Development and real-life use assessment of a self-management smartphone application for patients with inflammatory arthritis. A user-centred step-by-step approach.

BACKGROUND: Mobile health applications (apps) are increasing in interest to enhance patient self-management. Few apps are actually used by patients and have been developed for patients with inflammatory arthritis (IA) treated with disease-modifying anti-rheumatic drugs which use entails risk of adverse effects such as infections. OBJECTIVE: To develop Hiboot, a self-management mobile app for patients with IA, by using a user-centred step-by-step approach and assess its real-life use. METHODS: The app development included first a qualitative study with semi-guided audiotaped interviews of 21 patients to identify the impact of IA on daily life and patient treatments practices and an online cross-sectional survey of 344 patients to assess their health apps use in general and potential user needs. A multidisciplinary team developed the first version of the app via five face-to-face meetings. After app launch, a second qualitative study of 21 patients and a users' test of 13 patients and 3 rheumatologists led to the app's current version. The number of app installations, current users and comments were collected from the Google Play store and the Apple store. RESULTS: The qualitative study revealed needs for counselling, patient-health professional partnership, and skills to cope with risk situations; 86.8% participants would be ready to use an app primarily on their rheumatologist's recommendation. Six functionalities were implemented: a safety checklist before treatment administration, aids in daily life situations based on the French academic recommendations, treatment reminders, global well-being self-assessment, periodic counselling messages, and a diary. The Hiboot app was installed 20,500 times from September 2017 to October 2020, with 4300 regular current users. Scores were 4.4/5 stars at Android and iOS stores. CONCLUSION: Hiboot is a free self-management app for patients with IA developed by a step-by-step process including patients and health professionals. Further evaluation of the Hiboot benefit is needed.

Risk of malignancy in rheumatoid arthritis patients initiating biologics: an historical propensity score matched cohort study within the French nationwide healthcare database.

OBJECTIVE: To compare the risk of malignancy between patients with rheumatoid arthritis (RA) initiating their first biological disease-modifying antirheumatic drug (bDMARD) and those continuing conventional synthetic DMARDs (csDMARDs). METHODS: Nine-year historical Propensity Score (PS) matched cohort study within the French national healthcare database (87% of the French population; ~57 million people), including adults RA without malignancy. Exposures started with the first use of any systemic treatment (csDMARDs and/or bDMARDs). Incident users of bDMARDs were matched on a dynamic PS to patients continuing csDMARDs. Their risk of malignancy was compared by Cox model. RESULTS: From 1 January 2007 to 31 December 2014, 83 706 patients with RA started their first systemic treatment (63 837 remained on csDMARDs and 19 869 initiated a bDMARD during follow-up). After dynamic PS matching, 19 727 bDMARD initiators were compared with 19 727 RA remaining on csDMARDs. They did not statistically differ in risk of overall malignancies (HR 0.99 (95% CI 0.86 to 1.14)), solid cancer (HR 0.95 (95% CI 0.82 to 1.11)), nor lymphoma (HR 1.35 (95% CI 0.72 to 2.53)). Results were similar when bDMARDs were given as monotherapy or in association with csDMARDs. Analyses restricted to patients starting TNF inhibitor as first bDMARD compared with matched RA remaining on csDMARDs, provided similar results (HR for overall malignancy 1.03 (95% CI 0.88 to 1.21)). Sensitivity analyses, varying carry-over periods (up to 5 years) to define risk periods, provided similar results. CONCLUSIONS: In this historical cohort study within the French nationwide healthcare database, the risk of overall, solid or haematological malignancies did not significantly differ between patients with RA initiating bDMARD and those continuing csDMARDs.

Aortic valve repair versus mechanical valve replacement for root aneurysm: the CAVIAAR multicentric study.

OBJECTIVES: Despite growing evidence that aortic valve repair improves long-term patient outcomes and quality of life, aortic valves are mostly replaced. We evaluate the effect of aortic valve repair versus replacement in patients with dystrophic aortic root aneurysm up to 4 years. METHODS: The multicentric CAVIAAR (Conservation Aortique Valvulaire dans les Insuffisances Aortiques et les Anévrismes de la Racine aortique) prospective cohort study enrolled 261 patients: 130 underwent standardized aortic valve repair (REPAIR) consisting of remodelling root repair with expansible aortic ring annuloplasty, and 131 received mechanical composite valve and graft replacement (REPLACE). Primary outcome was a composite criterion of mortality, reoperation, thromboembolic or major bleeding events, endocarditis or operating site infections, pacemaker implantation and heart failure, analysed with propensity score-weighted Cox model analysis. Secondary outcomes included major adverse valve-related events and components of primary outcome. RESULTS: The mean age was 56.1 years, and valve was bicuspid in 115 patients (44.7%). Up to 4 years, REPAIR did not significantly differ from REPLACE in terms of primary outcome [Hazard Ratio (HR) 0.66 (0.39; 1.12)] but showed significantly less valve-related deaths (HR 0.09 [0.02; 0.34]) and major bleeding events (HR 0.37 [0.16; 0.85]) without an increased risk of valve-related reoperation (HR 2.10 [0.64; 6.96]). When accounting for the occurrence of multiple events in a single patient, the REPAIR group had half the occurrence of major adverse valve-related events (HR 0.51 [0.31; 0.86]). CONCLUSIONS: Although the primary outcome did not significantly differ between the REPAIR and REPLACE groups, the trend is in favour of REPAIR by a significant reduction of valve-related deaths and major bleeding events. Long-term follow-up beyond 4 years is needed to confirm these findings.

Positive impact on 10-year outcome of the window of opportunity for conventional synthetic DMARDs in rheumatoid arthritis: results from the ESPOIR cohort.

OBJECTIVE: This study aimed to assess the impact of disease-modifying antirheumatic drugs (DMARDs) on 10-year outcomes in rheumatoid arthritis (RA). METHODS: Patients with RA from the ESPOIR cohort with complete data on Disease Activity Score in 28 Joints (DAS28) and Health Assessment Questionnaire (HAQ) at 10 years (n=418) and complete radiographic data at baseline and 10 years (n=343) were included in this study. Outcomes were favourable outcome (FavOut) at 10 years, defined as DAS28 of <2.6 and HAQ score of <0.5 at 10 years, and absence of structural damage progression (AbsSDP) at 10 years, defined as change in Sharp-van der Heijde Score less than the smallest detectable change at 10 years (11.5 points). Three multivariate logistic regression models predicting 10-year outcome were built, considering (1) baseline variables only, (2) baseline variables and DMARD exposure (ever exposed, yes/no) and (3) baseline variables and DMARD exposure as weighted cumulative exposure (WCE) variables. RESULTS: Overall, 196/418 (46.9%) patients showed FavOut and 252/343 (73.5%) AbsSDP. WCE models had the best predictive performance, with area under the curve=0.80 (95% CI 0.74 to 0.87) for FavOut and 0.87 (95% CI 0.83 to 0.92) for AbsSDP. In the WCE model, the odds of FavOut and AbsSDP were reduced with conventional synthetic disease-modifying antirheumatic drug (csDMARD) initiation at 12 months versus at baseline (OR 0.78, 95% CI 0.65 to 0.94, and OR 0.89, 95% CI 0.76 to 0.98, respectively). Early biologics initiation was not significantly associated with either outcome. CONCLUSIONS: WCE models can identify and quantify the long-term benefit of early csDMARD initiation on 10-year functional and structural outcomes in patients with RA.

Long-Term Disabilities of Survivors of Out-of-Hospital Cardiac Arrest: The Hanox Study.

BACKGROUND: Long-term outcomes of awakened survivors of out-of-hospital cardiac arrest (OHCA) are poorly known. RESEARCH QUESTION: What are the month (M) 18 outcomes of survivors of out-of-hospital cardiac arrest (OHCA) who awakened during the first 2 weeks' post-OHCA and their poor-outcome risk factors? STUDY DESIGN AND METHODS: All OHCA survivors with a Glasgow Coma Scale score ≥12 during the first 2 weeks' post-OHCA were enrolled in six ICUs and followed up at M3, M6, M12, and M18. The primary outcome measure was Glasgow Outcome Scale-Extended (GOS-E) score at M18. Secondary outcome measures included evaluation at M18 of neurologic, behavioral, and cognitive disabilities; health-related quality of life (HR-QOL), anxiety and depression; and poor-outcome risk factors (GOS-E score ≤ 6). RESULTS: Among the 139 included patients, 98 were assessable for the primary outcome measure. At M18, 64 (65%) had full recovery or minor disabilities (GOS-E score > 6), 18 (18%) had moderate disabilities but were autonomous for daily-life activities (GOS-E score = 6), 12 (12%) had poor autonomy (GOS-E score < 6 but > 1), and four had died. Percentages of patients with GOS-E scores > 6 increased significantly over the 18-month study period. At M18, no patients had major neurologic disabilities, 20% had cognitive disabilities, 32% had anxiety symptoms, 25% had depression symptoms, and their HR-QOL was impaired compared with a sex- and age-matched population. Low-flow time, Sequential Organ Failure Assessment score at admission, coma duration > 3 days after cardiac arrest, and mechanical ventilation on days 3 and 7 were associated with poor functional outcome. INTERPRETATION: Among patients who awoke (Glasgow Coma Scale score ≥12) in the 14 days following OHCA, 35% had moderate to severe disabilities or had died at M18. Interestingly, patients improved until M18 post-OHCA. Risk factors associated with poor functional outcome were low-flow time, clinical severity at ICU admission, prolonged coma duration, and mechanical ventilation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT02292147; URL: www.clinicaltrials.gov.

Impact of Point-of-care Testing on Length of Stay of Patients in the Emergency Department: A Cluster-randomized Controlled Study.

OBJECTIVES: Crowding is a frequent concern in the emergency department (ED). Laboratory point-of-care testing (POCT) has been proposed to decrease patients' length of stay (LOS). Our objective was to determine whether an extended panel of POCT solutions could reduce LOS. METHODS: This was a single-center, prospective, open-label, controlled cluster-randomized study. Blood test processing was randomized into 1-week inclusion periods: interventional arm (laboratory analyses performed on POCT analyzers implemented in the ED) or control arm (central laboratory). The primary endpoint was LOS of patients in the ED. Secondary endpoints were time to result (TTR), ED crowding surrogates, and average total cost of an ED visit in each arm. RESULTS: A total of 23,231 patients were included and 20,923 were analyzed for the main outcome measure. Mean ± SD age was 46 ± 20 years, and 7,905 (36%) underwent blood sampling. Mean ± SD LOSs were 203 ± 161 and 210 ± 168 minutes in the POCT and control arms, respectively. LOS reduction for the entire ED population was -9 minutes (95% confidence interval [CI] = -22 to 5, p = 0.22) compared to the control arm and -17 minutes (95% CI = -34.0 to 0.6, p = 0.06) for patients undergoing blood sampling. The mean ± SD TTRs were 28 ± 31 and 79 ± 34 minutes in the POCT and control arms, respectively (TTR reduction = -51 minutes, 95% CI = -54 to -48 minutes, p < 0.001). CONCLUSIONS: The implementation of an extended panel of POCT solutions in an ED did not significantly reduce the LOS, but reduced the TTR.

Cervical cancer screening coverage, management of squamous intraepithelial lesions and related costs in France.

Until 2018, cervical cancer screening in France was an unorganized individual screening, with the exception of some pilot programs in some territories. We aimed to assess, before the implementation of organized cervical cancer screening and human papillomavirus (HPV) nonavalent vaccine introduction in the vaccination schedule in 2018, (i) the individual cervical cancer screening coverage, (ii) the management of squamous intraepithelial lesions (SIL) and (iii) the related costs. We used the Système National des Données de Santé (SNDS) (Echantillon Généraliste de Bénéficiaires [EGB] and Programme de Médicalisation des systèmes d'information [PMSI]) to assess the cervical screening coverage rate in France between January 1st, 2012 and December 31st, 2014, and to describe diagnostic investigations and therapeutic management of SIL in 2013. After extrapolation to the general population, a total of 10,847,814 women underwent at least one smear test over the 3-year study period, corresponding to a coverage rate of 52.4% of the women aged 25 to 64 included. In 2013, 126,095 women underwent HPV test, 327,444 women underwent colposcopy, and 9,653 underwent endocervical curettage; 31,863 had conization and 12,162 had laser ablation. Besides, 34,067 women experienced hospital stays related to management of SIL; 25,368 (74.5%) had high-grade lesions (HSIL) and 7,388 (21.7%) low-grade lesions (LSIL). Conization was the most frequent in-hospital therapeutic procedure: 89.5% (22,704) of women with an in-hospital procedure for HSIL and 64.7% (4,781) for LSIL. Mean cost of smear test, colposcopy and HPV tests were around 50€. Total cost for hospital stays in 2013 was estimated at M41€, or a mean cost of 1,211€ per woman; 76% were due to stays with HSIL. This study highlights the low coverage rate of individual cervical cancer screening and a high burden related to SIL management.

Impact of a population-based asthma management program in France (Sophia Asthme): A matched controlled before-and-after quasi-experimental study using the French health insurance database (SNDS).

PURPOSE: Sophia Asthme (SA) is a chronic disease management program of the French national health insurance for adult patients with asthma. We evaluated the early impact of this intervention. METHODS: We conducted a matched controlled, before-and-after quasi-experimental study within the French Health Insurance Database (Système National Des Données de Santé [SNDS]). The SA program was implemented in a set of 18 Départements in France and targeted 18- to 44-year-old subjects, with at least two reimbursement dates for asthma drug therapy during the 12-month period prior to program targeting. Change in outcomes was assessed from the "before program" period (January-December 2014) to the "after program implementation" period (March 2015-February 2016) in the program group (eligible to SA program in the 18 Départements) and in the matched controlled group. The main outcome measure was the before-after change in proportion of subjects with a controllers/(controllers+relievers) ratio greater than 50%. RESULTS: Of the 99 578 subjects of the program group, 9225 (9.3%) actually participated in SA program. The program had no significant impact on the proportion of subjects with a ratio greater than 50%. However, subjects exposed to SA program were significantly more likely to be dispensed controller medications (OR = 1.04; 95% CI, 1.01-1.07) and to sustain their use of these medications (OR = 1.08; 95% CI, 1.05-1.12). CONCLUSION: We did not demonstrate any significant impact of the program on the primary outcome. The modest yet encouraging findings of this early evaluation suggest the need for reformulation of the program and its evaluation.

The effect of local anesthetic continuous wound infusion for the prevention of postoperative pneumonia after on-pump cardiac surgery with sternotomy: the STERNOCAT randomized clinical trial.

PURPOSE: Postoperative pain after cardiac surgery, exacerbated by cough and sternal mobilization, limits clearance of bronchopulmonary secretions and may predispose to postoperative pneumonia. In this study, we tested the ability of local anesthetic continuous wound infusion to prevent pneumonia after cardiac surgery with sternotomy and cardiopulmonary bypass (CPB) owing to better analgesia and bronchopulmonary drainage. METHODS: In this randomized, double-blind, placebo-controlled trial conducted in five academic centers, patients undergoing cardiac surgery with sternotomy and CPB were enrolled from February 2012 until November 2014, and were followed over 30 days. Patients were assigned to a 48-h infusion (10 ml h-1) of L-bupivacaine (12.5 mg h-1) or placebo (saline) via a pre-sternal multiperforated catheter. Anesthesia and analgesia protocols were standardized. The primary end point was the incidence of pneumonia during the study period, i.e., until hospital discharge or 30 days. We hypothesized a 30% reduction in the incidence of pneumonia. RESULTS: Among 1493 randomized patients, 1439 completed the trial. Pneumonia occurred in 36/746 patients (4.9%) in the L-bupivacaine group and in 42/739 patients (5.7%) in the placebo group (absolute risk difference taking into account center and baseline risk of postoperative pneumonia, - 1.3% [95% CI - 3.4; 0.8] P = 0.22). In the predefined subgroup of patients at high risk, L-bupivacaine decreased the incidence of pneumonia (absolute risk difference, - 5.6% [95% CI - 10.0; - 1.1], P = 0.01). CONCLUSIONS: After cardiac surgery with sternotomy, continuous wound infusion of L-bupivacaine failed to decrease the incidence of pneumonia. These findings do not support the use of local anesthetic continuous wound infusion in this indication. Further study should investigate its effect in high-risk patients. TRIAL REGISTRATION: EudraCT Number: 2011-003292-10; Clinicaltrials.gov Identifier: NCT01648777.

A musical intervention for respiratory comfort during noninvasive ventilation in the ICU.

Discomfort associated with noninvasive ventilation (NIV) may participate in its failure. We aimed to determine the effect of a musical intervention on respiratory discomfort during NIV in patients with acute respiratory failure (ARF).An open-label, controlled trial was performed over three centres. Patients requiring NIV for ARF were randomised to either a musical intervention group (where they received a musical intervention and were subjected to visual deprivation during the first 30 min of each NIV session), a sensory deprivation group (where they wore insulating headphones and were subjected to visual deprivation during the first 30 min of each NIV session), or a control group (where they received NIV as routinely performed). The primary outcome was the change in respiratory discomfort before and after 30 min of the first NIV session.A total of 113 patients were randomised (36 in the musical intervention group, 38 in the sensory deprivation group and 39 in the control group). Median (interquartile range (IQR)) change in respiratory discomfort was 0 (-1; 1) between the musical intervention and control groups (p=0.7). Between groups comparison did not evidence any significant variation of respiratory parameters across time or health-related quality of life (HRQoL) at day-90. The Peri-traumatic Distress Inventory (PDI) at intensive care unit (ICU) discharge was reduced in musical intervention group patients. However, a 30 min musical intervention did not reduce respiratory discomfort during NIV for ARF in comparison to conventional care or sensory deprivation.

Closed-form variance estimator for weighted propensity score estimators with survival outcome.

Propensity score (PS) methods are widely used in observational studies for evaluating marginal treatment effects. PS-weighting is a popular PS-based method that allows for estimating both the average treatment effect on the overall population (ATE) and the average treatment effect on the treated population (ATT). Previous research has shown that the variance of the treatment effect is accurately estimated only if the variance estimator takes into account the fact that the propensity score is itself estimated from the available data in a first step of the analysis. In 2016, Austin showed that the bootstrap-based variance estimator was the only existing estimator resulting in approximately correct estimates of standard errors when evaluating a survival outcome and a Cox model was used to estimate a marginal hazard ratio (HR). This author stressed the need to develop a closed-form variance estimator of the marginal HR accounting for the estimation of the PS. In the present research, we developed such variance estimators both for the ATE and ATT. We evaluated their performance with an extensive simulation study and compared them to bootstrap-based variance estimators and to naive variance estimators that do not account for the estimation step. We found that the performance of the proposed variance estimators was similar to that of the bootstrap-based estimators. The proposed variance estimators provide an alternative to the bootstrap estimator, particularly interesting in situations in which time-consumption and/or reproducibility are an important issue. An implementation has been developed for the R software and is freely available (package hrIPW).

Effect of cumulative exposure to corticosteroid and DMARD on radiographic progression in rheumatoid arthritis: results from the ESPOIR cohort.

Objectives: Several authors have tried to predict the risk of radiographic progression in RA according to baseline characteristics, considering exposure to treatment only as a binary variable (Treated: Yes/No). This study aims to model the risk of 5-year radiographic progression taking into account both baseline characteristics and the cumulative time-varying exposure to corticosteroids or DMARDs. Methods: The study population consisted of 403 patients of the Etude et Suivi des Polyarthrites Indifférenciées Récentes cohort meeting the 1987 ACR or 2010 ACR/EULAR criteria for RA at inclusion and having complete radiographic data at baseline and 5 years. Radiographic progression was defined at 5 years as a significant increase of the Sharp/van der Heidje score (smallest detectable difference ⩾5). The best logistic regression model was selected from the following: model including only clinico-biological baseline characteristics; model considering baseline characteristics and treatments as binary variables; and model considering baseline characteristics and treatments as weighted cumulative exposure variables. Results: Radiographic progression occurred in 143 (35.5%) patients. The best model combined anti-citrullinated peptide antibody positivity, ESR, swollen joint count >14 and erosion score at baseline, as well as corticosteroids, MTX/LEF (MTX or LEF) and biologic DMARDs (bDMARDs) as weighted cumulative exposure variables. Recent cumulative exposure to high doses of corticosteroids (⩽ 3months) was significantly associated with the risk of 5-year radiographic progression and a significant protective association was highlighted for a 36-month exposure to bDMARDs. Conclusion: Corticosteroids and bDMARDs play an important role in radiographic progression. Accounting for treatment class and intensity of exposure is a major concern in predictive models of radiographic progression in RA patients.

Multiparametric MRI for Suspected Recurrent Prostate Cancer after HIFU:Is DCE still needed?

PURPOSE: To assess the added value of the dynamic contrast-enhanced sequence (DCE) to combination T2-weighted imaging (T2w) + diffusion-weighted imaging (DWI) in detecting prostate cancer (PCa) recurrence after HIFU (high-intensity focused ultrasound). METHODS: Forty-five males with clinical and biological suspected PCa recurrence were retrospectively selected. All underwent multi-parametric MRI (mpMRI) before biopsies. Two readers independently assigned a Likert score of cancer likelihood on T2w + DWI + DCE and T2w + DWI images. Prostatic biopsies were taken as the gold standard. RESULTS: Recurrent PCa was identified at biopsy for 37 patients (82%). Areas under the receiver-operating curve of T2w + DWI and T2w + DWI + DCE imaging were not significantly different for both readers. Using a Likert score ≥ 3 for the PCa diagnosis threshold, sensitivity at the lobe level for the (1) senior and (2) junior reader for T2w +DWI +DCE sensitivity was (1) 0.97 and (2) 0.94 vs. (1) 0.94 and (2) 0.97 for T2w + DWI. CONCLUSION: Accuracy of mpMRI was not significantly improved by adding DCE to T2w + DWI. Sensitivity was high for T2w + DWI + DCE and T2w + DWI with no significant difference for either the junior or senior reader. KEY POINTS: • MpMRI has the capability to detect PCa recurrence in post-HIFU monitoring. • The sensitivity of T2w and DWI for detecting PCa recurrence was not improved by DCE. • Readers with different degrees of experience did not improve their performance with DCE.

Factors associated with breast cancer recurrences or mortality and dynamic prediction of death using history of cancer recurrences: the French E3N cohort.

BACKGROUND: In addition to tumor characteristics and lifestyle factors, cancer relapses are often related to the risk of death but have not been jointly studied. We investigate the prognostic factors of recurrent events and death after a diagnosis of breast cancer and predict individual deaths including a history of recurrences. METHODS: The E3N (Etude Epidémiologique auprès de Femmes de la Mutuelle Générale de l'Education Nationale) study is a prospective cohort study that was initiated in 1990 to investigate factors associated with the most common types of cancer. Overall survival and three types of recurrent events were considered: locoregional recurrence, metastasis, and second primary breast cancer. Recurrent events and death were analyzed using a joint frailty model. RESULTS: The analysis included 4926 women from the E3N cohort diagnosed with a first primary invasive breast cancer between June 1990 and June 2008; during the follow-up, 1334 cases had a recurrence (median time of follow-up is 7.2 years) and 469 women died. Cases with high grade, large tumor size, axillary nodal involvement, and negative estrogen and progesterone receptors had a higher risk of recurrence or death. Furthermore, smoking increased the risk of relapse. For cases with a medium risk profile in terms of tumor characteristics and lifestyle factors, the probability of dying between 5 and 10 years after diagnosis was 6, 20 and 36% for 0, 1 or 2 recurrences within the first 5 years after diagnosis, respectively. CONCLUSIONS: Our study showed the importance of considering baseline lifestyle characteristics and history of relapses to dynamically predict the risk of death in breast cancer cases. Medical experience coupled with an estimate of a patient's survival probability that considers all available information for this patient would enable physicians to make better informed decisions regarding their actions and thus improve clinical output.

Plasma oxysterols: biomarkers for diagnosis and treatment in spastic paraplegia type 5.

The hereditary spastic paraplegias are an expanding and heterogeneous group of disorders characterized by spasticity in the lower limbs. Plasma biomarkers are needed to guide the genetic testing of spastic paraplegia. Spastic paraplegia type 5 (SPG5) is an autosomal recessive spastic paraplegia due to mutations in CYP7B1, which encodes a cytochrome P450 7α-hydroxylase implicated in cholesterol and bile acids metabolism. We developed a method based on ultra-performance liquid chromatography electrospray tandem mass spectrometry to validate two plasma 25-hydroxycholesterol (25-OHC) and 27-hydroxycholesterol (27-OHC) as diagnostic biomarkers in a cohort of 21 patients with SPG5. For 14 patients, SPG5 was initially suspected on the basis of genetic analysis, and then confirmed by increased plasma 25-OHC, 27-OHC and their ratio to total cholesterol. For seven patients, the diagnosis was initially based on elevated plasma oxysterol levels and confirmed by the identification of two causal CYP7B1 mutations. The receiver operating characteristic curves analysis showed that 25-OHC, 27-OHC and their ratio to total cholesterol discriminated between SPG5 patients and healthy controls with 100% sensitivity and specificity. Taking advantage of the robustness of these plasma oxysterols, we then conducted a phase II therapeutic trial in 12 patients and tested whether candidate molecules (atorvastatin, chenodeoxycholic acid and resveratrol) can lower plasma oxysterols and improve bile acids profile. The trial consisted of a three-period, three-treatment crossover study and the six different sequences of three treatments were randomized. Using a linear mixed effect regression model with a random intercept, we observed that atorvastatin decreased moderately plasma 27-OHC (∼30%, P < 0.001) but did not change 27-OHC to total cholesterol ratio or 25-OHC levels. We also found an abnormal bile acids profile in SPG5 patients, with significantly decreased total serum bile acids associated with a relative decrease of ursodeoxycholic and lithocholic acids compared to deoxycholic acid. Treatment with chenodeoxycholic acid restored bile acids profile in SPG5 patients. Therefore, the combination of atorvastatin and chenodeoxycholic acid may be worth considering for the treatment of SPG5 patients but the neurological benefit of these metabolic interventions remains to be evaluated in phase III therapeutic trials using clinical, imaging and/or electrophysiological outcome measures with sufficient effect sizes. Overall, our study indicates that plasma 25-OHC and 27-OHC are robust diagnostic biomarkers of SPG5 and shall be used as first-line investigations in any patient with unexplained spastic paraplegia.

A Fully Automated Web-Based Program Improves Lifestyle Habits and HbA1c in Patients With Type 2 Diabetes and Abdominal Obesity: Randomized Trial of Patient E-Coaching Nutritional Support (The ANODE Study).

BACKGROUND: The prevalence of abdominal obesity and type 2 diabetes mellitus (T2DM) is a public health challenge. New solutions need to be developed to help patients implement lifestyle changes. OBJECTIVE: The objective of the study was to evaluate a fully automated Web-based intervention designed to help users improve their dietary habits and increase their physical activity. METHODS: The Accompagnement Nutritionnel de l'Obésité et du Diabète par E-coaching (ANODE) study was a 16-week, 1:1 parallel-arm, open-label randomized clinical trial. Patients with T2DM and abdominal obesity (n=120, aged 18-75 years) were recruited. Patients in the intervention arm (n=60) had access to a fully automated program (ANODE) to improve their lifestyle. Patients were asked to log on at least once per week. Human contact was limited to hotline support in cases of technical issues. The dietetic tool provided personalized menus and a shopping list for the day or the week. Stepwise physical activity was prescribed. The control arm (n=60) received general nutritional advice. The primary outcome was the change of the dietary score (International Diet Quality Index; DQI-I) between baseline and the end of the study. Secondary endpoints included changes in body weight, waist circumference, hemoglobin A1c (HbA1c) and measured maximum oxygen consumption (VO2 max). RESULTS: The mean age of the participants was 57 years (standard deviation [SD] 9), mean body mass index was 33 kg/m² (SD 4), mean HbA1c was 7.2% (SD 1.1), and 66.7% (80/120) of participants were women. Using an intention-to-treat analysis, the DQI-I score (54.0, SD 5.7 in the ANODE arm; 52.8, SD 6.2 in the control arm; P=.28) increased significantly in the ANODE arm compared to the control arm (+4.55, SD 5.91 vs -1.68, SD 5.18; between arms P<.001). Body weight, waist circumference, and HbA1c changes improved significantly in the intervention. CONCLUSIONS: Among patients with T2DM and abdominal obesity, the use of a fully automated Web-based program resulted in a significant improvement in dietary habits and favorable clinical and laboratory changes. The sustainability of these effects remains to be determined. TRIAL REGISTRATION: ClinicalTrials.gov NCT02343107; http://clinicaltrials.gov/ct2/show/NCT02343107 (Archived by WebCite at http://www.webcitation.org/6uVMKPRzs).

Is home blood pressure monitoring feasible and well accepted in nephrectomized patients for renal cancer? (STAFF study).

AIMS: Few studies have looked at blood pressure (BP) evolution after nephrectomy, except for in living kidney donors with no clinical relevant modifications. STAFF is a pilot, open-label, observational study to evaluate the feasibility of following BP by home blood pressure monitoring (HBPM) after nephrectomy for cancer. MAJOR FINDINGS: 56 patients (66.1% previously treated for hypertension) were included between November 1, 2011, and December 31, 2012; 95.8% of the patients realized five of six primary end-points in HBPM, but the last monitoring session at 6 months was often lacking (60%) probably because of a lack of understanding. When BP was controlled before surgery, 36% of the patients underwent new hypertension or hypertension dysregulation, without any correlating factor found; 33% of the patients presented the presence of proteinuria or an increase during the follow-up. Previous hypertension or high body mass index were risk factors for proteinuria increase (p = 0.036 and 0.032) but not treatment by an renin-angiotensin system blocker. There was no statistical link between HTA control and proteinuria. CONCLUSION: Our study shows that most patients undergoing nephrectomy for cancer are able to follow HBPM. It should be encouraged for detecting high BP or proteinuria, especially if antiangiogenic therapies are envisaged because of the supplementary risk of hypertension and proteinuria induced by these treatments.