Analysis of clinical and methodological characteristics of early COVID-19 treatment clinical trials: so much work, so many lost opportunities.

BACKGROUND: The COVID-19 pandemic continues to rage on, and clinical research has been promoted worldwide. We aimed to assess the clinical and methodological characteristics of treatment clinical trials that have been set forth as an early response to the COVID-19 pandemic. METHODS: First, we reviewed all registered clinical trials on COVID-19. The World Health Organization International Trials Registry Platform and national trial registries were searched for COVID-19 trials through April 19th, 2020. For each record, independent researchers extracted interventions, participants, and methodological characteristics. Second, on September 14th, 2020 we evaluated the recruitment status and availability of the results of COVID-19 treatment trials previously identified. RESULTS: In April 2020, a total of 580 trials evaluating COVID-19 treatment were registered. Reporting quality was poor (core participant information was missing in 24.1 to 92.7%). Between 54.0 and 93.8% of the trials did not plan to include older people or those with a higher baseline risk. Most studies were randomised (67.9%), single-centre (58.3%), non-industry-funded (81.1%), to be conducted in China (47.6%), with a median duration of 184 days and a median sample size of 100 participants. Core endpoints (mortality, clinical status, and hospitalization length) were planned to be assessed in 5.2 to 13.1% of the trials. Five months later, 66 trials (11.4%) were reported as "Completed", and only 46 (7.9%) had public results available. One hundred forty-four of 580 trials (24.8%) either had the status "Not yet recruiting" or "Suspended", and 18 (3.1%) trials were prematurely stopped ("Terminated" or "Withdrawn") The number of completed trials and trials with results are much lower than anticipated, considering the planned follow-up. CONCLUSIONS: Our results raise concerns about the success of the initial global research effort on COVID-19 treatment. The clinical and methodological characteristics of early COVID-19 treatment trials limit their capability to produce clear answers to critical questions in the shortest possible time.

A systematic review of the characteristics and validity of monitoring technologies to assess Parkinson's disease.

BACKGROUND: There is growing interest in having objective assessment of health-related outcomes using technology-based devices that provide unbiased measurements which can be used in clinical practice and scientific research. Many studies have investigated the clinical manifestations of Parkinson's disease using such devices. However, clinimetric properties and clinical validation vary among the different devices. METHODS: Given such heterogeneity, we sought to perform a systematic review in order to (i) list, (ii) compare and (iii) classify technological-based devices used to measure motor function in individuals with Parkinson's disease into three groups, namely wearable, non-wearable and hybrid devices. A systematic literature search of the PubMed database resulted in the inclusion of 168 studies. These studies were grouped based on the type of device used. For each device we reviewed availability, use, reliability, validity, and sensitivity to change. The devices were then classified as (i) 'recommended', (ii) 'suggested' or (iii) 'listed' based on the following criteria: (1) used in the assessment of Parkinson's disease (yes/no), (2) used in published studies by people other than the developers (yes/no), and (3) successful clinimetric testing (yes/no). RESULTS: Seventy-three devices were identified, 22 were wearable, 38 were non-wearable, and 13 were hybrid devices. In accordance with our classification method, 9 devices were 'recommended', 34 devices were 'suggested', and 30 devices were classified as 'listed'. Within the wearable devices group, the Mobility Lab sensors from Ambulatory Parkinson's Disease Monitoring (APDM), Physilog®, StepWatch 3, TriTrac RT3 Triaxial accelerometer, McRoberts DynaPort, and Axivity (AX3) were classified as 'recommended'. Within the non-wearable devices group, the Nintendo Wii Balance Board and GAITRite® gait analysis system were classified as 'recommended'. Within the hybrid devices group only the Kinesia® system was classified as 'recommended'.

Substantia nigra neuromelanin-MR imaging differentiates essential tremor from Parkinson's disease.

BACKGROUND: Essential tremor (ET) is a very common movement disorder that has no diagnostic markers. Differentiation with Parkinson's disease (PD) can be clinically challenging in some cases, with a high rate of misdiagnosis. Magnetic resonance imaging (MRI) studies have been able to identify neuromelanin changes in the substantia nigra (SN) of PD patients, but they have thus far not been investigated in ET. In this study, we aimed to characterize neuromelanin-MR signal changes in ET and evaluate its diagnostic accuracy in the differential diagnosis with PD. METHODS: The inclusion criteria were patients with ET and untreated "de novo" PD patients; in addition, age-matched controls were enrolled. These were studied with a high-resolution T1-weighted MRI sequence at 3.0 Tesla to visualize neuromelanin. The primary outcomes were the area and width of the SN region with high signal. RESULTS: A total of 15 ET patients and 12 "de novo" PD patients were evaluated. The area and width of the T1 high signal in the SN region were markedly decreased in the PD group compared with the ET and age-matched controls, and a greater decrease was seen in the ventrolateral segment. The neuromelanin measures in the ET group, although slightly lower, were not significantly different from the healthy control group. We obtained a sensitivity of 66.7% and a specificity of 93.3% in discriminating ET from early-stage PD. CONCLUSIONS: Neuromelanin-sensitive MRI techniques can discriminate ET from early-stage tremor-dominant PD and can be a useful clinical tool in the evaluation of tremor disorders. © 2015 International Parkinson and Movement Disorder Society.

Quantitative home-based assessment of Parkinson's symptoms: the SENSE-PARK feasibility and usability study.

BACKGROUND: Currently, assessment of symptoms associated with Parkinson's disease is mainly performed in the clinic. However, these assessments have limitations because they provide only a snapshot of the condition. METHODS: The feasibility and usability of an objective, continuous and relatively unobtrusive system (SENSE-PARK System), which consists of wearable sensors (three worn during the day and one worn at night), a smartphone-based App, a balance board and computer software, was tested 24/7 over 12 weeks in a study including 22 PD patients. During the first four weeks of the study, patients did not get feedback about their performance, during the last eight weeks they did. The study included seven clinical visits with standardized interviews, and regular phone contact. The primary outcome was the number of drop-outs during the study. As secondary outcomes, the Post-Study System Usability Questionnaire (PSSUQ), score and information obtained from the standardized interviews were used to evaluate the usability of the system. RESULTS: All patients completed the study. The participants rated the usability of the SENSE-PARK System with a mean score of 2.67 (±0.49) on the PSSUQ. The interviews revealed that most participants liked using the system and appreciated that it signaled changes in their health condition. CONCLUSIONS: This 12 week controlled study demonstrates that the acceptance level of PD patients using the SENSE-PARK System as a home-based 24/7 assessment is very good. Particular emphasis should be given to a user-friendly design. Motivation to wear such a system can be increased by providing direct feedback about the individual health condition.

Risk of renal failure with the non-vitamin K antagonist oral anticoagulants: systematic review and meta-analysis.

PURPOSE: Vitamin K antagonists (VKA)-related nephropathy is a novel entity characterized by acute kidney injury related to International Normalized Ratio supratherapeutic levels. Non-vitamin K antagonists oral anticoagulants (NOACs) have a predictable dose-response relationship and an improved safety profile. We hypothesized that these drugs do not have an increased risk of incident renal failure, which may be detrimental for the use of NOACs. METHODS: Systematic review and meta-analysis of phase III randomized controlled trials (RCTs). Trials were searched through Medline, Cochrane Library and public assessment reports in August 2014. Primary outcome was renal failure. NOACs were evaluated against any comparator. Random-effects meta-analysis was performed by default, and pooled estimates were expressed as Risk Ratio (RR) and 95%CI. Heterogeneity was evaluated with I(2) test. RESULTS: Ten RCTs fulfilled inclusion criteria (one apixaban RCT, three dabigatran RCTs, and six rivaroxaban RCTs), enrolling 75 100 patients. Overall NOACs did not increase the risk of renal failure with an RR 0.96, 95%CI 0.88-1.05 compared with VKA or Low-molecular weight heparin (LMWH), without significant statistical heterogeneity (I(2) = 3.5%). Compared with VKA, NOACs did not increase the risk of renal failure (RR 0.96, 95%CI 0.87-1.07; I(2) = 17.8%; six RCTs). Rivaroxaban did not show differences in the incidence of renal failure compared with LMWH (RR 1.20, 95%CI 0.37-3.94; four trials), but there was an increased risk of creatinine elevation RR 1.25, 95%CI 1.08-1.45; I(2) = 0%. CONCLUSIONS: NOACs had a similar risk of renal failure compared with VKA/LMWH in phase III RCTs. Post-marketing surveillance should be warranted.

Potential drug-drug interactions in acute poisonings managed in the intensive care unit: Occurrence, risk factors and relationship to patient severity on admission.

Beyond the direct toxicity resulting from each drug in the poisoned patient, additional toxicities may result from drug-drug interactions (DDIs). We aimed to determine the frequency of potential DDIs in the poisoned patient and investigate whether DDIs are associated with severity. We conducted a 1-year cohort study in a toxicological ICU. DDIs were identified using an electronic interaction-checker tool. Among our 354 ICU poisoned patients, 134 (38%) presented at least one potential DDI between acute poisoning drugs and 180 (51%) at least one potential DDI between acute poisoning and long-term treatment drugs. Using multivariate analyses, previous suicide attempt was associated with the presence of potential DDIs between acute poisoning drugs in suicide attempt patients (P = 0.014). Chronic alcoholism (P = 0.005) and tobacco smoking (P = 0.022) were associated with the presence of potential DDIs between acute poisoning and long-term treatment drugs in recreational drug users. Presence of potential DDIs between acute poisoning and long-term treatment drugs was associated with catecholamine infusion (P = 0.022) in suicidal self-exposure patients. Presence of potential pharmacodynamic DDIs between acute poisoning and long-term treatment drugs was associated with aspiration pneumonia onset in recreational drug users (P = 0.03). ICU poisoned patients present a high rate of potential DDIs that may influence the outcome.

COVID-19 fatality rates in hospitalized patients: systematic review and meta-analysis.

BACKGROUND: Coronavirus disease (COVID-19) is an infectious disease caused by a newly discovered coronavirus. Although general and local public health report deathly cases, case fatality rates are still largely unknown. Thus, we sought to evaluate the mortality of COVID-19. METHODS: We searched PubMed and EMBASE databases for articles evaluating the clinical characteristics of COVID-19 patients that included clinical outcomes, between December 2020 and 24 April 2020. Two authors performed an independent selection using predefined terms of search. RESULTS: We retrieved 33 studies with a total of 13,398 patients with COVID-19 diagnosis. The mortality rate of the COVID-19 patients was 17.1% (95% CI 12.7; 22.7, I2 = 96.9%). For general patients admitted to the hospital (excluding critical care-only studies) the mortality rate of the COVID-19 was 11.5% (95% CI 7.7; 16.9, I2 = 96.7%). Among critical illness studies (n = 7) we found a 40.5% mortality (95% CI 31.2; 50.6, I2 = 91.8%). CONCLUSION: High COVID-19 mortality among general admitted patients and critical care cases should guide resources allocations and economic burden calculations during the pandemics.

Cross-cultural adaptation and validation of the Swallowing Disturbance Questionnaire and the Sialorrhea Clinical Scale in Portuguese patients with Parkinson's disease.

INTRODUCTION: To date, no valid outcome measure has been developed in European Portuguese (EP) to evaluate the Parkinsons' Disease (PD) patients' (PwP) reports regarding their swallowing disturbances. OBJECTIVES: The aim of this study was to translate and cross-culturally adapt the Swallowing Disturbance Questionnaire (SDQ) and the Sialorrhea Clinical Scale for PD (SCS-PD) into EP and to determine its clinimetric properties in PwP. MATERIALS AND METHODS: The original English SDQ and SCS-PD versions were cross-culturally adapted following recommendations established in international guidelines. The validation process involved 75 PwP and 65 healthy sex- and age-matched participants. RESULTS: The EP versions of the SDQ and SCS-PD are equivalent to the original versions (content, depth, and scoring). Statistical analyses for the SDQ tool revealed good feasibility (missing data <5%), acceptability (no floor or ceiling effects), excellent internal consistency (Cronbach´s α = 0.95), good construct validity (78.5% revealed large to moderate loadings), moderate convergent validity (r = 0.60), good divergent validity (r = 0.40), good known-groups validity (p-value < .05) and a fair sensitivity and specificity (AUC = 0.700). Statistical analyses for the SCS-PD tool shows good feasibility, reasonable acceptability (floor effect), good internal consistency (Cronbach´s α = 0.85), good construct validity (85.7% showed between large to moderate loadings), good convergent validity (r = 0.78), good divergent validity (r = 0.39), good known groups validity (p-value < .05) and a fair sensitivity and specificity (AUC = 0.704). CONCLUSIONS: The EP versions of the SDQ and SCS-PD maintained the characteristics of the original versions and therefore consistent tools to be used in PwP.

Analysis of malaria associated genetic traits in Cabo Verde, a melting pot of European and sub Saharan settlers.

Malaria has occurred in the Cabo Verde archipelago with epidemic characteristics since its colonization. Nowadays, it occurs in Santiago Island alone and though prophylaxis is not recommended by the World Health Organization, studies have highlight the prospect of malaria becoming a serious public health problem as a result of the presence of antimalarial drug resistance associated with mutations in the parasite populations and underscore the need for tighter surveillance. Despite the presumptive weak immune status of the population, severe symptoms of malaria are not observed and many people present a subclinical course of the disease. No data on the prevalence of sickle-cell trait and red cell glucose-6-phosphate dehydrogenase deficiency (two classical genetic factors associated with resistance to severe malaria) were available for the Cabo Verde archipelago and, therefore, we studied the low morbidity from malaria in relation to the particular genetic characteristics of the human host population. We also included the analysis of the pyruvate kinase deficiency associated gene, reported as putatively associated with resistance to the disease. Allelic frequencies of the polymorphisms examined are closer to European than to African populations and no malaria selection signatures were found. No association was found between the analyzed human factors and infection but one result is of high interest: a linkage disequilibrium test revealed an association of distant loci in the PKLR gene and adjacent regions, only in non-infected individuals. This could mean a more conserved gene region selected in association to protection against the infection and/or the disease.

Should the Energy Contribution of Commercial Thickeners Be Considered in the Nutrition Plan of Patients With Dysphagia?

BACKGROUND: Clinical management options for dysphagia include the use of thickeners to increase the consistency of liquids. Health professionals may not be aware of the nutrition value of these products, since there are no such recommendation in clinical guidelines. Our aim was to estimate the added nutrition value of the 2 types of commercial thickeners (starch and xanthan gum) to daily nutrition intake and compare their nutrition value for nectar, honey, and pudding consistencies. Additionally, we compared the nutrition value of both thickeners with a high-energy powder, since they share the same main ingredients. METHODS: We collected recommended dosages for obtaining the 3 different consistencies and nutrition content from the technical food labels. Daily intake of fluids was estimated from the Portuguese National Food, Nutrition and Physical Activity Survey. Total daily amount of thickener needed was estimated, as well as their correspondent nutrition contributions. RESULTS: Estimated daily fluid intake was 2439 mL. Starch thickeners provide significantly more energy at all consistencies than xanthan gum provides (423-846 kcal, P < 0.05, and 103-308 kcal, P < 0.05, respectively). Significantly more fiber is provided by xanthan gum thickeners (9 g in nectar and 27 g in pudding consistencies, P < 0.05). Median energy and carbohydrate values per 100 g of high-energy powder modules and starch thickeners are similar. CONCLUSION: The nutrition value of thickeners should be routinely considered in the nutrition assessment and planning of patients with dysphagia for liquids, since they contribute significantly with energy, carbohydrate, and fiber.

Outcome Measures for Evaluating the Effect of a Multidisciplinary Intervention on Axial Symptoms of Parkinson's Disease.

Introduction: The satisfactory symptomatic control of the axial symptoms of Parkinson's disease (PD) remains challenging. As these symptoms are an important cause of disability, new therapeutic strategies should be developed and evaluated. To do this, it is necessary to select the outcomes to be measured and reported in a clinical trial. In this study, we sought to identify the most responsive outcome measures for assessing the efficacy of a multidisciplinary intervention on the axial symptoms of PD. Methods: An exploratory prospective clinical study was conducted. PD patients engaged in a pre-defined multidisciplinary intervention program for parkinsonian patients were assessed at admission and discharge by a multidisciplinary team. The responsiveness to intervention was evaluated and the smallest sample size needed to enable statistically significant results for an expected 30% change from baseline for each outcome was calculated. Results: Twenty-two patients were included in the study. The effect size detected varied between 0.04 and 0.83. The Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) total score and each subsection, the N-FOG questionnaire, the 10-m walk test, and Frenchay Dysarthria Assessment-2 Edition (FDA-2) showed a medium to large effect size. Sample size calculations for 90% power and assuming 30% change from baseline ranged from eight to 180 participants. The outcome measures that require a small number of participants to enable statistically significant results were the FDA-2 rating scale (n = 4 participants), the MDS-UPDRS total score (n = 9), the 10-m walk test (n = 9), and the MDS-UPDRS motor examination (n = 10). Conclusions: The MDS-UPDRS part III and total score and the 10-m walk test were the outcomes with the best responsiveness to a multidisciplinary intervention and required a small number of participants to enable statistically significant results. Further studies are needed to clarify the suitability of the Timed Up and Go test.

Neuromelanin Magnetic Resonance Imaging of the Substantia Nigra in Huntington's Disease.

BACKGROUND: Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder inducing motor, psychiatric changes and cognitive decline, characterized pathologically by striatal atrophy. Pathological changes in the extra-striatal structures, such as the substantia nigra (SN), and abnormalities in pre-synaptic striatal dopamine neurotransmission are also known to occur. Neuromelanin (NM)-sensitive magnetic resonance imaging (NM-MRI) is an innovative technique that was recently developed allowing the in vivo study of pathological changes in the dopaminergic neurons of the SN. OBJECTIVE: To investigate the SN MR signal in HD patients. METHODS: We performed a cross-sectional study using a specific T1-weighted MR sequence to visualize NM. The areas and signal intensity contrast ratios of the T1 hyperintense SN regions were obtained using a semi-automatic segmentation method. RESULTS: A total of 8 HD patients and 12 healthy subjects were evaluated. The SN area was markedly reduced in the HD group compared with the control group (p = 0.02), even after normalization of the SN area with the midbrain area and age correction (p = 0.01). There was a significant reduction in the intensity contrast ratio of the hyperintense SN areas to crus cerebri in HD patients comparing with controls (p = 0.04) after correction for age. CONCLUSIONS: NM-sensitive MR techniques were used for the first time to study the SN in HD patients, showing loss of NM in this region, supporting the implication of dopaminergic neuronal changes in disease pathology. Future research needs to be conducted to evaluate the potential of SN area and intensity contrast as biomarkers for HD.

Circulating Inflammatory miRNAs Associated with Parkinson's Disease Pathophysiology.

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, being largely characterized by motor features. MicroRNAs (miRNAs) are small non-coding RNAs, whose deregulation has been associated with neurodegeneration in PD. In this study, miRNAs targeting cell death and/or inflammation pathways were selected and their expression compared in the serum of PD patients and healthy controls. We used two independent cohorts (discovery and validation) of 20 idiopathic PD patients (iPD) and 20 healthy controls each. We also analyzed an additional group of 45 patients with a mutation in the leucine-rich repeat kinase 2 (LRRK2) gene (LRRK2-PD). miRNA expression was determined using Taqman qRT-PCR and their performance to discriminate between groups was assessed by receiver operating characteristic (ROC) curve analysis. We found miR-146a, miR-335-3p, and miR-335-5p downregulated in iPD and LRRK2-PD patients versus controls in both cohorts. In addition, miR-155 was upregulated in LRRK2-PD compared to iPD patients showing an appropriate value of area under the ROC curve (AUC 0.80) to discriminate between the two groups. In conclusion, our study identified a panel of inflammatory related miRNAs differentially expressed between PD patients and healthy controls that highlight key pathophysiological processes and may contribute to improve disease diagnosis.

Patients and Health Professional's Perspective of Functional Mobility in Parkinson's Disease.

Background: Functional mobility (FM) is the person's ability to move to accomplish daily living tasks and activities. FM limitations are common in Parkinson's disease, increase with disease progression, and can be highly disabling. Although several studies in Parkinson's disease (PD) field use this concept, only recently, a formal definition has been proposed. Objective: We aimed to explore patient's and health professional's perspectives of FM in PD. Methods: A focus group methodology has been used. Four focus groups, with a total of 10 patients and 10 health professionals, were performed. Six patients were early stage and four advanced stage. The health professional's group was composed of five neurologists and five physiotherapists. The suitability of the new concept, the impact of FM limitations in PD patient's daily routine, and the potential benefit of walking aids have been discussed. Results: All participants were able to provide a spontaneous definition of FM, matching with the proposed concept. All agreed that PD affects patient's FM, increasing the limitations with disease progression, and with the existence of a serious prejudice with walking aids that hinders its use. Early-stage patient's perspective seems to be more in line with neurologist's perspective, while the views of advanced-stage patients were closer to physiotherapist's views. Conclusion: FM concept was considered as intuitive and useful. FM limitations have an important physical and social impact in the advanced stage of the disease. Although patients and health professionals acknowledge walking aid's benefit improving patient's FM, the prejudice associated with this type of tools limits its recommendation and use.

Psychosocial impact of Parkinson's disease-associated dysarthria: Cross-cultural adaptation and validation of the Dysarthria Impact Profile into European Portuguese.

AIM: The present study sought to make a cross-cultural adaptation of the Dysarthria Impact Profile (DIP) for European Portuguese (EP) and validate it for use in Parkinson's disease (PD) patients. METHODS: The cross-cultural adaptation was carried out in accordance with the guidelines. The EP version of the DIP was administered to 80 people with PD, and 30 sex- and age-matched control participants. Psychometric properties, acceptability, feasibility reliability (internal consistency and intrarater agreement) and validity (construct, convergent and known-groups validity) were assessed using other assessment tools (motor disability and impairment, and voice impact). RESULTS: Overall, the EP-DIP final version has the same conceptual meaning, semantics, idiomatic and score equivalences as the original version. Statistical analyses showed adequate feasibility (missing data <5%), good acceptability (ceiling or floor effects <15%; high requests of assistance to complete the questionnaire), satisfactory internal consistency (Cronbach's α = 0.9), weak-to-moderate intrarater reliability, good construct validity, strong convergent validity (with the Voice Handicap Index; Spearman's P = -0.8) and good known-groups validity (between those with PD and control participants). CONCLUSIONS: The EP-DIP version displays the salient features of a valid patient-based assessment tool used to measure the psychosocial impact of slight-to-mild dysarthria in people with PD. Geriatr Gerontol Int 2018; 18: 767-774.

Cardiac Harms of Sofosbuvir: Systematic Review and Meta-Analysis.

INTRODUCTION: Sofosbuvir is a new direct-acting pyrimidine nucleotide analogue antiviral drug that has shown remarkable efficacy in the treatment of hepatitis C in clinical trials. However, observational anecdotal data have recently suggested an increased risk of serious bradycardia among patients treated with sofosbuvir and amiodarone. OBJECTIVE: We aimed to estimate and characterize the cardiac safety of sofosbuvir by performing a systematic review of randomized controlled trials (RCTs). METHODS: We conducted a systematic review of RCTs (PROSPERO 2016: CRD42016033109) comparing sofosbuvir and non-sofosbuvir regimens in patients with chronic hepatitis C by searching the MEDLINE, Embase, and Cochrane Library databases up to January 2017. Non-published data were obtained from the sofosbuvir marketing authorization holder. Random-effects meta-analysis was performed to derive pooled estimates of relative risks (RRs) and corresponding 95% confidence intervals (CIs). RESULTS: Six trials, enrolling 2346 patients (1625 treated with sofosbuvir), were included. The overall risk of bias across studies was moderate. The risk of reported cardiac events (RR 0.87; 95% CI 0.41-1.85), arrhythmias (RR 0.93; 95% CI 0.34-2.51), bradycardia (RR 0.47; 95% CI 0.04-5.20), and tachycardia (RR 0.91; 95% CI 0.20-4.20) were not significantly different between sofosbuvir and non-sofosbuvir regimens. The risks of reported syncope, presyncope, loss of consciousness, or palpitations were similar among those receiving sofosbuvir regimens and controls. CONCLUSIONS: The pooled data from RCTs did not show an increased risk of cardiac outcomes, including arrhythmias (and bradycardia), among sofosbuvir-treated patients, although the overall quality of the evidence supporting this conclusion was very low. Registration: PROSPERO 2016:CRD42016033109 at http://www.crd.york.ac.uk/PROSPERO/ .

Survival, Mortality, Causes and Places of Death in a European Huntington's Disease Prospective Cohort.

BACKGROUND: Huntington's disease (HD) is a rare and fatal inherited genetic disorder characterized by progressive motor, cognitive, and behavioral impairment. It leads to premature death, but data regarding advanced-stage disease are scarce. We sought to determine HD-associated survival, mortality, and causes and places of death. METHODS: Data from the European HD Network prospective study (REGISTRY) collected from 2001 through 2013 were used, including the Unified Huntington's Disease Rating Scale and death report forms. Group comparisons were performed using the t test or the χ2 test. Survival analyses were computed through Kaplan-Meier estimates of median survival. All tests were 2-sided with a significance level of P = 0.05. RESULTS: In total, 5164 participants were analyzed. The mean age at diagnosis was 49 years, and the mean age at death was 58 years. At the end of the study period, there were 533 deaths (10.3% of patients). Median survival was 24 years from diagnosis and 35 years from symptom onset. The most frequent causes of death were pneumonia (19.5%), other infections (6.9%), and suicide (6.6%). The most frequent places of death were the hospital (29.8%), the home (23.9%), and nursing houses (19.8%). CONCLUSIONS: Patients with HD tend to die from the same conditions as patients with other neurodegenerative diseases. However, compared with nonhereditary Parkinson's disease and Alzheimer's disease, the median time from onset to death is longer, and the places of death are distinctive.