Safety and efficacy of subcutaneous night-time only apomorphine infusion to treat insomnia in patients with Parkinson's disease (APOMORPHEE): a multicentre, randomised, controlled, double-blind crossover study.

BACKGROUND: Insomnia is a frequent complaint of patients with Parkinson's disease, and it negatively affects quality of life. Drugs that improve both sleep and parkinsonism would be of major benefit to patients with Parkinson's disease-related insomnia. We aimed to test the safety and efficacy of subcutaneous night-time only apomorphine infusion in patients with Parkinson's disease and insomnia. METHODS: We did a randomised, multicentre, double-blind, placebo-controlled, crossover trial in 11 expert centres in Parkinson's disease and sleep centres in France. Participants aged 35-90 years with fluctuating Parkinson's disease and moderate to severe insomnia (Insomnia Severity Index score ≥15) were randomly assigned to either first receive night-time subcutaneous apomorphine (up to 5 mg/h) or matching placebo. Randomisation was done using a computer-generated plan in blocks of four, stratified by centre. This first intervention was followed by a 14-night washout period, then crossover to the other intervention. The treatment periods consisted of a 10-night titration phase followed by a 7-night fixed-dose phase. The dose was adjusted during the titration phase on the basis of a daily telephone call assessing sleep quality and treatment tolerability. The primary efficacy endpoint was the difference in Parkinson's disease sleep scale (PDSS) scores from the beginning to the end of each treatment period. Analysis was done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, NCT02940912. FINDINGS: Between Jan 31, 2017, and Jan 29, 2021, 46 participants were enrolled. 25 (54%) patients were randomly assigned to receive apomorphine first and 21 (46%) patients to receive placebo first. Mean change in PDSS score was significantly greater with night-time apomorphine infusion (15·18 [SD 24·34]) compared with placebo (5·23 [21·52]; treatment effect 9·95 [95% CI 0·88-19·03]; p=0·041). Adverse events were reported in 25 (54%) participants during the apomorphine period and in 17 (37%) participants during the placebo period (p=0·16). Apomorphine was associated with more frequent dizziness than was placebo (seven [15%] vs 0; p=0·041). INTERPRETATION: Subcutaneous night-time only apomorphine infusion improved sleep disturbances according to difference on PDSS score, with an overall safety profile consistent with previous studies in Parkinson's disease. This treatment might be useful to manage sleep disturbances in patients with advanced Parkinson's disease and moderate to severe insomnia. FUNDING: Orkyn and Aguettant Pharma. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Classifying Idiopathic Rapid Eye Movement Sleep Behavior Disorder, Controls, and Mild Parkinson's Disease Using Gait Parameters.

BACKGROUND: Subtle gait changes associated with idiopathic rapid eye movement sleep behavior disorder (iRBD) could allow early detection of subjects with future synucleinopathies. OBJECTIVE: The aim of this study was to create a multiclass model, using statistical learning from probability distribution of gait parameters, to distinguish between patients with iRBD, healthy control subjects (HCs), and patients with Parkinson's disease (PD). METHODS: Gait parameters were collected in 21 participants with iRBD, 21 with PD, and 21 HCs, matched for age, sex, and education level. Lasso sparse linear regression explored gait features able to classify the three groups. RESULTS: The final model classified iRBD from HCs and from patients with PD equally well, with 95% accuracy, 100% sensitivity, and 90% specificity. CONCLUSIONS: Gait parameters and a pretrained statistical model can robustly distinguish participants with iRBD from HCs and patients with PD. This could be used to screen subjects with future synucleinopathies in the general population and to identify a conversion threshold to PD. © 2022 International Parkinson and Movement Disorder Society.

Sleep disorders in Wilson's disease.

BACKGROUND/OBJECTIVES: Wilson's disease (WD) is a rare genetic disorder that leads to copper overload, mainly in the liver then, in the brain. Patients with WD often complain about sleep disorders. We aimed to explore them. PATIENTS/METHODS: Sleep complaints and disease symptoms were compared in 40 patients with WD (20 patients with hepatic phenotype matched to 20 neurologic one) and 40 age, sex and BMI matched healthy controls. RESULTS: Patients with WD had more frequently (32.5 vs 10.0%, p < 0.05) and more severe (10.5 ± 6.0 vs 7.6 ± 4.8, p < 0.01) insomnia than controls and insomnia was more severe in neurologic than hepatic form of the disease (12.25 ± 5.89 vs 8.73 ± 5.8, p < 0.05). Insomnia severity was correlated with the severity of depressive symptoms (r = 0.53, p < 0.001). Compared to controls, patients reported more difficulties staying asleep and more consequences of insomnia on their quality of life. REM sleep behavior disorder was more frequent in WD (20 vs 0%, p = 0.005) than controls. Patients complained more frequently of nycturia (22.8 vs 7.6%, p = 0.003) than controls. Patients did not differ from controls for sleepiness, restless legs syndrome and obstructive sleep apnea syndrome. Patients did not report cataplexia. CONCLUSION: In patients with WD, insomnia and REM sleep behavior disorder are the two main sleep complaints. Insomnia is more frequent in neurologic than hepatic form of the disease. Severity of insomnia is associated with the severity of depressive symptoms.

BeatWalk: Personalized Music-Based Gait Rehabilitation in Parkinson's Disease.

Taking regular walks when living with Parkinson's disease (PD) has beneficial effects on movement and quality of life. Yet, patients usually show reduced physical activity compared to healthy older adults. Using auditory stimulation such as music can facilitate walking but patients vary significantly in their response. An individualized approach adapting musical tempo to patients' gait cadence, and capitalizing on these individual differences, is likely to provide a rewarding experience, increasing motivation for walk-in PD. We aim to evaluate the observance, safety, tolerance, usability, and enjoyment of a new smartphone application. It was coupled with wearable sensors (BeatWalk) and delivered individualized musical stimulation for gait auto-rehabilitation at home. Forty-five patients with PD underwent a 1-month, outdoor, uncontrolled gait rehabilitation program, using the BeatWalk application (30 min/day, 5 days/week). The music tempo was being aligned in real-time to patients' gait cadence in a way that could foster an increase up to +10% of their spontaneous cadence. Open-label evaluation was based on BeatWalk use measures, questionnaires, and a six-minute walk test. Patients used the application 78.8% (±28.2) of the prescribed duration and enjoyed it throughout the program. The application was considered "easy to use" by 75% of the patients. Pain, fatigue, and falls did not increase. Fear of falling decreased and quality of life improved. After the program, patients improved their gait parameters in the six-minute walk test without musical stimulation. BeatWalk is an easy to use, safe, and enjoyable musical application for individualized gait rehabilitation in PD. It increases "walk for exercise" duration thanks to high observance. Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT02647242.

Efficacy and tolerance of botulinum toxin injections after sacral nerve stimulation failure for idiopathic overactive bladder.

INTRODUCTION: Management of idiopathic overactive bladder (iOAB) after the failure of sacral nerve modulation (SNM) is very challenging. To the best of our knowledge, no study has evaluated the use of botulinum toxin A (BoNT-A) after SNM failure for iOAB. The aim of this study is to evaluate the tolerance and efficacy of BoNT-A injection after the failure of SNM for iOAB. METHODS: We conducted a retrospective multicentric analysis of all patients who had received either onabotulinumtoxinA or abobotulinumtoxinA intradetrusor injection for iOAB after SNM failure, between January 2004 and December 2017. The primary outcome was the percentage of success of first BoNT-A injection (either resolution of their urinary incontinence or their frequency or more than 50% reduction in frequency). Secondary outcomes were results of urodynamic studies, complications, total number of injections, causes of withdrawal, and subsequent treatment. RESULTS: Seventy-six patients (62 female) were included. The percentage of success of first BoNT-A injection was 43.4% (n = 33). All overactive bladder symptoms were significantly improved on the 3-day bladder diary. Twenty-eight patients (36.8%) were put under clean intermittent self-catheterization transitory. After a mean follow-up of 57.7 (±38.5) months, median number of injections was 2 (1-15). Overall, 42 patients (55.2%) stopped injections during follow-up. The estimated 36-months discontinuation-free rate was 48.1%. Mean cause of discontinuation was a primary failure (n = 32; 42.1%). CONCLUSION: BoNT-A can be used in SNM nonresponders with a success rate of 43.4% but is associated with a high long-term discontinuation rate.

Prospective feasability study of ambulatory surgery for pelvic organ prolapse.

STUDY OBJECTIVE: The aim of this study was the evaluation of ambulatory surgery (AS) rate for pelvic organ prolapse (POP). DESIGN: It was a prospective observational study. DESIGN CLASSIFICATION: Level II-2. SETTING: Patients were divided in two groups: Group EAS: patients eligible to ambulatory surgery and Group NEAS: patients not eligible to AS. PATIENTS: all patients from August 2015 to November 2016 undergoing surgery for POP in our institution. MEASUREMENTS: The main outcome was overall AS rate in the population. Secondary outcomes were in NEAS group: reasons for ineligibility; in EAS group: AS success rate, reasons of failure and patient satisfaction related to AS; in each group: post operative re-admission or consultation, morbidity and global satisfaction. MAIN RESULTS: There was 157patients included in the study. Eligibility criteria for AS was met for 111/157 (707%). Overall AS rate was 58% and success rate of AS was 82%. Reasons for ineligibility to AS were lack of home support (50%), home >1 h from hospital (109%), poor home conditions (2,2%), associated comorbidity (21.7%), associated procedure (4,3%) and refusal for AS (109%). Reasons for failure (20/111, 18%) of AS were unsuccessful trial of void (TOV) (65%), post operative nausea-vomiting (PONV) (15%), sub-cutaneous emphysema (5%), post-operative bleeding (5%) and faulty organization (10%). There was no unscheduled re-admission the night after surgery in EAS group. 7,2% in EAS group and 13% in the NEAS group had an unscheduled consultation. There were 4 re-admissions (3,6%) in the EAS group and 1 (2,2%) in the NEAS group during follow-up. Patient satisfaction to AS was 100% on next-day call and 923% at 6 weeks. CONCLUSION: Ambulatory surgery rate was 58% in this population of surgically managed prolapses; AS success rate was 82%. There was no adverse events related to AS and patient satisfaction to AS at 6 weeks is high.

Magnetic Resonance Imaging of Parotid Gland Tumors: Dynamic Contrast-Enhanced Sequence Evaluation.

OBJECTIVE: The aim of the study was to evaluate dynamic contrast-enhanced magnetic resonance (MR) imaging in the characterization of parotid gland tumors. METHODS: Fifty-five parotid lesions in 55 patients were retrospectively included. Two observers interpreted 2 reading protocols derived from all MR imaging in 2 distinct sessions, independently and blinded. Benign versus malignant distinction was carried out for protocol 1 (without contrast administration) and protocol 2 (with dynamic contrast-enhanced sequence). Histopathological results after surgical resection were used as the criterion standard. Diagnostic accuracy was compared between protocols using McNemar test. A P values of less than 0.05 indicated significant difference. RESULTS: There was no intraobserver statistical discordance between protocols for both observers (P = 0.27 and P = 1). Interobserver reliability showed moderate agreement for protocol 1 (κ = 0.591; 95% confidence interval [CI], 0.376-0.806) and 2 (κ = 0.463, 95% CI, 0.226-0.701). Intraobserver reliability showed moderate agreement for observer 1 (κ = 0.507; 95% CI, 0.279-0.736) and 2 (κ = 0.477; 95% CI, 0.241-0.712). CONCLUSIONS: Magnetic resonance imaging protocol including dynamic sequence for the characterization of parotid gland lesion yielded nonsignificant increases in sensitivity, specificity, or positive predictive values, and negative predictive values over noninjected protocol.

French Medical-Administrative Database for Epidemiology and Safety in Ophthalmology (EPISAFE): The EPISAFE Collaboration Program in Cataract Surgery.

Medical-administrative databases are an important source of big data to assess the epidemiology of diseases and interventions, compare drugs, and investigate rare adverse events. We describe the French national health insurance system databases and the Epidemiology and Safety (EPISAFE) collaboration program in ophthalmology and illustrate the paper with recent studies that used the databases to investigate cataract surgery. The Système national d'information inter-régime de l'assurance maladie (SNIIR-AM) is one of the largest databases of medical and administrative data for a general population, covering nearly 65 million people. The SNIIR-AM database links data for all outpatient-reimbursed health expenditures, hospitalization in all 1,546 French private or public healthcare facilities, and date of death. The use of this database provides information at the scale of the entire country, allowing measurement of the impact of changes in practices and new guidelines. Between 2009 and 2012, a total of 2,717,203 eyes in 1,817,865 patients underwent cataract surgery in France, and the incidence of cataract surgery increased from 9.86 to 11.08/1,000 person-years. The 4-year cumulative risk of retinal detachment was 0.99%, and patients <60 years of age were at higher risk of retinal detachment. The incidence of pseudophakic cystoid macular edema was 0.95%. From 2005 to 2014, from data including more than 6 million procedures, the incidence of endophthalmitis after cataract surgery decreased from 0.15 to 0.05%. The EPISAFE collaboration program encompasses the key issues facing ophthalmology, including public health and public policy concerning disease incidence and prevalence, safety and adverse event monitoring, and clinical guidelines.

Effectiveness and Safety of an Intracameral Injection of Cefuroxime for the Prevention of Endophthalmitis After Cataract Surgery With or Without Perioperative Capsular Rupture.

IMPORTANCE: Postoperative endophthalmitis (POE) often results in severe visual impairment. In clinical studies, an intracameral cefuroxime injection at the end of surgery was found to be effective at reducing the incidence of POE. Two important issues are the retinal safety of cefuroxime and its use for patients with perioperative capsular rupture where the risk of POE is dramatically increased. OBJECTIVE: To assess the effectiveness and retinal safety of an intracameral injection of cefuroxime sodium for the prevention of POE and its possible use in cases of a perioperative capsular rupture of the lens. DESIGN, SETTING, AND PARTICIPANTS: Population-based cohort study of patients 40 years of age or older who underwent cataract surgery at 1 of 1546 French health care facilities, public or private, and whose medical records were obtained from the national administrative database. Data analyses were performed between March and November 2015. MAIN OUTCOMES AND MEASURES: The effectiveness and safety of the prophylactic injection of cefuroxime as measured by the incidence of POE and cystoid macular edema. RESULTS: From January 2010 to October 2014, a total of 3 351 401 eyes of 2 434 008 patients 40 years of age or older (58.9% were women, and the mean [SD] age was 73.9 [9.5] years) underwent cataract surgery; 1941 patients (0.08%) developed POE during the 6 weeks after cataract surgery. The incidence of POE after cataract surgery decreased over the course of the study (0.11%, 0.09%, 0.08%, 0.06%, and 0.05% in 2010, 2011, 2012, 2013, and 2014, respectively [P = .001 for trend]) as the use of cefuroxime prophylactic injections increased (11.1%, 14.4%, 32.8%, 64.8%, and 79.1% in 2010, 2011, 2012, 2013, and 2014, respectively [P = .001 for trend]). After multivariate adjustment, the risk of POE was reduced with the use of cefuroxime (odds ratio, 0.61 [95% CI, 0.56-0.68]). The retinal safety of an injection of cefuroxime, which was assessed by multiadjusted odds of retinal cystoid macular edema, was not increased for patients receiving cefuroxime injections (odds ratio, 0.86 [95% CI, 0.71-1.05]). For patients with a perioperative capsular rupture of the lens (the major risk factor for POE), the incidence of POE was lower for those who received an injection of cefuroxime than for those who did not (0.37% vs 0.51%, respectively [P = .001]), whereas an increased risk of cystoid macular edema was not identified for those who received or did not receive an injection of cefuroxime (5.6% vs 7.3%, respectively [P = .12]). CONCLUSIONS AND RELEVANCE: These data suggest that, in routine practice, the intracameral injection of cefuroxime at the conclusion of cataract surgery is associated with a lower risk of POE and is safe for patients with or without a perioperative capsular rupture. While these data might be used to support the consideration of its routine use to prevent POE, in the absence of a randomized clinical trial, they cannot prove a direct cause-and-effect relationship between the injection of cefuroxime and POE.

A Prospective Study on Skin-Sparing Mastectomy for Immediate Breast Reconstruction with Latissimus Dorsi Flap After Neoadjuvant Chemotherapy and Radiotherapy in Invasive Breast Carcinoma.

BACKGROUND: Skin-sparing mastectomy (SSM) with immediate breast reconstruction (IBR) is increasingly used in invasive breast cancer. However, adjuvant chemotherapy (CT) and radiotherapy (RT) can increase the rate of local complications. OBJECTIVE: The aim of this study was to assess the morbidity of SSM-IBR after neoadjuvant CT and RT. METHODS: A French prospective pilot study of women aged 18-75 years with invasive breast cancer requiring mastectomy after CT and RT. Reconstruction was performed using autologous latissimus dorsi flap with or without prosthesis. The primary endpoint was the skin necrosis rate within 6 months, while secondary endpoints included pathological complete response rate (pCR) and global morbidity. RESULTS: Among 94 patients included in this study, 83 were analyzed (mean age 45.2 ± 9.5 years, T1 23.6 %, T2 55.6 %, T3 18.1 %). All but one patient received anthracyclines and taxanes, and all patients received RT (49.3 ± 5.2 Gy) before SSM-IBR. Prostheses were used for IBR in 32 patients (mean volume 256 ± 73 mm(3)). Five patients had necrosis (≤2 cm(2), 2-10 cm(2) and >10 cm(2), in three, one, and one cases, respectively), and they all recovered without revision surgery. Among 50 patients who underwent upfront mastectomy, 36 % achieved pCR. CONCLUSIONS: SSM-IBR performed after CT and RT is safe, with an acceptable local morbidity rate. Long-term data are needed to evaluate recurrence rates.

Investigating the completeness of a histopathological cancer registry: estimation by capture-recapture analysis in a French geographical unit Alpes-Maritimes, 2008.

INTRODUCTION: Cancer population studies require reliable and complete baseline data, which should theoretically be available by collecting histopathology records. The completeness of such a collection was evaluated using capture-recapture analysis based on three data sources concerning breast and colorectal cancers over an identical period and within the same geographical area. METHOD: The total number of breast and colon cancer cases was estimated using capture-recapture analysis based on the number of cases which were common or not between sources recording screened, diagnosed and treated cancers in the French Alpes Maritimes district. RESULT: The estimated total number of new cases of breast cancer diagnosed among Alpes Maritimes residents women aged 50-75 was 791 (95% CI: 784-797) in 2008. Of these 791 cases, 729 were identified through histopathology records, thus amounting to 92.2% completeness (95% CI: 91.5-93.0%). The total estimated number of new cases of colorectal cancer diagnosed among Alpes Maritimes residents aged 50-75 was 527 (95% CI: 517-536). Of these 527 cases, 481 were identified through histopathology records, thus amounting to 91.3% completeness (95% CI: 89.7-93.0%). CONCLUSION: The estimated completeness of cancer records collected from histopathology laboratories was higher than 90% for new cases of breast and colorectal cancer within the age range concerned by the screening programme. A verified and validated histopathology data collection may be useful for cancer population studies.