F: Clinical studies: case reports, oberservational studies and trials最新文献

{"title":"F08 Huntington’s disease burden of illness (HDBOI): study methodology, sample representativeness and fieldwork risk mitigation strategy during the COVID-19 pandemic","authors":"Idaira Rodríguez, S. Frank, A. Fisher, R. Fuller, J. Hamilton, H. Hubberstey, C. Stanley, M. Winkelmann, L. Ruiz, R. Willock, A. Finnegan, R. Dolmetsch, Nanxin Li, S. Ratsch, T. Ali","doi":"10.1136/jnnp-2021-EHDN.51","DOIUrl":"https://doi.org/10.1136/jnnp-2021-EHDN.51","url":null,"abstract":"Background The prevalence of Huntington’s Disease (HD) has increased over time, augmenting the associated economic and humanistic burden. The HDBOI study aims to provide an up-to-date assessment of the burden of HD from a multinational perspective. Methods The HDBOI is a retrospective, cross-sectional dataset that captures demographic, clinical, and health resource utilization (HRU) of a cohort of HD patients, reported by treating physicians in multiple centres across the USA, Germany, Spain, Italy, France and the UK. Patients and caregivers reported information on health-related quality of life (HRQoL), non-medical and indirect costs associated with HD through optional questionnaires. The study has been governed by an Expert Review Group (ERG) that provided recommendations on the study design. Data was collected between September 2020 and May 2021. Patients and caregivers reported their HRQoL at the time of questionnaire completion, whereas physicians reported patient’s HRU for the 12-month period between March 2019 and March 2020, to avoid months with limited access to healthcare due to COVID-19. Other strategies were taken to mitigate the effect of COVID-19 on the fieldwork process: online questionnaires, extending the time in fieldwork, questions monitoring the effect of the pandemic on patients HRQoL and HRU. Results The HDBOI sample has 2,094 HD patients, of which 40% were early stage, 34% mid stage and 26% advanced stage, as assessed by the treating physician. Patient representation across countries was similar. For a subsample (N=718) the Shoulson and Fahn stages were determined by the treating physician: stage I (14.6%), II (24.4%), III (31.6%), IV (28.1%) and V (1.1%). The last figure was expected by the ERG, as advanced stage patients usually live in care homes and do not attend regular consultations. Conclusion The HDBOI study is a representative sample of the HD population across disease stages and studied countries, as confirmed by the ERG.","PeriodicalId":277670,"journal":{"name":"F: Clinical studies: case reports, oberservational studies and trials","volume":"4 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128340158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"F26 Identical twins .. Are they identical?","authors":"J. Hoblyn, Muthukumaran Thangaramanujam, C. Kenny, Melanie Ryberg, K. O'Driscoll","doi":"10.1136/jnnp-2021-ehdn.69","DOIUrl":"https://doi.org/10.1136/jnnp-2021-ehdn.69","url":null,"abstract":"Background Reports of monozygotic HD twins are rare (Panas et al, 2008) and phenotypic concordance reported as the rule (Sudarsky et al, 1973). Reports are of twins with the same number of trinucleotide repeats, with different clinical behavioral difficulties but not significant motor differences (Gomed-Esteban et al, 2007). Such phenotypic discordance was reported as very rare (Friedman et al, 2005) and thus be used to explore environmental factors (Ketelaar, Hofstra and Hayden, 2012). Case History Two female monozygotic twins with HD were born 6 weeks premature and raised in the same environment. Voluntary predictive testing for HD was done when both (Heimler and Zanko, 1995) were aged 21 years. We will report on motor, neuropsychological and psychiatric manifestations along with MRI findings. Twin 2 required admission in 2015 while Twin 1 required admission in 2020. Twin 1 (first born): Referred to Liaison Psychiatry with Eating disorder and low mood aged 23, followed by two suicide attempts and aggressive impulsive behavior. Neurocognitive difficulties included memory impairment, dysarthria and balance difficulties, poor levels of motivation and self-care. OT assessment found a sensory level of activities and exploratory activities were required. MRI: Generalised and bifrontal cerebral atrophy appeared was unusual given the patient‘s age. There was no acute area of infarction on diffusion weighted imaging. Generalised cerebral and bifrontal cerebral atrophy noted. Twin 2: Diagnosed with a heart murmur aged 4 years and surgery aged 10 years. Presented at 18 years with low mood and history of OCD symptoms. Multiple episodes of self-harm and becoming more aggressive and violent. Irritability, impulsivity, and aggressive behavior has continued with word funding difficulties. OT assessment recommended exploratory level of activities. MRI: There was parenchymal atrophy reported, most marked in the frontal and temporal lobes with prominence of sulci and ventricles. Signal return from grey-white matter was normal. Conclusion A detailed comparison of motor, cognitive, and behavioural profile is currently in progress.","PeriodicalId":277670,"journal":{"name":"F: Clinical studies: case reports, oberservational studies and trials","volume":"39 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123361465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"F18 The ethics of exploring social cognition in hd using ethnography during a pandemic","authors":"A. Fisher, Anna Lavis, H. Rickards, S. Greenfield","doi":"10.1136/jnnp-2021-EHDN.61","DOIUrl":"https://doi.org/10.1136/jnnp-2021-EHDN.61","url":null,"abstract":"Aim Using ethnography to study social cognition through social functioning in HD will begin to address the empirical gap in our knowledge of everyday life with HD from the perspective of both people with HD and their companions. As ethnography moves into the messiness of real life in that the researcher is an observer of the participants in their own space and this now needs to include Covid safe strategies (i.e. online observation) risks to all parties may be seen as greater due to the nature of HD alongside exploring the intimacies of interaction remotely. Primacy needs to be given to the principle of ‘do no harm’. Method Whilst our fears often do not come to fruition, researchers using this methodology with people with HD and their companions need to consider: Involving a patient participant group Building trust and rapport amongst the community through the life of the project and beyond Family dynamics Tensions which may have been worsened by the pandemic A distress strategy Adjusting the way we as researchers do things and not the other way round Giving more structure, planning and prompting to optimise HD engagement Fluid revisiting of consent Access to technology The limitations of technology in this population Outcome Thoughtful preparation although time consuming may enable equitable access to all interested participants but also reduce risks. As Markham notes methods = ethics.","PeriodicalId":277670,"journal":{"name":"F: Clinical studies: case reports, oberservational studies and trials","volume":"112 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115801198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"F14 Collaborating with the community to conduct clinical trials in huntington’s disease: lessons from the tominersen phase iii generation HD1 study","authors":"Victoria Liddy, David West, Maileah Nguyen, L. Boak, S. Schobel, Nolwen Olivier, Keir Hodge, J. Townhill","doi":"10.1136/jnnp-2021-EHDN.57","DOIUrl":"https://doi.org/10.1136/jnnp-2021-EHDN.57","url":null,"abstract":"BackgroundGENERATION HD1 (NCT03761849) is an ongoing Phase III study of tominersen, developed in collaboration with the Huntington’s disease (HD) community. In March 2021, dosing of tominersen in GENERATION HD1 was stopped, although participants continue to be assessed for safety and clinical outcomes.AimsTo describe the role of the HD community in successful site activation and recruitment in GENERATION HD1.MethodsSite start-up times and recruitment rates for GENERATION HD1 were compared with estimates from other trials conducted at the same sites and countries in the last 10 years.ResultsFeedback from the HD-COPE family coalition and global patient representatives were reflected in the study protocol design. The protocol was reviewed and formally endorsed by EHDN, HSG and EHA. Existing research networks and HD clinical expertise were leveraged, with input from Enroll-HD, HDSA, EHDN and HSG, to select study sites.Recruitment from January 2019 to April 2020 led to a total enrolment of 899 people with manifest HD. Average site activation times were faster in all countries than for other Roche studies conducted at the same sites in the last 10 years. The recruitment rate for GENERATION HD1 was nearly 2 times faster than the median rate for other non-Roche HD trials with >250 participants recruited, and was nearly 4 times faster than the median rate for other Roche trials in rare diseases conducted over the past 10 years.Additionally, collaboration with the HD community and knowledge sharing of mitigation measures were critical to mitigate the effects of the COVID-19 pandemic.ConclusionsCollaboration with the HD community resulted in successful and rapid activation and recruitment in GENERATION HD1.Roche would like to thank the patients and families who have participated and who are currently still participating in our research, and the ongoing partnership of the HD community.GENERATION HD1 is sponsored by F. Hoffmann-La Roche Ltd.","PeriodicalId":277670,"journal":{"name":"F: Clinical studies: case reports, oberservational studies and trials","volume":"52 4","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134544448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"F04 Linear mixed model for the age of onset prediction in huntington disease from a peruvian cohort","authors":"Diana Cubas-Montecino, Mario R Cornejo-Olivas, P. Mazzetti, D. Véliz-Otani","doi":"10.1136/jnnp-2021-ehdn.47","DOIUrl":"https://doi.org/10.1136/jnnp-2021-ehdn.47","url":null,"abstract":"Background Based on heritability analyses, unidentified genetic modifiers explain up to 38% of the remaining genetic variance after accounting for the CAG repeat number. We hypothesized that pedigree information can harness unknown genetic modifiers to increase the accuracy of age of onset prediction Aims To assess whether pedigree information can increase the accuracy of age of onset predictive models. Methods We included 139 unrelated subjects and 81 related individuals from 33 families (total n=220) from the HD registry of the Neurogenetics Research Center at the Instituto Nacional de Ciencias Neurologicas, Lima, Peru. We fit a mixed linear model (MLM) of the age of onset with CAG repeat number, age, and sex as covariates. Polygenic additive effects were modeled by a matrix of kinship coefficients. Next, we measure the prediction accuracy by the Variance Explained based on Leve-one-out cross-validation (VEcv). The prediction accuracy was separately measured for test subjects with relatives in the training set and for subjects without relatives in the training set. The training sample size was kept constant for both groups. As a reference, we also fit a linear regression including only unrelated subjects (n=172), and repeated the MLM matching the sample size (81 subjects from 33 families + 91 unrelated subjects). Results The MLM (n=172) for subjects with relatives in the training set had a greater accuracy (VEcv=63%) than subjects without relatives (VEcv=56%). The linear regression of unrelated subjects (n=172) had a lower accuracy (VEcv=53%) than the MLM with matched sample size (n=172, VEcv=63%). Conclusion Including pedigree information in age of onset predictive models increases their accuracy.","PeriodicalId":277670,"journal":{"name":"F: Clinical studies: case reports, oberservational studies and trials","volume":"9 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131520449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"F02 Modelling huntington’s disease progression: interpretation, staging and prognosis","authors":"P. Wijeratne, R. Scahill, S. Tabrizi, Daniel C. Alexander","doi":"10.1136/jnnp-2021-ehdn.45","DOIUrl":"https://doi.org/10.1136/jnnp-2021-ehdn.45","url":null,"abstract":"","PeriodicalId":277670,"journal":{"name":"F: Clinical studies: case reports, oberservational studies and trials","volume":"23 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127058337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"F40 Proof-of-concept study testing SOM3355, a VMAT2 inhibitor for the treatment of chorea in huntington’s disease","authors":"J. Gámez, M. Calopa, E. Muñoz, Aileen Ferré, Óscar Huertas, Kevin J McAllister, N. Reig, C. Scart-Grès, R. Insa, J. Kulisevsky","doi":"10.1136/jnnp-2021-ehdn.83","DOIUrl":"https://doi.org/10.1136/jnnp-2021-ehdn.83","url":null,"abstract":"Background SOM3355 (bevantolol hydrochloride), a β1-adrenoceptor blocker used in hypertension, was identified as a vesicular monoamine transporter type 2 (VMAT2) inhibitor by artificial intelligence screening, and then selected by in vitro functional studies as the best candidate to be repositioned for treatment of dyskinetic movement disorders, such as chorea in Huntington’s disease (HD). Aim A proof-of-concept phase IIa study was performed to assess SOM3355 efficacy and safety in patients with HD presenting chorea. Methods In this double-blind, randomized, crossover, placebo-controlled study, 32 patients were randomly assigned to one of the two arms of 4 sequential 6-week periods to receive placebo and SOM3355 at 100 and 200 mg BID in a crossover design. The primary endpoint was the improvement of at least 2 points in the total maximal chorea (TMC) score of the Unified Huntington’s Disease Rating Scale (UHDRS) in any SOM3355 period compared with the placebo period. Results Almost 60% of the patients had improvements in the TMC score of at least 2 points in any period with SOM3355 compared with placebo, thus reaching the primary endpoint. Even greater TMC score improvements of 3, 4, 5, and 6 points compared with placebo were seen with SOM3355 in 28.6%, 25.0%, 17.9%, and 10.7% of the patients, respectively. The mixed-model analysis comparing the different periods revealed significant improvement in the TMC score with SOM3355 at 200 mg BID compared with placebo (P = 0.0224), as confirmed in Clinical and Patient Global Impression of Change ratings. Mild elevations in plasma prolactin levels were recorded with SOM3355 (P Conclusion This study confirms that SOM3355 reduces chorea in patients with HD and has a good safety profile.","PeriodicalId":277670,"journal":{"name":"F: Clinical studies: case reports, oberservational studies and trials","volume":"21 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124458410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"F12 Research participation: the view of persons at risk and persons with premanifest huntington’s disease","authors":"F. Júlio, Ruth Blanco, Josè Perez Casanova, B. D’Alessio, Beatrice De Schepper, Dina De Sousa, Paul A. De Sousa, Cristina Ferreira, Hans Gommans, R. Haselberg, Émilie Hermant, Danuta Lis, Sabrina Maffi, Svein Olaf Olsen, Marios Papantoniou, F. Squitieri, M. Tretyakova, Zaynab Umakhanova, Vladimír Václavík, M. Winkelmann, A. Arnesen","doi":"10.1136/jnnp-2021-ehdn.55","DOIUrl":"https://doi.org/10.1136/jnnp-2021-ehdn.55","url":null,"abstract":"Background The development of effective therapies for Huntington’s disease (HD) requires an active, informed, and lasting commitment from HD families to research. Specifically, those traditionally less involved in studies should be heard and engaged in this process: persons at risk for HD (HDRisk) and persons with premanifest HD (PreHD). Aim To determine which factors affect the willingness of persons with HDrisk and PreHD to participate in research and check for differences related to HD status. Methods The European Huntington Association (EHA) created an online survey to assess the perceptions and experiences about research participation among persons with HDRisk and PreHD. The two groups were compared on their answers to questions about research experience and knowledge, sources of information about research, the importance of reasons for getting involved and not getting involved in studies, and factors preventing and facilitating study participation. Results/Outcome The survey was filled by 263 persons with HDRisk and 262 persons with PreHD. While the overall motivation of both groups to engage in research was high, respondents with PreHD reported significantly more research experience and better research knowledge than respondents with HDRisk. Respondents with HDRisk identified more barriers to research participation and the need for more support to engage in studies compared to respondents with PreHD. Conclusions Motivation to take part in studies is high, despite limited research experience and literacy. This motivation is strongly influenced by HD status. Our findings highlight the relevance of planning tailored interventions to better support an informed participation of specific HD groups in research.","PeriodicalId":277670,"journal":{"name":"F: Clinical studies: case reports, oberservational studies and trials","volume":"28 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125992383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"F44 Huntington’s disease patients and families facing COVID-19 emergency in Italy","authors":"Marcella Solito, M. Petracca, P. Zinzi, A. Bentivoglio, Maria Rita Lo Monaco","doi":"10.1136/jnnp-2021-EHDN.87","DOIUrl":"https://doi.org/10.1136/jnnp-2021-EHDN.87","url":null,"abstract":"Background The coronavirus disease 2019 (COVID-19) pandemic could be a condition of increased vulnerability for patients and families with Huntington’s disease (HD). Social isolation with loss of the usual support system may worsen the chronic assistance burden and, if protracted, may exhacerbate the risk of distress and mental suffering. Method A telephone structured survey was conducted between April 1st and April 15th 2020 , and we report the survey data on the impact of the COVID-19 pandemic outbreak in eighty consecutive HD patients and their families in Italy during the first wave of the pandemic . Results Out of 80 HD patients, apparently no patient had contact with COVID-19 positive cases, no one directly linked with the virus nor swab confirmed infection, even if flu-like symptomatology was experienced in first trimester 2020, with fever reported by 8,7% and cough/sore throat by 27,3%. Only one performed the swab test with a negative result. Regarding disease management during the pandemic outbreak, five individuals needed urgent neurological care, fourteen suspended physiotherapies, seven individuals reported subjective worsening of neurological symptoms. The three patients living in nursing homes were reported being healthy and safe: isolation measures were promptly adopted by the structures in order to protect residents from external contacts. Compliance with hospital decision to stop activities and openness to the proposal of telemedicine was shown. No worrying signs of crisis or distress related to social restriction rules worsening caregiving burden were evident. Conclusions In general, an excellent attitude to cope with the emergency and social restrictions was observed in HD Italian families during the COVID-19 first pandemic wave, we can imagine that they used previously adopted adaptive solutions to cope with this lockdown.Telemedicine will be implemented in the post pandemic and HD families seems to be ready to benefit.","PeriodicalId":277670,"journal":{"name":"F: Clinical studies: case reports, oberservational studies and trials","volume":"130 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121201821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"F54 ‘Spazio huntington – a place for children’: an Italian observational, multicentre, program to detect pediatric huntington disease cases","authors":"Federica Graziola, A. Capuano, G. Colafati, A. Carboni, Melissa Grasso, Sabrina Maffi, S. Migliore, E. Scaricamazza, A. Morella, A. Luca, Giacomo Garone, R. Carrozzo, B. D’Alessio, F. Squitieri","doi":"10.1136/jnnp-2021-ehdn.97","DOIUrl":"https://doi.org/10.1136/jnnp-2021-ehdn.97","url":null,"abstract":"","PeriodicalId":277670,"journal":{"name":"F: Clinical studies: case reports, oberservational studies and trials","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131097977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}