Spontaneous-Breathing Trials with Pressure-Support Ventilation or a T-Piece.

BACKGROUND: Spontaneous-breathing trials can be performed with the use of either pressure-support ventilation (PSV) or a T-piece. Whether PSV trials may result in a shorter time to tracheal extubation than T-piece trials, without resulting in a higher risk of reintubation, among patients who have a high risk of extubation failure is unknown. METHODS: In this multicenter, open-label trial, we randomly assigned patients who had a high risk of extubation failure (i.e., were >65 years of age or had an underlying chronic cardiac or respiratory disease) to undergo spontaneous-breathing trials performed with the use of either PSV (with a pressure-support level of 8 cm of water and no positive end-expiratory pressure) or a T-piece. The primary outcome was the total time without exposure to invasive ventilation (reported as the number of ventilator-free days) at day 28 after the initial spontaneous-breathing trial. Secondary outcomes included extubation within 24 hours and extubation within 7 days after the initial spontaneous-breathing trial, as well as reintubation within 7 days after extubation. RESULTS: A total of 969 patients (484 in the PSV group and 485 in the T-piece group) were included in the analysis. At day 28, the median number of ventilator-free days was 27 (interquartile range, 24 to 27) in the PSV group and 27 (interquartile range, 23 to 27) in the T-piece group (difference, 0 days; 95% confidence interval [CI], -0.5 to 1; P = 0.31). Extubation was performed within 24 hours in 376 patients (77.7%) in the PSV group and in 350 patients (72.2%) in the T-piece group (difference, 5.5 percentage points; 95% CI, 0.01 to 10.9), and extubation was performed within 7 days in 473 patients (97.7%) and 458 patients (94.4%), respectively (difference, 3.3 percentage points; 95% CI, 0.8 to 5.9). Reintubation was performed in 72 of 481 patients (14.9%) in the PSV group and in 65 of 477 patients (13.6%) in the T-piece group (difference, 1.3 percentage points; 95% CI, -3.1 to 5.8). Cardiac or respiratory arrest was a reason for reintubation in 9 patients (3 in the PSV group and 6 in the T-piece group). CONCLUSIONS: Among patients who had a high risk of extubation failure, spontaneous-breathing trials performed with PSV did not result in significantly more ventilator-free days at day 28 than spontaneous-breathing trials performed with a T-piece. (Supported by the French Ministry of Health; TIP-EX ClinicalTrials.gov number, NCT04227639.).

QRS-T angle: is it a specific parameter associated with sudden cardiac death in type 2 diabetes? Results from the SURDIAGENE and the Mini-Finland prospective cohorts.

AIMS/HYPOTHESIS: Type 2 diabetes is associated with a high risk of sudden cardiac death (SCD), but the risk of dying from another cause (non-SCD) is proportionally even higher. The aim of the study was to identify easily available ECG-derived features associated with SCD, while considering the competing risk of dying from non-SCD causes. METHODS: In the SURDIAGENE (Survie, Diabete de type 2 et Genetique) French prospective cohort of individuals with type 2 diabetes, 15 baseline ECG parameters were interpreted among 1362 participants (mean age 65 years; HbA1c 62±17 mmol/mol [7.8±1.5%]; 58% male). Competing risk models assessed the prognostic value of clinical and ECG parameters for SCD after adjusting for age, sex, history of myocardial infarction, N-terminal pro b-type natriuretic peptide (NT-proBNP), HbA1c and eGFR. The prospective Mini-Finland cohort study was used to externally validate our findings. RESULTS: During median follow-up of 7.4 years, 494 deaths occurred including 94 SCDs. After adjustment, frontal QRS-T angle ≥90° (sub-distribution HR [sHR] 1.68 [95% CI 1.04, 2.69], p=0.032) and NT-proBNP level (sHR 1.26 [95% CI 1.06, 1.50] per 1 log, p=0.009) were significantly associated with a higher risk of SCD. Nevertheless, frontal QRS-T angle was the only marker not to be associated with causes of death other than SCD (sHR 1.08 [95% CI 0.84, 1.39], p=0.553 ). These findings were replicated in the Mini-Finland study subset of participants with diabetes (sHR 2.22 [95% CI 1.05, 4.71], p=0.04 for SCD and no association for other causes of death). CONCLUSIONS/INTERPRETATION: QRS-T angle was specifically associated with SCD risk and not with other causes of death, opening an avenue for refining SCD risk stratification in individuals with type 2 diabetes.

Dyspnea is severe and associated with a higher intubation rate in de novo acute hypoxemic respiratory failure.

BACKGROUND: Dyspnea is a key symptom of de novo acute hypoxemic respiratory failure. This study explores dyspnea and its association with intubation and mortality in this population. METHODS: This was a secondary analysis of a multicenter, randomized, controlled trial. Dyspnea was quantified by a visual analog scale (dyspnea-VAS) from zero to 100 mm. Dyspnea was measured in 259 of the 310 patients included. Factors associated with intubation were assessed with a competing risks model taking into account ICU discharge. The Cox model was used to evaluate factors associated with 90-day mortality. RESULTS: At baseline (randomization in the parent trial), median dyspnea-VAS was 46 (interquartile range, 16-65) mm and was ≥ 40 mm in 146 patients (56%). The intubation rate was 45%. Baseline variables independently associated with intubation were moderate (dyspnea-VAS 40-64 mm) and severe (dyspnea-VAS ≥ 65 mm) dyspnea at baseline (sHR 1.96 and 2.61, p = 0.023), systolic arterial pressure (sHR 2.56, p < 0.001), heart rate (sHR 1.94, p = 0.02) and PaO2/FiO2 (sHR 0.34, p = 0.028). 90-day mortality was 20%. The cumulative probability of survival was lower in patients with baseline dyspnea-VAS ≥ 40 mm (logrank test, p = 0.049). Variables independently associated with mortality were SAPS 2 ≥ 25 (p < 0.001), moderate-to-severe dyspnea at baseline (p = 0.073), PaO2/FiO2 (p = 0.118), and treatment arm (p = 0.046). CONCLUSIONS: In patients admitted to the ICU for de novo acute hypoxemic respiratory failure, dyspnea is associated with a higher risk of intubation and with a higher mortality. TRIAL REGISTRATION: clinicaltrials.gov Identifier # NCT01320384.

Bisphenol A and chlorinated derivatives of bisphenol A assessment in end stage renal disease patients: Impact of dialysis therapy.

Patients with end stage kidney disease treated by dialysis (ESKDD) process dialysis sessions to remove molecules usually excreted by kidneys. However, dialysis therapy could also contribute to endocrine disruptors (ED) burden. Indeed, materials like dialyzer filters, ultrapure dialysate and replacement fluid could exposed ESKDD patients to Bisphenol A (BPA) and chlorinated derivatives of BPA (ClxBPAs). Thus, our aim was to compare BPA and ClxBPAs exposure between ESKDD patients, patients with stage 5 chronic kidney disease (CKD5) not dialyzed and healthy volunteers. Then we describe the impact of a single dialysis session, according to dialysis modalities (hemodialysis therapy (HD) versus online hemodiafiltration therapy (HDF)) and materials used with pre-post BPA and ClxBPAs concentrations. The plasma levels of BPA and four ClxBPAs, were assessed for 64 ESKDD patients in pre and post dialysis samples (32 treated by HD and 32 treated by HDF) in 36 CKD5 patients and in 24 healthy volunteers. BPA plasma concentrations were 22.5 times higher for ESKDD patients in pre-dialysis samples versus healthy volunteers (2.208 ± 5.525 ng/mL versus 0.098 ± 0.169 ng/mL) (p < 0.001). BPA plasma concentrations were 16 times higher for CKD5 patients versus healthy volunteers, but it was not significant (1.606 ± 3.230 ng/mL versus 0.098 ± 0.169 ng/mL) (p > 0.05). BPA plasma concentrations for ESKDD patients in pre-dialysis samples were 1.4 times higher versus CKD5 patients (2.208 ± 5.525 ng/mL versus 1.606 ± 3.230 ng/mL) (p < 0.001). For healthy volunteers, ClxBPAs were never detected, or quantified while for CKD5 and ESKDD patients one ClxBPAs at least has been detected or quantified in 14 patients (38.8%) and 24 patients (37.5%), respectively. Dialysis therapy was inefficient to remove BPA either for HD (1.983 ± 6.042 ng/mL in pre-dialysis versus 3.675 ± 8.445 ng/mL in post-dialysis) or HDF (2.434 ± 5.042 ng/mL in pre-dialysis versus 7.462 ± 15.960 ng/mL in post dialysis) regarding pre-post BPA concentrations (p > 0.05). The same result was observed regarding ClxBPA analysis. Presence of polysulfone in dialyzer fibers overexposed ESKDD patients to BPA in pre-dialysis samples with 3.054 ± 6.770 for ESKDD patients treated with a polysulfone dialyzer versus 0.708 ± 0.638 (p = 0.040) for ESKDD patients treated without a polysulfone dialyzer and to BPA in post-dialysis samples with 6.629 ± 13.932 for ESKDD patients treated with a polysulfone dialyzer versus 3.982 ± 11.004 (p = 0.018) for ESKDD patients treated without a polysulfone dialyzer. This work is to our knowledge the first to investigate, the impact of a dialysis session and materials used on BPA and ClxBPAs plasma concentrations and to compare these concentrations to those found in CKD5 patients and in healthy volunteers.

Paving the Way for Personalized Medicine in First Kidney Transplantation: Interest of a Creatininemia Latent Class Analysis in Early Post-transplantation.

Plasma creatinine is a marker of interest in renal transplantation but data on its kinetics in the first days following transplantation are scarce. The aim of this study was to identify clinically relevant subgroups of creatinine trajectories following renal transplantation and to test their association with graft outcome. Among 496 patients with a first kidney transplant included in the French ASTRE cohort at the Poitiers University hospital, 435 patients from donation after brain death were considered in a latent class modeling. Four distinct classes of creatinine trajectories were identified: "poor recovery" (6% of patients), "intermediate recovery" (47%), "good recovery" (10%) and "optimal recovery" (37%). Cold ischemia time was significantly lower in the "optimal recovery" class. Delayed graft function was more frequent and the number of hemodialysis sessions was higher in the "poor recovery" class. Incidence of graft loss was significantly lower in "optimal recovery" patients with an adjusted risk of graft loss 2.42 and 4.06 times higher in "intermediate recovery" and "poor recovery" patients, respectively. Our study highlights substantial heterogeneity in creatinine trajectories following renal transplantation that may help to identify patients who are more likely to experience a graft loss.

Beneficial Effects of Noninvasive Ventilation after Extubation in Obese or Overweight Patients: A Post Hoc Analysis of a Randomized Clinical Trial.

Rationale: Although noninvasive ventilation (NIV) may prevent reintubation in patients at high risk of extubation failure in ICUs, this oxygenation strategy has not been specifically assessed in obese patients. Objectives: We hypothesized that NIV may decrease the risk of reintubation in obese patients compared with high-flow nasal oxygen. Methods:Post hoc analysis of a multicenter randomized controlled trial (not prespecified) comparing NIV alternating with high-flow nasal oxygen versus high-flow nasal oxygen alone after extubation, with the aim of assessing NIV effects according to patient body mass index (BMI). Measurements and Main Results: Among 623 patients at high risk of extubation failure, 206 (33%) were obese (BMI ⩾ 30 kg/m2), 204 (33%) were overweight (25 kg/m2 ⩽ BMI < 30 kg/m2), and 213 (34%) were normal or underweight (BMI < 25 kg/m2). Significant heterogeneity of NIV effects on the rate of reintubation was found according to BMI (Pinteraction = 0.007). Reintubation rates at Day 7 were significantly lower with NIV alternating with high-flow nasal oxygen than with high-flow nasal oxygen alone in obese or overweight patients: 7% (15/204) versus 20% (41/206) (difference, -13% [95% confidence interval, -19 to -6]; P = 0.0002), whereas it did not significantly differ in normal or underweight patients. In-ICU mortality was significantly lower with NIV than with high-flow nasal oxygen alone in obese or overweight patients (2% vs. 9%; difference, -6% [95% confidence interval, -11 to -2]; P = 0.006). Conclusions: Prophylactic NIV alternating with high-flow nasal oxygen immediately after extubation significantly decreased the risk of reintubation and death compared with high-flow nasal oxygen alone in obese or overweight patients at high risk of extubation failure. By contrast, NIV was not effective in normal or underweight patients. Clinical trial registered with www.clinicaltrials.gov (NCT03121482).

Nebulised liposomal amphotericin-B as maintenance therapy in allergic bronchopulmonary aspergillosis: a randomised, multicentre trial.

BACKGROUND: In allergic bronchopulmonary aspergillosis (ABPA), prolonged nebulised antifungal treatment may be a strategy for maintaining remission. METHODS: We performed a randomised, single-blind, clinical trial in 30 centres. Patients with controlled ABPA after 4-month attack treatment (corticosteroids and itraconazole) were randomly assigned to nebulised liposomal amphotericin-B or placebo for 6 months. The primary outcome was occurrence of a first severe clinical exacerbation within 24 months following randomisation. Secondary outcomes included the median time to first severe clinical exacerbation, number of severe clinical exacerbations per patient, ABPA-related biological parameters. RESULTS: Among 174 enrolled patients with ABPA from March 2015 through July 2017, 139 were controlled after 4-month attack treatment and were randomised. The primary outcome occurred in 33 (50.8%) out of 65 patients in the nebulised liposomal amphotericin-B group and 38 (51.3%) out of 74 in the placebo group (absolute difference -0.6%, 95% CI -16.8- +15.6%; OR 0.98, 95% CI 0.50-1.90; p=0.95). The median (interquartile range) time to first severe clinical exacerbation was longer in the liposomal amphotericin-B group: 337 days (168-476 days) versus 177 days (64-288 days). At the end of maintenance therapy, total immunoglobulin-E and Aspergillus precipitins were significantly decreased in the nebulised liposomal amphotericin-B group. CONCLUSIONS: In ABPA, maintenance therapy using nebulised liposomal amphotericin-B did not reduce the risk of severe clinical exacerbation. The presence of some positive secondary outcomes creates clinical equipoise for further research.

Nutritional biomarkers and heart failure requiring hospitalization in patients with type 2 diabetes: the SURDIAGENE cohort.

BACKGROUND: Heart failure (HF) is a growing complication and one of the leading causes of mortality in people living with type 2 diabetes (T2D). Among the possible causes, the excess of red meat and the insufficiency of vegetables consumption are suspected. Such an alimentation is associated with nutritional biomarkers, including trimethylamine N-oxide (TMAO) and its precursors. Here, we aimed to study these biomarkers as potential prognostic factors for HF in patients with T2D. METHODS: We used the SURDIAGENE (SURvival DIAbetes and GENEtics) study, a large, prospective, monocentric cohort study including 1468 patients with T2D between 2001 and 2012. TMAO and its precursors (trimethylamine [TMA], betaine, choline, and carnitine) as well as thio-amino-acids (cysteine, homocysteine and methionine) were measured by liquid chromatography-tandem mass spectrometry. The main outcome was HF requiring Hospitalization (HFrH) defined as the first occurrence of acute HF leading to hospitalization and/or death, established by an adjudication committee, based on hospital records until 31st December 2015. The secondary outcomes were the composite event HFrH and/or cardiovascular death and all-cause death. The association between the biomarkers and the outcomes was studied using cause-specific hazard-models, adjusted for age, sex, history of coronary artery disease, NT-proBNP, CKD-EPI-derived eGFR and the urine albumin/creatinine ratio. Hazard-ratios (HR) are expressed for one standard deviation. RESULTS: The data of interest were available for 1349/1468 of SURDIAGENE participants (91.9%), including 569 (42.2%) women, with a mean age of 64.3 ± 10.7 years and a median follow-up of 7.3 years [25th-75th percentile, 4.7-10.8]. HFrH was reported in 209 patients (15.5%), HFrH and/or cardiovascular death in 341 (25.3%) and all-cause death in 447 (33.1%). In unadjusted hazard-models, carnitine (HR = 1.20, 95% CI [1.05; 1.37]), betaine (HR = 1.34, [1.20; 1.50]), choline (HR = 1.35, [1.20; 1.52]), TMAO (HR = 1.32, [1.16; 1.50]), cysteine (HR = 1.38, [1.21; 1.58]) and homocysteine (HR = 1.28, [1.17; 1.39]) were associated with HFrH, but not TMA and methionine. In the fully adjusted models, none of these associations was significant, neither for HFrH nor for HFrH and/or CV death, when homocysteine only was positively associated with all-cause death (HR = 1.16, [1.06; 1.27]). CONCLUSIONS: TMAO and its precursors do not appear to be substantial prognosis factors for HFrH, beyond usual cardiac- and kidney-related risk factors, whereas homocysteine is an independent risk factor for all-cause death in patients with T2D.

Benefit of Simulation-Based Training in Medical Adverse Events Disclosure in Pediatrics.

INTRODUCTION: Adverse events (AEs) in health care are a public health issue. Although mandatory, error disclosure is experienced by health providers as a difficult task. METHODS: In this prospective study, the primary objective was to assess performance in disclosing AEs to simulated parents using a validated scale before and after training among a pediatric residents' population. Secondary objectives were to assess correlation with year of residency, sex, and previous experience and to analyze gain in knowledge (theoretical pretest/posttest scores) and satisfaction. Two evaluation simulations (simulation [SIM] 1 and SIM 2) were scheduled at 3-week interval. In the intervention group, mastery learning was offered after SIM 1 including a didactic approach and a training session using role-playing games. For the control group, the course was carried out after SIM 2. Assessments were performed by 2 independent observers and simulated parents. RESULTS: Forty-nine pediatric residents performed 2 scenarios of AE disclosure in front of simulated parents. In the intervention group, performance scores on SIM 2 (72.36 ± 5.40) were higher than on SIM 1 (65.08 ± 9.89, P = 0.02). In the control group, there was no difference between SIM 1 and SIM 2 (P = 0.62). The subjective scores from simulated parents showed the same increase on SIM 2 (P < 0.01). There was no correlation with the residents' previous experience or their residency year. There was an increase in self-confidence (P = 0.04) for SIM 2. There was also an increase in posttest theoretical scores (P = 0.02), and residents were satisfied with the training. CONCLUSIONS: This study showed the benefits of simulation-based training associated with mastery learning in AE disclosure among pediatric residents. It is important to train residents for these situations to avoid traumatic disclosure generating a loss of confidence of the family regarding physicians and possible lawsuits.

Effect of High-Flow Nasal Cannula Oxygen vs Standard Oxygen Therapy on Mortality in Patients With Respiratory Failure Due to COVID-19: The SOHO-COVID Randomized Clinical Trial.

Importance: The benefit of high-flow nasal cannula oxygen (high-flow oxygen) in terms of intubation and mortality in patients with respiratory failure due to COVID-19 is controversial. Objective: To determine whether the use of high-flow oxygen, compared with standard oxygen, could reduce the rate of mortality at day 28 in patients with respiratory failure due to COVID-19 admitted in intensive care units (ICUs). Design, Setting, and Participants: The SOHO-COVID randomized clinical trial was conducted in 34 ICUs in France and included 711 patients with respiratory failure due to COVID-19 and a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen equal to or below 200 mm Hg. It was an ancillary trial of the ongoing original SOHO randomized clinical trial, which was designed to include patients with acute hypoxemic respiratory failure from all causes. Patients were enrolled from January to December 2021; final follow-up occurred on March 5, 2022. Interventions: Patients were randomly assigned to receive high-flow oxygen (n = 357) or standard oxygen delivered through a nonrebreathing mask initially set at a 10-L/min minimum (n = 354). Main Outcomes and Measures: The primary outcome was mortality at day 28. There were 13 secondary outcomes, including the proportion of patients requiring intubation, number of ventilator-free days at day 28, mortality at day 90, mortality and length of stay in the ICU, and adverse events. Results: Among the 782 randomized patients, 711 patients with respiratory failure due to COVID-19 were included in the analysis (mean [SD] age, 61 [12] years; 214 women [30%]). The mortality rate at day 28 was 10% (36/357) with high-flow oxygen and 11% (40/354) with standard oxygen (absolute difference, -1.2% [95% CI, -5.8% to 3.4%]; P = .60). Of 13 prespecified secondary outcomes, 12 showed no significant difference including in length of stay and mortality in the ICU and in mortality up until day 90. The intubation rate was significantly lower with high-flow oxygen than with standard oxygen (45% [160/357] vs 53% [186/354]; absolute difference, -7.7% [95% CI, -14.9% to -0.4%]; P = .04). The number of ventilator-free days at day 28 was not significantly different between groups (median, 28 [IQR, 11-28] vs 23 [IQR, 10-28] days; absolute difference, 0.5 days [95% CI, -7.7 to 9.1]; P = .07). The most common adverse events were ventilator-associated pneumonia, occurring in 58% (93/160) in the high-flow oxygen group and 53% (99/186) in the standard oxygen group. Conclusions and Relevance: Among patients with respiratory failure due to COVID-19, high-flow nasal cannula oxygen, compared with standard oxygen therapy, did not significantly reduce 28-day mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT04468126.

Plasma concentrations of lipoproteins and risk of lower-limb peripheral artery disease in people with type 2 diabetes: the SURDIAGENE study.

AIMS/HYPOTHESIS: The lipid profile has not been fully investigated in individuals with peripheral artery disease (PAD). We aimed to evaluate the relationship between plasma concentrations of lipoproteins and the prevalence of lower-limb PAD at baseline and its incidence during follow-up in people with type 2 diabetes. METHODS: Plasma concentrations of total cholesterol, HDL-cholesterol, triacylglycerol and apolipoprotein (Apo) A-I, ApoA-II, ApoB-100 and Apo(a) were measured at baseline using colorimetric or MS methods in the SURDIAGENE cohort. Total cholesterol/HDL-cholesterol ratio, non-HDL-cholesterol and LDL-cholesterol were estimated using computation formulas. Logistic and Cox proportional hazard regression models were fitted to estimate OR or HR, with related 95% CI, for baseline prevalence or incidence of major PAD (lower-limb amputation or requirement of revascularisation) during follow-up by increasing lipoprotein tertiles, after adjustment for key confounders. RESULTS: Among 1468 participants (women 42%, mean ± SD age 65 ± 11 years, duration of diabetes 14 ± 10 years at baseline), 129 (8.8%) had a baseline history of major PAD. Major PAD was less prevalent at baseline in the highest (vs lowest) tertile of HDL-cholesterol (OR 0.42 [95% CI 0.26, 0.71], p = 0.001) and ApoA-I (OR 0.39 [95% CI 0.23, 0.67], p = 0.0007), and more frequent in the highest tertile of total cholesterol/HDL-cholesterol ratio (OR 1.95 [95% CI 1.18, 3.24], p = 0.01). Among 1339 participants without a history of PAD at baseline, incident PAD occurred in 97 (7.2%) during a median (25th-75th percentile) duration of follow-up of 7.1 (4.4-10.7) years, corresponding to 9685 person-years and an incidence rate of 9.8 (95% CI 8.0, 12.0) per 1000 person-years. The risk of incident PAD was lower in the top (vs bottom) tertile of HDL-cholesterol (HR 0.54 [95% CI 0.30, 0.95], p = 0.03) or ApoA-I (HR 0.50 [95% CI 0.28, 0.86], p = 0.01) and higher in the top tertile of total cholesterol/HDL-cholesterol ratio (HR 2.81 [95% CI 1.61, 5.04], p = 0.0002) and non-HDL-cholesterol (HR 1.80 [95% CI 1.06, 3.12], p = 0.03). CONCLUSIONS/INTERPRETATION: We reported independent associations between HDL-cholesterol, ApoA-I, total cholesterol/HDL-cholesterol ratio or non-HDL-cholesterol and the prevalence or the incidence of major PAD in people with type 2 diabetes. Our findings provide a picture of lipoprotein profile in people with type 2 diabetes. Graphical abstract.

Predicting response to a community-based educational workshop on incontinence among community-dwelling older women: Post hoc analysis of the CACTUS-D trial.

AIMS: Our goal was to identify which women participating in an educational workshop on incontinence were most likely to benefit from it. METHODS: We included women aged 65 or older, living in the community, and not treated for incontinence despite reporting urinary leakage at least twice a week. The workshop's aims were to change beliefs about accepting incontinence as a normal part of ageing, explain that incontinence is not irreversible, and that solutions exist. We performed structured interviews at 6 and 12 months to assess impressions of improvement (PGI-I) and changes in both continence (ICIQ-FLUTS) and quality of life (I-QOL). RESULTS: The analysis included 392 women, 39% aged 80 or older and 57% with daily urinary incontinence. Twelve months after the workshop, 16% of women were "much better" (PGI-I); factors associated with impression of improvement were refusal to believe that incontinence is part of normal ageing at baseline and improvement of urinary symptoms. The median improvement was 4 points on the ICIQ-FLUTS and 8 on the I-QOL. Factors associated with a clinically significant improvement in urinary symptoms were more severe baseline urinary incontinence, obesity, and starting Kegel exercises. Factors associated with a clinically significant improvement in quality of life were a poor urinary quality of life at baseline and an age younger than 81 years. CONCLUSIONS: A short, inexpensive and nonmedical intervention can change the mind-set and behavior of older women with incontinence who are not seeking care. A clinically significant improvement is possible even in women with severe symptoms.

Non-invasive ventilation versus high-flow nasal oxygen for postextubation respiratory failure in ICU: a post-hoc analysis of a randomized clinical trial.

BACKGROUND: In intensive care units (ICUs), patients experiencing post-extubation respiratory failure have poor outcomes. The use of noninvasive ventilation (NIV) to treat post-extubation respiratory failure may increase the risk of death. This study aims at comparing mortality between patients treated with NIV alternating with high-flow nasal oxygen or high-flow nasal oxygen alone. METHODS: Post-hoc analysis of a multicenter, randomized, controlled trial focusing on patients who experienced post-extubation respiratory failure within the 7 days following extubation. Patients were classified in the NIV group or the high-flow nasal oxygen group according to oxygenation strategy used after the onset of post-extubation respiratory failure. Patients reintubated within the first hour after extubation and those promptly reintubated without prior treatment were excluded. The primary outcome was mortality at day 28 after the onset of post-extubation respiratory failure. RESULTS: Among 651 extubated patients, 158 (25%) experienced respiratory failure and 146 were included in the analysis. Mortality at day 28 was 18% (15/84) using NIV alternating with high-flow nasal oxygen and 29% (18/62) with high flow nasal oxygen alone (difference, - 11% [95% CI, - 25 to 2]; p = 0.12). Among the 46 patients with hypercapnia at the onset of respiratory failure, mortality at day 28 was 3% (1/33) with NIV and 31% (4/13) with high-flow nasal oxygen alone (difference, - 28% [95% CI, - 54 to - 6]; p = 0.006). The proportion of patients reintubated 48 h after the onset of post-extubation respiratory failure was 44% (37/84) with NIV and 52% (32/62) with high-flow nasal oxygen alone (p = 0.21). CONCLUSIONS: In patients with post-extubation respiratory failure, NIV alternating with high-flow nasal oxygen might not increase the risk of death. Trial registration number The trial was registered at http://www.clinicaltrials.gov with the registration number NCT03121482 the 20th April 2017.

A core outcome set development for a French national prospective study about the effect of mediolateral episiotomy on obstetric anal sphincter injury during operative vaginal delivery (INSTRUMODA).

BACKGROUND: We aimed at developing a core outcome and variables of interest set to investigate the effects of mediolateral episiotomy on Obstetric Anal Sphincter Injury (OASI) during and after operative delivery in nulliparous women in a large-scale one-year observational French study including 15,000 women (INSTRUMODA). METHODS: A list of outcomes and variables of interest was suggested to obstetricians participating in the INSTRUMODA study using online questionnaires divided into 7 categories: the woman's history and course of pregnancy, course of labor, modalities of operative delivery, episiotomy characteristics, immediate maternal morbidity, one-year maternal morbidity, immediate neonatal morbidity. We used a three-round DELPHI method to reach a consensus. In the first round, outcomes and variables considered as essential by 70% or more of obstetricians were included in the corpus whereas they were excluded when 70% rated them as "not important". In the second round, non-consensual outcomes and variables were reassessed and excluded or definitively included if considered as "not important" or essential by 50% or more of the obstetricians. During the first round, obstetricians were invited to suggest new outcomes and/or variables that were then assessed in the second and third round. We used the same method to develop a core outcome and variables of interest set in a population of women in the community recruited via an association of patients. At the end of the procedure the core outcome and variables of interest sets were merged to provide the final core outcome set for the INSTRUMODA study. RESULTS: Fifty-three obstetricians and 16 women filled out questionnaires. After the 3 rounds of Delphi procedure in each population, 74 outcomes and variables were consensually reported by obstetricians and 92 by women in the community. By mixing these two consensual corpora we reported a final consensual list of 114 variables of interest and outcomes for both obstetricians and women. CONCLUSION: We established a core outcome and variables of interest set among obstetricians and women in the community to investigate the association between mediolateral episiotomy and OASI during operative delivery. TRIAL REGISTRATION: The INSTRUMODA study was registered on https://clinicaltrials.gov on June 25, 2020 ( NCT04446780 ).

Impact of Sleep Deprivation on Respiratory Motor Output and Endurance. A Physiological Study.

Rationale: Sleep deprivation can alter endurance of skeletal muscles, but its impact on respiratory command is unknown.Objectives: We aimed to assess the effect of sleep deprivation on respiratory motor output and inspiratory endurance.Methods: Inspiratory endurance was investigated twice in random order, following a normal sleep night and a sleepless night. Healthy participants were asked to breathe as long as possible until task failure against a moderate inspiratory threshold constraint. Transdiaphragmatic pressure and diaphragm electrical activity were measured throughout the trial to assess pressure output of the diaphragm and overall respiratory motor output. Cortical contribution to respiratory motor output was assessed by measurement of preinspiratory motor potential amplitude and by cervical magnetic simulation.Measurements and Main Results: Twenty healthy male participants were studied. Time to task failure was significantly shorter after sleep deprivation than after normal sleep: (30 min [interquartile range [IQR], 17-41] vs. 60 min [IQR, 45-60], P = 0.002). At the beginning of the trial, preinspiratory motor potential amplitude was significantly lower in the sleep-deprivation condition (4.5 µV [IQR, 2.5-6.4] vs. 7.3 µV [IQR, 4.3-10.4], P = 0.02) and correlated significantly with the duration of the endurance trial. In the sleep-deprivation condition, preinspiratory motor potential amplitude, electrical activity of the diaphragm, pressure output of the diaphragm, and Vt decreased and the respiratory rate increased significantly from the beginning to the end of the trial. Such decreases did not occur in the normal-sleep condition.Conclusions: One night of sleep deprivation reduces respiratory motor output by altering its cortical component with subsequent reduction of inspiratory endurance by half. These results suggest that altered sleep triggers severe brain dysfunctions that could precipitate respiratory failure.

Low-dose tyrosine kinase inhibitors before treatment discontinuation do not impair treatment-free remission in chronic myeloid leukemia patients: Results of a retrospective study.

BACKGROUND: Long-term treatment-free remission (TFR) represents a new goal for chronic myeloid leukemia (CML). In clinical practice, tyrosine kinase inhibitor (TKI) dose reductions can be considered a means of preventing adverse effects and improving quality of life. We hypothesized that administration of low-dose TKIs before treatment discontinuation does not impair TFR in patients with CML who have a deep molecular response (DMR, ≥MR4 ). METHODS: We conducted a retrospective analysis of 77 patients with CML who discontinued treatment with TKIs. Twenty-six patients had been managed with low-dose TKIs before stopping treatment. Patients were to be exposed to TKIs for ≥5 years and to low-dose TKIs for ≥1 year and in DMR for ≥2 years. The loss of major molecular response (MMR) was considered a trigger for restarting therapy. RESULTS: In the low-dose group, 61.5% of patients received second-generation TKIs, and dose reduction was ≥50% for 65.4% of patients. With a median follow-up of 61.5 months, TFR at 12 months was 56.8% in the full-dose TKI group and 80.8% in the low-dose group, and TFR at 60 months was 47.5% and 58.8%, respectively. The median time to molecular recurrence (≥MMR) from TKI discontinuation in the entire cohort was 6.2 months. All patients quickly achieved MMR after resuming TKI therapy. Results appear independent of both dose reduction and potential pretreatment with interferon-α. CONCLUSION: This retrospective study shows that TFR was not impaired by low-dose TKI regimens before TKI cessation in Patients with CML. Nevertheless, prospective randomized clinical trials must be undertaken to analyze the probability of successful TFR in patients managed with TKI dose de-escalation strategies before TKI discontinuation.

Balloon catheter vs oxytocin alone for induction of labor in women with a previous cesarean section: A randomized controlled trial.

INTRODUCTION: The aim of this study was to compare the efficacy and maternal-neonatal morbidity between balloon catheter and oxytocin for induction of labor in women with a previous cesarean section and an unfavorable cervix. MATERIAL AND METHODS: This open-label randomized controlled trial took place in seven French hospitals. Inclusion criteria were medical indication for labor induction in pregnant women, ≥37 weeks, with lower segment cesarean section, Bishop score ≤4, no pre-labor rupture of membranes, singleton fetus in cephalic presentation. Women were allocated randomly to induction with a 50-mL balloon catheter for 12 hours or a low-dose oxytocin infusion. Primary outcome was the rate of vaginal birth. Secondary outcomes were maternal and neonatal complications. RESULTS: The study enrolled 204 women from 26 December 2010 to 31 December 2013: 101 were allocated to receive balloon catheter and 103 to oxytocin. Vaginal birth rate was 50% (n = 51) in the balloon catheter group vs 37% (n = 38) in the oxytocin group (P = 0.050). Maternal and neonatal morbidity did not differ between balloon catheter and oxytocin groups: two uterine dehiscences vs one, one vs four maternal infections, five vs two hemorrhages and 11 vs five neonatal transfers, respectively. Heterogeneity of treatment effect for vaginal delivery was observed across initial Bishop scores. Balloon catheter was more effective for low values of bishop score. CONCLUSIONS: Balloon catheter tended to be associated with a higher probability of vaginal delivery as compared with low-dose intravenous oxytocin when used for induction of labor in women with a previous cesarean section and low Bishop score at induction.

Frailty and diabetes status in older patients with cancer: impact on mortality in the ANCRAGE cohort.

BACKGROUND: Frailty, diabetes and cancer are associated with aging, but the relationship between these conditions is not well defined. AIMS: We studied older patients with cancer from the prospective single-center cohort ANCRAGE (ANalyses of CanceR in AGEd) aiming to determine the impact of type 2 diabetes (T2D) and its vascular complications (VC) on frailty and adverse outcomes (mortality, unplanned readmission) during follow-up. METHODS: Analysis of cohort patients ≥ 75 years, included between 2009 and 2017, who underwent a comprehensive geriatric assessment (CGA). Variables of interest were history of T2D and VC, tumor site and metastatic status, CGA including eight domains (social environment, functional status, mobility, nutrition, mood, cognition, polypharmacy and comorbidities) and frailty. RESULTS: Among 1092 patients (47% female, mean age 82 ± 5 years), 219 (20%) had a reported diagnosis of T2D at baseline including 152 (69%) with VC. The most common tumor sites were prostate (15%), breast (15%), skin (12%), and colorectum (11%); 29% of patients had a metastatic disease. Frailty was highly prevalent (84%). During follow-up (median of 15.3 months), 653 (60%) patients died (60% no T2D, 43% T2D without VC, 66% with VC). After adjustment for age, gender and metastatic status, diabetics with VC had a higher risk of all-cause death (aHR1.89, 1.24-2.86, p = 0.004). Death was more frequently due to a non-cancer cause (p < 0.001). No difference in unplanned readmissions was observed in the three groups. Frailty was an independent risk factor for mortality and unplanned readmissions (p < 0.001 both). CONCLUSION: In older cancer patients from the prospective ANCRAGE cohort, all-cause mortality was significantly higher in frail patients and those with complicated T2D, a finding questioning the quality of care management in such vulnerable patients, and stimulating further research in this multidisciplinary field.

Lower limb events in individuals with type 2 diabetes: evidence for an increased risk associated with diuretic use.

AIMS/HYPOTHESIS: Recently, safety data signalled an increased risk of amputations in people taking canagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor. If this side effect is due to drug-induced hypovolaemia, diuretics should also increase that risk. The aim of this study was to analyse the association between diuretic use and the risk of lower limb events (LLEs) in people with type 2 diabetes. METHODS: SURDIAGENE (SUivi Rénal, DIAbète de type 2 et GENEtique) is a prospective observational cohort that includes people with type 2 diabetes enrolled from 2002 to 2012 and followed-up until onset of LLE, death or 31 December 2015, whichever came first. Primary outcome was the first occurrence of LLE, a composite of lower limb amputation (LLA) and lower limb revascularisation (LLR). The rates of primary outcome were compared between participants taking and not taking diuretics at baseline in a Cox-adjusted model. RESULTS: At baseline, of the 1459 participants included, 670 were taking diuretics. In participants with and without diuretics, the mean ages were 67.1 and 62.9 years and 55.8% and 59.8% were men, respectively. During a median follow-up of 7.1 years, the incidence of LLE was 1.80 per 100 patient-years in diuretic users vs 1.00 in non-users (p < 0.001). The HR for LLE in users vs non-users was 2.08 (95% CI 1.49, 2.93), p < 0.001. This association remained significant in a multivariable-adjusted model (1.49 [1.01, 2.19]; p = 0.04) and similar after considering death as a competing risk (subhazard ratio 1.89 [1.35, 2.64]; p < 0.001). When separated, LLA but not LLR, was associated with the use of diuretics: 2.01 (1.14, 3.54), p = 0.02 and 1.05 (0.67, 1.64), p = 0.84, respectively, in the multivariable-adjusted model. CONCLUSIONS/INTERPRETATION: Among people with type 2 diabetes treated with diuretics, there was a significant increase in the risk of LLE, predominantly in the risk of LLA.