Reproductive choices and intrafamilial communication in neurogenetic diseases with different self-estimated severities.

BACKGROUND: Low uptake of presymptomatic testing and medically assisted reproduction in families impacted by neurogenetic diseases prompted us to investigate how reproductive options are considered and whether there is a relationship with perceived severity of the disease. We hypothesised that self-estimated severity would influence opinion on reproductive options and that prenatal/preimplantation diagnosis would be a motivation to inform relatives about their risk. METHODS: We invited people impacted by neurogenetic diseases to evaluate the severity of their familial disease using analogic visual scales and to answer questionnaires about reproductive choices and intrafamilial communication. We compared answers between diseases and with the perceived severity of each disease. RESULTS: We analysed 562 questionnaires. Participants were impacted by Huntington disease (n=307), spinocerebellar ataxias (n=114), Steinert myotonic dystrophy (n=82) and amyotrophic lateral sclerosis/frontotemporal dementia (n=59). Self-estimated severity differed between pathologies (p<0.0001). Overall, participants considered prenatal diagnosis (78.0±34.4 out of 100) and preimplantation diagnosis (75.2±36.1 out of 100) justified more than termination of pregnancy (68.6±38.5 out of 100). They were less in favour of gamete donation (48.3±39.8 out of 100) or pregnancy abstention (43.3±40.3 out of 100). The greater the perceived severity of the disease, the more reproductive options were considered justified, except for gamete donation. Prenatal/preimplantation diagnosis was a motivation to inform relatives for only 55.3% of participants (p=0.01). CONCLUSION: Self-estimated severity minimally impacts opinions towards reproductive options. Medically assisted reproduction procedures are rarely sought and do not motivate familial communication.

Temporal Dynamics of the Scale for the Assessment and Rating of Ataxia in Spinocerebellar Ataxias.

BACKGROUND: The Scale for the Assessment and Rating of Ataxia (SARA) is the reference clinical scale to assess the severity of cerebellar ataxia. In the context of upcoming therapeutic trials, a reliable clinical outcome is needed to assess the efficiency of treatments. OBJECTIVE: The aim is to precisely assess and compare temporal dynamics of SARA and a new f-SARA. METHODS: We analyzed data from four cohorts (EUROSCA, RISCA, CRC-SCA, and SPATAX) comprising 1210 participants and 4092 visits. The linearity of the progression and the variability were assessed using an ordinal Bayesian mixed-effect model (Leaspy). We performed sample size calculations for therapeutic trials with different scenarios to improve the responsiveness of the scale. RESULTS: Seven of the eight different items had a nonlinear progression. The speed of progression was different between most of the items, with an average time for a one-point increase from 3.5 years [3.4; 3.6] (median, 95% credible interval) for the fastest item to 11.4 [10.9; 12.0] years. The total SARA score had a linear progression with an average time for a one-point increase of 0.95 [0.92; 0.98] years. After removing the four last items and rescaling all items from 0 to 4, variability increased and progression was slower and thus would require a larger sample size in a future therapeutic trial. CONCLUSION: Despite a heterogeneous temporal dynamics at the item level, the global progression of SARA was linear. Changing the initial scale deteriorates the responsiveness. This new information about the temporal dynamics of the scale should help design the outcome of future clinical trials. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Major interregional differences in France of COVID-19 hospitalization and mortality from January to June 2020.

INTRODUCTION: Even though France was severely hit by the COVID-19 pandemic, few studies have addressed the dynamics of the first wave on an exhaustive, nationwide basis. We aimed to describe the geographic and temporal distribution of COVID-19 hospitalisations and in-hospital mortality in France during the first epidemic wave, from January to June 2020. METHODS: This retrospective cohort study used the French national database for all acute care hospital admissions (PMSI). Contiguous stays were assembled into "care sequences" for analysis so as to limit bias when estimating incidence and mortality. The incidence rate and its evolution, mortality and hospitalized case fatality rates (HCFR) were compared between geographic areas. Correlations between incidence, mortality, and HCFR were analyzed. RESULTS: During the first epidemic wave, 98,366 COVID-19 patients were hospitalized (incidence rate of 146.7/100,000 inhabitants), of whom 18.8% died. The median age was 71 years, the male/female ratio was 1.16, and 26.2% of patients required critical care. The Paris area and the North-East region were the first and most severely hit areas. A rapid increase of incidence and mortality within 4 weeks was followed by a slow decrease over 10 weeks. HCFRs decreased during the study period, and correlated positively with incidence and mortality rates. DISCUSSION: By detailing the geographical and temporal evolution of the COVID-19 epidemic in France, this study revealed major interregional differences, which were otherwise undetectable in global analyses. The precision afforded should help to understand the dynamics of future epidemic waves.

Development of SARAhome , a New Video-Based Tool for the Assessment of Ataxia at Home.

BACKGROUND: Clinical scales such as the Scale for the Assessment and Rating of Ataxia (SARA) cannot be used to study ataxia at home or to assess daily fluctuations. The objective of the current study was to develop a video-based instrument, SARAhome , for measuring ataxia severity easily and independently at home. METHODS: Based on feasibility of self-application, we selected 5 SARA items (gait, stance, speech, nose-finger test, fast alternating hand movements) for SARAhome (range, 0-28). We compared SARAhome items with total SARA scores in 526 patients with spinocerebellar ataxia types 1, 2, 3, and 6 from the EUROSCA natural history study. To prospectively validate the SARAhome , we directly compared the self-applied SARAhome and the conventional SARA in 50 ataxia patients. To demonstrate feasibility of independent home recordings in a pilot study, 12 ataxia patients were instructed to obtain a video each morning and evening over a period of 14 days. All videos were rated offline by a trained rater. RESULTS: SARAhome extracted from the EUROSCA baseline data was highly correlated with conventional SARA (r = 0.9854, P < 0.0001). In the prospective validation study, the SARAhome was highly correlated with the conventional SARA (r = 0.9254, P < 0.0001). Five of 12 participants of the pilot study obtained a complete set of 28 evaluable videos. Seven participants obtained 13-27 videos. The intraindividual differences between the lowest and highest SARAhome scores ranged from 1 to 5.5. CONCLUSION: The SARAhome and the conventional SARA are highly correlated. Application at home is feasible. There was a considerable degree of intraindividual variability of the SARAhome scores. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Risk Score of Neck Hematoma: How to Select Patients for Ambulatory Thyroid Surgery?

BACKGROUND: The risk of postoperative compressive hematoma is the major limitation for a wide development of ambulatory thyroidectomy (AT). The aim of this study was to establish a risk score of hematoma on the basis of preoperative criteria. METHODS: All patients who underwent thyroidectomy between 2002 and 2017 were reviewed in a high-volume endocrine surgery center. Multivariate analysis of risk factors associated with hematoma was performed in lobectomy and total thyroidectomy (TT). We assigned the risk factors identified by multivariate analysis weighted points proportional to the regression coefficient values. A simple sum of all accumulated points for each patient calculated the total score. RESULTS: For lobectomy [31 hematoma among 3912 patients (0.8%)], the weighted points of Vit K antagonist (VKA) were 3 (OR 9.86), and 1 in male gender (OR 2.4). For TT [162 hematoma among 13,903 patients (1.2%)], the weighted points of VKA were 4 (OR 12.18), 1 in male gender (OR 1.89), and 1 for diabetes (OR 1.86). Other factors weighted 0 in both groups. A total score >1 was linked to a risk of hematoma > 1.3% for lobectomy or TT. AT should not be proposed to any patient under VKA, and in case of TT, to male patients with diabetes. Prospectively, patients had AT from May 2018 to February 2020, 529 patients underwent ambulatory TL (483) or TT (46) and only one patient experienced neck hematoma. CONCLUSION: We established a simple and reproducible predictive score of early discharge for lobectomy and TT that could be useful for patients' management.

Psychogeriatric Inventory of Disconcerting Symptoms and Syndromes (PGI-DSS): validity and reliability of a new brief scale compared to the Neuropsychiatric Inventory for Nursing Homes (NPI-NH).

OBJECTIVES: To validate the Psychogeriatric Inventory of Disconcerting Symptoms and Syndromes (PGI-DSS), a single scale in A4 format comprising four disconcerting syndromes (violence, refusal, words, and acts). The scale enables an immediate conversion of a qualitative assessment to a quantitative assessment. The PGI-DSS was compared with the Neuro Psychiatric Inventory for Nursing Homes (NPI-NH). DESIGN: Cross-sectional descriptive and correlational studies. SETTING: Thirty geriatric care units and nursing homes. PARTICIPANTS: Raters interviewed nurses and nursing assistants in charge of older adults hospitalized in geriatric care units or living in nursing homes (N = 226). MEASUREMENTS: The French version of the PGI-DSS and the French version of the NPI-NH. RESULTS: The correlation coefficient between the PGI-DSS and the NPI-NH was 0.70 (p < 0.0001). The PGI-DSS threshold score corresponding to the NPI threshold score was 17 (specificity: 87%, sensitivity: 63%). Four statistical factors, corresponding to the four clinical syndromes, explained 53.4% of the total variance. The internal consistency of the PGI-DSS (Cronbach's alpha = 0.695) was higher than that of the NPI-NH (Cronbach's alpha = 0.474). Test-retest reliability was better for the PGI-DSS than for the NPI-NH. The intraclass correlations were 0.80 [0.73; 0.86] and 0.75 [0.67; 0.83], respectively. Interrater reliability was better for the PGI-DSS than for the NPI-NH. The intraclass correlations were 0.65 [0.55-0.76] and 0.55 [0.43-0.68], respectively. CONCLUSION: The PGI-DSS was developed to overcome the limitations of the NPI-NH. New, brief, easy to administer in less than 4 minutes, foldable in four parts, pocket-sized, easy-to-read in the palm of the hand, PGI-DSS could have similar or better statistical properties than the NPI-NH. Whereas the 10 domains in the NPI-NH have clinical utility for clinicians, the four easily understandable syndromes in the PGI-DSS can help avoid inappropriate attitudes and can guide psychosocial interventions. It could likewise improve dialogue between caregivers and clinicians.

Access to the waiting list and to kidney transplantation for people living with HIV: A national registry study.

We compared access to a kidney transplantation (KT) waiting list (WL) and to KT between people living with HIV (PLHIV) and HIV-uninfected controls. Using the REIN (the national Renal Epidemiology and Information Network registry), we included all PLHIV initiating dialysis in France throughout 2006-2010 and HIV-uninfected controls matched for age, sex, year of dialysis initiation, and the existence of a diabetic nephropathy. Patients were prospectively followed until December 2015. We used a competitive risk approach to assess the cumulative incidence of enrollment on WL and of KT, with death as a competing event (subdistribution hazard ratio adjusted on comorbidities, asdHR). There were 255 PLHIV in the REIN (median age 47 years) of whom 180 (71%) were also found in the French Hospital Database on HIV (FHDH-ANRS CO4) including 126 (70%) known to be on antiretroviral therapy with HIV viral suppression (VS). Five years after dialysis initiation, 65%, and 76%, of treated PLHIV with VS, and of HIV-uninfected controls were enrolled on a WL (asdHR 0.68; 95% CI 0.50-0.91). Access to KT was also less frequent and delayed for treated PLHIV with VS (asdHR 0.75, 95% CI, 0.52-1.10). PLHIV continue to face difficulties to access KT.

Prediction of Survival With Long-Term Disease Progression in Most Common Spinocerebellar Ataxia.

BACKGROUND: Spinocerebellar ataxias are rare dominantly inherited neurodegenerative diseases that lead to severe disability and premature death. OBJECTIVE: To quantify the impact of disease progression measured by the Scale for the Assessment and Rating of Ataxia on survival, and to identify different profiles of disease progression and survival. METHODS: Four hundred sixty-two spinocerebellar ataxia patients from the EUROSCA prospective cohort study, suffering from spinocerebellar ataxia type 1, spinocerebellar ataxia type 2, spinocerebellar ataxia type 3, and spinocerebellar ataxia type 6, and who had at least two measurements of Scale for the Assessment and Rating of Ataxia score, were analyzed. Outcomes were change over time in Scale for the Assessment and Rating of Ataxia score and time to death. Joint model was used to analyze disease progression and survival. RESULTS: Disease progression was the strongest predictor for death in all genotypes: An increase of 1 standard deviation in total Scale for the Assessment and Rating of Ataxia score increased the risk of death by 1.28 times (95% confidence interval: 1.18-1.38) for patients with spinocerebellar ataxia type 1; 1.19 times (1.12-1.26) for spinocerebellar ataxia type 2; 1.30 times (1.19-1.42) for spinocerebellar ataxia type 3; and 1.26 times (1.11-1.43) for spinocerebellar ataxia type 6. Three subgroups of disease progression and survival were identified for patients with spinocerebellar ataxia type 1: "severe" (n = 13; 12%), "intermediate" (n = 31; 29%), and "moderate" (n = 62; 58%). Patients in the severe group were more severely affected at baseline with higher Scale for the Assessment and Rating of Ataxia scores and frequency of nonataxia signs compared to those in the other groups. CONCLUSION: Rapid ataxia progression is associated with poor survival of the most common spinocerebellar ataxia. Theses current results have implications for the design of future interventional studies of spinocerebellar ataxia. © 2019 International Parkinson and Movement Disorder Society.

Spastic paraplegia due to SPAST mutations is modified by the underlying mutation and sex.

Hereditary spastic paraplegias (HSPs) are rare neurological disorders caused by progressive distal degeneration of the corticospinal tracts. Among the 79 loci and 65 spastic paraplegia genes (SPGs) involved in HSPs, mutations in SPAST, which encodes spastin, responsible for SPG4, are the most frequent cause of both familial and sporadic HSP. SPG4 is characterized by a clinically pure phenotype associated with restricted involvement of the corticospinal tracts and posterior columns of the spinal cord. It is rarely associated with additional neurological signs. However, both age of onset and severity of the disorder are extremely variable. Such variability is both intra- and inter-familial and may suggest incomplete penetrance, with some patients carrying mutations remaining asymptomatic for their entire life. We analysed a cohort of 842 patients with SPG4-HSP to assess genotype-phenotype correlations. Most patients were French (89%) and had a family history of SPG4-HSP (75%). Age at onset was characterized by a bimodal distribution, with high inter-familial and intra-familial variability, especially concerning first-degree relatives. Penetrance of the disorder was 0.9, complete after 70 years of age. Penetrance was lower in females (0.88 versus 0.94 in males, P = 0.01), despite a more diffuse phenotype with more frequent upper limb involvement. Seventy-seven per cent of pathogenic mutations (missense, frameshift, splice site, nonsense, and deletions) were located in the AAA cassette of spastin, impairing its microtubule-severing activity. A comparison of the missense and truncating mutations revealed a significantly lower age at onset for patients carrying missense mutations than those carrying truncating mutations, explaining the bimodal distribution of the age at onset. The age at onset for patients carrying missense mutations was often before 10 years, sometimes associated with intellectual deficiency. Neuropathological examination of a single case showed degeneration of the spinocerebellar and spinocortical tracts, as well as the posterior columns. However, there were numerous small-diameter processes among unusually large myelinated fibres in the corticospinal tract, suggesting marked regeneration. In conclusion, this large cohort of 842 individuals allowed us to identify a significantly younger age at onset in missense mutation carriers and lower penetrance in females, despite a more severe disorder. Neuropathology in one case showed numerous small fibres suggesting regeneration.

Online information and support for carers of people with young-onset dementia: A multi-site randomised controlled pilot study.

OBJECTIVES: The European RHAPSODY project sought to develop and test an online information and support programme for caregivers of individuals diagnosed with young onset dementia. The objectives were to assess user acceptability and satisfaction with the programme and to test outcome measures for a larger effectiveness study. DESIGN: A pilot randomised controlled trial in England, France, and Germany was conducted with 61 caregivers for adults with young onset Alzheimer's disease or frontotemporal degeneration. Evaluations at baseline, week 6, and week 12 assessed user acceptability and satisfaction. Use of the programme was measured from online back-end data. Qualitative feedback on user experiences was collected via semi-structured interviews. Measures of caregiver well-being (self-efficacy, stress, burden, frequency of patient symptoms, and caregiver reactions) were explored for use in a subsequent trial. RESULTS: Participants logged in online on average once a week over a 6-week period, consulting approximately 31% of programme content. Seventy percent of participants described the programme as useful and easy to use. Eighty-five percent expressed intent to use the resource in the future. Reductions in reported levels of stress and caregivers' negative reactions to memory symptoms were observed following use of the programme. CONCLUSIONS: Results indicated that the RHAPSODY programme was acceptable and useful to caregivers. The programme may be complementary to existing services in responding to the specific needs of families affected by young onset dementia. Distribution of the programme is underway in England, France, Germany, and Portugal.

Surgical internal iliac artery preservation associated with endovascular repair of infrarenal aortoiliac aneurysms to avoid buttock claudication and distal type I endoleaks.

OBJECTIVE: The objective of this study was to assess outcomes of a hybrid technique for treatment of abdominal aortic aneurysm (AAA) associated with iliac aneurysm without distal neck by combining an AAA endovascular repair approach with open surgery for preservation of the internal iliac artery (IIA). METHODS: The files of 51 patients operated on between 1998 and 2017 in a single vascular surgery department were retrospectively analyzed. Inclusion criteria were patients with AAA associated with uni-iliac or bi-iliac aneurysm without suitable distal sealing zone. Surgery consisted of deployment of an aortouni-iliac stent graft combined with an extra-anatomic crossover prosthetic bypass. With use of a limited retroperitoneal approach, the contralateral proximal common iliac aneurysm was surgically excluded and the IIA revascularized by direct ilioiliac anastomosis or terminal common iliac suture, preserving the iliac bifurcation. RESULTS: The patients' mean age was 74 years (58-88 years), and 92% were men. The mean follow-up was 5.8 years (0.1-18 years). Twenty-nine patients (57%) had one or more high-risk criteria for open surgery. Nineteen patients (37.3%) had aortouni-iliac aneurysms, 19 (37.3%) aortobi-iliac aneurysms, 5 (10%) isolated iliac aneurysms, and 8 (15.7%) bi-iliac aneurysms without aortic location. Four patients (7.8%) also had IIA aneurysms. Surgery was successful in all cases. Two patients (4%) died during the 30 days after surgery. One surgically preserved IIA occluded within the first month, resulting in buttock claudication. The 5-year IIA primary patency rate was 96%. Type I proximal endoleaks occurred in two patients, requiring additional surgery 3 years and 13 years after the initial surgery, respectively. CONCLUSIONS: This hybrid technique, consisting of AAA endovascular exclusion combined with open IIA revascularization, is safe and effective for preservation of pelvic vascularization. It is associated with long-term patency and low morbidity rates. We have been using this technique since before the advent of branched dedicated devices, allowing preservation of the IIA with good results. This technique should continue to be proposed, especially in patients not eligible for endovascular iliac branch repair because of anatomic contraindications, to avoid pelvic ischemia if the IIA has to be sacrificed.

Friedreich and dominant ataxias: quantitative differences in cerebellar dysfunction measurements.

BACKGROUND: Sensitive outcome measures for clinical trials on cerebellar ataxias are lacking. Most cerebellar ataxias progress very slowly and quantitative measurements are required to evaluate cerebellar dysfunction. METHODS: We evaluated two scales for rating cerebellar ataxias: the Composite Cerebellar Functional Severity (CCFS) Scale and Scale for the Assessment and Rating of Ataxia (SARA), in patients with spinocerebellar ataxia (SCA) and controls. We evaluated these scales for different diseases and investigated the factors governing the scores obtained. All patients were recruited prospectively. RESULTS: There were 383 patients with Friedreich's ataxia (FRDA), 205 patients with SCA and 168 controls. In FRDA, 31% of the variance of cerebellar signs with the CCFS and 41% of that with SARA were explained by disease duration, age at onset and the shorter abnormal repeat in the FXN gene. Increases in CCFS and SARA scores per year were lower for FRDA than for SCA (CCFS index: 0.123±0.123 per year vs 0.163±0.179, P<0.001; SARA index: 1.5±1.2 vs 1.7±1.7, P<0.001), indicating slower cerebellar dysfunction indexes for FRDA than for SCA. Patients with SCA2 had higher CCFS scores than patients with SCA1 and SCA3, but similar SARA scores. CONCLUSIONS: Cerebellar dysfunction, as measured with the CCFS and SARA scales, was more severe in FRDA than in patients with SCA, but with lower progression indexes, within the limits of these types of indexes. Ceiling effects may occur at late stages, for both scales. The CCFS scale is rater-independent and could be used in a multicentre context, as it is simple, rapid and fully automated. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT02069509.

Suggestive association between OPRM1 and impulse control disorders in Parkinson's disease.

BACKGROUND: Impulse control disorders are frequently associated with dopaminergic therapy in Parkinson's disease. Genetic studies have suggested a high heritability of impulse control disorders in the general population and in PD. The aim of this study was to identify candidate gene variants associated with impulse control disorders and related behaviors in PD. METHODS: We performed a multicenter case-control study in PD patients with (cases) or without impulse control disorders and related behaviors despite significant dopamine agonist exposure of >300 mg levodopa-equivalent daily dose during 12 months (controls). Behavioral disorders were assessed using the Ardouin scale. We investigated 50 variants in 24 candidate genes by a multivariate logistic regression analysis adjusted for sex and age at PD onset. RESULTS: The analysis was performed on 172 cases and 132 controls. Cases were younger (60 ± 8 vs 63 ± 8 years; P < 0.001) and had a higher family history of pathological gambling (12% vs 5%, P = 0.03). No variant was significantly associated with impulse control disorders or related behaviors after correction for multiple testing, although the 2 top variants were close to significant (OPRM1 rs179991, OR, 0.49; 95%CI, 0.32-0.76; P = 0.0013; Bonferroni adjusted P = 0.065; DAT1 40-base pair variable number tandem repeat, OR, 1.82; 95%CI, 1.24-2.68; P = 0.0021; Bonferroni adjusted P = 0.105). CONCLUSIONS: Our results are suggestive of a novel association of the opioid receptor gene OPRM1 with impulse control disorders and related behaviors in PD and confirm a previous association with DAT1. Although replication in independent studies is needed, our results bring potential new insights to the understanding of molecular mechanisms of impulse control disorders. © 2018 International Parkinson and Movement Disorder Society.

Effects of L-Carnitine on Mineral Metabolism in the Multicentre, Randomized, Double Blind, Placebo-Controlled CARNIDIAL Trial.

BACKGROUND: The use of L-carnitine has been proposed in haemodialysis (HD) when deficiency is present to improve anaemia resistant to erythropoietin stimulating agent, intradialytic hypotension or cardiac failure. We tested the effects of L-carnitine supplementation on parameters of chronic kidney disease-mineral bone disorder. METHODS: CARNIDIAL was a randomized, double-blinded trial having included 92 incident HD subjects for a 1-year period to receive L-carnitine versus placebo. Determinant factors of C-terminal fibroblast growth factor 23 (cFGF23) and intact FGF23 were studied including Klotho level. The L-carnitine effect on mineral metabolism was analyzed between groups by mixed linear models for repeated measurements. RESULTS: Klotho was below the lower limit of quantification (LLOQ) in 55% of the 163 samples. In multivariate analysis, cFGF23 was positively correlated with calcium and phosphate and was higher in subjects having Klotho > LLOQ. No correlation existed between Klotho and phosphate and phosphate was even higher in subjects having Klotho > LLOQ (p < 0.001). Both forms of FGF23 were not related to iron markers nor to IV iron dose. No L-carnitine effect was detected on parathyroid hormone (PTH) or FGF23 during the study period where PTH slightly decreased over time, whereas FGF23 increased. But calcium and phosphate increased more in the L-carnitine group. CONCLUSION: L-carnitine supplementation increased calcium and phosphate plasma concentrations with no detected downregulation effect on PTH and FGF23. (Clinical Trial 00322322, May 5, 2006).

Multimorbidity Is Associated with Preclinical Alzheimer's Disease Neuroimaging Biomarkers.

BACKGROUND: Identifying comorbidities that influence preclinical Alzheimer's disease (AD) can give some insight into the AD early stages trajectories to allow new treatment venues and to guide public health systems to prevent subsequent dementia. OBJECTIVE: To examine the association of multimorbidity with AD neuroimaging markers in cognitively normal older adults. METHODS: This study had a cross-sectional design. Data regarding 14 comorbidities were obtained for all 318 adults aged 70-85 years, recruited from the community to an ongoing prospective monocentric cohort. They underwent standardized neuropsychological and neuroimaging assessment with automated methods that measured hippocampal volumes, white matter hyperintensity volumes, fluorodeoxyglucose positron emission tomography (FDG-PET) standardized uptake values (SUV) in AD signature regions, and amyloid positron emission tomography (amyloid-PET) SUV ratios. Linear regression was used to assess the association of multimorbidity with AD neuroimaging biomarkers. RESULTS: Multimorbidity is signif icantly associated with lower hippocampal volumes (-0.03 ± 0.01; p = 0.012; R2 = 0.017) and lower FDG-PET SUV (-0.027 ± 0.009; p = 0.005; R2 = 0.022), with no association with amyloid deposition (0.001 ± 0.007; p = 0.884; R2 = 0.0001). Taken individually, obesity and excessive alcohol use are associated with lower FDG-PET values, whereas obstructive sleep apnea and mood disorders are related to lower amyloid-PET SUV ratios. CONCLUSION: Multimorbidity is associated with preclinical AD imaging markers of neurodegeneration, but not with amyloid.

A liminal stage after predictive testing for Huntington disease.

BACKGROUND: Following predictive testing for Huntington disease (HD), knowledge of one's carrier status may have consequences on disease onset. Our study aimed to address two questions. First, does knowledge of being a carrier of the pathological HD mutation trigger onset of the disease? Second, does this knowledge influence self-awareness and allow carriers to identify signs and symptoms of disease onset? METHODS: Between 2012 and 2015, 75 HD mutation carriers were examined using the Unified Huntington's Disease Rating Scale (UHDRS) motor score. Onset estimation made with the disease burden score was compared with UHDRS findings. We collected qualitative data with questionnaires and semistructured interviews. RESULTS: 38 women and 37 men, aged 43.7 years±10.5 (20-68), were interviewed after a mean delay between test and study interview of 10.5 years±4.7 (from 4 to 21 years). Estimation of age at onset was 4.5±8.5 years earlier than data-derived age at onset. Participants were categorised according to their motor score: scores <5 were premanifest (n=35), and scores >5 were manifest carriers (n=40). Self-observation was a major preoccupation for all, independent of their clinical status (82% vs 74%, p=0.57). Among manifest carriers, 56% thought they showed symptoms, but only 33% felt ill. Interestingly, this was also observed in those without motor signs (20% and 9%). Being a mutation carrier did not significantly facilitate recognition of motor signs. Interviews with premanifest carriers allowed the burden of self-observation to be illustrated despite lack of motor signs. CONCLUSIONS: Estimating age at onset based on disease burden score may not be accurate. The transition to disease was experienced as an ambiguous or liminal experience. The view of mutation carriers is not always concordant with medical onset estimation, highlighting the difficulties involved in the concept of onset and its use as an outcome in future disease-modifying trials.

Disease activity trajectories in early axial spondyloarthritis: results from the DESIR cohort.

BACKGROUND: Disease activity may change over time in axial spondyloarthritis (axSpA). The objectives were to identify patterns of disease activity evolution in patients with early axSpA. METHODS: Patients from the prospective early axSpA cohort (DEvenir des Spondyloarthrites Indifférenciées Récentes (DESIR)) who fulfilled the Assessment in SpondyloArthritis Society (ASAS) criteria for axSpA at baseline and with at least three Ankylosing Spondylitis Disease Activity Score (ASDAS) values available over the 3 years of follow-up were analysed. Statistical analyses: trajectories were estimated by group-based trajectory modelling; predisposing baseline factors for such trajectories were identified by univariate and multivariable multinomial (logit) regression; work disability over time was compared between the trajectories by Cox hazard model. RESULTS: In all, 370 patients were analysed: mean disease duration was 1.6 (±0.9) years. The five distinct trajectories of disease activity over the 3 years were (t1) 'persistent moderate disease activity' (n=134 (36.2%)); (t2) 'persistent inactive disease' (n=66 (17.8%); (t3) 'changing from very high disease activity to inactive disease' ((n=29 (7.8%)); (t4) 'persistent high disease activity' (n=126 (34.1%)) and (t5) 'persistent very high disease activity' (n=15 (4.1%)). After adjustment for other characteristics, t2 was associated with a white-collar job (OR=2.6 (95% CI 1.0 to 6.7)) and t3 with male gender (OR=7.1 (1.6 to 32.2)), higher education level (OR=9.4 (1.4 to 63.4)) and peripheral joint involvement (OR=6.2 (1.23 to 31.32)). Patients from (t4) and (t5) were more often declared work disabled over follow-up (HR=5.2 (1.5 to 18.0) and HR=8.0 (1.3 to 47.9), respectively). CONCLUSIONS: Trajectory modelling of disease activity was feasible in early axSpA: more than 30% patients (141/370) were in a trajectory with a persistent high disease activity. Persistent high disease activity trajectories were significantly associated with consequences on work. TRIAL REGISTRATION NUMBER: NCT01648907.

Epidemiology update for hepatitis C virus and hepatitis B virus in end-stage renal disease in France.

BACKGROUND & AIMS: Risk for HCV/HBV infection is increased in end-stage renal disease patients. We generate updated epidemiological data. METHODS: Based on the National French registry for end-stage renal disease patients, we extracted data for patients who started dialysis or pre-emptive transplantation between January 2005 and December 2013. A positive serum HBs Ag and/or a positive HCV RNA defined HBV and HCV infections, respectively. RESULTS: In all, 72 948 patients were included among which 62.5% were men. At inclusion, 615 patients were HBV+ and 1026 HCV+. The prevalence of HBV and HCV infections were 0.84% (95% PI: 0.78-0.91) and 1.41% (95% PI: 1.32-1.49), respectively. The prevalence of HBV infection by age group increased progressively until a maximum rate at 1.80% (95% PI: 1.46-2.20) in the 4th decade, then regularly decreased. Same profile was observed for HCV prevalence, with a maximum rate at 3.14% (95% PI: 2.68-3.65) in the 4th decade. During the follow-up, we identified new HBV or HCV infections in 117 and 81 patients, respectively, with an overall incidence of 0.076% (95% PI: 0.062-0.090) and 0.053% (95%PI: 0.041-0.065) between 2005 and 2013, respectively. During the first dialysis year, HBV incidence was 0.35% (95% PI: 0.28-0.43) and that of HCV 0.21% (95% PI: 0.16-0.28). CONCLUSION: Our data highlight the need for HCV therapy for more than 1000 end-stage renal disease patients in France, sustained systematic immunization campaigns (HBV) and underlines the persistence of HBV/HCV new hand-borne nosocomial cases.

Peripheral Neuropathy in Spinocerebellar Ataxia Type 1, 2, 3, and 6.

Spinocerebellar ataxias (SCAs) are characterized by autosomal dominantly inherited progressive ataxia but are clinically heterogeneous due to variable involvement of non-cerebellar parts of the nervous system. Non-cerebellar symptoms contribute significantly to the burden of SCAs, may guide the clinician to the underlying genetic subtype, and might be useful markers to monitor disease. Peripheral neuropathy is frequently observed in SCA, but subtype-specific features and subclinical manifestations have rarely been evaluated. We performed a multicenter nerve conduction study with 162 patients with genetically confirmed SCA1, SCA2, SCA3, and SCA6. The study proved peripheral nerves to be involved in the neurodegenerative process in 82 % of SCA1, 63 % of SCA2, 55 % of SCA3, and 22 % of SCA6 patients. Most patients of all subtypes revealed affection of both sensory and motor fibers. Neuropathy was most frequently of mixed type with axonal and demyelinating characteristics in all SCA subtypes. However, nerve conduction velocities of SCA1 patients were slower compared to other genotypes. SCA6 patients revealed less axonal damage than patients with other subtypes. No influence of CAG repeat length or biometric determinants on peripheral neuropathy could be identified in SCA1, SCA3, and SCA6. In SCA2, earlier onset and more severe ataxia were associated with peripheral neuropathy. We proved peripheral neuropathy to be a frequent site of the neurodegenerative process in all common SCA subtypes. Since damage to peripheral nerves is readily assessable by electrophysiological means, nerve conduction studies should be performed in a longitudinal approach to assess these parameters as potential progression markers.

Isonatric Dialysis Biofeedback in Hemodiafiltration with Online Regeneration of Ultrafiltrate in Hypertensive Hemodialysis Patients: A Randomized Controlled Study.

UNLABELLED: Dialysis biofeedback in hemodiafiltration with online regeneration of ultrafiltrate (HFR) could help to improve arterial hypertension. We evaluated the impact of isonatric HFR (HFR-iso) on hypertension control compared to conventional HFR. Forty-seven hemodialysis patients were included and randomized (ratio 2/1) HFR-iso versus HFR during 24 dialysis sessions. In the HFR-iso group (32 patients, 768 dialysis sessions), the predialytic systolic blood pressure (BP) decreased from S1 to S24 of 9 ± 20 mm Hg and increased of 5 ± 24 mm Hg in the HFR group (15 patients, 360 dialysis sessions), variation that differed between the 2 groups (x0394;S1-S24, p = 0.035; interaction group*time, p = 0.012). The diastolic BP (HFR-iso -3 ± 14 mm Hg vs. HFR 5 ± 13 mm Hg; p = 0.088), the DDD of antihypertensive treatment and the dry weight did not vary significantly during the study. Number of sessions complicated by symptomatic hypotension was similar in the 2 groups. HFR-iso improved BP control without increasing dialysis hypotension episodes. SHORT SUMMARY: In this multicenter, open-label, controlled, randomized study, we evaluated the impact of dialysis biofeedback in HFR on arterial hypertension compared to conventional HFR. We observed that HFR-iso improved arterial BP control without increasing dialysis hypotension episodes.