Using PROMs during routine medical consultations: The perspectives of people with Parkinson’s disease and their health professionals

Background: The use of patient-reported outcomes measures (PROMs), such as quality of life or symptoms like pain or fatigue, is increasingly embraced within patient-centred care and shared decision making. Objectives: To investigate: (a) how patients and health professionals think about using PROMs during routine medical consultations; (b) for which purpose(s), patients and health professionals want to use PROMs during those consultations; and (c) how patients interpret PROMs information presented in various formats. People with Parkinson's disease and their health professionals served as case example. Methods: We performed semi-structured interviews with patients (N = 13) and professionals (N = 7 neurologists; N = 7 physiotherapists). We also used a survey in which patients (N = 115) were shown six figures displaying different information types. Presentation formats of this information varied (line/bar graphs). Interpretation by patients, perceived usefulness of information, attitude towards using information during routine medical consultations and (hypothetical) decisions were assessed. Findings: Patients and professionals were generally positive about using PROMs during medical consultations. Professionals stressed the opportunity to monitor changes in individual PROMs over time. Patients were primarily positive about aggregated PROMs to make treatment decisions. This information was also most often interpreted correctly, especially when presented through a line graph (90.1% correct). Professionals thought patients should take the initiative in discussing PROMs, whereas patients thought professionals should do so. Conclusion/Discussion: When used in routine medical consultations, PROMs seem to have potential to support shared decision making and facilitate patient-professional communication. However, training seems needed for both patients and professionals to facilitate actual discussion and proper interpretation

Detection of atrial fibrillation in primary care with radial pulse palpation, electronic blood pressure measurement and handheld single-lead electrocardiography:a diagnostic accuracy study

OBJECTIVE: To determine the diagnostic accuracy of three tests-radial pulse palpation, an electronic blood pressure monitor and a handheld single-lead ECG device-for opportunistic screening for unknown atrial fibrillation (AF). DESIGN: We performed a diagnostic accuracy study in the intention-to-screen arm of a cluster randomised controlled trial aimed at opportunistic screening for AF in general practice. We performed radial pulse palpation, followed by electronic blood pressure measurement (WatchBP Home A) and handheld ECG (MyDiagnostick) in random order. If one or more index tests were positive, we performed a 12-lead ECG at shortest notice. Similarly, to limit verification bias, a random sample of patients with three negative index tests received this reference test. Additionally, we analysed the dataset using multiple imputation. We present pooled diagnostic parameters. SETTING: 47 general practices participated between September 2015 and August 2018. PARTICIPANTS: In the electronic medical record system of the participating general practices (n=47), we randomly marked 200 patients of ≥65 years without AF. When they visited the practice for any reason, we invited them to participate. Exclusion criteria were terminal illness, inability to give informed consent or visit the practice or having a pacemaker or an implantable cardioverter-defibrillator. OUTCOMES: Diagnostic accuracy of individual tests and test combinations to detect unknown AF. RESULTS: We included 4339 patients; 0.8% showed new AF. Sensitivity and specificity were 62.8% (range 43.1%-69.7%) and 91.8% (91.7%-91.8%) for radial pulse palpation, 70.0% (49.0%-80.6%) and 96.5% (96.3%-96.7%) for electronic blood pressure measurement and 90.1% (60.8%-100%) and 97.9% (97.8%-97.9%) for handheld ECG, respectively. Positive predictive values were 5.8% (5.3%-6.1%), 13.8% (12.2%-14.8%) and 25.2% (24.2%-25.8%), respectively. All negative predictive values were ≥99.7%. CONCLUSION: In detecting AF, electronic blood pressure measurement (WatchBP Home A), but especially handheld ECG (MyDiagnostick) showed better diagnostic accuracy than radial pulse palpation. TRIAL REGISTRATION NUMBER: Netherlands Trial Register No. NL4776 (old NTR4914)

Opportunistic screening versus usual care for detection of atrial fibrillation in primary care:cluster randomised controlled trial

OBJECTIVE: To investigate whether opportunistic screening in primary care increases the detection of atrial fibrillation compared with usual care. DESIGN: Cluster randomised controlled trial. SETTING: 47 intention-to-screen and 49 usual care primary care practices in the Netherlands, not blinded for allocation; the study was carried out from September 2015 to August 2018. PARTICIPANTS: In each practice, a fixed sample of 200 eligible patients, aged 65 or older, with no known history of atrial fibrillation in the electronic medical record system, were randomly selected. In the intention-to-screen group, 9218 patients eligible for screening were included, 55.0% women, mean age 75.2 years. In the usual care group, 9526 patients were eligible for screening, 54.3% women, mean age 75.0 years. INTERVENTIONS: Opportunistic screening (that is, screening in patients visiting their general practice) consisted of three index tests: pulse palpation, electronic blood pressure measurement with an atrial fibrillation algorithm, and electrocardiography (ECG) with a handheld single lead electrocardiographic device. The reference standard was 12 lead ECG, performed in patients with at least one positive index test and in a sample of patients (10%) with three negative tests. If 12 lead ECG showed no atrial fibrillation, patients were invited for more screening by continuous monitoring with a Holter electrocardiograph for two weeks. MAIN OUTCOME MEASURES: Difference in the detection rate of newly diagnosed atrial fibrillation over one year in intention-to-screen versus usual care practices. RESULTS: Follow-up was complete for 8874 patients in the intention-to-screen practices and for 9102 patients in the usual care practices. 144 (1.62%) new diagnoses of atrial fibrillation in the intention-to-screen group versus 139 (1.53%) in the usual care group were found (adjusted odds ratio 1.06 (95% confidence interval 0.84 to 1.35)). Of 9218 eligible patients in the intention-to-screen group, 4106 (44.5%) participated in the screening protocol. In these patients, 12 lead ECG detected newly diagnosed atrial fibrillation in 26 patients (0.63%). In the 266 patients who continued with Holter monitoring, four more diagnoses of atrial fibrillation were found. CONCLUSIONS: Opportunistic screening for atrial fibrillation in primary care patients, aged 65 and over, did not increase the detection rate of atrial fibrillation, which implies that opportunistic screening for atrial fibrillation is not useful in this setting. TRIAL REGISTRATION: Netherlands Trial Register No NL4776 (old NTR4914)

Screening for paroxysmal atrial fibrillation in primary care using Holter monitoring and intermittent, ambulatory single-lead electrocardiography

BACKGROUND: Timely detection of atrial fibrillation (AF) is important because of its increased risk of thrombo-embolic events. Single time point screening interventions fall short in detection of paroxysmal AF, which requires prolonged electrocardiographic monitoring, usually using a Holter. However, traditional 24-48 h Holter monitoring is less appropriate for screening purposes because of its low diagnostic yield. Intermittent, ambulatory screening using a single-lead electrocardiogram (1 L-ECG) device can offer a more efficient alternative. METHODS: Primary care patients of ≥65 years participated in an opportunistic screening study for AF. We invited patients with a negative 12 L-ECG to wear a Holter monitor for two weeks and to use a MyDiagnostick 1 L-ECG device thrice daily. We report the yield of paroxysmal AF found by Holter monitoring and calculate the diagnostic accuracy of the 1 L-ECG device's built-in AF detection algorithm with the Holter monitor as reference standard. RESULTS: We included 270 patients, of whom four had AF in a median of 8.0 days of Holter monitoring, a diagnostic yield of 1.5% (95%-CI: 0.4-3.8%). In 205 patients we performed simultaneous 1 L-ECG screening. For diagnosing AF based on the 1 L-ECG device's AF detection algorithm, sensitivity was 66.7% (95%-CI: 9.4-99.2%), specificity 68.8% (95%-CI: 61.9-75.1%), positive predictive value 3.1% (95%-CI: 1.4-6.8%) and negative predictive value 99.3% (95%-CI: 96.6-99.9%). CONCLUSION: We found a low diagnostic yield of paroxysmal AF using Holter monitoring in elderly primary care patients with a negative 12 L-ECG. The diagnostic accuracy of an intermittently, ambulatory used MyDiagnostick 1 L-ECG device as interpreted by its built-in AF detection algorithm is limited

Screening for paroxysmal atrial fibrillation in primary care using Holter monitoring and intermittent, ambulatory single-lead electrocardiography

Background: Timely detection of atrial fibrillation (AF) is important because of its increased risk of thrombo-embolic events. Single time point screening interventions fall short in detection of paroxysmal AF, which requires prolonged electrocardiographic monitoring, usually using a Holter. However, traditional 24-48 h Holter monitoring is less appropriate for screening purposes because of its low diagnostic yield. Intermittent, ambulatory screening using a single-lead electrocardiogram (1 L-ECG) device can offer a more efficient alternative. Methods: Primary care patients of ≥65 years participated in an opportunistic screening study for AF. We invited patients with a negative 12 L-ECG to wear a Holter monitor for two weeks and to use a MyDiagnostick 1 L-ECG device thrice daily. We report the yield of paroxysmal AF found by Holter monitoring and calculate the diagnostic accuracy of the 1 L-ECG device's built-in AF detection algorithm with the Holter monitor as reference standard. Results: We included 270 patients, of whom four had AF in a median of 8.0 days of Holter monitoring, a diagnostic yield of 1.5% (95%-CI: 0.4–3.8%). In 205 patients we performed simultaneous 1 L-ECG screening. For diagnosing AF based on the 1 L-ECG device's AF detection algorithm, sensitivity was 66.7% (95%-CI: 9.4–99.2%), specificity 68.8% (95%-CI: 61.9–75.1%), positive predictive value 3.1% (95%-CI: 1.4–6.8%) and negative predictive value 99.3% (95%-CI: 96.6–99.9%). Conclusion: We found a low diagnostic yield of paroxysmal AF using Holter monitoring in elderly primary care patients with a negative 12 L-ECG. The diagnostic accuracy of an intermittently, ambulatory used MyDiagnostick 1 L-ECG device as interpreted by its built-in AF detection algorithm is limited

Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation-based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions

Genome-wide study of DNA methylation shows alterations in metabolic, inflammatory, and cholesterol pathways in ALS

Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation-based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions.The research reported in this publication was supported by grants from The Dutch Research Council (NWO) (VENI scheme grant 09150161810018 to W.v.R.) and Prinses Beatrix Spierfond (neuromuscular fellowship grant W.F19-03 to W.v.R.), The Prinses Beatrix Spierfonds (W.OR20-08 to J.J.F.A.v.V. and J.H.V.), The Canadian Institutes of Health Research (FRN 159279 to J.P.R.), The Dutch Research Council (NWO) (VIDI grant 91719350 to K.P.K.), The European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement no. 772376-EScORIAL to J.H.V.), the Swedish Brain Foundation (grant nos. 2012-0262, 2012-0305, 2013-0279, 2016-0303, 2018-0310, and 2020-0353 to P.M.A.), the Swedish Research Council (grant nos. 2012-3167 and 2017-03100 to P.M.A.), the Knut and Alice Wallenberg Foundation (grant nos. 2012.0091, 2014.0305, and 2020.0232 to P.M.A.), the Ulla-Carin Lindquist Foundation and the Västerbotten County Council (grant no. 56103-7002829 to P.M.A.), and King Gustaf V’s and Queen Victoria’s Freemason’s Foundation. This is an EU Joint Programme–Neurodegenerative Disease Research (JPND) project. The project is supported through the following funding organizations under the aegis of JPND (www.jpnd.eu) [United Kingdom, Medical Research Council (MR/L501529/1; MR/R024804/1) and Economic and Social Research Council (ES/L008238/1)] and through the Motor Neurone Disease Association (MNDA). This study represents independent research part funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. A.A.-C. is supported by an NIHR Senior Investigator Award. Samples used in this research were entirely/in part obtained from the U.K. National DNA Bank for MND Research, funded by the MND Association and the Wellcome Trust. We would like to thank people with MND and their families for their participation in this project. We acknowledge sample management undertaken by Biobanking Solutions funded by the Medical Research Council at the Centre for Integrated Genomic Medical Research, University of Manchester. R.J.P. is funded through the Gravitation program of the Dutch Ministry of Education, Culture, and Science and the Netherlands Organization for Scientific Research (BRAINSCAPES). G.L.S. was supported by a PhD studentship from the Alzheimer’s Society. S.T.N. acknowledges support through a FightMND Mid-Career Fellowship. V.S. is supported by the Italian Ministry of Health, AriSLA, and E-Rare Joint Transnational Call. A.A.K. is funded by the MNDA and NIHR Maudsley Biomedical Research Centre. D.B., E.T., and H.R. are employees of Biogen. L.H.v.d.B. reports grants from the Netherlands ALS Foundation, grants from The Netherlands Organization for Health Research and Development (Vici scheme), grants from The European Community’s Health Seventh Framework Programme [grant agreement no. 259867 (EuroMOTOR) to L.H.v.d.B.], and grants from The Netherlands Organization for Health Research and Development (the STRENGTH project, funded through the EU Joint Programme–Neurodegenerative Disease Research, JPND), during the conduct of the study. Project MinE Belgium was supported by a grant from IWT (no. 140935), the ALS Liga België, the National Lottery of Belgium, and the KU Leuven Opening the Future Fund. P.V.D. holds a senior clinical investigatorship of FWO-Vlaanderen and is supported by the E. von Behring Chair for Neuromuscular and Neurodegenerative Disorders, the ALS Liga België, and the KU Leuven funds “Een Hart voor ALS”, “Laeversfonds voor ALS Onderzoek”, and the “Valéry Perrier Race against ALS Fund”. This work was supported by the Italian Ministry of Health (Ministero della Salute, Ricerca Sanitaria Finalizzata, grant RF-2016-02362405 to A. Chiò), the Progetti di Rilevante Interesse Nazionale program of the Ministry of Education, University and Research (grant 2017SNW5MB to A. Chiò); the European Commission’s Health Seventh Framework Programme (FP7/2007-2013 under grant agreement 259867 to A. Chiò), and the Joint Programme–Neurodegenerative Disease Research (Strength, ALS-Care and Brain-Mend projects), granted by Italian Ministry of Education, University, and Research. This study was performed under the Department of Excellence grant of the Italian Ministry of Education, University and Research to the “Rita Levi Montalcini” Department of Neuroscience, University of Torino, Italy. We acknowledge funding from the Australian National Health and Medical Research (NHMRC) Council: 1151854, 1083187, 1173790, 1078901, 1113400, 1095215, and 1176913 Enabling Grant #402703 to N.R.W. Additional funding was provided by the Motor Neurone Disease Research Institute of Australia Ice Bucket Challenge grant for the SALSA-SGC consortium. The OATS (used for controls) was facilitated through Twins Research Australia, a national resource in part supported by a Centre for Research Excellence from the Australian NHMRC Council (NHMRC 1079102 to N.R.W.). Funding for this study was awarded by the (NHMRC)/Australian Research Council Strategic Award (grant 401162 to N.R.W.) and NHMRC grants (1405325, 1024224, 1025243, 1045325, 1085606, 568969, and 1093083 to N.R.W.). The collaboration project is cofunded by the PPP Allowance made available by Health~Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships. This study was supported by the ALS Foundation Netherlands. This work was sponsored by NWO Domain Science for the use of the national computer facilities. A.N.B. is grateful to the Suna and Inan Kirac Foundation and Koc University for the excellent research environment created and for financial support. G.A.R. is supported by the Canadian Institutes of Health. Several authors of this publication are members of the Netherlands Neuromuscular Center (NL-NMD) and the European Reference Network for rare neuromuscular diseases EURO-NMD. French ALS patients of the Pitié-Salpêtrière hospital (Paris) have been collected with ARSla funding support.info:eu-repo/semantics/publishedVersio

Cerebral microbleeds and stroke risk after ischaemic stroke or transient ischaemic attack:a pooled analysis of individual patient data from cohort studies

BACKGROUND Cerebral microbleeds are a neuroimaging biomarker of stroke risk. A crucial clinical question is whether cerebral microbleeds indicate patients with recent ischaemic stroke or transient ischaemic attack in whom the rate of future intracranial haemorrhage is likely to exceed that of recurrent ischaemic stroke when treated with antithrombotic drugs. We therefore aimed to establish whether a large burden of cerebral microbleeds or particular anatomical patterns of cerebral microbleeds can identify ischaemic stroke or transient ischaemic attack patients at higher absolute risk of intracranial haemorrhage than ischaemic stroke. METHODS We did a pooled analysis of individual patient data from cohort studies in adults with recent ischaemic stroke or transient ischaemic attack. Cohorts were eligible for inclusion if they prospectively recruited adult participants with ischaemic stroke or transient ischaemic attack; included at least 50 participants; collected data on stroke events over at least 3 months follow-up; used an appropriate MRI sequence that is sensitive to magnetic susceptibility; and documented the number and anatomical distribution of cerebral microbleeds reliably using consensus criteria and validated scales. Our prespecified primary outcomes were a composite of any symptomatic intracranial haemorrhage or ischaemic stroke, symptomatic intracranial haemorrhage, and symptomatic ischaemic stroke. We registered this study with the PROSPERO international prospective register of systematic reviews, number CRD42016036602. FINDINGS Between Jan 1, 1996, and Dec 1, 2018, we identified 344 studies. After exclusions for ineligibility or declined requests for inclusion, 20 322 patients from 38 cohorts (over 35 225 patient-years of follow-up; median 1·34 years [IQR 0·19-2·44]) were included in our analyses. The adjusted hazard ratio [aHR] comparing patients with cerebral microbleeds to those without was 1·35 (95% CI 1·20-1·50) for the composite outcome of intracranial haemorrhage and ischaemic stroke; 2·45 (1·82-3·29) for intracranial haemorrhage and 1·23 (1·08-1·40) for ischaemic stroke. The aHR increased with increasing cerebral microbleed burden for intracranial haemorrhage but this effect was less marked for ischaemic stroke (for five or more cerebral microbleeds, aHR 4·55 [95% CI 3·08-6·72] for intracranial haemorrhage vs 1·47 [1·19-1·80] for ischaemic stroke; for ten or more cerebral microbleeds, aHR 5·52 [3·36-9·05] vs 1·43 [1·07-1·91]; and for ≥20 cerebral microbleeds, aHR 8·61 [4·69-15·81] vs 1·86 [1·23-1·82]). However, irrespective of cerebral microbleed anatomical distribution or burden, the rate of ischaemic stroke exceeded that of intracranial haemorrhage (for ten or more cerebral microbleeds, 64 ischaemic strokes [95% CI 48-84] per 1000 patient-years vs 27 intracranial haemorrhages [17-41] per 1000 patient-years; and for ≥20 cerebral microbleeds, 73 ischaemic strokes [46-108] per 1000 patient-years vs 39 intracranial haemorrhages [21-67] per 1000 patient-years). INTERPRETATION In patients with recent ischaemic stroke or transient ischaemic attack, cerebral microbleeds are associated with a greater relative hazard (aHR) for subsequent intracranial haemorrhage than for ischaemic stroke, but the absolute risk of ischaemic stroke is higher than that of intracranial haemorrhage, regardless of cerebral microbleed presence, antomical distribution, or burden. FUNDING British Heart Foundation and UK Stroke Association