dietary factors (sodium and protein intakes): odds ratio [95 %CI] 2.39 [1.52-3.76] (p < 0.001) for overweight versus lean and 4.10[2.31-7.27] (p < 0.001) for obesity versus lean. CONCLUSIONS: BMI categories and glomerular hyperfiltration are positively associated, independently of other known CKD risk factors and dietary confounders, suggesting that glomerular hyperfiltration may represent an early renal phenotype in obesity. Our observations confirm the significant association of glomerular hyperfiltration with sodium and protein intakes and identify sodium intake as an important modifying factor of the association between hyperfiltration and obesity.


Assuntos
Proteínas Alimentares/efeitos adversos , Nefropatias/epidemiologia , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Fumar/efeitos adversos , Sódio na Dieta/efeitos adversos , Adulto , Índice de Massa Corporal , Creatinina/urina , Estudos Transversais , Proteínas Alimentares/administração & dosagem , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/fisiopatologia , Nefropatias/complicações , Nefropatias/urina , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/urina , Sobrepeso/complicações , Sobrepeso/urina , Prevalência , Fatores de Risco , Sódio na Dieta/administração & dosagem , Suíça
7.
Pflugers Arch ; 467(12): 2413-21, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26089029

RESUMO

Interactions between sodium and calcium regulating systems are poorly characterized but clinically important. Parathyroid hormone (PTH) levels are increased shortly after furosemide treatment by an unknown mechanism, and this effect is blunted by the previous administration of a calcimimetic in animal studies. Here, we explored further the possible underlying mechanisms of this observation in a randomized crossover placebo-controlled study performed in 18 human males. Volunteers took either cinacalcet (60 mg) or placebo and received a 20 mg furosemide injection 3 h later. Plasma samples were collected at 15-min intervals and analyzed for intact PTH, calcium, sodium, potassium, magnesium, phosphate, plasma renin activity (PRA), and aldosterone up to 6 h after furosemide injection. Urinary electrolyte excretion was also monitored. Subjects under placebo presented a sharp increase in PTH levels after furosemide injection. In the presence of cinacalcet, PTH levels were suppressed and marginal increase of PTH was observed. No significant changes in electrolytes and urinary excretion were identified that could explain the furosemide-induced increase in PTH levels. PRA and aldosterone were stimulated by furosemide injection but were not affected by previous cinacalcet ingestion. Expression of NKCC1, but not NKCC2, was found in parathyroid tissue. In conclusion, our results indicate that furosemide acutely stimulates PTH secretion in the absence of any detectable electrolyte changes in healthy adults. A possible direct effect of furosemide on parathyroid gland needs further studies.


Assuntos
Diuréticos/farmacologia , Furosemida/farmacologia , Hormônio Paratireóideo/sangue , Receptores de Detecção de Cálcio/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Renina/sangue , Adolescente , Adulto , Aldosterona/sangue , Calcimiméticos/farmacologia , Cálcio/sangue , Cinacalcete/farmacologia , Diuréticos/administração & dosagem , Feminino , Furosemida/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Glândulas Paratireoides/metabolismo , Membro 1 da Família 12 de Carreador de Soluto/genética , Membro 1 da Família 12 de Carreador de Soluto/metabolismo , Membro 2 da Família 12 de Carreador de Soluto/genética , Membro 2 da Família 12 de Carreador de Soluto/metabolismo
8.
BMC Med ; 13: 40, 2015 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-25858764

RESUMO

BACKGROUND: Urinary creatinine excretion is used as a marker of completeness of timed urine collections, which are a keystone of several metabolic evaluations in clinical investigations and epidemiological surveys. METHODS: We used data from two independent Swiss cross-sectional population-based studies with standardised 24-hour urinary collection and measured anthropometric variables. Only data from adults of European descent, with estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m2 and reported completeness of the urinary collection were retained. A linear regression model was developed to predict centiles of the 24-hour urinary creatinine excretion in 1,137 participants from the Swiss Survey on Salt and validated in 994 participants from the Swiss Kidney Project on Genes in Hypertension. RESULTS: The mean urinary creatinine excretion was 193 ± 41 µmol/kg/24 hours in men and 151 ± 38 µmol/kg/24 hours in women in the Swiss Survey on Salt. The values were inversely correlated with age and body mass index (BMI). CONCLUSIONS: We propose a validated prediction equation for 24-hour urinary creatinine excretion in the general European population, based on readily available variables such as age, sex and BMI, and a few derived normograms to ease its clinical application. This should help healthcare providers to interpret the completeness of a 24-hour urine collection in daily clinical practice and in epidemiological population studies.


Assuntos
Biomarcadores/urina , Creatinina/urina , Urinálise/normas , Adulto , Idoso , Antropometria , Índice de Massa Corporal , Estudos Transversais , Etnicidade , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Valores de Referência , Suíça
9.
Eur J Nutr ; 53(5): 1281-90, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24374796

RESUMO

PURPOSE: Obesity represents a growing public health concern worldwide. The latest data in Switzerland rely on self-reported body mass index (BMI), leading to underestimation of prevalence. We reassessed the prevalence of obesity and overweight in a sample of the Swiss population using measured BMI and waist circumference (WC) and explored the association with nutritional factors and living in different linguistic-cultural regions. METHODS: Data of 1,505 participants of a cross-sectional population-based survey in the three linguistic regions of Switzerland were analyzed. BMI and WC were measured, and a 24-h urine collection was performed to evaluate dietary sodium, potassium and protein intake. RESULTS: The prevalence of overweight, obesity and abdominal obesity was 32.2, 14.2 and 33.6%, respectively. Significant differences were observed in the regional distribution, with a lower prevalence in the Italian-speaking population. Low educational level, current smoking, scarce physical activity and being migrant were associated with an higher prevalence of obesity. Sodium, potassium and protein intake increased significantly across BMI categories. CONCLUSIONS: Obesity and overweight affect almost half of the Swiss adolescents and adults, and the prevalence appears to increase. Using BMI and WC to define obesity led to different prevalences. Differences were furthermore observed across Swiss linguistic-cultural regions, despite a common socio-economic and governmental framework. We found a positive association between obesity and salt intake, with a potential deleterious synergistic effect on cardiovascular risk.


Assuntos
Estado Nutricional , Obesidade Abdominal/epidemiologia , Sobrepeso/epidemiologia , Adolescente , Adulto , Índice de Massa Corporal , Estudos Transversais , Proteínas Alimentares/administração & dosagem , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Potássio na Dieta/administração & dosagem , Prevalência , Fatores de Risco , Fatores Socioeconômicos , Sódio na Dieta/administração & dosagem , Suíça/epidemiologia , Circunferência da Cintura , População Branca , Adulto Jovem
10.
Rev Med Suisse ; 10(441): 1668-72, 2014 Sep 10.
Artigo em Francês | MEDLINE | ID: mdl-25322626

RESUMO

Hypertension is a frequent finding in patients with chronic kidney disease. Whether primary or secondary to renal disease, hypertension remains an important risk factory for the progression of chronic kidney disease and the occurrence of cardiovascular events. The objective of this paper is to review different treatment strategies in hypertensive CKD patients, with the exclusion of patients with renal replacement therapy such as dialysis or renal transplantation.


Assuntos
Hipertensão/complicações , Hipertensão/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Dieta , Humanos , Insuficiência Renal Crônica/fisiopatologia , Sistema Renina-Angiotensina/efeitos dos fármacos
11.
Front Nephrol ; 4: 1394990, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38915821

RESUMO

Introduction: Hemodialysis (HD) populations have a high prevalence of Obstructive Sleep Apnea (OSA), which was specifically linked with fluid overload. HD fluid management targeting a low dry weight was shown to reduce OSA severity, opening to novel therapeutic options. We assessed nephrologists' awareness of OSA diagnosis in HD patients and whether they integrate the current knowledge into their fluid management strategy. Material and methods: We performed a multicenter, cross-sectional study between July 2022 and July 2023, screening all HD patients of four HD units, and included those with confirmed OSA. We collected anthropometric parameters and fluid status from electronic dossiers. Predialysis fluid overload was measured by multifrequency bioelectrical impedance (BCM®). Nephrologists were asked to identify patients with known OSA, without consulting medical dossiers. The fluid management of patients identified as "OSA positive" was compared to that of patients misclassified as "OSA negative". Results: Among 193 HD patients, 23.0% (n=45) had confirmed OSA. The mean age was 76.0 ± 7.5 years, 82.2% were men. Only 60% were correctly identified as "OSA positive" by nephrologists; 14.7% of patients on CPAP were identified. BMI was the only factor associated with correct OSA identification. The predialysis fluid overload tended to be greater in "OSA positive" patients than in the "OSA negative" patients (2.2 ± 1.4 kg vs 1.5 ± 1.3 kg; p=0.08), but there was no difference in postdialysis achievement of dry weight between the groups (residual overweight 0.2 ± 1.0 kg and 0.1 ± 0.7 kg; p= 0.672). Conclusions: Our study suggests that the application of scientific evidence to the management of OSA in dialysis patients is not systematic. However, nephrologists have attempted to strictly achieve dry weight in all patients, regardless of OSA status. Sensibilization of nephrologists on the clinical and diagnostic peculiarities of OSA in HD patients may improve OSA diagnosis and therapeutic care.

12.
Nutr Hosp ; 39(5): 1101-1105, 2022 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-35545880

RESUMO

Introduction: Objectives: the study describes the evolution over the years of the use of artificial nutrition, in particular after the introduction of a dedicated Clinical Nutrition and Dietetic Service. Methods: a single-center, retrospective observational study performed with data collected from 2014 to 2019 at the Regional Hospital of Locarno, Switzerland. Results: from 2014 to 2019, there has been an increase in the number of patients identified as being at risk of malnutrition. We observed a reduction in the use of parenteral nutrition in all services, especially after the introduction of the dedicated Clinical Nutrition and Dietetic Service. There would seem to be a switch from enteral to oral nutrition with increased use of oral nutritional supplements. Conclusions: the introduction of a dedicated Clinical Nutrition and Dietetic Service in the care of patients with nutritional issues would seem to reduce the use of artificial invasive nutrition, despite an increase in the number of patients identified as being at risk of malnutrition.


Introducción: Objetivos: el estudio describe la evolución a lo largo de los años del uso de la nutrición artificial, en particular después de la introducción de un Servicio de Nutrición Clínica y Dietética dedicado. Métodos: estudio observacional retrospectivo de un solo centro realizado con datos recopilados de 2014 a 2019 en el Hospital Regional de Locarno, Suiza. Resultados: del 2014 al 2019 ha habido un aumento en el número de pacientes identificados en riesgo de desnutrición. Observamos una reducción en el uso de la nutrición parenteral en todos los servicios, especialmente después de la introducción del Servicio de Nutrición Clínica y Dietética dedicado. Parecería haber un cambio de nutrición enteral a oral con un mayor uso de suplementos nutricionales orales. Conclusiones: la introducción de un Servicio de Nutrición Clínica y Dietética dedicado a la atención de pacientes con problemas nutricionales parecería reducir el uso de la nutrición artificial invasiva, a pesar del aumento en el número de pacientes identificados con riesgo de desnutrición.


Assuntos
Nutrição Enteral , Desnutrição , Hospitais , Humanos , Desnutrição/terapia , Estado Nutricional , Nutrição Parenteral
13.
PLoS One ; 17(2): e0263328, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35143540

RESUMO

Patients on dialysis are at risk of severe course of SARS-CoV-2 infection. Understanding the neutralizing activity and coverage of SARS-CoV-2 variants of vaccine-elicited antibodies is required to guide prophylactic and therapeutic COVID-19 interventions in this frail population. By analyzing plasma samples from 130 hemodialysis and 13 peritoneal dialysis patients after two doses of BNT162b2 or mRNA-1273 vaccines, we found that 35% of the patients had low-level or undetectable IgG antibodies to SARS-CoV-2 Spike (S). Neutralizing antibodies against the vaccine-matched SARS-CoV-2 and Delta variant were low or undetectable in 49% and 77% of patients, respectively, and were further reduced against other emerging variants. The fraction of non-responding patients was higher in SARS-CoV-2-naïve hemodialysis patients immunized with BNT162b2 (66%) than those immunized with mRNA-1273 (23%). The reduced neutralizing activity correlated with low antibody avidity. Patients followed up to 7 months after vaccination showed a rapid decay of the antibody response with an average 21- and 10-fold reduction of neutralizing antibodies to vaccine-matched SARS-CoV-2 and Delta variant, which increased the fraction of non-responders to 84% and 90%, respectively. These data indicate that dialysis patients should be prioritized for additional vaccination boosts. Nevertheless, their antibody response to SARS-CoV-2 must be continuously monitored to adopt the best prophylactic and therapeutic strategy.


Assuntos
Anticorpos Neutralizantes/imunologia , Testes de Neutralização , Diálise Renal , SARS-CoV-2/imunologia , Vacinação , Animais , Anticorpos Neutralizantes/sangue , Afinidade de Anticorpos , Células CHO , Vacinas contra COVID-19/imunologia , Estudos de Casos e Controles , Cricetulus , Relação Dose-Resposta Imunológica , Seguimentos , Células HEK293 , Humanos , Imunoglobulina G/sangue , Fatores de Risco , Vacinas de mRNA/imunologia
14.
Endocrine ; 70(3): 454-460, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32870469

RESUMO

PURPOSE: The length of time a critically ill coronavirus disease 2019 (COVID-19) patient remains infectious and should therefore be isolated remains unknown. This prospective study was undertaken in critically ill patients to evaluate the reliability of single negative real-time polymerase chain reaction (RT-PCR) in lower tracheal aspirates (LTA) in predicting a second negative test and to analyze clinical factors potentially influencing the viral shedding. METHODS: From April 9, 2020 onwards, intubated COVID-19 patients treated in the intensive care unit were systematically evaluated for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by RT-PCR of nasopharyngeal swabs and LTA. The time to negativity was defined as the time between the onset of symptoms and the viral clearance in LTA. In order to identify risk factors for prolonged viral shedding, we used univariate and multivariate Cox proportional hazards models. RESULTS: Forty-eight intubated SARS-CoV-2 patients were enrolled. Overall, we observed that the association of the first negative RT-PCR with a second negative result was 96.7%. Median viral shedding was 25 (IQR: 21.5-28) days since symptoms' onset. In the univariate Cox model analysis, type 2 diabetes mellitus was associated with a prolonged viral RNA shedding (hazard ratio [HR]: 0.41, 95% CI: 0.06-3.11, p = 0.04). In the multivariate Cox model analysis, type 2 diabetes was associated with a prolonged viral RNA shedding (HR: 0.31, 95% CI: 0.11-0.89, p = 0.029). CONCLUSION: Intubated patients with type 2 diabetes mellitus may have prolonged SARS-CoV-2 shedding. In critically ill COVID-19 patients, one negative LTA should be sufficient to assess and exclude infectivity.


Assuntos
Betacoronavirus/fisiologia , Infecções por Coronavirus/virologia , Estado Terminal , Diabetes Mellitus Tipo 2/virologia , Pneumonia Viral/virologia , Sistema Respiratório/virologia , Eliminação de Partículas Virais , Idoso , Betacoronavirus/genética , COVID-19 , Teste para COVID-19 , Vacinas contra COVID-19 , Técnicas de Laboratório Clínico/métodos , Técnicas de Laboratório Clínico/normas , Comorbidade , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Progressão da Doença , Feminino , Humanos , Unidades de Terapia Intensiva , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Sistema Respiratório/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/normas , Fatores de Risco , SARS-CoV-2 , Manejo de Espécimes/métodos , Manejo de Espécimes/normas , Suíça/epidemiologia , Fatores de Tempo
16.
Front Pharmacol ; 8: 738, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29118712

RESUMO

Aims: Dual platelet inhibition using anti-P2Y12 drugs and aspirin is the standard of care in patients after percutaneous coronary interventions (PCI). Prasugrel and ticagrelor have been shown to be more potent than clopidogrel with less high on-treatment platelet reactivity. Whether differences in long-term adherence to these drugs can partly explain different antiplatelet efficacy has not been studied so far. The objective was to compare the long-term P2Y12 receptor inhibition and drug adherence to different anti-P2Y12 drugs, and to assess the impact of adherence on the pharmacodynamic effect. Methods: Monocentric, prospective, observational study. Stable outpatients treated with clopidogrel 75 mg once daily, prasugrel 10 mg once daily or ticagrelor 90 mg twice daily after PCI with stent implantation were included. Drug adherence was recorded during 6 months using electronic monitoring. Platelet responsiveness was assessed with the vasodilator-stimulated phosphoprotein platelet reactivity index (VASP-PRI) at inclusion, 3 and 6 months. Results: 120 patients had VASP-PRI and adherence data available. At 6-months, mean VASP-PRI (±SD) was 17.7 ± 11.0% with ticagrelor, 29.2 ± 15.5% with prasugrel and 47.2 ± 17.6% with clopidogrel (ANOVA, P < 0.0001). Median [IQR] taking adherence was 96 [82-100]% with ticagrelor, 100 [97-101]% with prasugrel and 100 [99-101]% with clopidogrel (p = 0.0001). Median [IQR] correct dosing was 88 [73-95]% with ticagrelor, 97 [92.5-98]% with prasugrel and 98 [96-99]% with clopidogrel (p = 0.0001). Anti-P2Y12 drug (p ≤ 0.001) and diabetes (p = 0.014) emerged as predictors of poor antiplatelet response after adjusting for age, BMI, sex, and CYP2C19∗2 carriers status. Conclusion: Drug adherence to anti-P2Y12 drugs assessed with electronic monitoring was very high. However, anti-P2Y12 drugs showed significant differences in antiplatelet activity, with newer anti-P2Y12 drugs ticagrelor and prasugrel exerting a stronger P2Y12 receptor inhibition. These data suggest that pharmacokinetic-pharmacodynamic differences between oral anti-P2Y12 drugs are more important than adherence in determining antiplatelet efficacy when adherence to prescription is high. The study was registered (Current Controlled Trials ISRCTN85949729).

17.
PLoS One ; 12(5): e0177329, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28542241

RESUMO

BACKGROUND AND OBJECTIVES: Hypocitraturia has been associated with metabolic acidosis and mineral disorders. The aim of this study was to investigate the occurrence of urinary acidification defects underlying hypocitraturia. MATERIALS AND METHODS: This retrospective observational study included 67 patients (32 men), aged 40.7±15.1 years with hypocitraturia (<1.67 mmol/24-h) and nephrolithiasis, nephrocalcinosis, and/or bone demineralization, referred to our center from 2000 to 2015. We aimed to assess renal distal acidification capacity, prevalence and mechanisms of urinary acidification defects. Patients with low baseline plasma HCO3- (<22 mmol/L) were studied by bicarbonate loading or furosemide/fludrocortisone tests. Patients with normal baseline plasma HCO3- had an ammonium-chloride challenge test. A normal response was a decrease in urinary pH <5.3 and an increase in urinary NH4+ ≥33 µmol/min and defined idiopathic hypocitraturia. RESULTS: Eleven patients (16.4%) had low HCO3- and overt distal acidification defect. Three had a mutation in the gene encoding AE1, 4 had Gougerot-Sjögren syndrome and no cause was found in the remaining 4 cases. Fifty-six patients (83.6%) had normal HCO3-; of those, 33 (58.9%) had idiopathic hypocitraturia. Among the 23 (41%) remaining patients, 12 were unable to increase urinary NH4+ excretion (among them, 8 were able to decrease urinary pH and 4 were not) whereas 11 were able to increase urinary NH4+ excretion but unable to decrease urinary pH. These 11 patients had higher fasting urinary calcium, reflecting bone resorption, than the other 12 patients: median 0.41 [0.24-0.47] vs. 0.22 [0.08-0.37] mmol/mmol creatinine (P = 0.04). CONCLUSIONS: Patients with hypocitraturia and normal plasma HCO3- frequently show a latent acidification defect that can be further dissected into one of several subtypes based on urinary pH and NH4+ response to the acid load. Those patients with impaired urine acidification capacity but preserved NH4+ excretion exhibit particularly high calciuria and should be identified to optimize nephrolithiasis prevention.


Assuntos
Citrato de Potássio/urina , Adulto , Feminino , Humanos , Concentração de Íons de Hidrogênio , Rim/metabolismo , Masculino , Pessoa de Meia-Idade , Citrato de Potássio/metabolismo , Estudos Retrospectivos , Adulto Jovem
18.
Sleep ; 39(4): 945-53, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26715230

RESUMO

STUDY OBJECTIVES: To evaluate the association between early stages of chronic kidney disease (CKD) and sleep disordered breathing (SDB), restless legs syndrome (RLS), and subjective and objective sleep quality (SQ). METHODS: Cross-sectional analysis of a general population-based cohort (HypnoLaus). 1,760 adults (862 men, 898 women; age 59.3 (± 11.4) y) underwent complete polysomnography at home. RESULTS: 8.2% of participants had mild CKD (stage 1-2, estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73 m(2) with albuminuria) and 7.8% moderate CKD (stage 3, eGFR 30-60 mL/min/1.73 m(2)). 37.3% of our sample had moderate-to-severe SDB (apnea-hypopnea index [AHI] ≥ 15/h) and 15.3% had severe SDB (AHI ≥ 30/h). SDB prevalence was positively associated with CKD stages and negatively with eGFR. In multivariate analysis, age, male sex, and body mass index were independently associated with SDB (all P < 0.001), but kidney function was not. The prevalence of RLS was 17.5%, without difference between CKD stages. Periodic leg movements index (PLMI) was independently associated with CKD stages. Subjective and objective SQ decreased and the use of sleep medication was more frequent with declining kidney function. Older age, female sex, and the severity of SDB were the strongest predictors of poor SQ in multivariate regression analysis but CKD stage was also independently associated with reduced objective SQ. CONCLUSIONS: Patients with early stages of CKD have impaired SQ, use more hypnotic drugs, and have an increased prevalence of SDB and PLM. After controlling for confounders, objective SQ and PLMI were still independently associated with declining kidney function.


Assuntos
Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologia , Síndrome das Pernas Inquietas/epidemiologia , Síndrome das Pernas Inquietas/fisiopatologia , Síndromes da Apneia do Sono/epidemiologia , Síndromes da Apneia do Sono/fisiopatologia , Sono/fisiologia , Adulto , Idoso , Envelhecimento , Índice de Massa Corporal , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Rim/fisiopatologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Polissonografia , Prevalência , Insuficiência Renal Crônica/diagnóstico , Síndrome das Pernas Inquietas/diagnóstico , Caracteres Sexuais , Medicamentos Indutores do Sono , Síndromes da Apneia do Sono/diagnóstico
19.
Swiss Med Wkly ; 146: w14313, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27152492

RESUMO

QUESTIONS UNDER STUDY: The prevalence of chronic kidney disease (CKD) is increasing worldwide, corresponding to an increased risk of cardiovascular disease. The latest study on prevalence of CKD involving the three linguistic regions of Switzerland dates back to 2002-2003 and definitions have changed since then. We aimed to assess the current prevalence and determinants of CKD in the Swiss general population. METHODS: We analysed the data of 1353 participants from a cross-sectional population-based survey performed in 2010-2012 in the three linguistic regions of Switzerland. The prevalence of CKD and the derived cardiovascular risk categories were assessed according to the Kidney Disease - Improving Global Outcomes (KDIGO) 2012 classification, using estimated glomerular filtration rate (GFR; CKD-Epidemiological Collaboration equation) and albuminuria level. Multivariate logistic regression was used to analyse factors associated with CKD. RESULTS: We included 660 men and 693 women, equally distributed in four age categories (15-29, 30-44, 45-59 and over 60 years). The overall prevalence of CKD was 10.4%. The prevalence in the low, moderate, high and very high risk KDIGO categories were 89.6%, 8.4%, 1.6% and 0.5%, respectively. The prevalence of CKD was similar in all linguistic regions. In multivariate analysis, female gender, older age, diabetes and uric acid were independently associated with CKD in persons ≥45 y. In younger participants, diabetes and lower educational level were associated with CKD. CONCLUSIONS: In the general Swiss population, CKD affects one in ten adults. Subjects older than 60 years, as well as patients with diabetes and hypertension, show a high prevalence of CKD. Systematic screening may be recommended in this population.


Assuntos
Albuminúria , Taxa de Filtração Glomerular , Insuficiência Renal Crônica/epidemiologia , Adolescente , Adulto , Fatores Etários , Albuminúria/epidemiologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Hipertensão/epidemiologia , Pessoa de Meia-Idade , Prevalência , Insuficiência Renal Crônica/complicações , Fatores de Risco , Fatores Sexuais , Suíça/epidemiologia
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