Health-related quality of life in children and adolescents with Marfan syndrome or related disorders: a controlled cross-sectional study.

BACKGROUND: This cross-sectional controlled study aims to assess health-related quality of life (HRQoL) of children and adolescents with a molecular diagnosis of Marfan syndrome (MFS) or related disorders and to evaluate the factors associated with HRQoL in this population. Sixty-three children with MFS and 124 age- and sex-matched healthy children were recruited. HRQoL was assessed using the Pediatric Quality of Life Inventory (PedsQL™) generic questionnaire. The correlation between HRQoL scores and the different continuous parameters (age, body mass index, disease severity, systemic score, aortic sinus diameter, and aerobic physical capacity) was evaluated using Pearson's or Spearman's coefficient. A multiple linear regression analysis was performed on the two health summary self-reported PedsQL™ scores (physical and psychosocial) to identify the factors associated with HRQoL in the MFS group. RESULTS: Except for emotional functioning, all other domains of HRQoL (psychosocial and physical health, social and school functions) were significantly lower in children with MFS compared to matched healthy children. In the MFS group, the physical health summary score was significantly lower in female than in male patients (self-report: absolute difference [95%CI] = -8.7 [-17.0; -0.47], P = 0.04; proxy-report: absolute difference [95%CI] = -8.6 [-17.3; 0.02], P = 0.05) and also negatively correlated with the systemic score (self-report: R = -0.24, P = 0.06; proxy-report: R = -0.29, P = 0.03) and with the height Z-score (proxy-report: R = -0.29, P = 0.03). There was no significant difference in the physical health summary scores between the different genetic subgroups. In the subgroup of 27 patients who performed a cardiopulmonary exercise test, self- and proxy-reported physical health summary scores were highly correlated with their aerobic physical capacity assessed by peak oxygen consumption (VO2max) and ventilatory anaerobic threshold (VAT). In the multivariate analysis, the most important independent predictors of decreased physical health were increased height, decreased body mass index, decreased VAT and use of prophylactic therapy. CONCLUSIONS: This study reports an impaired HRQoL in children and adolescents with MFS or related conditions, in comparison with matched healthy children. Educational and rehabilitation programs must be developed and evaluated to improve exercise capacity and HRQoL in these patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03236571 . Registered 28 July 2017.

Early hybrid cardiac rehabilitation in congenital heart disease: the QUALIREHAB trial.

BACKGROUND AND AIMS: Cardiopulmonary fitness in congenital heart disease (CHD) decreases faster than in the general population resulting in impaired health-related quality of life (HRQoL). As the standard of care seems insufficient to encourage and maintain fitness, an early hybrid cardiac rehabilitation programme could improve HRQoL in CHD. METHODS: The QUALIREHAB multicentre, randomized, controlled trial evaluated and implemented a 12-week centre- and home-based hybrid cardiac rehabilitation programme, including multidisciplinary care and physical activity sessions. Adolescent and young adult CHD patients with impaired cardiopulmonary fitness were randomly assigned to either the intervention (i.e. cardiac rehabilitation) or the standard of care. The primary outcome was the change in HRQoL from baseline to 12-month follow-up in an intention-to-treat analysis. The secondary outcomes were the change in cardiovascular parameters, cardiopulmonary fitness, and mental health. RESULTS: The expected number of 142 patients was enroled in the study (mean age 17.4 ± 3.4 years, 52% female). Patients assigned to the intervention had a significant positive change in HRQoL total score [mean difference 3.8; 95% confidence interval (CI) 0.2; 7.3; P = .038; effect size 0.34], body mass index [mean difference -0.7 kg/m2 (95% CI -1.3; -0.1); P = .022; effect size 0.41], level of physical activity [mean difference 2.5 (95% CI 0.1; 5); P = .044; effect size 0.39], and disease knowledge [mean difference 2.7 (95% CI 0.8; 4.6); P = .007; effect size 0.51]. The per-protocol analysis confirmed these results with a higher magnitude of differences. Acceptability, safety, and short-time effect of the intervention were good to excellent. CONCLUSIONS: This early hybrid cardiac rehabilitation programme improved HRQoL, body mass index, physical activity, and disease knowledge, in youth with CHD, opening up the possibility for the QUALIREHAB programme to be rolled out to the adult population of CHD and non-congenital cardiac disease.

Dementia and glaucoma: Results from a Nationwide French Study between 2006 and 2018.

PURPOSE: Glaucoma is the leading cause of irreversible blindness worldwide. The brain and eye share many characteristics, so the eye may provide an easy-access window on brain processes. The aim of the study was to evaluate the link between glaucoma as well as intraocular pressure (IOP)-lowering drops load and all-cause dementia. METHODS: This was a nested case-control study based on the French national healthcare database from 1 January 2006 to 31 December 2018in individuals aged ≥60 years. We compared cases of incident all-cause dementia with 1:5 controls matched by date of case diagnosis (index date), age, sex, and income. We set a 5-year exposure to glaucoma period ending 2 years before the index date (lag-time period to avoid protopathic bias). The main outcome was glaucoma defined with hospitalization related to POAG and/or dispensations of IOP-lowering drops. The secondary outcome was the IOP-lowering drops load. RESULTS: In total, 4810 incident all-cause dementia and 24 050 matched controls were analysed (median [IQR] age 82 [10] years; 66.6% women). The prevalence of glaucoma was 14.0% in controls and cases. Risk of all-cause dementia was not associated with glaucoma (crude OR, 1.02; 95% CI [0.93-1.11]; p = 0.7; adjusted OR, 0.99; 95% CI [0.91-1.09]; p = 0.9) or IOP-lowering drops load (p = 0.2). CONCLUSION: The present study in general population ≥60 years old in France did not find any association between glaucoma and incident all-cause dementia.

Reference Values of Cardiopulmonary Exercise Test Parameters in the Contemporary Paediatric Population.

BACKGROUND: The evaluation of health status by cardiopulmonary exercise test (CPET) has shown increasing interest in the paediatric population. Our group recently established reference Z-score values for paediatric cycle ergometer VO2max, applicable to normal and extreme weights, from a cohort of 1141 healthy children. There are currently no validated reference values for the other CPET parameters in the paediatric population. This study aimed to establish, from the same cohort, reference Z-score values for the main paediatric cycle ergometer CPET parameters, apart from VO2max. RESULTS: In this cross-sectional study, 909 healthy children aged 5-18 years old underwent a CPET. Linear, quadratic, and polynomial mathematical regression equations were applied to identify the best CPET parameters Z-scores, according to anthropometric parameters (sex, age, height, weight, and BMI). This study provided Z-scores for maximal CPET parameters (heart rate, respiratory exchange ratio, workload, and oxygen pulse), submaximal CPET parameters (ventilatory anaerobic threshold, VE/VCO2 slope, and oxygen uptake efficiency slope), and maximum ventilatory CPET parameters (tidal volume, respiratory rate, breathing reserve, and ventilatory equivalent for CO2 and O2). CONCLUSIONS: This study defined paediatric reference Z-score values for the main cycle ergometer CPET parameters, in addition to the existing reference values for VO2max, applicable to children of normal and extreme weights. Providing Z-scores for CPET parameters in the paediatric population should be useful in the follow-up of children with various chronic diseases. Thus, new paediatric research fields are opening up, such as prognostic studies and clinical trials using cardiopulmonary fitness outcomes. Trial registration NCT04876209-Registered 6 May 2021-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04876209 .

Sodium bicarbonate for the treatment of severe metabolic acidosis with moderate or severe acute kidney injury in the critically ill: protocol for a randomised clinical trial (BICARICU-2).

INTRODUCTION: When both severe metabolic acidemia (pH equal or less than 7.20; PaCO2 equal or less than 45 mm Hg and bicarbonate concentration equal or less than of 20 mmol/L) and moderate-to-severe acute kidney injury are observed, day 28 mortality is approximately 55%-60%. A multiple centre randomised clinical trial (BICARICU-1) has suggested that sodium bicarbonate infusion titrated to maintain the pH equal or more than 7.30 is associated with a higher survival rate (secondary endpoint) in a prespecified stratum of patients with both severe metabolic acidemia and acute kidney injury patients. Whether sodium bicarbonate infusion may improve survival at day 90 (primary outcome) in these severe acute kidney injury patients is currently unknown. METHODS AND ANALYSIS: The sodium bicarbonate for the treatment of severe metabolic acidosis with moderate or severe acute kidney injury in the critically ill: a randomised clinical trial (BICARICU-2) trial is an investigator-initiated, multiple centre, stratified, parallel-group, unblinded trial with a computer-generated allocation sequence and an electronic system-based randomisation. After randomisation, the intervention group will receive 4.2% sodium bicarbonate infusion to target a plasma pH equal or more than 7.30 while the control group will not receive sodium bicarbonate. The primary outcome is the day 90 mortality. Main secondary outcomes are organ support dependences. ETHICS AND DISSEMINATION: The trial has been approved by the appropriate ethics committee (CPP Nord Ouest, Rouen, France, 25 April 2019, number: 19.03.15.72446). Informed consent is required. If sodium bicarbonate improves day 90 mortality, it will become part of the routine care. TRIAL REGISTRATION NUMBER: NCT04010630.

Correlation between three-dimensional echocardiography and cardiopulmonary fitness in patients with univentricular heart: A cross-sectional multicentre prospective study.

BACKGROUND: The prognosis of patients with a functional single ventricle has improved, with better cardiopulmonary fitness, health-related quality of life and survival. Conventional echocardiography remains the first-line technique in single ventricle follow-up. Three-dimensional (3D) echocardiography has shown recent value in congenital cardiology, but its ability to predict functional status in patients with a single ventricle remains unknown. AIM: To evaluate, in patients with a single ventricle, the association between 3D echocardiography variables and functional status determined by cardiopulmonary fitness. METHODS: Children and adults with a functional single ventricle were prospectively enrolled in this multicentre study. Cardiopulmonary fitness was assessed by cardiopulmonary exercise test, with measures of maximum oxygen uptake (VO2max) and ventilatory efficiency (VE/VCO2 slope). 3D echocardiography was performed with off-line reproducibility analyses, using TomTec Arena™ software. Health-related quality of life was assessed using the SF-36 questionnaire. RESULTS: A total of 33 patients were screened, and 3D echocardiography analyses were feasible in 22 subjects (mean age 28±9years). 3D echocardiography ejection fraction correlated with percent-predicted VO2max (r=0.64, P<0.01), VE/VCO2 slope (r=-0.41, P=0.05), two-dimensional echocardiography ejection fraction (r=0.55, P<0.01) and health-related quality of life physical functioning dimension (r=0.56, P=0.04). 3D echocardiography indexed end-systolic volume correlated with percent-predicted VO2max (r=-0.45, P=0.03) and VE/VCO2 slope (r=0.65, P<0.01). 3D echocardiography reproducibility was good. CONCLUSIONS: Single ventricle ejection fraction and volumes measured by 3D echocardiography correlated with cardiopulmonary fitness, as determined by two main prognostic cardiopulmonary exercise test variables: VO2max and VE/VCO2 slope. Despite good reproducibility, 3D echocardiography feasibility remained limited. 3D echocardiography may be of value in single ventricle follow-up, provided that the technique and analysis software are improved.

Reference values of aerobic fitness in the contemporary paediatric population.

AIMS: There has been a growing interest in the use of markers of aerobic physical fitness (VO2max assessed by cardiopulmonary exercise test (CPET)) in the follow-up of paediatric chronic diseases. The dissemination of CPET in paediatrics requires valid paediatric VO2max reference values to define the upper and lower normal limits. This study aimed to establish VO2max reference Z-score values, from a large cohort of children representative of the contemporary paediatric population, including those with extreme weights. METHODS AND RESULTS: In this cross-sectional study, 909 children aged 5 to 18 years old from the general French population (development cohort) and 232 children from the general German and US populations (validation cohort) underwent a CPET, following the guidelines on high-quality CPET assessment. Linear, quadratic, and polynomial mathematical regression equations were applied to identify the best VO2max Z-score model. Predicted and observed VO2max values using the VO2max Z-score model, and the existing linear equations were compared, in both development and validation cohorts. For both sexes, the mathematical model using natural logarithms of VO2max, height, and BMI was the best fit for the data. This Z-score model could be applied to normal and extreme weights and was more reliable than the existing linear equations, in both internal and external validity analyses (https://play.google.com/store/apps/details?id=com.d2l.zscore). CONCLUSION: This study established reference Z-score values for paediatric cycloergometer VO2max using a logarithmic function of VO2max, height, and BMI, applicable to normal and extreme weights. Providing Z-scores to assess aerobic fitness in the paediatric population should be useful in the follow-up of children with chronic diseases. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT04876209.

Risk factors for early occurrence of malnutrition in infants with severe congenital heart disease.

To identify the risk factors of early occurrence of malnutrition in infants with severe congenital heart disease (CHD) during their first year of life. Retrospective longitudinal multicenter study carried out from January 2014 to December 2020 in two tertiary care CHD centers. Four CHD hemodynamic groups were identified. Malnutrition was defined by a Waterlow score under 80% and/or underweight under -2 standard deviations. A total of 216 infants with a severe CHD, e.g., requiring cardiac surgery, cardiac catheterization, or hospitalization for heart failure during their first year of life, were included in the study. Malnutrition was observed among 43% of the cohort, with the highest prevalence in infants with increased pulmonary blood flow (71%) compared to the other hemodynamic groups (p < 0.001). In multivariate analysis, low birthweight (OR 0.62, 95% CI 0.44-0.89, p = 0.009), CHD with increased pulmonary blood flow (OR 4.80, 95% CI 1.42-16.20, p = 0.08), heart failure (OR 9.26, 95% CI 4.04-21.25, p < 0.001), and the number of hospitalizations (OR 1.35, 95% CI 1.08 l-1.69, p = 0.009) during the first year of life were associated with malnutrition (AUC 0.85, 95% CI 0.79-0.90).  Conclusions: In infants with a severe CHD, early occurrence of malnutrition during the first year of life affected a high proportion of subjects. CHD with increased pulmonary blood flow, low birthweight, heart failure, and repeated hospitalizations were risk factors for malnutrition. Further studies are required to identify optimal nutritional support in this population. What is Known: • Malnutrition is a known morbidity and mortality factor in children with severe congenital heart disease. What is New: • Early occurrence of malnutrition during the first year of life in infant severe congenital heart disease (CHD) was high (43%). • CHD with increased pulmonary blood flow, low birthweight, heart failure, and repeated hospitalizations during the first year of life were risk factors for malnutrition.

Effect of non-invasive ventilation after extubation in critically ill patients with obesity in France: a multicentre, unblinded, pragmatic randomised clinical trial.

BACKGROUND: Non-invasive ventilation (NIV) and oxygen therapy (high-flow nasal oxygen [HFNO] or standard oxygen) following extubation have never been compared in critically ill patients with obesity. We aimed to compare NIV (alternating with HFNO or standard oxygen) and oxygen therapy (HFNO or standard oxygen) following extubation of critically ill patients with obesity. METHODS: In this multicentre, parallel group, pragmatic randomised controlled trial, conducted in 39 intensive care units in France, critically ill patients with obesity undergoing extubation were randomly assigned (1:1) to either the NIV group or the oxygen therapy group. Two randomisations were performed: first, randomisation to either NIV or oxygen therapy, and second, randomisation to either HFNO or standard oxygen (also 1:1), which was nested within the first randomisation. Blinding of the randomisation was not possible, but the statistician was masked to group assignment. The primary outcome was treatment failure within 3 days after extubation, a composite of reintubation for mechanical ventilation, switch to the other study treatment, or premature discontinuation of study treatment. The primary outcome was analysed by intention to treat. Effect of medical and surgical status was assessed. The reintubation within 3 days was analysed by intention to treat and after a post-hoc crossover analysis. This study is registered with ClinicalTrials.gov, number NCT04014920. FINDINGS: From Oct 2, 2019, to July 17, 2021, of the 1650 screened patients, 981 were enrolled. Treatment failure occurred in 66 (13·5%) of 490 patients in the NIV group and in 130 (26·5%) of 491 patients in the oxygen-therapy group (relative risk 0·43; 95% CI 0·31-0·60, p<0·0001). Medical or surgical status did not modify the effect of NIV group on the treatment-failure rate. Reintubation within 3 days after extubation was similar in the non-invasive ventilation group and in the oxygen therapy group in the intention-to-treat analysis (48 (10%) of 490 patients and 59 (12%) of 491 patients, p=0·26) and lower in the NIV group than in the oxygen-therapy group in the post-hoc cross-over (51 (9%) of 560 patients and 56 (13%) of 421 patients, p=0·037) analysis. No severe adverse events were reported. INTERPRETATION: Among critically ill adults with obesity undergoing extubation, the use of NIV was effective to reduce treatment-failure within 3 days. Our results are relevant to clinical practice, supporting the use of NIV after extubation of critically ill patients with obesity. However, most of the difference in the primary outcome was due to patients in the oxygen therapy group switching to NIV, and more evidence is needed to conclude that an NIV strategy leads to improved patient-centred outcomes. FUNDING: French Ministry of Health.

Impaired aerobic capacity in adolescents and young adults after treatment for cancer or non-malignant haematological disease.

PURPOSE: Childhood cancer survivors are at increased risk for cardiovascular disease. Maximal oxygen uptake (VO2max) is a major determinant of cardiovascular morbidity. The aim of this study was to compare aerobic capacity, measured by cardiopulmonary exercise test (CPET), of adolescents and young adults in remission with that of healthy controls and to identify the predictors of aerobic capacity in this population. METHOD: This is a controlled cross-sectional study. RESULTS: A total of 477 subjects (77 in remission and 400 controls), aged from 6 to 25 years, were included, with a mean delay between end of treatment and CPET of 2.9 ± 2.3 years in the remission group. In this group, the mean VO2max was significantly lower than in controls (37.3 ± 7.6 vs. 43.3 ± 13.1 mL/kg/min, P < 0.01, respectively), without any clinical or echocardiographic evidence of heart failure. The VAT was significantly lower in the remission group (26.9 ± 6.0 mL/kg/min vs. 31.0 ± 9.9 mL/kg/min, P < 0.01, respectively). A lower VO2max was associated with female sex, older age, higher BMI, radiotherapy, and hematopoietic stem cell transplantation. CONCLUSION: Impaired aerobic capacity had a higher prevalence in adolescents and young adults in cancer remission. This impairment was primarily related to physical deconditioning and not to heart failure. TRIAL REGISTRY: NCT04815447. IMPACT: In childhood cancer survivors, aerobic capacity is five times more impaired than in healthy subjects. This impairment mostly reflects early onset of physical deconditioning. No evidence of heart failure was observed in this population.

Cardiopulmonary fitness in children with asthma versus healthy children.

OBJECTIVES: To evaluate, with a cardiopulmonary exercise test (CPET), the cardiopulmonary fitness of children with asthma, in comparison to healthy controls, and to identify the clinical and CPET parameters associated with the maximum oxygen uptake (VO2max) in childhood asthma. DESIGN: This cross-sectional controlled study was carried out in CPET laboratories from two tertiary care paediatric centres. The predictors of VO2max were determined using a multivariable analysis. RESULTS: A total of 446 children (144 in the asthma group and 302 healthy subjects) underwent a complete CPET. Mean VO2max was significantly lower in children with asthma than in controls (38.6±8.6 vs 43.5±7.5 mL/kg/min; absolute difference (abs. diff.) of -4.9 mL/kg/min; 95% CI of (-6.5 to -3.3) mL/kg/min; p<0.01) and represented 94%±9% and 107%±17% of predicted values, respectively (abs. diff. -13%; 95% CI (-17 to -9)%; p<0.01). The proportion of children with an impaired VO2max was four times higher in the asthma group (24% vs 6%, p<0.01). Impaired ventilatory efficiency with increased VE/VCO2 slope and low breathing reserve (BR) were more marked in the asthma group. The proportion of children with a decreased ventilatory anaerobic threshold (VAT), indicative of physical deconditioning, was three times higher in the asthma group (31% vs 11%, p<0.01). Impaired VO2max was associated with female gender, high body mass index (BMI), FEV1, low VAT and high BR. CONCLUSION: Cardiopulmonary fitness in children with asthma was moderately but significantly altered compared with healthy children. A decreased VO2max was associated with female gender, high BMI and the pulmonary function. TRIAL REGISTRATION NUMBER: NCT04650464.

Aerobic fitness change with time in children with congenital heart disease: A retrospective controlled cohort study.

BACKGROUND: To evaluate the change in aerobic fitness (VO2max), measured by cardio-pulmonary exercise test (CPET), in children with congenital heart disease (CHD), compared to matched healthy controls, and identify predictors of VO2max change with time in this specific population. METHOD: This longitudinal retrospective multicentre cohort study was carried out from 2010 to 2020. We included CHD paediatric patients from the cohort of a previous cross-sectional study, who had a second CPET at least 1 year after the first one, during their follow-up. RESULTS: We included 936 children, 296 in the CHD group and 640 controls. Mean time between baseline and final CPET was 4.4 ± 1.7 years. After matching on age and gender and adjustment for age and BMI, the mean VO2max group difference was 10.5% ± 1.0% of percent-predict VO2max at baseline and increased to 19.1% ± 1.3% at final assessment. In the CHD group, the proportion of children with impaired aerobic fitness was significantly higher at final than at baseline CPET assessment (51.4% vs 20.3%; P < 0.01). The mean annual VO2max decrease was significantly worse in the CHD group than in controls (-1.88% ± 0.19% of percent-predict VO2max/year vs. -0.44% ± 0.27% of percent-predict VO2max/year, P < 0.01, respectively). In multivariate analyse, male gender, a high initial VO2max, a high BMI, and the number of cardiac surgical procedures ≥2, were predictors of the VO2max decrease with time. CONCLUSION: The VO2max decrease with time is more pronounced in children with CHD compared to healthy matched controls. This study highlighted the importance of serial CPET assessment in children with CHD. Trial registration NCT04815577.

Which risk score best predicts cardiovascular outcome in pregnant women with congenital heart disease?

BACKGROUND: Management of pregnancy and risk stratification in women with congenital heart diseases (CHD) are challenging, especially due to physiological haemodynamic modifications that inevitably occur during pregnancy. AIMS: To compare the accuracy of the existing pregnancy cardiovascular risk scores in prediction of maternal complications during pregnancy in CHD patients. METHOD AND RESULTS: From 2007 to 2018, all pregnant women with a CHD who delivered birth after 20 weeks of gestation were identified. The discriminating power and the accuracy of the five existing pregnancy cardiovascular risk scores [CARPREG, CARPREG II, HARRIS, ZAHARA risk scores, and modified WHO (mWHO)] were evaluated.Out of 104 pregnancies in 65 CHD patients, 29% experienced cardiovascular complications during pregnancy or post-partum. For the five scores, the observed rate of cardiovascular events was higher than the expected risk. The values of area under the ROC curve were 0.75 (0.62-0.88) for mWHO, 0.65 (0.53-0.77) for CARPREG II, 0.60 (0.40-0.80) for HARRIS, 0.59 (0.47-0.72) for ZAHARA, and 0.58 (0.43-0.73) for CARPREG. CONCLUSION: The modified WHO classification appeared to better predict cardiovascular outcome in pregnant women with CHD than the four other existing risk scores.Clinical Trial Registration: Clinicaltrials.gov: NCT04221048.

Dementia Associated with Anticholinergic Drugs Used for Overactive Bladder: A Nested Case-Control Study Using the French National Medical-Administrative Database.

PURPOSE: We analyzed the relationship between use of anticholinergic drugs to treat overactive bladder (OAB) and risk of incident dementia in older patients, overall and for each drug separately. MATERIALS AND METHODS: We conducted a nested case-control study using the French National Medical-Administrative Database. We identified incident dementia cases and controls from January 1, 2013 to December 31, 2018 in individuals aged ≥60 years. Controls were matched 5:1 to cases by date of case diagnosis (index date), age, sex, and income. We set a 5-year exposure period ending 2 years before the index date (lag-time period to avoid protopathic bias). We quantified cumulative exposure to flavoxate, oxybutynin, solifenacin, trospium, and fesoterodine using defined daily doses (DDDs). We performed conditional logistic regression analyses adjusted for factors known to be associated with OAB and/or dementia including obesity, diabetes, stroke, coronary heart disease, and psychotic disorders. RESULTS: We analyzed 4,810 cases and 24,050 matched controls with a median age of 82 years. OAB anticholinergic use was associated with an increased risk of dementia (adjusted OR [aOR]=1.23, 95% CI 1.10-1.37) with a cumulative dose-response: aOR=1.07 (95% CI 0.91-1.25) for 1-90 DDDs, aOR=1.29 (1.05-1.58) for 91-365 DDDs and aOR=1.48 (1.22-1.80) for >365 DDDs. Considering each OAB anticholinergic separately showed a particularly marked increased risk of dementia for oxybutynin and solifenacin, but no increased risk for trospium. CONCLUSIONS: When treating OAB in older patients, OAB anticholinergics should be used with caution, taking into account the patient's cognitive status, the anticholinergic load, and the different therapeutic options.

In patients with anorexia nervosa, myokine levels are altered but are not associated with bone mineral density loss and bone turnover alteration.

Objectives: The two-fold aim of this study was: (i) to determine the effects of undernutrition on the myokines in patients with restrictive anorexia nervosa (AN) and (ii) to examine the potential link between myokines and bone parameters. Methods: In this study, 42 young women with restrictive AN and 42 age-matched controls (CON) (mean age, 18.5 ± 4.2 years and 18.6 ± 4.2 years, respectively) were enrolled. aBMD and body composition were determined with DXA. Resting energy expenditure (REEm), a marker of energy status, was indirectly assessed by calorimetry. Bone turnover markers and myokines (follistatin, myostatin and irisin) were concomitantly evaluated. Results: AN patients presented low aBMD at all bone sites. REEm, bone formation markers, myostatin and IGF-1 were significantly lower, whereas the bone resorption marker and follistatin were higher in AN compared with controls. No difference was observed between groups for irisin levels. When the whole population was studied, among myokines, only myostatin was positively correlated with aBMD at all bone sites. However, multiple regression analyses showed that in the AN group, the independent variables for aBMD were principally amenorrhoea duration, lean tissue mass (LTM) and procollagen type I N-terminal propeptide (PINP). For CON, the independent variables for aBMD were principally LTM, age and PINP. Whatever the group analysed, none of the myokines appeared as explicative independent variables of aBMD. Conclusion: This study demonstrated that despite the altered myokine levels in patients with AN, their direct effect on aBMD loss and bone turnover alteration seems limited in comparison with other well-known disease-related factors such as oestrogen deprivation.

Non-invasive ventilation versus oxygen therapy after extubation in patients with obesity in intensive care units: the multicentre randomised EXTUB-OBESE study protocol.

INTRODUCTION: Patients with obesity are considered to be at high risk of acute respiratory failure (ARF) after extubation in intensive care unit (ICU). Compared with oxygen therapy, non-invasive ventilation (NIV) may prevent ARF in high-risk patients. However, these strategies have never been compared following extubation of critically ill patients with obesity. Our hypothesis is that NIV is associated with less treatment failure compared with oxygen therapy in patients with obesity after extubation in ICU. METHODS AND ANALYSIS: The NIV versus oxygen therapy after extubation in patients with obesity in ICUs protocol (EXTUB-obese) trial is an investigator-initiated, multicentre, stratified, parallel-group unblinded trial with an electronic system-based randomisation. Patients with obesity defined as a body mass index ≥30 kg/m² will be randomly assigned in the 'NIV-group' to receive prophylactic NIV applied immediately after extubation combined with high-flow nasal oxygen (HFNO) or standard oxygen between NIV sessions versus in the 'oxygen therapy group' to receive oxygen therapy alone (HFNO or standard oxygen,). The primary outcome is treatment failure within the 72 hours, defined as reintubation for mechanical ventilation, switch to the other study treatment, or premature study-treatment discontinuation (at the request of the patient or for medical reasons such as gastric distention). The single, prespecified, secondary outcome is the incidence of ARF until day 7. Other outcomes analysed will include tracheal intubation rate at day 7 and day 28, length of ICU and hospital stay, ICU mortality, day 28 and day 90 mortality. ETHICS AND DISSEMINATION: The study project has been approved by the appropriate ethics committee 'Comité-de-Protection-des-Personnes Ile de FranceV-19.04.05.70025 Cat2 2019-A00956-51'. Informed consent is required. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences. If use of NIV shows positive effects, teams (medical and surgical) will use NIV following extubation of critically ill patients with obesity. TRIAL REGISTRATION NUMBER: NCT04014920.

Cataract extraction and intraocular pressure-lowering agents delivery: A nationwide French study between 2005 and 2017.

PURPOSE: Cataract and glaucoma are among the leading causes of blindness worldwide in older people, and they are often concomitant. To assess topical intraocular (IOP)-lowering agents delivery changes after cataract extraction. MATERIAL AND METHODS: Longitudinal matched exposed-unexposed study from the French national healthcare database from January 1, 2005 to January 1, 2017. We compared individuals using topical IOP-lowering agents who underwent bilateral cataract extraction with individuals matched on IOP-lowering agents load, age, and sex who did not undergo cataract extraction. IOP-lowering agents number of drops was assessed 12 months before the first cataract extraction and compared with number of drops 12 months after the second cataract extraction. RESULTS: About 1194 individuals treated with IOP-lowering agents were included, 597 exposed to bilateral cataract extraction and 597 unexposed to any surgery (total mean age 74.8 ± 8.3 years; 69.0% women). Mean IOP-lowering agents delivery at baseline was 1.4 daily drops in both groups. The mean number of drops decreased greater in the exposed than unexposed group (-25.5% vs -3.5%; p < 0.0001). Overall, 159 (26.6%) and 48 (8.0%) individuals in the exposed and unexposed groups interrupted medication (p < 0.0001). CONCLUSIONS: A decrease of around one quarter of IOP-lowering agents delivery was observed after cataract extraction in the present real-life study with a longstanding interruption observed in one quarter of patients. Phacoemulsification as a standalone procedure reduces IOP-lowering agents delivery in ocular hypertension and glaucoma.

CRB1-Related Retinal Dystrophies in a Cohort of 50 Patients: A Reappraisal in the Light of Specific Müller Cell and Photoreceptor CRB1 Isoforms.

Pathogenic variants in CRB1 lead to diverse recessive retinal disorders from severe Leber congenital amaurosis to isolated macular dystrophy. Until recently, no clear phenotype-genotype correlation and no appropriate mouse models existed. Herein, we reappraise the phenotype-genotype correlation of 50 patients with regards to the recently identified CRB1 isoforms: a canonical long isoform A localized in Müller cells (12 exons) and a short isoform B predominant in photoreceptors (7 exons). Twenty-eight patients with early onset retinal dystrophy (EORD) consistently had a severe Müller impairment, with variable impact on the photoreceptors, regardless of isoform B expression. Among them, two patients expressing wild type isoform B carried one variant in exon 12, which specifically damaged intracellular protein interactions in Müller cells. Thirteen retinitis pigmentosa patients had mainly missense variants in laminin G-like domains and expressed at least 50% of isoform A. Eight patients with the c.498_506del variant had macular dystrophy. In one family homozygous for the c.1562C>T variant, the brother had EORD and the sister macular dystrophy. In contrast with the mouse model, these data highlight the key role of Müller cells in the severity of CRB1-related dystrophies in humans, which should be taken into consideration for future clinical trials.

Physical activity and aerobic fitness in children with inherited cardiac diseases.

BACKGROUND: Because of sports and exercise restrictions, children with inherited cardiac disease are at risk of physical deconditioning. Guidelines on sports participation in cardiovascular disease have become less restrictive over time, but their real-life application and behavioural impact have seldom been evaluated in children. AIMS: We aimed to evaluate adherence to the 2020 European Society of Cardiology guidelines on sports and exercise in children with inherited cardiac arrhythmia and inherited cardiomyopathy; we also sought to evaluate their aerobic fitness, and the behavioural impact of inherited cardiac diseases on physical activity in children. METHODS: Children aged 6-18 years with inherited cardiomyopathy or inherited cardiac arrhythmia were eligible for this cross-sectional study. Clinical, demographic and qualitative data were analysed. RESULTS: A total of 32 children were included in the study (mean age 12.7±3.5 years). Most children (81.3%) complied with the 2020 European Society of Cardiology guidelines; they were physically active and had good overall aerobic fitness, with a mean peak oxygen uptake (VO2) value of 36.5±8.0mL/kg/min (84.0±17.2% of theoretical value). As a result of personal or parental behaviour, some children at risk of sudden cardiac death did not comply with the recommended upper limit of physical activity intensity, whereas others at low risk did not comply with the lower limit. CONCLUSION: Most children with inherited cardiac arrhythmia or inherited cardiomyopathy complied with current 2020 European Society of Cardiology guidelines on sports cardiology and exercise in cardiovascular disease.

Characterization of SSBP1-related optic atrophy and foveopathy.

Dominant optic atrophy (DOA) is genetically heterogeneous and most commonly caused by mutations in OPA1. To distinguish between the classical OPA1-related and the recently identified SSBP1-related DOAs, the retina and fovea of 27 patients carrying the SSBP1 p.Arg38Gln variant were scrutinized using 20° × 20° macular cube and 30° and 55° field fundus autofluorescence photographs. Age of onset, visual acuity, retinal nerve fiber layer and macular thicknesses were recorded. Three SSBP1-patients were asymptomatic, 10 had isolated DOA, and 12 had a combined DOA plus foveopathy. The foveopathy, with a tiny defect of the ellipsoid and interdigitation lines, was similar in all patients, independent of age. There were no significant statistical differences in terms of visual acuity and SD-OCT measurements between patients with isolated DOA (mean visual acuity in decimals: 0.54 ± 0.41) and those with combined foveopathy (0.50 ± 0.23). Two patients over 50 years of age developed a progressive rod-cone dystrophy, leading to severe visual impairment. SSBP1-related DOA shares similarities with OPA1-related DOA with an incomplete penetrance and an early childhood visual impairment. Nevertheless, the presence of a congenital foveopathy with no impact on visual acuity is a major criterion to distinguish SSBP1 cases and orient the appropriate genetic analysis.