Efficacy of a Transition Program in Adolescents and Young Adults With Congenital Heart Disease: The TRANSITION-CHD Randomized Controlled Trial.

PURPOSE: Currently, nearly 90% of patients with congenital heart disease (CHD) reach adulthood in relatively good health. Structured transition programs have emerged to support adolescents and young adults in transitioning to adult care structures, improve their autonomy, and limit healthcare ruptures. The TRANSITION-CHD randomized controlled trial aimed to assess the impact of a transition program on health-related quality of life (HRQoL) in adolescents and young adults with CHD. METHODS: From January 2017 to February 2020, 200 subjects with a CHD, aged 13-25 years, were enrolled in a prospective, controlled, multicenter study and randomized in two balanced groups (transition program vs. standard of care). The primary outcome was the change in PedsQL self-reported HRQoL score between baseline and 12-month follow-up, using an intention-to-treat analysis. The secondary outcomes were the change in disease knowledge, physical health (cardiopulmonary fitness, physical activity), and mental health (anxiety, depression). RESULTS: The change in HRQoL differed significantly between the transition group and the control group (mean difference = 3.03, 95% confidence interval (CI) = [0.08; 5.98]; p = .044; effect size = 0.30), in favor of the intervention group. A significant increase was also observed in the self-reported psychosocial HRQoL (mean difference = 3.33, 95% CI = [0.01; 6.64]; p = .049; effect size = 0.29), in the proxy-reported physical HRQoL (mean difference = 9.18, 95% CI = [1.86; 16.51]; p = .015; effect size = 0.53), and in disease knowledge (mean difference = 3.13, 95% CI = [1.54; 4.72]; p < .001; effect size = 0.64). DISCUSSION: The TRANSITION-CHD program improved HRQoL and disease knowledge in adolescents and young adults with CHD, supporting the generalization and systematization of similar preventive interventions in pediatric and congenital cardiology.

Circulating Tumor Cell Detection by Liquid Biopsy during Early-Stage Endometrial Cancer Surgery: A Pilot Study.

The recurrence of non-metastatic endometrial carcinoma (EC) (6 to 21%) might be due to disseminated tumor cells. This feasibility study investigated whether circulating tumor cells (CTCs) were detectable in blood samples from the peripheral and ovarian veins of 10 patients undergoing laparoscopic resection of stage I-II EC between July 2019 and September 2021. CTCs were detected using the CellSearch® system (i) preoperatively (T0) in peripheral blood, (ii) after ovary suspensory ligament pediculation in ovarian vein blood (T1), and (iii) before colpotomy in peripheral blood (T2). CTCs were detected only in ovarian vein samples in 8/10 patients. The CTC median number did not differ with patient age (37 (min-max: 0-91) in <70-year-old vs. 11 (0-65) in ≥70 year-old women, p = 0.59), tumor grade (15 (0-72) for grade 1 vs. 15 (0-91) for grade 2, p = 0.97), FIGO stage (72 (27-91) vs. 2 (0-65) vs. 3 (0-6]) for stage IA, B, and II, respectively; p = 0.08), and tumor size (40 (2-72) for size < 30 mm vs. 4 (0-91) for size ≥ 30 mm, p = 0.39). Estrogen receptor-positive CTCs and CTC clusters were identified. The prognostic and therapeutic values of CTCs released during EC surgery need to be determined.

Risk of infection in elderly patients with inflammatory bowel disease under biologics: A prospective, multicenter, observational, one-year follow-up comparative study.

OBJECTIVES: The emergence of biologics has improved the course of inflammatory bowel diseases (IBD) in the elderly population despite a potential higher risk of infections. We conducted a one-year, prospective, multicenter, observational study to determine the frequency of occurrence of at least one infectious event in elderly IBD patients under anti-TNF therapy compared with that in elderly patients under vedolizumab or ustekinumab therapies. METHODS: All IBD patients over 65 years exposed to anti-TNF, vedolizumab or ustekinumab therapies were included. The primary endpoint was the prevalence of at least one infection during the whole one year follow-up. RESULTS: Among the 207 consecutive elderly IBD patients prospectively enrolled, 113 were treated with anti-TNF and 94 with vedolizumab (n=63) or ustekinumab (n=31) (median age 71 years, 112 Crohn's disease). The Charlson index was similar between patients under anti-TNF and those under vedolizumab or ustekinumab as well as the proportion of patients under combination therapy and under concomitant steroid therapy did not differ between both both groups. The prevalence of infections was similar in patients under anti-TNF and in those under vedolizumab or ustekinumab (29% versus 28%, respectively; p=0.81). There was no difference in terms of type and severity of infection and of infection-related hospitalization rate. In multivariate regression analysis, only the Charlson comorbidity index (≥ 1) was identified as a significant and independent risk factor of infection (p=0.03). CONCLUSION: Around 30 % of elderly patients with IBD under biologics experienced at least one infection during the one-year study follow-up period. The risk of occurrence of infection does not differ between anti-TNF and vedolizumab or ustekinumab therapies, and only the associated comorbidity was linked with the risk of infection.

Atrial fibrillation screening on systematic ambulatory electrocardiogram monitoring after percutaneous patent foramen ovale closure: A prospective study.

BACKGROUND: Increased risk of new-onset atrial fibrillation (AF) after patent foramen ovale (PFO) closure was observed in randomized trials without however systematic AF screening. We aimed to evaluate the incidence of AF within 6-month following PFO closure with serial 24-hour ambulatory electrocardiogram (AECG) monitoring. METHODS: All patients undergoing PFO closure were prospectively included in 2 centers. AF was defined as irregular rhythm without discernible P waves > 30 s on AECG at day 0, 1-month and 6-month follow-up. Primary endpoint was the incidence of AF within the study period. Secondary endpoints evaluated clinical outcomes within 6-month follow-up. RESULTS: Between February 2018 and March 2019, 62 patients underwent PFO closure including 40 male (64.5%) with a mean age of 48 ± 9.5. Atrial septal aneurysm was observed in 37 patients (64.9%), 57 patients (91.9%) received an Amplatzer Occluder device (Abbott Vascular) and 5 (8.1%) an Occlutech device (Occlutech). After a mean follow-up of 7.7 ± 2.8 months, new-onset AF occurred in 3 patients (4.8%), all within the first month following PFO closure, including one per-procedural, all were asymptomatic and paroxysmal. Two patients with AF (3.2%) required chronic oral anticoagulant therapy. No adverse outcomes occurred at follow-up. No predictive factors of AF were highlighted. A total of 16 patients (25.8%) reported palpitations without AF on the AECGs. CONCLUSION: In highly selected patients, incidence of AF, evaluated with 3 systematic 24-hour AECG within 6-month following PFO closure, was low (<5%). Always paroxysmal, AF occurred within the first month after the procedure and was not associated with adverse outcomes.

Recommendations for risk management and better living with epilepsy. Phenomenological study of the experience of patients, relatives, and bereaved families.

OBJECTIVE: To understand the lived experience of people with epilepsy (PWE) and their relatives, the risks associated with epilepsy, the information received from healthcare professionals, and the reaction to this information. METHODS: Qualitative phenomenological study conducted between 2016 and 2018. Individual semi-directive in-depth interviews were performed based on a triangulation of sources in three study groups: PWE, relatives of PWE, and bereaved families. Interviews were analyzed continuously, using a semiopragmatic method until data saturation. RESULTS: Interviews with PWE (N = 16), relatives of PWE (N = 8), and bereaved families (N = 10) led to several observations: (i) The stigmatizing representations of epilepsy and its constraints lead to a feeling of abnormality which determines the behavior of patients and their relatives; (ii) The global uncertainty surrounding epilepsy is an obstacle to the delivery of clear and personalized information by professionals, and, consequently, to empowerment; (iii) The communication skills of the physician have an impact on the lived experiences of patients and relatives; (iv) Better knowledge on direct mortal epilepsy-related risk could influence the perception of danger to oneself, and help find a balance between overprotection and trivialization. The experience of the patients and relatives led them to formulate concrete recommendations: (i) for the general public: to run information campaigns in order to limit stigmatization; (ii) for caregivers: to provide personalized and detailed information without minimizing the risks, in order to enable patients to "live by setting these risks"; (iii) for patients: to have a trusted person who is informed and trained in seizure management, to join patient associations. CONCLUSION: Our study points out that stigma, uncertainty, and lack of clarity of information are all barriers to patient empowerment. In order to provide prompt and personalized information on how to live with epilepsy while managing the risks, physicians need to develop person-centered communication skills. Future research is also required for the development of tools to facilitate this communication.

Diagnostic Value of Patient-Reported and Clinically Tested Olfactory Dysfunction in a Population Screened for COVID-19.

Importance: Recent studies have suggested that olfactory dysfunction and gustatory dysfunction are associated with coronavirus disease 2019 (COVID-19). However, olfaction has been evaluated solely on reported symptoms, after COVID-19 diagnosis, and in both mild and severe COVID-19 cases, but rarely has it been assessed in prospectively unselected populations. Objective: To evaluate the diagnostic value of a semiobjective olfactory test developed to assess patient-reported chemosensory dysfunction prior to testing for the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients attending a COVID-19 screening facility. Design, Setting, and Participants: This prospective diagnostic study with participants and observers blinded to COVID-19 status was conducted in a COVID-19 screening center of a tertiary university hospital in France from March 23 to April 22, 2020. Participants were 854 consecutively included health care workers or outpatients with symptoms or with close contact with an index case. Exclusion criteria were prior chemosensory dysfunction, testing inability, or contraindications (n = 45). Main Outcomes and Measures: Participants were interviewed to ascertain their symptoms and then underwent Clinical Olfactory Dysfunction Assessment (CODA), an ad hoc test developed for a simple and fast evaluation of olfactory function. This assessment followed a standardized procedure in which participants identified and rated the intensity of 3 scents (lavender, lemongrass, and mint) to achieve a summed score ranging from 0 to 6. The COVID-19 status was assessed using reverse transcriptase-polymerase chain reaction to detect the presence of SARS-CoV-2 in samples collected via nasopharyngeal swab (reference standard) to calculate the diagnostic values of patient-reported chemosensory dysfunction and CODA. Results: Of 809 participants, the female to male sex ratio was 2.8, and the mean (SD) age was 41.8 (13.0) years (range, 18-94 years). All participants, if symptomatic, had mild disease at the time of testing, and 58 (7.2%) tested positive for SARS-CoV-2. Chemosensory dysfunction was reported by 20 of 58 participants (34.5%) with confirmed COVID-19 vs 29 of 751 participants (3.9%) who tested negative for COVID-19 (absolute difference, 30.6% [95% CI, 18.3%-42.9%]). Olfactory dysfunction, either self-reported or clinically ascertained (CODA score ≤3), yielded similar sensitivity (0.31 [95% CI, 0.20-0.45] vs 0.34 [95% CI, 0.22-0.48]) and specificity (0.97 [95% CI, 0.96-0.98) vs 0.98 [95% CI, 0.96-0.99]) for COVID-19 diagnosis. Concordance was high between reported and clinically tested olfactory dysfunction, with a Gwet AC1 of 0.95 (95% CI, 0.93-0.97). Of 19 participants, 15 (78.9%) with both reported olfactory dysfunction and a CODA score of 3 or lower were confirmed to have COVID-19. The CODA score also revealed 5 of 19 participants (26.3%) with confirmed COVID-19 who had previously unperceived olfactory dysfunction. Conclusions and Relevance: In this prospective diagnostic study of outpatients with asymptomatic or mild to moderate COVID-19, systematically assessed anamnesis and clinical testing with the newly developed CODA were complementary and specific for chemosensory dysfunction. Olfactory dysfunction was suggestive of COVID-19, particularly when clinical testing confirmed anamnesis. However, normal olfaction was most common among patients with COVID-19.

Impact of a transition education program on health-related quality of life in pediatric patients with congenital heart disease: study design for a randomised controlled trial.

BACKGROUND: Recent advances in the field of congenital heart disease (CHD) led to an improved prognosis of the patients and in consequence the growth of a new population: the grown up with congenital heart disease. Until recently, more than 50% of these patients were lost to follow up because of the lack of specialized structures. The critical moment is the transition between paediatric and adult unit. Therapeutic education is crucial to solve this issue by helping patients to become independent and responsible. The TRANSITION-CHD randomized trial aims to assess the impact of a transition education program on health-related quality of life (HRQoL) of adolescents and young adults with CHD. METHODS: Multicentre, randomised, controlled, parallel arm study in CHD patients aged from 13 to 25 years old. Patients will be randomised into 2 groups (education program vs. no intervention). The primary outcome is the change in self-reported HRQoL between baseline and 12-month follow-up. A total of 100 patients in each group is required to observe a significant increase of the overall HRQoL score of 7 ± 13.5 points (on 100) with a power of 80% and an alpha risk of 5%. The secondary outcomes are: clinical outcomes, cardiopulmonary exercise test parameters (peak VO2, VAT, VE/VCO2 slope), level of knowledge of the disease using the Leuven knowledge questionnaire for CHD, physical and psychological status. DISCUSSION: As the current research is opening on patient related outcomes, and as the level of proof in therapeutic education is still low, we sought to assess the efficacy of a therapeutic education program on HRQoL of CHD patients with a randomized trial. TRIAL REGISTRATION: This study was approved by the National Ethics Committee (South-Mediterranean IV 2016-A01681-50) and was registered on Clinicaltrials.gov (NCT03005626).

Excessive buccal saliva in patients with Parkinson's disease of the French COPARK cohort.

We describe excessive buccal saliva (EBS) prevalence in patients with Parkinson's Disease (PD) and controls of the COPARK study, its changes between "ON" and OFF" conditions and over time, its impact on Health-related Quality of life (HRQoL), and factors associated with this condition. We studied 671 ambulatory PD patients and 177 age/sex-matched controls. We defined "sialorrhea" as UPDRS item #6 (salivation) = 1 or 2; and "drooling" as item #6 = 3 or 4. SCOPA-Aut drooling score (item #2) was also available in a subset (45%) of the cohort. HRQoL was assessed by the PDQ-39 and SF-36 scales. Twenty-four months' follow-up data were available in 401/671 patients. EBS as assessed by UPDRS was present in 38% of PD patients in the "ON" condition ("Sialorrhea": 35%; "drooling": 3%). There were also more PD patients reporting "drooling" than controls according to the SCOPA-Aut (49% vs 19%, p < 0.01). UPDRS salivation score was worse in the "OFF" vs "ON" condition in PD patients with motor fluctuations (0.90 ± 0.94 vs 0.54 ± 0.79, p < 0.01). UPDRS salivation score worsened after ~ 24 months of follow-up (0.47 ± 0.70 vs 0.64 ± 0.81, p < 0.01). Worse PDQ-39 scores were observed in PD patients with EBS in bivariate but not in multivariate analyses. EBS was directly related to PD duration and severity, male gender, dysphagia, hypomimia, and autonomic dysfunction (logistic regression). EBS was more frequent in PD patients than controls, worsened in the "OFF" condition and after ~ 24 months of follow-up, moderately affected HRQoL, and was correlated with indices of bradykinesia, dysphagia, and autonomic dysfunction.

Impact of Sophrology on cardiopulmonary fitness in teenagers and young adults with a congenital heart disease: The SOPHROCARE study rationale, design and methods.

BACKGROUND: Recent advances in the field of congenital heart disease (CHD) have significantly improved the overall prognosis. Now more attention is being given to health-related quality of life (HRQoL) and promotion of physical activity. Non-invasive relaxation therapy may be effective in cardiac patients concerned with exercise-induced dyspnoea. The SOPHROCARE randomised trial aims to assess the impact of Caycedian Sophrology on cardiopulmonary fitness in adolescents and young adults with CHD. METHODS: The SOPHROCARE trial is a nationwide, multicentre, randomised, controlled study in CHD patients aged from 13 to 25 years old. Patients will be randomised into 2 groups (8 Sophrology group sessions vs. no intervention). The primary outcome is the change in percent predicted maximum oxygen uptake (VO2max) between baseline and 12-month follow-up. A total of 94 patients in each group is required to observe a significant increase of 10% in VO2max with a power of 80% and an alpha risk of 5%. The secondary outcomes are: clinical outcomes, cardiopulmonary exercise test parameters (VE/VCO2 slope, ventilatory anaerobic threshold, oxygen pulse, respiratory response to hypercapnia), health-related quality of life score (PedsQL), physical and psychological status. CONCLUSION: After focusing on the survival in CHD, current research is opening on secondary prevention and patient-related outcomes. We sought to assess in the SOPHROCARE trial, if a Sophrology program, could improve exercise capacity and quality of life in youth with CHD. TRIAL REGISTRATION: Clinicaltrials.gov (NCT03999320).

Utilization Patterns of Amantadine in Parkinson's Disease Patients Enrolled in the French COPARK Study.

INTRODUCTION: Immediate-release (IR) amantadine has been marketed for Parkinson's disease (PD) therapy for 50 years, while two novel extended-release formulations have only recently reached the market in the US. OBJECTIVES: The aim of this study was to describe amantadine IR utilization patterns in the French COPARK cohort, at baseline and after 2 years of follow-up. METHODS: Overall, 683 PD patients from the COPARK survey were evaluated. All patients were assessed in a standardized manner (demographics, treatments, Unified Parkinson's Disease Rating Scale [UPDRS], Hospital Anxiety and Depression Scale, Pittsburg Questionnaire and health-related quality-of-life scales (Short Form-36 [SF-36], 39-item Parkinson's Disease Questionnaire [PDQ-39]). Longitudinal data were only available for 401/683 patients (59%) with a median (P25-75) follow-up period of 23 months (18-31). Patients were assessed in the same way as in the baseline visit. RESULTS: At baseline, amantadine was prescribed to 61/683 (9%) patients (median dose 200 mg/day, range 100-300 mg/day). Amantadine was initiated after a median of 7 years from PD diagnosis, and its prescription was correlated with the presence of dyskinesia (logistic regression odds ratio [OR] 3.72, 95% confidence interval [CI] 1.95-7.08) and hallucinations (UPDRS I.2) [OR 1.57, 95% CI 1.08-2.29]. After 2 years, the amantadine prescription increased from 33 (8%) patients at baseline to 54 (14%) patients in the subset of 401 patients analysed twice (p = 0.001). Among the 33 patients receiving amantadine at baseline, 9 (27%) stopped amantadine, 5 (15%) increased the dose, 6 (18%) reduced the dose and 13 (40%) stayed at the same doses. Treatment was initiated in 30/54 new patients (55%). Patients who started amantadine or increased its dose (n = 35) had more levodopa-induced dyskinesias at baseline (OR 7.02, 95% CI 3.09-15.90) and higher Mini-Mental State Examination score at follow-up (OR 1.37, 95% CI 1.06-1.79). Undergoing deep brain stimulation was related to stopping or downtitrating amantadine (OR 22.02, 95% CI 4.24-114.44; n = 15). CONCLUSIONS: In this cohort, amantadine was used in 10% of patients. Its use increased during follow-up, despite the fact that one-third of patients who received amantadine at baseline stopped taking it. Amantadine prescription was mainly correlated with the presence of dyskinesia.

Listeria monocytogenes and ocular abscess: an atypical but yet potential association.

PURPOSE: To report a farmer's corneal abscess caused by an unusual pathogen: Listeria monocytogenes fluoroquinolone resistant. METHODS: A 78-year-old farmer presented a central corneal abscess associated with 1-mm hypopyon and decreased visual acuity evolving since 2 weeks. First an antibiotic therapy associating oral ofloxacin and topical ciprofloxacin, vancomycin and ceftazidime was started. Different samples of the abscess were performed and sent to different microbiological laboratories. RESULT: Listeria monocytogenes was isolated after 2 days of culture. Antibiotics sensitivity showed resistance to ciprofloxacin, fosfomycin and fusidic acid. Ceftazidime was changed for gentamicin, and after 1 month of treatment the abscess decreased considerably. CONCLUSION: This case demonstrated that even if Listeria is rarely involved in ocular abscess, it must be evocated for people with risk factors as farmers. This suspicion should lead to an extended incubation to identify the pathogen. The analysis of Listeria resistance is essential to start an efficient therapy.

Subjective sleep dysfunction and insomnia symptoms in Parkinson's disease: Insights from a cross-sectional evaluation of the French CoPark cohort.

INTRODUCTION: Twenty-seven to 80% of patients with Parkinson's Disease (PD) complain of subjective sleep dysfunction and insomnia symptoms. Our aim is to describe the prevalence and features of subjective sleep dysfunction and insomnia symptoms in patients with PD compared to other patients. METHODS: Cross-sectional analysis of 636 adult PD patients compared to 143 age and sex-matched non-PD control patients consulting their general practitioners. Insomnia symptoms and other sleep features were assessed by the Pittsburgh Sleep Quality Index (PSQI), a global score > 5 defining impaired sleep. The Chi-square test or the Student's t-test were used to assess the potential clinical and demographic differences between groups and between PD patients with vs. without sleep dysfunction. Logistic regression analysis was employed to test multivariate effects. RESULTS: Sleep dysfunction and insomnia symptoms were more frequent in PD patients compared to control patients (63 vs. 45%, p = 0.001). Female gender, PD duration, presence of depression and anxiety were associated with the presence of insomnia in PD. Subjective sleep efficiency, habitual sleep quality, sleep disturbance and daytime dysfunction, but not sleep latency, were reduced in PD patients compared to controls. CONCLUSIONS: The prevalence of sleep dysfunction is higher in PD than in other general medical conditions. Insomnia in PD seems to affect sleep maintenance and consolidation, but not sleep onset.

Falls in ambulatory non-demented patients with Parkinson's disease.

This study aimed at determining the prevalence of falling in PD patients, to assess generic and disease-specific clinical and pharmacological factors, relationship with health-related quality of life (HR-QoL) and changes in falls from OFF to ON in patients with motor fluctuations. Six-hundred and eighty-three PD patients of the COPARK survey were evaluated (11 had missing data and were excluded from the analysis). Patients with falls were identified as those with a UPDRS Item 13 ≥ 1 in the ON condition. All patients were assessed in a standardized manner [demographics, treatments, Unified PD Rating Scale (UPDRS), Hospital Anxiety and Depression Scale, Pittsburg questionnaire and HR-QoL scales (SF36, PDQ39)]. Falling was reported by 108/672 (16%) PD patients during the ON state and prevalence increased according to PD severity, from 5% in Hoehn and Yahr stage 1-60% in stage 4. Falling was significantly related to lower HR-QoL. Falling correlated with (1) generic factors such as female gender, age at the end of academic studies and diuretics consumption, (2) motor PD-specific factors including disease severity, frozen gait, difficulties when arising from a chair, dyskinesia and higher levodopa daily equivalent dose and (3) non-motor PD-specific factors such as orthostatic hypotension and hallucinations. Falling was more frequent in OFF than in ON in 48/74 (64%) patients with motor fluctuations and remained unchanged in 27 patients (36%). In summary, falling affected a significant proportion of PD patients, especially in advanced stages. It was associated with a variety of generic and PD-specific factors and was related to reduced HR-QoL.

Prevalence, determinants, and effect on quality of life of freezing of gait in Parkinson disease.

IMPORTANCE: Freezing of gait (FOG) is a common axial symptom of Parkinson disease (PD). OBJECTIVE: To determine the prevalence of FOG in a large group of PD patients, assess its relationship with quality of life and clinical and pharmacological factors, and explore its changes from the off to on conditions in patients with motor fluctuations. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional survey of 683 patients with idiopathic PD. Scores for FOG were missing in 11 patients who were not included in the analysis. Patients were recruited from referral centers and general neurology clinics in public or private institutions in France. EXPOSURE: Patients with FOG were identified as those with a score of 1 or greater on item 14 of the Unified Parkinson's Disease Rating Scale (UPDRS) in the on condition. Item 14 scores for FOG in the off condition were also collected in patients with fluctuating motor symptoms. MAIN OUTCOMES AND MEASURES: Quality of life (measured by the 39-item Parkinson's Disease Questionnaire and 36-Item Short Form Health Survey), anxiety and depression (Hospital Anxiety and Depression Scale), clinical features (UPDRS), and drug consumption. RESULTS: Of 672 PD patients, 257 reported FOG during the onstate (38.2%), which was significantly related to lower quality of life scores (P < .01). Freezing of gait was also correlated with longer PD duration (odds ratio, 1.92 [95% CI, 1.28-2.86]), higher UPDRS parts II and III scores (4.67 [3.21-6.78]), the presence of apathy (UPDRS item 4) (1.94 [1.33-2.82]), a higher levodopa equivalent daily dose (1.63 [1.09-2.43]), and more frequent exposure to antimuscarinics (3.07 [1.35-6.97]) (logistic regression). The FOG score improved from the off to on states in 148 of 174 patients with motor fluctuations (85.1%) and showed no change in 13.8%. The FOG score improved by more than 50% in 43.7% of patients. Greater improvement in the on state was observed in younger patients (r = -0.25; P < .01) with lower UPDRS II and III scores (r = -0.50; P < .01) and no antimuscarinic use (r = -0.21; P < .01). CONCLUSIONS AND RELEVANCE: Freezing of gait in PD patients correlates with poor quality of life, disease severity, apathy, and exposure to antimuscarinics. Dopaminergic therapy improved FOG in most patients with motor fluctuations, especially younger ones with less severe disease and no antimuscarinic use. This finding suggests that quality of life is impaired in PD patients with FOG and that optimizing dopaminergic therapy and avoiding antimuscarinics should be considered.

Simvastatin decreases levodopa-induced dyskinesia in monkeys, but not in a randomized, placebo-controlled, multiple cross-over ("n-of-1") exploratory trial of simvastatin against levodopa-induced dyskinesia in Parkinson's disease patients.

BACKGROUND: Simvastatin may improve levodopa-induced dyskinesia through striatal Ras-extracellular signal-regulated kinase pathway modulation. METHODS: (1) Six 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated macaques were assessed for parkinsonism and dyskinesia severity following acute co-administration of levodopa and simvastatin (0, 1.5, 3 and 6 mg/kg). (2) A "n-of-1" design randomized, placebo-controlled, 3 cross-over trial was then conducted in 10 Parkinson's disease patients with troublesome dyskinesia. The primary endpoint was a 7-point scale rating subjective discomfort caused by troublesome dyskinesia. Secondary endpoints related to dyskinesia severity and duration and functional impairment, severity and duration of OFF periods, motor scores and investigator- and patient-rated global impressions. (3) The pharmacodynamic variable for both studies consisted in a multiplex analysis of kinase-induced phosphorylation in T and B-lymphocytes by flow cytometry. RESULTS: (1) In the macaque, simvastatin reduced dyskinesia scores (45%), at the dose of 3 mg/kg (2) In the "n-of-1" trial no significant response was observed in the primary end point and all secondary endpoints. No serious adverse events were reported. (3) Simvastatin 3 mg/kg significantly reduce kinase-induced phosphorylation in monkeys but not simvastatin 40 mg in patients. CONCLUSIONS: Simvastatin reduced dyskinesia in primates using high doses over 3 mg/kg but the exploratory trial in patients revealed no effect at 40 mg/d suggesting that higher doses, not compatible with a safe prolonged administration, are necessary.

A proof-of-concept, randomized, placebo-controlled, multiple cross-overs (n-of-1) study of naftazone in Parkinson's disease.

To explore for the first time the tolerability and efficacy of naftazone in patients with Parkinson's disease (PD). Proof-of-concept, randomized, double-blind, placebo-controlled, multiple-cross-over n-of-1 study in patients with PD with wearing-off and dyskinesias. Naftazone was titrated up to 120 mg/day during an initial single-blind dose-finding phase. Seven patients entered the placebo-controlled phase (four consecutive 28-day cross-overs). Three outcome measures were used to collect preliminary indices of efficacy: (i) 48-h ON-OFF diaries; (ii) Unified PD Rating Scale (UPDRS) part III while ON; (iii) seven-point Likert scale to assess "patients' discomfort caused by dyskinesias" (Q1) and 'disability during OFF-periods' (Q2). A 'responder' analysis (proportion of patients with mean treatment effect [naftazone minus placebo] favoring naftazone over the 4 cross-over periods) was used. Treatment effects were derived from mixed-effects anova. On diaries, 5/7 patients responded to naftazone for 'ON-time with troublesome dyskinesia' (reduced time, treatment effect: -49 [95% CI: -93/-4] min, P = 0.03), 6/7 regarding 'ON-time without troublesome dyskinesia' (increased time, treatment effect: 35 [-19/88], P = 0.2). No trend was observed for 'OFF' time. There were 7/7 'responders' regarding UPDRSIII (reduced score, treatment effect: -2.1[-4.5/0.2], P = 0.08). The 7-point scales did not show clear trends in favor of naftazone (3/7 responders for Q1 and 4/7 for Q2). Four of the seven patients reported adverse events after randomization, mostly related to the CNS (mild: 2, severe: 2). These pilot findings are consistent with preclinical data in primates and support the hypothesis that naftazone may have antiparkinsonian and antidyskinetic effects in humans that deserve further clinical investigation.

The interest of gait markers in the identification of subgroups among fibromyalgia patients.

BACKGROUND: Fibromyalgia (FM) is a heterogeneous syndrome and its classification into subgroups calls for broad-based discussion. FM subgrouping, which aims to adapt treatment according to different subgroups, relies in part, on psychological and cognitive dysfunctions. Since motor control of gait is closely related to cognitive function, we hypothesized that gait markers could be of interest in the identification of FM patients' subgroups. This controlled study aimed at characterizing gait disorders in FM, and subgrouping FM patients according to gait markers such as stride frequency (SF), stride regularity (SR), and cranio-caudal power (CCP) which measures kinesia. METHODS: A multicentre, observational open trial enrolled patients with primary FM (44.1 ± 8.1 y), and matched controls (44.1 ± 7.3 y). Outcome measurements and gait analyses were available for 52 pairs. A 3-step statistical analysis was carried out. A preliminary single blind analysis using k-means cluster was performed as an initial validation of gait markers. Then in order to quantify FM patients according to psychometric and gait variables an open descriptive analysis comparing patients and controls were made, and correlations between gait variables and main outcomes were calculated. Finally using cluster analysis, we described subgroups for each gait variable and looked for significant differences in self-reported assessments. RESULTS: SF was the most discriminating gait variable (73% of patients and controls). SF, SR, and CCP were different between patients and controls. There was a non-significant association between SF, FIQ and physical components from Short-Form 36 (p = 0.06). SR was correlated to FIQ (p = 0.01) and catastrophizing (p = 0.05) while CCP was correlated to pain (p = 0.01). The SF cluster identified 3 subgroups with a particular one characterized by normal SF, low pain, high activity and hyperkinesia. The SR cluster identified 2 distinct subgroups: the one with a reduced SR was distinguished by high FIQ, poor coping and altered affective status. CONCLUSION: Gait analysis may provide additional information in the identification of subgroups among fibromyalgia patients. Gait analysis provided relevant information about physical and cognitive status, and pain behavior. Further studies are needed to better understand gait analysis implications in FM.

Thought disorders among non-demented outpatients with Parkinson's disease: prevalence and associated factors.

The objectives of the study are to evaluate the prevalence and the associated factors of thought disorders in a large cross-sectional population of non-demented out patients with Parkinson's disease (PD). Four-hundred and nineteen consecutive non-demented PD patients were studied through the DoPaMiP cross-sectional study. Demographic and clinical variables were recorded, including motor and cognitive status, dependency, depressive and anxious symptoms, dysautonomia and sleep disorders. The presence of thought disorders over the past 15 days was assessed by the Unified Parkinson's Disease Rating Scale part I. Patients with and without thought disorders were compared using parametric tests. Logistic regression was applied to significant data. Thought disorders were present in 105 patients (25%) including vivid dreams in 83 (19.8%), benign hallucinations in 17 (4.1%), and hallucinations without insight in 5 (1.2%). No patient had delusion. Patients with thought disorders were more dependent than the others. Thought disorders were associated with longer PD duration, greater UPDRS scores and the presence of motor complications. Conversely, UPDRS tremor sub-score was lower in patients without thought disorders. Thought disorders were also associated with dysautonomia, lower MMSE score, depression and sleep disorders. Logistic regression identified PD duration, lower MMSE score, depressive and dysautonomic signs as independent risk factors. In conclusion, mild thought disorders were present in 25% of non-demented outpatients with PD, but hallucinations were present in 5% only. Thought disorders were associated with PD duration, depressive and dysautonomic symptoms and lower MMSE score.

Anxious and depressive symptoms in Parkinson's disease: the French cross-sectionnal DoPaMiP study.

Anxiety has been less extensively studied than depression in Parkinson's disease (PD). The DoPaMiP survey allowed assessing simultaneously anxiety and depressive symptoms in PD and comparing correlations of both symptoms with clinical and therapeutic features of the disease. Cross sectional survey conducted prospectively in 450 ambulatory nondemented PD patients and 98 patients with other disorders than PD. Anxiety and depressive symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS), parkinsonism using the Unified Parkinson's Disease Rating Scale (UPDRS). Other clinical factors were measured using a structured standardized examination/questionnaire. The mean HADS-A (anxiety) subscore was higher in PD patients than in the others (8.2 +/- 3.9 vs. 6.5 +/- 3.2, P < 10(-4)) as was the HADS-D (depressive) subscore (6.6 +/- 3.8 vs. 3.9 +/- 3.2, P < 10(-4)). Patients with possible/probable anxious signs (HADS-A >or= 8) were more prevalent in PD (51% vs. 29%, P < 10(-4)) as were those with depressive symptoms (40% vs. 10%, P < 10(-4)). Conversely, anxiolytic and antidepressant medications consumption was not different between the 2 groups. Patients with anxious symptoms were more frequently female and younger than those without such symptoms, while those with depressive symptoms had more severe indices of parkinsonism, more comorbidities and lower cognitive function (Mini Mental State Exam). The logistic regression model revealed that patients with depressive symptoms received more frequently levodopa and less frequently a dopamine agonist. Anxiety and depressive symptoms were more frequent in PD patients than in medical control group. Both symptoms were commonly associated in the same PD patients, but were correlated with different clinical/therapeutic features, suggesting different underlying pathophysiological mechanisms.