Effect of mandibular advancement therapy on inflammatory and metabolic biomarkers in patients with severe obstructive sleep apnoea: a randomised controlled trial.

Systemic inflammation and metabolic disorders are among the mechanisms linking obstructive sleep apnoea (OSA) and cardiovascular disease (CVD). In 109 patients with severe OSA and no overt CVD, biomarkers of inflammation (C reactive protein, interleukin-6, tumour necrosis factor-α and its receptors, adiponectin, leptin and P-selectin), glucose and lipid metabolism, and N-terminal pro-brain natriuretic peptide, were measured before and after 2 months of treatment with a mandibular advancement device (MAD) (n=55) or a sham device (n=54). MAD reduced the Apnoea-Hypopnoea Index (p<0.001) but had no effect on circulating biomarkers compared with the sham device, despite high treatment adherence (6.6 hour/night). TRIAL REGISTRATION NUMBER: NCT01426607.

Physical activity prescription for general practice patients with cardiovascular risk factors-the PEPPER randomised controlled trial protocol.

BACKGROUND: The health benefits of physical exercise have been shown to be important in the prevention of cardiovascular diseases in patients with hypertension, dyslipidaemia or diabetes. However, few strategies have demonstrated efficacy and practicality in the promotion of physical exercise among this group of patients in general practice. METHODS: The PEPPER clinical study is a randomised controlled trial to evaluate the efficacy over a period of 12 months, in terms of physical activity level, of an intervention based on structured information delivery, a personalised written physical activity prescription in number of steps per day, a pedometer and a pedometer logbook, in 35 to 74-year-old patients with cardiovascular risk factors. 140 patients will be recruited in 15 GP practices and randomised in the intervention group or in the control group where patients will receive verbal advice of physical exercise. The primary outcome is the change at three months in total energy expenditure measured by an accelerometer over a 7-day period. Secondary outcomes include changes at 3 and 12 months in physical activity levels (accelerometer and International Physical Activity Questionnaire), quality of life (SF-36), blood pressure, weight, waist circumference, perceived obstacles to physical activity and patient compliance with the recommended strategy. Both groups will be compared using mixed models. DISCUSSION: The results are expected at the end of 2019. If the intervention proves effective in durably increasing the level of physical activity, this strategy could be tested in a larger trial to examine its impact on cardiovascular diseases. TRIAL REGISTRATION: US National Institutes of Health Clinical Trials Registry NCT02317003 , December 15, 2014.

Impact of Mandibular Advancement Therapy on Endothelial Function in Severe Obstructive Sleep Apnea.

RATIONALE: Endothelial dysfunction, a major predictor of late cardiovascular events, is linked to the severity of obstructive sleep apnea (OSA). OBJECTIVES: To determine whether treatment with mandibular advancement device, the main alternative to continuous positive airway pressure, improves endothelial function in patients with severe OSA. METHODS: In this trial, we randomized patients with severe OSA and no overt cardiovascular disease to receive 2 months of treatment with either effective mandibular advancement device or a sham device. The primary outcome, change in reactive hyperemia index, a validated measurement of endothelial function, was assessed on an intention-to-treat basis. An embedded microsensor objectively measured treatment compliance. MEASUREMENTS AND MAIN RESULTS: A total of 150 patients (86% males; mean [SD] age, 54 [10] yr; median [interquartile range] apnea-hypopnea index, 41 [35-53]; mean [SD] Epworth sleepiness scale, 9.3 [4.2]) were randomized to effective mandibular advancement device (n = 75) or sham device (n = 75). On intention-to-treat analysis, effective mandibular advancement device therapy was not associated with improvement of endothelial function compared with the sham device. Office and ambulatory blood pressure outcomes did not differ between the two groups. Effective mandibular advancement device therapy was associated with significant improvements in apnea-hypopnea index (P < 0.001); microarousal index (P = 0.008); and symptoms of snoring, fatigue, and sleepiness (P < 0.001). Mean (SD) objective compliance was 6.6 (1.4) h/night with the effective mandibular advancement device versus 5.6 (2.3) h/night with the sham device (P = 0.006). CONCLUSIONS: In moderately sleepy patients with severe OSA, mandibular advancement therapy reduced OSA severity and related symptoms but had no effect on endothelial function and blood pressure despite high treatment compliance. Clinical trial registered with www.clinicaltrials.gov (NCT 01426607).

Simultaneous pain intensity rating and quantification of ischemia throughout exercise and recovery in proximal versus distal arterial claudication.

Data on simultaneous hemodynamic changes and pain rating estimation in arterial claudication while walking are lacking. This study was conducted to determine if a difference in transcutaneous oxygen pressure (tc pO2) exists between proximal and distal localization at pain appearance (PAINapp), maximal pain (PAINmax) and pain relief (PAINrel) in proximal or distal claudication and if a relationship exists between tc pO2 changes and pain intensity. We analyzed the pain rating (Visual Analog Scale (VAS)) to lower limb ischemia, measured with the decrease from rest of oxygen pressure (DROP) tc pO2 index during constant-load treadmill tests in patients with calf ( n = 41) or buttock ( n = 19) claudication. Calves versus buttocks results were analyzed with ANOVA tests. The R2 correlation coefficient between individual VAS versus DROP was calculated. Ischemia intensity versus pain rating changes were correlated. Significant ischemia was required for pain appearance, but pain disappeared despite the persistence of ischemia. We observed no statistical difference for DROP at PAINapp, PAINmax or PAINrel between proximal or distal claudication. A significant correlation between pain rating versus DROP was found: from PAINapp to PAINmax, R2 = 0.750 (calves) and 0.829 (buttocks), and from PAINmax to PAINrel, R2 = 0.608 (calves) and 0.560 (buttocks); p<0.05. Pain appeared after a significant decrease of hemodynamic parameters but disappeared while parameters were not normalized. No difference in pain rating was found in proximal versus distal claudication.

Proposal of a new classification of postoperative ileus based on its clinical impact-results of a global survey and preliminary evaluation in colorectal surgery.

PURPOSE: There is no consensual definition of postoperative ileus (POI), which leads to a lack of reproducibility. The aims of this study were (i) to propose and evaluate a classification of postoperative ileus based on its consequences and (ii) to assess the reproducibility of the classification. METHODS: A national global survey was carried out according to the DELPHI method in order to create a classification of primary POI. The classification was subsequently tested on a cohort of patients who underwent colorectal surgery. Finally, a reproducibility test was performed in five teaching hospitals with junior and senior surgeons. RESULTS: A five-stage classification was proposed: grade A (least) to grade E (worst). For better differentiation, subcategories (D1/D2) were included. Overall, 173 patients were included who underwent colorectal surgery. Forty of them experienced primary postoperative ileus (23.1%). Grade A occurred in 10 cases, grade B in 10 cases, grade C in 14 cases, grade D1 in 2 cases, and grade D2 in 2 cases. POI-related death (grade E) occurred in 2 cases. Patients with grade A POI recovered their gastrointestinal function significantly faster than those with higher grades (p = 0.01), and were more likely to undergo laparoscopic surgery (p = 0.04). The Intraclass Correlation Coefficient (ICC) was 0.83 in the overall population, and 0.83 and 0.82 respectively in the junior and senior surgeon populations. CONCLUSION: This classification is easy to both use and reproduce. It will improve the reproducibility, evaluation, and assessment of POI. These preliminary results should be confirmed in a multi-centric international study.

The correlation of the "Walking Estimated-Limitation Calculated by History" (WELCH) questionnaire with treadmill maximal walking time is not impaired by age, in patients with claudication.

PURPOSE: The "Walking Estimated-Limitation Calculated by History" (WELCH) questionnaire is a short four-item questionnaire that estimates the walking capacity of a patient in comparison with relatives, friends or people the same age. As such, it should be relatively insensitive to age, yet this has never been tested. METHODS: A prospective study was performed among 525 patients presenting vascular-type claudication. Patients were grouped into quintiles of age-from quintile 1 for the youngest patients to quintile 5 for the oldest ones. Patients completed a self-administered questionnaire and then had their maximal walking time (MWT) measured on a treadmill. We estimated the coefficient of correlation, the slope and the intercept of the relationship between the WELCH score and the MWT, then the accuracy of a WELCH score under 25 to predict the ability to walk for 5 min on a treadmill. RESULTS: The slopes of the relationships and the correlation coefficients were not significantly different in each quintile, but a significant shift in the intercept of regressing lines was found with age. Nevertheless, the accuracy in predicting treadmill results from the WELCH score with a cut-off point of 25 was, respectively, 68.6, 72.4, 80.0, 72.4 and 73.3 % in quintiles 1, 2, 3, 4 and 5 (p = 0.45). CONCLUSIONS: The relationship of MWT on a treadmill and the WELCH score is slightly influenced by age, but a score superior to 25 seems to be of equal discriminatory performance in different quintiles of age to predict the ability to walk for 5 min on a treadmill. This makes this cut-off limit of interest for routine use, regardless of age.

Can the scoring of the walking estimated limitation calculated by history (WELCH) questionnaire be simultaneously simplified and improved?

BACKGROUND: The WELCH questionnaire includes 4 items (A, B, C and D) and estimates the maximal walking time (MWT) on treadmill in patients with claudication. Its scoring was empirically defined. We aimed to test various methods for scoring to estimate whether the scoring of the WELCH could be improved or simplified. PATIENTS AND METHODS: In 423 patients, we tested 8 methods (from H1 to H8) of weighing D or calculating α, ß and γ in the equation MWT = (αA + ßB + γC) * D. RESULTS: While the WELCH Pearson r was 0.639 and area under ROC curve for the ability to walk 5 minutes on treadmill was 0.795 for the reference empirical method, tested hypotheses resulted in values ranging 0.566 to 0.661 for the Pearson r values and 0.750 to 0.809 for the areas under ROC curve respectively. CONCLUSIONS: None of the tested methods simultaneously improved the correlation to MWT, remained simple enough to be scored by mental calculation and ranged between intuitive minimal and maximal values. The original empirical scoring seems a good compromise between accuracy and simplicity.

Comparison of two cancellation strategies to lower the risk of multiple pregnancies in gonadotropin stimulated intrauterine insemination cycles.

OBJECTIVE: To compare two cancellation policies in controlled ovarian stimulation-intrauterine insemination (COS-IUI) cycles to lower the risk of multiple pregnancies (MP). DESIGN: We performed a bicentric retrospective cohort study in two academic medical centers: Angers (group A) and Besançon (group B) University Hospitals. We included 7056 COS-IUI cycles between 2011 and 2019. In group A, cancellation strategy was based on an algorithm taking into account the woman's age, the serum estradiol level, and the number of follicles of 14 mm or greater on ovulation trigger day. In group B, cancellation strategy was case-by-case and physician-dependent, based on the woman's age, number of follicles of 15 mm or greater, and the previous number of failed COS-IUI cycles, without any predefined cut-off. Our main outcome measures were the MP rate (MPR) and the live-birth rate (LBR). RESULTS: We included 884 clinical pregnancies (790 singletons, 86 twins, and 8 triplets) obtained from 6582 COS-IUI cycles. MPR was significantly lower in group A compared with group B (8.1% vs 13.3%, P = 0.01), but LBR were comparable (10.8% vs 11.8%, P = 0.19). Multivariate logistic regression found the following to be risk factors for MP: the "cancellation strategy" effect (adjusted odds ratio [aOR] 1.63, 95% confidence interval [CI] 1.02-2.60) and the number of follicles of 14 mm or greater (aOR 1.39, 95% CI 1.16-1.66). Cycle cancellation rate for excessive response was significantly lower in group A compared with group B (1.3% vs 2.4%, P < 0.001). CONCLUSIONS: The use of an algorithm based on the woman's age, serum estradiol level and number of follicles of at least 14 mm on trigger day allows the MPR to be reduced without impacting the LBR.

Nurses' moral judgements during emergency department triage - A prospective mixed multicenter study.

INTRODUCTION: In EDs, triage ensures that patients whose condition requires immediate care are prioritized while reducing overcrowding. Previous studies have described the manifestation of caregivers' moral judgements of patients in EDs. The equal treatment of patients in clinical practice presents a major issue. Studying the impact of prejudice on clinical practice in the ED setting provides an opportunity to rethink clinical tools, organizations and future training needs. Our study sought to describe the moral judgements expressed by triage nurses during admission interviews in emergency departments and to assess their impact on patient management. METHODS: An exploratory sequential mixed-method study was performed. The study was conducted between January 1, 2018, and February 18, 2018, in the EDs of three French hospitals. Five hundred and three patients and 79 triage nurses participated in the study. Audio recordings, observations and written handover reports made by nurses during admission triage interviews were analyzed with a view to discerning whether moral judgements were expressed in them. We studied the impact of moral judgements on patient management in the emergency department. RESULTS: Abstract Moral judgements were made in 70% of the triage situations studied (n=351/503). They could be classified in seven categories. Patients were more likely to be subjected to moral judgements if they were over 75 years old, visibly disabled or if they had visible signs of alcohol intoxication. Being subjected to moral judgement was associated with differential treatment, including assignment of a triage score that differed from the theoretical triage score. CONCLUSION: More than two thirds of patients admitted to EDs were triaged using moral criteria. Patients who were morally judged at the admission interview were more likely to be treated differently.

Ferric derisomaltose and tranexamic acid, combined or alone, for reducing blood transfusion in patients with hip fracture (the HiFIT trial): a multicentre, 2 × 2 factorial, randomised, double-blind, controlled trial.

BACKGROUND: Anaemia and blood transfusion are associated with poor outcomes after hip fracture. We evaluated the efficacy of intravenous iron and tranexamic acid in reducing blood transfusions after hip fracture surgery. METHODS: In this double-blind, randomised, 2 × 2 factorial trial, we recruited adults hospitalised for hip fractures in 12 medical centres in France who had preoperative haemoglobin concentrations between 9·5 and 13·0 g/dL. We randomly allocated participants (1:1:1:1), via a secure web-based service, to ferric derisomaltose (20 mg/kg intravenously) and tranexamic acid (1 g bolus followed by 1 g over 8 h intravenously at inclusion and 3 g topically during surgery), iron plus placebo (normal saline), tranexamic acid plus placebo, or double placebo. Unmasked nurses administered study drugs; participants and other clinical and research staff remained masked to treatment allocation. The primary outcome was the percentage of patients transfused during hospitalisation (or by day 30). The primary analysis included all randomised patients. This study is registered on ClinicalTrials.gov (NCT02972294) and is closed to new participants. FINDINGS: Of 413 patients (51-104 years old, median [IQR] 86 [78-91], 312 [76%] women, 101 [24%] men), 104 received iron plus tranexamic acid, 103 iron plus placebo, 103 tranexamic acid plus placebo, and 103 double placebo between March 31, 2017 and June 18, 2021 (study stopped early for efficacy after the planned interim analysis done on the first 390 patients included on May 25, 2021). Data for the primary outcome were available for all participants. Among patients on double placebo, 31 (30%) were transfused versus 16 (15%) on both drugs (relative risk 0·51 [98·3% CI 0·27-0·97]; p=0·012). 27 (26%) participants on iron (0·81 [0·50-1·29]; p=0·28) and 28 (27%) on tranexamic acid (0·85 [0·54-1·33]; p=0·39) were transfused. 487 adverse events were reported with similar event rates among the groups; among prespecified safety endpoints, severe postoperative anaemia (haemoglobin <8 g/dL) was more frequent in the double placebo group. Main common adverse event were sepsis, pneumonia, and urinary infection, with similar rates among all groups. INTERPRETATION: In patients hospitalised for hip fracture surgery with a haemoglobin concentration 9·5-13·0 g/dL, preoperative infusion of ferric derisomaltose plus tranexamic acid reduced the risk of blood transfusion by 50%. Our results suggest that combining treatments from two different pillars improves patient blood-management programmes. Either treatment alone did not reduce transfusion rates, but we might not have had the power to detect it. FUNDING: French Ministry of Health, HiFIT trial.

Aging reduces the accuracy of self-reported walking limitation in patients with vascular-type claudication.

BACKGROUND: The published correlations between treadmill performance and the Walking Impairment Questionnaire (WIQ) score are generally fair. We hypothesized that the slope of the relationship of maximal treadmill walking time to WIQ would be lower in older than in younger patients, resulting in (1) a fair correlation in the population considered as a whole and (2) different cutoff points of the WIQ score to predict the ability to complete 5 minutes of treadmill walking in different age groups. METHODS: A 9-month prospective study was performed among patients referred for vascular-type claudication. Patients were divided into three age groups by years: <60 (group 1, n = 91), 60 to 70 (group 2, n = 80), and >70 (group 3, n = 77). Patients self-completed the WIQ, which was corrected with a nurse, if necessary, and then completed a treadmill test. We calculated the correlation coefficient and slope of the relationship between the WIQ and maximal treadmill walking time. We used receiver operating characteristics curve analysis to estimate the accuracy of the WIQ score to determine the ability of the patients to complete 5 minutes of treadmill walking. RESULTS: Differences in slopes were significant between groups 1 vs 2 (P = .02), 2 vs 3 (P < .002), and 1 vs 3 (P < .001). The R(2) for the regression lines also tended to decrease but was only significant between two extremes (1 vs 2, P = .11; 2 vs 3, P = .07; 1 vs 3, P < .001). In patients aged <60 years (group 1), a WIQ score of 47 predicted the ability to complete a 5-minute test on treadmill with 86.8% accuracy (area under the receiver operating characteristics curve, 0.906; P < .001). The accuracy in predicting treadmill results from the WIQ score was fair in group 2 and nonsignificant in group 3. CONCLUSIONS: Prediction of treadmill walking capacity from the WIQ score should account for age. The TransAtlantic Inter-Society Consensus suggests that self-reported limitation has an equal weight as measured walking distance in the treatment choices and follow-up of patients with peripheral arterial disease. The WIQ should probably be used with caution in clinical routine, and constant-load treadmill testing is probably not the ideal candidate in elderly patients. New or adapted tools are likely needed in such patients but remain to be studied.

The role of peak serum estradiol level in the prevention of multiple pregnancies in gonadotropin stimulated intrauterine insemination cycles.

The objective was to assess whether the measurement of serum estradiol (E2) level on trigger day in controlled ovarian stimulation with intrauterine insemination (COS-IUI) cycles helps lower the multiple pregnancy (MP) rate. We performed a unicentric observational study. We included all patients who underwent COS-IUI and had a subsequent clinical pregnancy (CP) between 2011 and 2019. Our main outcome measure was the area under Receiver-Operating Characteristic (ROC) curve. We included 455 clinical pregnancies (CP) obtained from 3387 COS-IUI cycles: 418 singletons, 35 twins, and 2 triplets. The CP, MP, and live birth rates were respectively 13.4%, 8.1% and 10.8%. The area under ROC curve for peak serum E2 was 0.60 (0.52-0.69). The mean E2 level was comparable between singletons and MP (260.1 ± 156.1 pg/mL vs. 293.0 ± 133.4 pg/mL, p = 0.21, respectively). Univariate and multivariate logistic regression analysis showed that E2 level was not predictive of MP rate (aOR: 1.13 (0.93-1.37) and 1.06 (0.85-1.32), respectively). Our study shows that, when strict cancelation criteria based on the woman's age and follicular response on ultrasound are applied, the measurement of peak serum E2 levels does not help reduce the risk of MP in COS-IUI cycles.

Self-reported estimation of usual walking speed improves the performance of questionnaires estimating walking capacity in patients with vascular-type claudication.

OBJECTIVE: Most questionnaires do not estimate the usual walking speed of the patient, although it is well known that patients may experience apparently different walking capacities if walking slow or fast. We hypothesized that correcting the self-reported estimated walking capacity by a coefficient issued from the self-reported estimation of usual walking speed would significantly improve the correlation between questionnaire-estimated and treadmill-measured walking capacity. METHODS: Three hundred ten consecutive patients complaining of vascular-type claudication were asked to estimate their usual walking speed in comparison to people of their age (or friends or relatives) with ratings ranging from much slower (1 pt) to much faster (5 pts), in addition to the filling out of the walking impairment questionnaire (WIQ) and the estimated ambulatory capacity by history questionnaire (EACH-Q). Corrected WIQ (WIQc) and corrected EACH-Q (EACH-Qc) scores were obtained by multiplying the scores of each questionnaire by the "usual-speed" coefficient and dividing by 5. Results for questionnaire scores were compared to maximal walking time (MWT) on a treadmill. RESULTS: All but four patients self-completed the usual-speed question. Median scores (25-75 centiles) were 41% (26-59) for the WIQ and 24% (11-41) for the EACH-Q. Coefficients of correlation of the three WIQ subscales and of the EACH-Q with treadmill results were significantly improved after correction by the "usual-speed" question. Overall, WIQ (mean of the three WIQ subscales) tended to improve but did not reach significance. CONCLUSION: Correcting the self-reported estimation of walking capacity by a self-reported estimation of usual walking pace significantly improves the correlation of all WIQ subscale scores and of the EACH-Q score with treadmill measurements of capacity. This confirms the interest of speed estimation in patients with peripheral arterial occlusive disease and claudication.

Health outcomes of continuous positive airway pressure versus mandibular advancement device for the treatment of severe obstructive sleep apnea: an individual participant data meta-analysis.

STUDY OBJECTIVES: The impact of therapy with continuous positive airway pressure (CPAP) and mandibular advancement device (MAD) has not been directly compared in patients with severe obstructive sleep apnea (OSA). The purpose of this individual participant data meta-analysis was to compare the treatment effects of CPAP and titratable MAD on sleepiness, quality of life, sleep-disordered breathing severity, and sleep structure in patients with severe OSA. METHODS: Randomized controlled trials (RCTs) that included severe OSA patients were identified in order to compare the impact of the two treatments. Individual data from severe OSA patients were extracted from the databases and pooled for analysis. RESULTS: Of the seven studies identified, three crossover RCT and one parallel-group RCT corresponding to 151 patients and 249 observations (125 in the CPAP treatment arm and 124 in the MAD treatment arm) were included in the analysis. Titratable MAD had a similar impact to CPAP on major patient-centered outcomes (sleepiness and quality of life). CPAP was more effective in reducing AHI and ODI. However, the two treatments had a similar impact on sleep structure with an increase of N3 and REM sleep. Finally, treatment adherence and preference were largely in favor of MAD. CONCLUSION: This meta-analysis suggests that MAD represents an effective alternative treatment in severe OSA patients intolerant to CPAP or who prefer alternate therapy.

Study protocol for a multicentre, 2×2 factorial, randomised, controlled trial evaluating the interest of intravenous iron and tranexamic acid to reduce blood transfusion in hip fracture patients (the HiFIT study).

INTRODUCTION: Blood transfusion and anaemia are frequent and are associated with poor outcomes in patients with hip fracture (HF). We hypothesised that preoperative intravenous iron and tranexamic acid (TXA) may reduce the transfusion rate in these patients. METHODS AND ANALYSIS: The HiFIT study is a multicentre, 2×2 factorial, randomised, double-blinded, controlled trial evaluating the effect of iron isomaltoside (IIM) (20 mg/kg) vs placebo and of TXA (intravenously at inclusion and topically during surgery) versus placebo on transfusion rate during hospitalisation, in patients undergoing emergency surgery for HF and having a preoperative haemoglobin between 95 and 130 g/L. 780 patients are expected. The primary endpoint is the proportion of patients receiving an allogenic blood transfusion of packed red blood cells from the day of surgery until hospital discharge (or until D30 if patient is still hospitalised). Enrolment started on March 2017 in 11 French hospitals. The study was stopped between July 2017 and August 2018 (because of investigation of serious AEs with IIM in Spain) and slowed down since March 2020 (COVID-19 crisis). The expected date of final follow-up is May 2022. Analyses of the intent-to-treat and per-protocol populations are planned. ETHICS AND DISSEMINATION: The HiFIT trial protocol has been approved by the Ethics Committee of Comité de Protection des Personnes Ouest II and the French authorities (ANSM). It will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals. The HiFIT trial will be the largest study evaluating iron and TXA in patients with HF. TRIAL REGISTRATION NUMBER: clinicalTrials.gov identifier: NCT02972294; EudraCT Number 2016-003087-40.

Hydroxychloroquine in mild-to-moderate coronavirus disease 2019: a placebo-controlled double blind trial.

OBJECTIVES: To determine whether hydroxychloroquine decreases the risk of adverse outcome in patients with mild to moderate coronavirus disease 2019 (COVID-19) at high risk of worsening. METHODS: We conducted a multicentre randomized double-blind placebo-controlled trial evaluating hydroxychloroquine in COVID-19 patients with at least one of the following risk factors for worsening: need for supplemental oxygen, age ≥75 years, age between 60 and 74 years and presence of at least one co-morbidity. Severely ill patients requiring oxygen therapy >3 L/min or intensive care were excluded. Eligible patients were randomized in a 1:1 ratio to receive either 800 mg hydroxychloroquine on day 0 followed by 400 mg per day for 8 days or a placebo. The primary end point was a composite of death or start of invasive mechanical ventilation within 14 days following randomization. Secondary end points included mortality and clinical evolution at days 14 and 28, and viral shedding at days 5 and 10. RESULTS: The trial was stopped after 250 patients were included because of a slowing down of the pandemic in France. The intention-to-treat population comprised 123 and 124 patients in the placebo and hydroxychloroquine groups, respectively. The median age was 77 years (interquartile range 58-86 years) and 151/250 (60.4%) patients required oxygen therapy. The primary end point occurred in 9/124 (7.3%) patients in the hydroxychloroquine group and 8/123 (6.5%) patients in the placebo group (relative risk 1.12; 95% CI 0.45-2.80). The rates of positive SARS-CoV-2 RT-PCR tests at days 5 and 10 were 72.8% (75/103) and 57.1% (52/91) in the hydroxychloroquine group, versus 73.0% (73/100) and 56.6% (47/83) in the placebo group, respectively. No difference was observed between the two groups in any of the other secondary end points. CONCLUSION: In this underpowered trial involving mainly older patients with mild to moderate COVID-19, patients treated with hydroxychloroquine did not experience better clinical or virological outcomes than those receiving the placebo. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04325893 (https://clinicaltrials.gov/ct2/show/NCT04325893).

Objective determination of the predefined duration of a constant-load diagnostic tests in arterial claudication.

OBJECTIVE: The predefined duration to arbitrarily stop the tests during constant-load treadmill exercise is a subject of debate and widely variable in the literature. We hypothesized that the upper and lower limits for predefined durations of constant-load 3.2 km/hour 10% grade tests could be derived from the distribution of walking distances observed on a treadmill in a population of subjects referred for claudication or from the optimal cutoff point distance on a treadmill to confirm a limitation self-reported by history. METHODS: We conducted a retrospective analysis using a referral center, institutional practice, and ambulatory patients. We studied 1290 patients (86% male), 62.1 +/- 11.2 years of age, 169 +/- 8 cm height, 75.7 +/- 14.2 kg weight. Patients performed a standard constant-load treadmill test: 3.2 km hour(-1), 10% slope, maximized to 1000 meters (approximately 20 minutes). We analyzed the maximal walking distance self-reported (MWD(SR)) by history and the maximal walking distance measured on the treadmill (MWD(TT)). Patients reporting MWD(SR) >or=1000 meters were considered unlimited by history. RESULTS: Only 197 patients (15.3%) completed the 20-minute treadmill test. Among the 504 patients who did not stop before 250 meters, 47.8% stopped within the next 250 meters (were unable to walk 500 meters). This proportion falls to 7.5% among the 213 patients who did not stop before 750 meters. When the final goal was to estimate whether the treadmill test can discriminate patients with or without limitation by history, area under the receiver operating characteristic (ROC) curve was 0.809 +/- 0.016 (95% confidence interval [CI], 0.778-0.841; P < .0001), the best diagnostic performance was attained for an MWD(TT) of 299 meters (approximately 6.15 minutes). CONCLUSION: In patients undergoing constant-load treadmill exercise with a protocol of 3.2 km hour(-1) and 10% slope: a predefined duration of 7 minutes could be proposed as a lower limit for the predefined duration of the tests specifically if one aims at confirming the limitation by history with treadmill testing. Owing to the low risk that patients that could walk 750 meters (approximately 15 minutes) will have to stop in the next 250 meters, 15 minutes seems a reasonable upper limit for the predefined test duration in clinical routine.