Intra-individual Dose Escalation of Abiraterone According to Its Plasma Exposure in Patients with Progressive Metastatic Castration-Resistant Prostate Cancer: Results of the OPTIMABI Trial.

BACKGROUND AND OBJECTIVE: Trough abiraterone concentration (ABI Cmin) of 8.4 ng/mL has been identified as an appropriate efficacy threshold in patients treated for metastatic castration-resistant prostate cancer (mCRPC). The aim of the phase II OPTIMABI study was to evaluate the efficacy of pharmacokinetics (PK)-guided dose escalation of abiraterone acetate (AA) in underexposed patients with mCRPC with early tumour progression. METHODS: This multicentre, non-randomised study consisted of two sequential steps. In step 1, all patients started treatment with 1000 mg of AA once daily. Abiraterone Cmin was measured 22-26 h after the last dose intake each month during the first 12 weeks of treatment. In step 2, underexposed patients (Cmin < 8.4 ng/mL) with tumour progression within the first 6 months of treatment were enrolled and received AA 1000 mg twice daily. The primary endpoint was the rate of non-progression at 12 weeks after the dose doubling. During step 1, adherence to ABI treatment was assessed using the Girerd self-reported questionnaire. A post-hoc analysis of pharmacokinetic (PK) data was conducted using Bayesian estimation of Cmin from samples collected outside the sampling guidelines (22-26 h). RESULTS: In the intention-to-treat analysis (ITT), 81 patients were included in step 1. In all, 21 (26%) patients were underexposed in step 1, and 8 of them (38%) experienced tumour progression within the first 6 months. A total of 71 patients (88%) completed the Girerd self-reported questionnaire. Of the patients, 62% had a score of 0, and 38% had a score of 1 or 2 (minimal compliance failure), without a significant difference in mean ABI Cmin in the two groups. Four patients were enrolled in step 2, and all reached the exposure target (Cmin > 8.4 ng/mL) after doubling the dose, but none met the primary endpoint. In the post-hoc analysis of PK data, 32 patients (39%) were underexposed, and ABI Cmin was independently associated with worse progression-free survival [hazard ratio (HR) 2.50, 95% confidence interval (CI) 1.07-5.81; p = 0.03], in contrast to the ITT analysis. CONCLUSION: The ITT and per-protocol analyses showed no statistical association between ABI underexposure and an increased risk of early tumour progression in patients with mCRPC, while the Bayesian estimator showed an association. However, other strategies than dose escalation at the time of progression need to be evaluated. Treatment adherence appeared to be uniformly good in the present study. Finally, the use of a Bayesian approach to recover samples collected outside the predefined blood collection time window could benefit the conduct of clinical trials based on drug monitoring. OPTIMABI trial is registered as National Clinical Trial number NCT03458247, with the EudraCT number 2017-000560-15).

[New collaborative and participatory program for malnutrition management in the elders after hospitalization]. / Nouveau programme collaboratif et participatif de lutte contre la dénutrition chez le sujet âgé en ville au sortir d'une hospitalisation.

BACKGROUND: Malnutrition in the elderly people is frequent and serious. Management of malnutrition at home after hospitalization is unsatisfactory. The objective of the study is to evaluate the feasibility and participation of a new collaborative and participative program involving the patient, the general practitioner and the dietician nutritionist, to fight against malnutrition in the elderly people at home after hospitalization. METHODS: This was a prospective and non-randomized study performed from May 2015 to February 2016, in subjects aged 75 and more, malnourished, with an MMSE score > 20 and returning homes after hospitalization. At home, a dietician worked with the patients and their general practitioner for 3 months. Patient participation and satisfaction of the 3 actors were assessed. RESULTS: Forty-four patients were included and 11.9% (n=8) benefited from the entire program. Present entourage (p=0.001), dietary education to the entourage (p=0,003), a high MMSE score (p=0.04), having an ulcer (p=0.0097), and a high weight at discharge (p=0.03) increased patients' participation. Patients (78.6%) and general practitioners (75%) were satisfied with the program. Patients criticized the lack of involvement of the general practitioner. General practitioners felt they had not acquired any knowledge of dietetics. CONCLUSION: Patient participation and collaboration between actors of the program of management of malnutrition in elderly people were considered weak.

Mid-regional proatrial natriuretic peptide for predicting prognosis in hypertrophic cardiomyopathy.

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.

Adrenergic reactions during N3 sleep arousals in sleepwalking and sleep terrors: The chicken or the egg?

To understand the mechanisms of N3 sleep interruptions in patients with sleepwalking episodes and/or sleep terrors (SW/ST), we evaluated whether autonomic reactions preceded or accompanied behavioural arousals from NREM sleep stage N3. In 20 adult patients with SW/ST and 20 matched controls without parasomnia, heart rate and pulse wave amplitude were measured beat-to-beat during the 10 beats preceding and during the 15 beats succeeding a motor arousal from N3 sleep. Respiratory rate and amplitude were measured during the same 25 successive beats. In patients with SW/ST, the N3 arousals were associated with a 33% increase in heart rate, a 57% decrease in pulse wave amplitude (indicating a major vasoconstriction), a 24% increase in respiratory rate and a doubling of respiratory amplitude. Notably, tachycardia and vasoconstriction started 4 s before motor arousals. A similar profile (tachycardia and vasoconstriction gradually increasing from the 4 s preceding arousal and post-arousal increase of respiratory amplitude, but no polypnea) was also observed, with a lower amplitude, during the less frequent 38 quiet N3 arousals in control subjects. Parasomniac arousals were associated with greater tachycardia, vasoconstriction and polypnea than quiet arousals, with the same pre-arousal gradual increases in heart rate and vasoconstriction. Autonomic arousal occurs 4 s before motor arousal from N3 sleep in patients with SW/ST (with a higher adrenergic reaction than in controls), suggesting that an alarming event during sleep (possibly a worrying sleep mentation or a local subcortical arousal) causes the motor arousal.

Long-term outcome of heart transplantation performed after ventricular assist device compared with standard heart transplantation.

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.

Case-Control Retrospective Study of Child Sexual Abuse History among Psychiatric Consultations in a General Hospital Emergency Room.

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.

The supplementary motor area modulates interhemispheric interactions during movement preparation.

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.

Modified ROTEM for the detection of rivaroxaban and apixaban anticoagulant activity in whole blood: A diagnostic test study.

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, and 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.

Alcohol Related Harm: Knowledge Assessment of Medical and Nursing Staff in a General Hospital.

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.

Preliminary results of a controlled educational intervention on alcohol related harm among medical students with a 12-month follow-up.

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.

Psychopathology of Israeli Soldiers Presenting to a General Hospital Emergency Department: Lessons for the Attending Physician and Psychiatrist.

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.

Human catalase gene promoter haplotype and cardiometabolic improvement after bariatric surgery.

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.

Validation of the Fautrel classification criteria for adult-onset Still's disease.

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.

Recalibrated MELD and hepatic encephalopathy are prognostic factors in cirrhotic patients with acute variceal bleeding.

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.

What Does the Sleeping Brain Say? Syntax and Semantics of Sleep Talking in Healthy Subjects and in Parasomnia Patients.

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.

Modification of Tracheal Cuff Shape and Continuous Cuff Pressure Control to Prevent Microaspiration in an Ex Vivo Pig Tracheal Two-Lung Model.

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.

Determinants of invasive strategy in elderly patients with non-ST elevation myocardial infarction.

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.

Evaluation of dabigatran, rivaroxaban and apixaban target-specific assays in a multicenter French study.

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.