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1.
Arch Cardiovasc Dis ; 2019 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-31353279

RESUMO

BACKGROUND: Data on the long-term outcome of heart transplantation in patients with a ventricular assist device (VAD) are scarce. AIM: To evaluate long-term outcome after heart transplantation in patients with a VAD compared with no mechanical circulatory support. METHODS: Consecutive all-comers who underwent heart transplantation were included at a single high-volume centre from January 2005 until December 2012, with 5 years of follow-up. Clinical and biological characteristics, operative results, outcomes and survival were recorded. Regression analyses were performed to determine predictors of 1-year and 5-year mortality. RESULTS: Fifty-two patients with bridge to transplantation by VAD (VAD group) and 289 patients transplanted without a VAD (standard group) were enrolled. The mean age was 46±11 years in the VAD group compared with 51±13 years in the standard group (P=0.01); 17% of the VAD group and 25% of the standard group were women (P=0.21). Ischaemic time was longer in the VAD group (207±54 vs 169±60minutes; P<0.01). There was no difference in primary graft failure (33% vs 25%; P=0.22) or 1-year mortality (17% vs 28%; P=0.12). In the multivariable analysis, preoperative VAD was an independent protective factor for 1-year mortality (odds ratio 0.40, 95% confidence interval 0.17-0.97; P=0.04). Independent risk factors for 1-year mortality were recipient age>60 years, recipient creatinine, body surface area mismatch and ischaemic time. The VAD and standard groups had similar long-term survival, with 5-year mortality rates of 35% and 40%, respectively (P=0.72). CONCLUSIONS: Bridge to transplantation by VAD was associated with a reduction in 1-year mortality, leading critically ill patients to similar long-term survival compared with patients who underwent standard heart transplantation. This alternative strategy may benefit carefully selected patients.

2.
Heart ; 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31350276

RESUMO

OBJECTIVES: N-terminal probrain natriuretic peptide (NT-proBNP) predicts mortality and the development of heart failure in hypertrophic cardiomyopathy (HCM). Mid-regional proatrial natriuretic peptide (MR-proANP) is a stable by-product of production of atrial natriuretic peptide. We sought to compare the prognostic value of MR-proANP and NT-proBNP in HCM. METHODS: We prospectively enrolled a cohort of patients with HCM from different European centres and followed them. All patients had clinical, ECG and echocardiographic evaluation and measurement of MR-proANP and NT-proBNP at inclusion. RESULTS: Of 357 patients enrolled, the median age was 52 (IQR: 36-65) years. MR-proANP and NT-proBNP were both independently associated with age, weight, New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF), wall thickness and left atrial dimension. During a median follow-up of 23 months, 32 patients had a primary end point defined as death (n=6), heart transplantation (n=8), left ventricular assist device implantation (n=1) or heart failure hospitalisation (n=17). Both NT-proBNP and MR-proANP (p<10-4) were strongly associated with the primary endpoint, and the areas under the receiver operating characteristic (ROC) curves for both peptides were not significantly different. However, in a multiple stepwise regression analysis, the best model for predicting outcome was NYHA 1-2 vs 3-4 (HR=0.35, 95% CI 0.16 to 0.77, p<0.01), LVEF (HR=0.96, 95% CI 0.94 to 0.98, p=0.0005) and MR-proANP (HR=3.77, 95% CI 2.01 to 7.08, p<0.0001). CONCLUSIONS: MR-proANP emerges as a valuable biomarker for the prediction of death and heart failure related events in patients with HCM.

3.
Isr Med Assoc J ; 21(2): 77-81, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30772955

RESUMO

BACKGROUND: A history of childhood sexual abuse (CSA) has been linked to a variety of physical and psychiatric illnesses, including ischemic heart disease and post-traumatic stress disorder (PTSD). OBJECTIVES: To determine the prevalence of past CSA and re-traumatization among hospital psychiatric consultations and to determine whether a CSA group in a hospital setting shared characteristics with community samples described in the literature. METHODS: We divided 228 consecutive psychiatric consultations into two groups. One group comprised patients with a past history of CSA while the other group had no such history. Both groups were further divided into a subgroup that presented with features of re-traumatization. RESULTS: In the cohort, 38% described a history of CSA. Twenty patients were identified as presenting with features of re-traumatization. There were significant differences between the two groups. The patients with a history of CSA were more likely to have arrived at the emergency department (ED) during the preceding 12 months with a diagnosis of PTSD, personality disorder, and substance use disorder. There was a greater proportion of patients in the CSA group who had grown up in an ultra-Orthodox Jewish household and who currently identified as being secular. CONCLUSIONS: The characteristics of the patients with past CSA in this study are similar to community-based samples, except for a significant gender difference. To the best of our knowledge, this study is the first to investigate CSA history during hospital ED psychiatric consultations. A history of CSA should be considered during psychiatric consultations in a general hospital ED admission.


Assuntos
Abuso Sexual na Infância/psicologia , Abuso Sexual na Infância/estatística & dados numéricos , Serviço Hospitalar de Emergência , Transtornos Mentais/epidemiologia , Transtornos Mentais/psicologia , Encaminhamento e Consulta , Adulto , Estudos de Casos e Controles , Criança , Feminino , Hospitais Gerais , Humanos , Israel/epidemiologia , Masculino , Prevalência , Estudos Retrospectivos , Inquéritos e Questionários , Adulto Jovem
4.
Hum Brain Mapp ; 40(7): 2125-2142, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30653778

RESUMO

The execution of coordinated hand movements requires complex interactions between premotor and primary motor areas in the two hemispheres. The supplementary motor area (SMA) is involved in movement preparation and bimanual coordination. How the SMA controls bimanual coordination remains unclear, although there is evidence suggesting that the SMA could modulate interhemispheric interactions. With a delayed-response task, we investigated interhemispheric interactions underlying normal movement preparation and the role of the SMA in these interactions during the delay period of unimanual or bimanual hand movements. We used functional MRI and transcranial magnetic stimulation in 22 healthy volunteers (HVs), and then in two models of SMA dysfunction: (a) in the same group of HVs after transient disruption of the right SMA proper by continuous transcranial magnetic theta-burst stimulation; (b) in a group of 22 patients with congenital mirror movements (CMM), whose inability to produce asymmetric hand movements is associated with SMA dysfunction. In HVs, interhemispheric connectivity during the delay period was modulated according to whether or not hand coordination was required for the forthcoming movement. In HVs following SMA disruption and in CMM patients, interhemispheric connectivity was modified during the delay period and the interhemispheric inhibition was decreased. Using two models of SMA dysfunction, we showed that the SMA modulates interhemispheric interactions during movement preparation. This unveils a new role for the SMA and highlights its importance in coordinated movement preparation.

5.
Isr J Psychiatry Relat Sci ; 55(2): 32-36, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30351278

RESUMO

BACKGROUND: The prevalence of alcohol related harm (ARH) in Israel has traditionally been low. The lack of familiarity with ARH may derive from the fact that in the past there was limited clinical exposure to these harms. However, ARH is becoming more common in Israel but it is unclear whether the medical and nursing workforce's knowledge is adequate to manage these problems. Our main objective was to assess knowledge regarding ARH among medical and nursing staff (MNS) in an Israeli university affiliated general hospital. We also aimed to compare knowledge of different MNS groups Methods: One hundred and twenty-seven MNS including consultants (senior physicians), residents, interns and nursing staff completed the Knowledge of Psychiatric Aspects of Alcohol Questionnaire (KPAAQ), a validated measure of knowledge concerning ARH comprised of five categories. RESULTS: There was no significant difference between the four MNS groups in overall mean KPAAQ scores that varied from 45% (nurses) to 54% (interns). However, direct comparisons indicate that physicians scored higher than nurses (p=0.02). overall. The mean score for the KPAAQ category "alcohol withdrawal syndrome" was below 40% for all MNS groups. Physicians scored significantly higher than nursing staff (p=0.005). All MNS mean scores were greater than 63% for the category "alcohol in pregnancy." This was the highest category score. CONCLUSIONS: Assessment of knowledge regarding ARH among MNS in a general hospital with a standardized instrument demonstrated no significant difference in knowledge of ARH among nursing staff, interns, residents and consultants apart from knowledge about alcohol withdrawal. However, the overall score of the physicians as a whole was significantly higher than the nursing group. These findings suggest a need to implement educational interventions in MNS to increase knowledge of ARH so as to promote the provision of brief interventions for patients with ARH.

6.
Isr J Psychiatry Relat Sci ; 55(2): 37-39, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30351279

RESUMO

BACKGROUND: There are no studies that use validated questionnaires on Alcohol Related Harm (ARH) in order to assess retention of educational programs among medical students. Objective of study to assess retention of an educational inter-vention on ARH among medical students. METHOD: Seventeen fifth year medical students were assessed with the Knowledge of Psychiatric Aspects of Alcohol Questionnaire (KPAAQ) 12 months after an educational intervention on ARH and compared with a control group. RESULTS: Significant retention was found in the study group. CONCLUSIONS: This preliminary research is the first controlled study on medical student retention of an ARH educational intervention using a validated questionnaire.

7.
Eur J Anaesthesiol ; 2018 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-30308522

RESUMO

BACKGROUND: Rapid detection of the anticoagulant effect of oral factor Xa (FXa) inhibitors may be essential in several emergency clinical situations. Specific assays quantifying the drugs are performed in plasma and require a turnaround time that is too long to be useful in emergency situations. Rotational thromboelastometry (ROTEM) is a whole blood coagulation assay of blood viscoelasticity and could be of interest for FXa inhibitor detection in emergency. However, conventional ROTEM reagents only detect high amounts of inhibitors. OBJECTIVE: The aim of this study was first to assess the effect of whole blood components on the viscoelastic measurement of the effects of FXa inhibitors, an second to evaluate whether a modified ROTEM, triggered with a low amount of tissue factor and a saturating amount of phospholipid vesicles, can reliably detect low levels of FXa inhibitor activity in whole blood. DESIGN: Diagnostic test study. SETTINGS: A university research laboratory. From November 2014 to April 2016. PATIENTS: Sixty-six patients: 30 treated with rivaroxaban, 17 with apixaban and 19 without treatment. INTERVENTION: ROTEM was triggered with 2.5 pmol l of tissue factor and 10 µmol l of phospholipid vesicles. MAIN OUTCOME MEASURES: Modified ROTEM parameters were measured in different experimental conditions: platelet-poor plasma (PPP), platelet-rich plasma, PPP supplemented with fibrinogen and reconstituted whole blood with various haematocrit levels adjusted between 30 and 60%. Modified ROTEM was further validated using whole blood from patients who were either treated or not treated with FXa inhibitors. RESULTS: Modified ROTEM allowed detection of as little as 25 ng ml FXa inhibitors in PPP, with at least a 1.4-fold increase of the clotting time (P ≤ 0.02). Neither changes of fibrinogen concentration nor variations of platelet count or haematocrit precluded FXa inhibitor detection. A lengthened modified ROTEM clotting time of more than 197 s allowed detection of FXa inhibitor concentrations above 30 ng ml in whole blood with 90% sensitivity and 85% specificity. CONCLUSION: Modified ROTEM may be applicable in emergency situations for the detection of FXa inhibitors in whole blood.

8.
Isr Med Assoc J ; 20(9): 561-566, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30221870

RESUMO

BACKGROUND: There is scant research on the psychopathology of Israeli soldiers who present to a general hospital emergency department (ED). OBJECTIVES: To assess the psychopathology among a cohort of Israeli soldiers who presented to a general hospital ED for mental health assessment. METHODS: The demographic and clinical characteristics of 124 consecutive soldiers who presented to the ED for psychiatric assessment between January 2008 and September 2012 were reviewed. Twenty-seven soldiers from the cohort were contacted for follow-up by telephone on average 52 months later. RESULTS: The reasons for presentation to the ED, usually during the early stages of military service, included self-harming behavior, suicidal ideation, somatoform complaints, and dissatisfaction with their military service. Psychiatric diagnoses included adjustment disorder and personality disorder. Self-harming behavior/suicidal ideation was significantly correlated with unspecified adjustment disorder (P = 0.02) and personality disorder (P = 0.001). At follow-up, there was a lack of substantial psychopathology: none of the subjects engaged in self-harming behavior/suicidal ideation and a consistent trend was observed toward clinical improvement. CONCLUSIONS: Psychiatric intervention of soldiers who present to a general hospital ED because of emotional difficulties may provide the opportunity for crisis intervention and validation of the soldier's distress. To the best of our knowledge this is the first Israeli study of psychopathology among soldiers who presented to an ED.

9.
Gene ; 656: 17-21, 2018 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-29496557

RESUMO

Although its powerful impact on most co-morbidities has been widely demonstrated, the metabolic outcomes of bariatric surgery (BS) show a great heterogeneity among patients. Haplotypes of one of the major antioxidant enzyme, catalase (CAT), are associated with hypertension, dyslipidemia, and diabetes. The haplotype referred to as CAT1 includes homozygous carriers of CATH1 [-844G,-89A,-20T], whereas CAT2 haplotype includes heterozygous carriers (CATH1/CATH2) and CATH2 homozygous [-844A,-89T,-20C]. The aim of our study was to evaluate the impact of CAT1 and CAT2 haplotypes on traditional cardiovascular and metabolic markers one year after BS in a women population. The 294 women with a body mass index (BMI) >35 kg/m2 were followed-up for one year after BS, monitoring their anthropometric, metabolic and inflammatory parameters. CAT1 patients had significantly improved diastolic blood pressure (DBP) and Creactive protein (CRP) levels compared to CAT2 one year after BS. In untreated women at baseline, the change of CRP one year after BS was higher in CAT1 patients. In the population of women receiving at least one anti-lipidic, anti-hypertensive or anti-diabetic treatment at baseline, DBP and fat mass were lower one year after BS in CAT1 patients and the greater change of fat mass was associated with a higher change of adiponectin. The results highlight the beneficial impact of the CAT1 haplotype on traditional cardiovascular and metabolic parameters after BS. Our findings suggest that the CAT1 haplotype could be implicated in the level of metabolic and cardiovascular improvement after BS.


Assuntos
Cirurgia Bariátrica , Glicemia/metabolismo , Sistema Cardiovascular/fisiopatologia , Catalase/genética , Obesidade Mórbida/cirurgia , Regiões Promotoras Genéticas , Adulto , Cirurgia Bariátrica/reabilitação , Glicemia/genética , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/prevenção & controle , Dislipidemias/genética , Dislipidemias/prevenção & controle , Feminino , Predisposição Genética para Doença , Haplótipos , Humanos , Hipertensão/genética , Hipertensão/prevenção & controle , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/genética , Obesidade Mórbida/metabolismo , Obesidade Mórbida/fisiopatologia
11.
Semin Arthritis Rheum ; 47(4): 578-585, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28760536

RESUMO

OBJECTIVES: To validate the Fautrel classification criteria for adult-onset Still's disease (AOSD) and to compare the discriminative performance to that of the Yamaguchi criteria. METHODS: We retrospectively reviewed the medical charts of 426 patients who had serum ferritin level and percentage glycosylated ferritin assayed at the biochemistry laboratory of Bichat Hospital. Medical data were extracted by use of a standardized form. All clinical, biological, and imaging features were collected, as well, evidence favoring an alternative diagnosis, specifically symptoms suggestive of other immune-mediated inflammatory diseases (IMID) or active infections. Patients were classified as AOSD patients or controls according to a predefined procedure, including consultation with a multidisciplinary expert group. Algorithms corresponding to the Fautrel and Yamaguchi classification criteria were applied for each patient. RESULTS: In all, 54 AOSD and 278 control patients were included. For the Fautrel criteria, the sensitivity was 87.0%, specificity 97.8%, and positive and negative predictive values 88.7% and 97.5%, respectively. For the standard Yamaguchi set-without strict application of exclusion criteria-the sensitivity was 96.3%, specificity 98.9%, and positive and negative predictive values 94.5% and 99.3%, respectively. If we applied a stricter definition of exclusion criteria, the sensitivity of the Yamaguchi set decreased to 31.5%. As wall, 37 AOSD diagnoses were missed. CONCLUSION: This study validates the Fautrel classification criteria with a cohort independent of that used for the original publication. This criteria set demonstrates good sensitivity and specificity, overcomes exclusion criteria, and includes glycosylated ferritin level. It also confirms the high discriminative power of the Yamaguchi criteria, albeit substantially affected by how exclusion criteria are interpreted.


Assuntos
Doença de Still de Início Tardio/diagnóstico , Adulto , Diagnóstico Diferencial , Feminino , Ferritinas/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Doença de Still de Início Tardio/sangue , Adulto Jovem
12.
Liver Int ; 38(3): 469-476, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29164762

RESUMO

BACKGROUND & AIMS: Early TIPS placement must be considered in patients with Child-Pugh B and active bleeding at endoscopy or in patients with Child-Pugh C 10-13 and variceal bleeding. However, active bleeding at endoscopy is a subjective criterion. Moreover, a previous study has shown that a MELD-based score accurately predicted 6-week mortality and helped to stratify patients. Using a prospective series of patients included in a multicentre study before the era of early TIPS, we aimed (i) to identify factors associated with 6-week mortality, focusing on the prognostic value of active bleeding; and (ii) to assess whether a recalibrated MELD-based score accurately predicted 6-week mortality. METHODS: Ancillary study of the prospective multicentre Baveno IV study, including patients with acute variceal bleeding. RESULTS: Two hundred and nineteen patients were analysed (Child-Pugh A/B/C = 18/45/37%). The overall actuarial likelihood of survival on day 42 was 84%. The variability for the diagnosis of active bleeding at endoscopy was high (range, 41.4% to 84.6% among the centres). Active bleeding at endoscopy was not associated with 6-week mortality in the entire population or in Child-Pugh B patients. In a multivariate analysis, independent factors associated with mortality were liver function, infection, HE and HCC. The recalibrated MELD-based score was accurate in predicting 6-week mortality (AUROC = 0.787). The recalibrated MELD-based score demonstrated better performance compared to the MELD score. CONCLUSION: The recalibrated MELD-based score accurately predicted mortality in our prospective cohort. Active bleeding at endoscopy had no prognostic value in cirrhotic patients presenting with acute variceal bleeding. Standardizing active bleeding assessment at endoscopy is warranted.

13.
Sleep ; 40(11)2017 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-29029239

RESUMO

Objectives: Speech is a complex function in humans, but the linguistic characteristics of sleep talking are unknown. We analyzed sleep-associated speech in adults, mostly (92%) during parasomnias. Methods: The utterances recorded during night-time video-polysomnography were analyzed for number of words, propositions and speech episodes, frequency, gaps and pauses (denoting turn-taking in the conversation), lemmatization, verbosity, negative/imperative/interrogative tone, first/second person, politeness, and abuse. Results: Two hundred thirty-two subjects (aged 49.5 ± 20 years old; 41% women; 129 with rapid eye movement [REM] sleep behavior disorder and 87 with sleepwalking/sleep terrors, 15 healthy subjects, and 1 patient with sleep apnea speaking in non-REM sleep) uttered 883 speech episodes, containing 59% nonverbal utterance (mumbles, shouts, whispers, and laughs) and 3349 understandable words. The most frequent word was "No": negations represented 21.4% of clauses (more in non-REM sleep). Interrogations were found in 26% of speech episodes (more in non-REM sleep), and subordinate clauses were found in 12.9% of speech episodes. As many as 9.7% of clauses contained profanities (more in non-REM sleep). Verbal abuse lasted longer in REM sleep and was mostly directed toward insulting or condemning someone, whereas swearing predominated in non-REM sleep. Men sleep-talked more than women and used a higher proportion of profanities. Apparent turn-taking in the conversation respected the usual language gaps. Conclusions: Sleep talking parallels awake talking for syntax, semantics, and turn-taking in conversation, suggesting that the sleeping brain can function at a high level. Language during sleep is mostly a familiar, tensed conversation with inaudible others, suggestive of conflicts.


Assuntos
Voluntários Saudáveis , Parassonias/fisiopatologia , Semântica , Sono , Fala/fisiologia , Adulto , Idoso , Encéfalo/fisiopatologia , Conflito (Psicologia) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terrores Noturnos/fisiopatologia , Polissonografia , Transtorno do Comportamento do Sono REM/fisiopatologia , Síndromes da Apneia do Sono/fisiopatologia , Sono REM , Sonambulismo/fisiopatologia , Vigília/fisiologia
14.
Crit Care Med ; 45(12): e1262-e1269, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29019852

RESUMO

OBJECTIVES: Microaspiration of subglottic secretions plays a pivotal role in ventilator-associated pneumonia. Impact of endotracheal tube cuff material and shape on tracheal sealing performance remains debated. The primary objective was to compare the tracheal sealing performance of polyvinyl chloride tapered, cylindrical and spherical cuffs. Secondary objectives were to determine the impact of continuous cuff pressure control on sealing performance and pressure variability. DESIGN: Prospective randomized ex vivo animal study. SETTING: French research laboratory. SUBJECTS: Seventy-two ex vivo pig tracheal two-lung blocks. INTERVENTIONS: Blocks were randomly intubated with cylindrical (n = 26), tapered (n = 24), or spherical (n = 22) polyvinyl chloride endotracheal tube cuffs. Two milliliter of methylene blue were instilled above the cuff to quantify microaspirations, and lungs were ventilated for 2 hours. Continuous cuff pressure control was implemented in 33 blocks. MEASUREMENTS AND MAIN RESULTS: Cuff pressures were continuously recorded, and after 2 hours, a microaspiration score was calculated. Tapered cuffs improved cuff sealing performance compared with spherical cuffs with or without continuous cuff pressure control. Compared with spherical cuffs, tapered cuffs reduced the microaspiration score without and with continuous pressure control by 65% and 72%, respectively. Continuous cuff pressure control did not impact sealing performance. Tapered cuffs generated higher cuff pressures and increased the time spent with overinflation compared with spherical cuffs (median [interquartile range], 77.9% [0-99.8] vs. 0% [0-0.5]; p = 0.03). Continuous cuff pressure control reduced the variability of tapered and spherical cuffs likewise the time spent with overinflation of tapered and cylindrical cuffs. CONCLUSIONS: Polyvinyl chloride tapered cuffs sealing enhanced performance at the cost of an increase in cuff pressure and in time spent with overinflation. Continuous cuff pressure control reduced the variability and normalized cuff pressures without impacting sealing performance.


Assuntos
Intubação Intratraqueal/instrumentação , Pneumonia Aspirativa/prevenção & controle , Pneumonia Associada à Ventilação Mecânica/prevenção & controle , Animais , Desenho de Equipamento , Cloreto de Polivinila , Estudos Prospectivos , Distribuição Aleatória , Suínos
15.
Thromb Res ; 158: 126-133, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28892657

RESUMO

Dabigatran etexilate, rivaroxaban and apixaban (DOACs) are widely used and measurement of their concentration is desirable in certain clinical situations. Target-specific assays are available but limited information exists on their performance especially in their ability to accurately measure low and high concentrations. AIMS: To define, in a multicenter study, the precision and accuracy of DOAC measurements in daily practice. METHODS: 15 plasma samples (kindly provided by Hyphen-Biomed) spiked with 5 blinded concentrations of dabigatran, rivaroxaban or apixaban (targeted 0-40-100-250-500ng/mL, actual concentrations measured by HPLC-MS/MS), were sent to 30 haemostasis laboratories. DOAC concentration, PT and aPTT were measured once in each sample using local reagents. Interlaboratory precision was determined by its coefficient of variation (CV) and accuracy by its bias. RESULTS: 464 DOAC measurements were performed in the 30 laboratories using 4 dabigatran and 5 rivaroxaban/apixaban calibrated assays on 3 analysers. Inter-laboratory CVs were below 18% for concentrations ≥100ng/mL, and higher for concentrations ~40ng/mL; biases were below 8% for all drugs and concentrations. In DOAC-free samples, concentrations were all below the lower limit of quantification except for one value (dabigatran: 35ng/mL). Depending on the concentrations, significant differences were found between reagents in rivaroxaban and apixaban concentration values. PT and aPTT ratios displayed a low sensitivity to apixaban. CONCLUSION: Our results suggest that calibrated DOAC assays allow the reliable measurement of a wide range of drug concentrations, even though improvement of their performances is necessary, especially for measuring low concentrations.


Assuntos
Anticoagulantes/sangue , Antitrombinas/sangue , Dabigatrana/sangue , Pirazóis/sangue , Piridonas/sangue , Rivaroxabana/sangue , Anticoagulantes/administração & dosagem , Antitrombinas/administração & dosagem , Dabigatrana/administração & dosagem , França , Humanos , Pirazóis/administração & dosagem , Piridonas/administração & dosagem , Rivaroxabana/administração & dosagem
16.
J Geriatr Cardiol ; 14(7): 465-472, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28868075

RESUMO

BACKGROUND: Knowledge gaps across literature prevent current guidelines from providing the profile of elderly patients most likely to derive benefit from invasive strategy (IS) in non ST-elevation myocardial infarction (NSTEMI). Furthermore, the benefit of IS in a real-world elderly population with NSTEMI remains unclear. The aims of this study were to determine factors that lead the cardiologist to opt for an IS in elderly patients with NSTEMI, and to assess the impact of IS on the 6-month all-cause mortality. METHODS: This multicenter prospective study enrolled all consecutive patients aged ≥ 75 years old who presented a NSTEMI and were hospitalized in cardiology intensive care unit between February 2014 and February 2015. Patients were compared on the basis of reperfusion strategy (invasive or conservative) and living status at six months, in order to determine multivariate predictors of the realization of an IS and multivariate predictors of 6-month mortality. RESULTS: A total of 141 patients were included; 87 (62%) underwent an IS. The strongest independent determinants of IS were younger age [odds ratio (OR): 0.85, 95%-confidence interval (CI): 0.78-0.92; P < 0.001) and lower "Cumulative Illness Rating Scale-Geriatric" number of categories score (OR: 0.83, 95%CI: 0.73-0.95; P = 0.002). IS was not significantly associated with 6-month survival (OR: 0.80, 95%CI: 0.27-2.38; P = 0.69). CONCLUSIONS: In real-world elderly patients with NSTEMI, younger patients with fewer comorbidities profited more often from an IS. However, IS did not modify 6-month all-cause mortality.

17.
Eur Heart J ; 38(31): 2431-2439, 2017 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-28821169

RESUMO

Aims: Patients receiving direct oral anticoagulants (DOACs) frequently undergo elective invasive procedures. Their management is challenging. We aimed to determine the optimal duration of DOAC discontinuation that ensures a minimal anticoagulant effect during the procedure. Methods and results: This prospective multicentre study included 422 DOAC-treated patients requiring an invasive procedure. Pre-procedural DOAC concentration ([DOAC]) and routine haemostasis assays were performed to determine i/the proportion of patients who achieved a minimal pre-procedural [DOAC] (≤30 ng/mL) according to the duration of DOAC discontinuation, ii/the predictors of minimal [DOAC] and, iii/the ability of routine assays to predict minimal [DOAC]. Lastly, we assessed the predictors of peri-procedural bleeding events. The duration of DOAC discontinuation ranged from 1 to 218 h and pre-procedural [DOAC] from ≤30 to 527 ng/mL. After a 49-72-h discontinuation, 95% of the [DOAC] were ≤30 ng/mL. A 72-h discontinuation predicted concentrations ≤30 ng/mL with 91% specificity. In multivariable analysis, duration of DOAC discontinuation, creatinine clearance <50 mL/min and antiarrhythmics were independent predictors of minimal pre-procedural [DOAC] (concordance statistic 0.869; 95% confidence interval: 0.829-0.912). Conversely, routine haemostasis assays were poor predictors. Last, creatinine clearance <50 mL/min, antiplatelets and high-bleeding risk procedures were predictors of bleeding events. Conclusion: A last DOAC intake 3 days before a procedure resulted in minimal pre-procedural anticoagulant effect for almost all patients. Moderate renal impairment, especially in dabigatran-treated patients, and antiarrhythmics in anti-Xa-treated patients should result in a longer DOAC interruption. In situations requiring testing, routine assays should not replace DOAC concentration measurement.


Assuntos
Anticoagulantes/administração & dosagem , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/metabolismo , Testes de Coagulação Sanguínea , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pré-Operatórios , Estudos Prospectivos , Fatores de Tempo
18.
Neuroscience ; 358: 181-189, 2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28673716

RESUMO

Several brain structures including the brainstem, the cerebellum and the frontal cortico-basal ganglia network, with the primary and premotor areas have been shown to participate in the functional organization of gait initiation and postural control in humans, but their respective roles remain poorly understood. The aim of this study was to better understand the role of the supplementary motor area (SMA) and posterior cerebellum in the gait initiation process. Gait initiation parameters were recorded in 22 controls both before and after continuous theta burst transcranial stimulation (cTBS) of the SMA and cerebellum, and were compared to sham stimulation, using a randomized double-blind design study. The two phases of gait initiation process were analyzed: anticipatory postural adjustments (APAs) and execution, with recordings of soleus and tibialis anterior muscles. Functional inhibition of the SMA led to a shortened APA phase duration with advanced and increased muscle activity; during execution, it also advanced muscle co-activation and decreased the duration of stance soleus activity. Cerebellar functional inhibition did not influence the APA phase duration and amplitude but increased muscle co-activation, it decreased execution duration and showed a trend to increase velocity, with increased swing soleus muscle duration and activity. The results suggest that the SMA contributes to both the timing and amplitude of the APAs with no influence on step execution and the posterior cerebellum in the coupling between the APAs and execution phases and leg muscle activity pattern during gait initiation.


Assuntos
Cerebelo/fisiologia , Função Executiva/fisiologia , Marcha/fisiologia , Córtex Motor/fisiologia , Equilíbrio Postural/fisiologia , Adulto , Fenômenos Biomecânicos , Eletromiografia , Feminino , Humanos , Masculino , Contração Muscular/fisiologia , Músculo Esquelético/inervação , Músculo Esquelético/fisiologia , Estimulação Magnética Transcraniana , Adulto Jovem
19.
J Neuroradiol ; 44(5): 298-307, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28602498

RESUMO

BACKGROUND: Long-term stability after intracranial aneurysm exclusion by coiling is still a matter of debate; after surgical clipping little is known. OBJECTIVE: To study outcome after endovascular and surgical treatments for unruptured intracranial aneurysms in terms of short- and long-term angiographic exclusion and risk factors for recanalization. METHODS: From 2004 and 2009, patients treated for unruptured berry intracranial aneurysms by coiling or clipping were reviewed. Aneurysmal exclusion was evaluated using the Roy-Raymond grading scale; immediate clinical outcome was also assessed. Clinical outcome, recanalization, risk factors for recurrence and bleeding during the follow-up period were analyzed by groups; "surgery" and "embolization". RESULTS: From 2004 to 2009, 178 consecutive unruptured aneurysms were treated. The post-procedure angiographic results for "surgery" were: total exclusion 75.6%; residual neck 13.5%; residual aneurysm 10.8%. For "embolization", the results were, respectively: 72%; 20.7%; and 7.2%. Morbidity was 3% for "surgery" and 1.6% for "embolization" (P=0.74); mortality was nil. Mean clinical and angiographic follow-up was 5years. Recurrence rate was of 11.5% for "surgery" vs. 44% for "embolization" with a mean follow-up of 4 and 5.75years, respectively (P=1.10-5). The retreatment rate was 8.4%. Two significant risk factors for recanalization were identified: maximum diameter of the aneurysm sac (P=0.0038) and pericallosal location (P=0.0388). No bleeding event occurred. CONCLUSION: Both techniques are safe. The rate of aneurismal recurrence was significantly higher for embolization, especially for large diameter aneurysms and pericallosal locations. No bleeding event occurred after recanalization.


Assuntos
Angiografia Cerebral/métodos , Embolização Terapêutica/métodos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/terapia , Humanos , Aneurisma Intracraniano/cirurgia , Recidiva , Fatores de Risco
20.
Target Oncol ; 12(3): 365-371, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28527094

RESUMO

BACKGROUND: Circulating tumor DNA (ctDNA) has been reported as a prognostic marker in melanoma. In BRAF V600-mutant melanoma, a plasma under-exposure to vemurafenib could favor emerging resistance but no biological data are available to support this hypothesis. OBJECTIVE: We aimed to investigate the relationship between vemurafenib plasma concentrations and the ctDNA plasma concentration during follow-up of BRAF-mutated melanoma patients. PATIENTS AND METHODS: Eleven patients treated with single-agent vemurafenib for advanced BRAF V600-mutant melanoma were analyzed in an exploratory monocentric study. The vemurafenib plasma concentration was measured by liquid chromatography. ctDNA was extracted from plasma samples and the ctDNA concentration was evaluated using picoliter droplet-based digital PCR with Taqman® detection probes targeting the BRAF p.V600E/K mutation and wild-type BRAF sequences. RESULTS: At baseline, plasma ctDNA was detectable in 72% (n = 8/11) of patients and the ctDNA concentration decreased in 88% of these patients (n = 7/8) from day (D) 0 to D15 after vemurafenib initiation. During follow-up, an increased ctDNA concentration was detected in nine patients: in five patients, the first increase in ctDNA concentrations followed a decrease in vemurafenib concentrations. More interestingly, an inverse correlation between vemurafenib concentration and ctDNA concentrations was demonstrated (p = 0.026). The ctDNA concentration at baseline was associated with overall survival (hazard ratio = 2.61, 95% CI 1.04-6.56; p = 0.04). CONCLUSIONS: This study demonstrates the relevance of vemurafenib plasma monitoring during the follow-up of metastatic melanoma patients. Plasma drug monitoring and ctDNA concentrations could be combined to monitor tumor evolution in melanoma patients treated with anti-BRAF therapies.


Assuntos
DNA/sangue , Indóis/sangue , Melanoma/diagnóstico , Reação em Cadeia da Polimerase/métodos , Sulfonamidas/sangue , Adulto , Idoso , Antineoplásicos/uso terapêutico , Feminino , Seguimentos , Humanos , Indóis/uso terapêutico , Masculino , Melanoma/tratamento farmacológico , Melanoma/mortalidade , Pessoa de Meia-Idade , Mutação/genética , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Proteínas Proto-Oncogênicas B-raf/genética , Sulfonamidas/uso terapêutico , Análise de Sobrevida , Vemurafenib
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