Rationale and design to evaluate the PRIME Parkinson care model:a prospective observational evaluation of proactive, integrated and patient-centred Parkinson care in The Netherlands (PRIME-NL)

Contains fulltext : 236935.pdf (Publisher’s version ) (Open Access

Corseto: A Kinesthetic Garment for Designing, Composing for, and Experiencing an Intersubjective Haptic Voice

We present a novel intercorporeal experience - an intersubjective haptic voice. Through an autobiographical design inquiry, based on singing techniques from the classical opera tradition, we created Corsetto, a kinesthetic garment for transferring somatic reminiscents of vocal experience from an expert singer to a listener. We then composed haptic gestures enacted in the Corsetto, emulating upper-body movements of the live singer performing a piece by Morton Feldman named Three Voices. The gestures in the Corsetto added a haptics-based \u27fourth voice\u27 to the immersive opera performance. Finally, we invited audiences who were asked to wear Corsetto during live performances. Afterwards they engaged in micro-phenomenological interviews. The analysis revealed how the Corsetto managed to bridge inner and outer bodily sensations, creating a feeling of a shared intercorporeal experience, dissolving boundaries between listener, singer and performance. We propose that \u27intersubjective haptics\u27 can be a generative medium not only for singing performances, but other possible intersubjective experiences

Urban-Rural Differences in Bone Mineral Density : A Cross Sectional Analysis Based on the Hyderabad Indian Migration Study

Background Fracture risk is rising in countries undergoing rapid rural to urban migration, but whether this reflects an adverse effect of urbanization on intrinsic bone strength, as reflected by bone mineral density (BMD), is currently unknown. Methods Lumbar spine (LS) and total hip (TH) BMD, and total body fat and lean mass, were obtained from DXA scans performed in the Hyderabad arm of the Indian Migration Study (54% male, mean age 49 years). Sib-pair comparisons were performed between rural-urban migrants (RUM) and rural non-migrated (RNM) siblings (N = 185 sib-pairs). Results In analyses adjusted for height, gender, age and occupation, rural to urban migration was associated with higher lumbar and hip BMD and greater predicted hip strength; Delta LS BMD 0.030 (0.005, 0.055) g/cm(2), Delta TH BMD 0.044 (0.024; 0.064) g/cm(2), Delta cross-sectional moment of inertia 0.162 (0.036, 0.289) cm(4). These differences were largely attenuated after adjusting for body composition, insulin levels and current lifestyle factors ie. years of smoking, alcohol consumption and moderate to vigorous physical activity. Further analyses suggested that differences in lean mass, and to a lesser extent fat mass, largely explained the BMD differences which we observed. Conclusions Rural to urban migration as an adult is associated with higher BMD and greater predicted hip strength, reflecting associated alterations in body composition. It remains to be seen how differences in BMD between migration groups will translate into fracture risk in becoming years.Peer reviewe

Clinical judgement by primary care physicians for the diagnosis of all-cause dementia or cognitive impairment in symptomatic people

Background: In primary care, general practitioners (GPs) unavoidably reach a clinical judgement about a patient as part of their encounter with patients, and so clinical judgement can be an important part of the diagnostic evaluation. Typically clinical decision making about what to do next for a patient incorporates clinical judgement about the diagnosis with severity of symptoms and patient factors, such as their ideas and expectations for treatment. When evaluating patients for dementia, many GPs report using their own judgement to evaluate cognition, using information that is immediately available at the point of care, to decide whether someone has or does not have dementia, rather than more formal tests. Objectives: To determine the diagnostic accuracy of GPs’ clinical judgement for diagnosing cognitive impairment and dementia in symptomatic people presenting to primary care. To investigate the heterogeneity of test accuracy in the included studies. Search methods: We searched MEDLINE (Ovid SP), Embase (Ovid SP), PsycINFO (Ovid SP), Web of Science Core Collection (ISI Web of Science), and LILACs (BIREME) on 16 September 2021. Selection criteria: We selected cross-sectional and cohort studies from primary care where clinical judgement was determined by a GP either prospectively (after consulting with a patient who has presented to a specific encounter with the doctor) or retrospectively (based on knowledge of the patient and review of the medical notes, but not relating to a specific encounter with the patient). The target conditions were dementia and cognitive impairment (mild cognitive impairment and dementia) and we included studies with any appropriate reference standard such as the Diagnostic and Statistical Manual of Mental Disorders (DSM), International Classification of Diseases (ICD), aetiological definitions, or expert clinical diagnosis. Data collection and analysis: Two review authors screened titles and abstracts for relevant articles and extracted data separately with differences resolved by consensus discussion. We used QUADAS-2 to evaluate the risk of bias and concerns about applicability in each study using anchoring statements. We performed meta-analysis using the bivariate method. Main results: We identified 18,202 potentially relevant articles, of which 12,427 remained after de-duplication. We assessed 57 full-text articles and extracted data on 11 studies (17 papers), of which 10 studies had quantitative data. We included eight studies in the meta-analysis for the target condition dementia and four studies for the target condition cognitive impairment. Most studies were at low risk of bias as assessed with the QUADAS-2 tool, except for the flow and timing domain where four studies were at high risk of bias, and the reference standard domain where two studies were at high risk of bias. Most studies had low concern about applicability to the review question in all QUADAS-2 domains. Average age ranged from 73 years to 83 years (weighted average 77 years). The percentage of female participants in studies ranged from 47% to 100%. The percentage of people with a final diagnosis of dementia was between 2% and 56% across studies (a weighted average of 21%). For the target condition dementia, in individual studies sensitivity ranged from 34% to 91% and specificity ranged from 58% to 99%. In the meta-analysis for dementia as the target condition, in eight studies in which a total of 826 of 2790 participants had dementia, the summary diagnostic accuracy of clinical judgement of general practitioners was sensitivity 58% (95% confidence interval (CI) 43% to 72%), specificity 89% (95% CI 79% to 95%), positive likelihood ratio 5.3 (95% CI 2.4 to 8.2), and negative likelihood ratio 0.47 (95% CI 0.33 to 0.61). For the target condition cognitive impairment, in individual studies sensitivity ranged from 58% to 97% and specificity ranged from 40% to 88%. The summary diagnostic accuracy of clinical judgement of general practitioners in four studies in which a total of 594 of 1497 participants had cognitive impairment was sensitivity 84% (95% CI 60% to 95%), specificity 73% (95% CI 50% to 88%), positive likelihood ratio 3.1 (95% CI 1.4 to 4.7), and negative likelihood ratio 0.23 (95% CI 0.06 to 0.40). It was impossible to draw firm conclusions in the analysis of heterogeneity because there were small numbers of studies. For specificity we found the data were compatible with studies that used ICD-10, or applied retrospective judgement, had higher reported specificity compared to studies with DSM definitions or using prospective judgement. In contrast for sensitivity, we found studies that used a prospective index test may have had higher sensitivity than studies that used a retrospective index test. Authors' conclusions: Clinical judgement of GPs is more specific than sensitive for the diagnosis of dementia. It would be necessary to use additional tests to confirm the diagnosis for either target condition, or to confirm the absence of the target conditions, but clinical judgement may inform the choice of further testing. Many people who a GP judges as having dementia will have the condition. People with false negative diagnoses are likely to have less severe disease and some could be identified by using more formal testing in people who GPs judge as not having dementia. Some false positives may require similar practical support to those with dementia, but some - such as some people with depression - may suffer delayed intervention for an alternative treatable pathology

Alendronate use and bone mineral density gains in women with moderate-severe (stages 3B-5) chronic kidney disease:an open cohort multivariable and propensity score analysis from Funen, Denmark

Funding: This project was funded by the NIHR HTA (project number or 14/36/02) and supported by the NIHR Biomedical Research Centre, Oxford.Bisphosphonates are contraindicated in moderate-to-severe chronic kidney disease patients. However, they are used to prevent fragility fractures in patients with impaired kidney function, despite a lack of evidence on their effects on bone density in these patients. We demonstrated that Alendronate had a positive effect on bone in these patients. This study aimed to assess the association between alendronate use and bone mineral density (BMD) change in subjects with moderate-severe chronic kidney disease (CKD). We created a cohort of CKD stage 3B-5 patients by linking all DXA-based measurements in the Funen area, Denmark, to biochemistry, national health registries and filled prescriptions. Exposure was dispensation of alendronate and the outcome was annualized percentage change in BMD at the femoral neck, total hip and lumbar spine. Individuals were followed from first BMD to the latest of subsequent DXA measurements. Alendronate non-users were identified using incidence density sampling and matched groups were created using propensity scores. Linear regression was used to estimate average differences in the annualized BMD. Use of alendronate was rare in this group of patients: propensity score matching (PSM) resulted in 71 alendronate users and 142 non-users with stage 3B-5 CKD (as in the 1 year before DXA). Whilst alendronate users gained an average 1.07% femoral neck BMD per year, non-users lost an average of 1.59% per annum. The PSM mean differences in annualized BMD were + 2.65% (1.32%, 3.99%), + 3.01% (1.74%, 4.28%) and + 2.12% (0.98%, 3.25%) at the femoral neck, total hip and spine BMD, respectively, all in favour of alendronate users. In a real-world cohort of women with stage 3B-5 CKD, use of alendronate appears associated with a significant improvement of 2-3% per year in the femoral neck, total hip and spine BMD. More data are needed on the anti-fracture effectiveness and safety of bisphosphonate therapy in moderate-severe CKD

Sex differences in heart failure patients assessed by combined echocardiographic and cardiopulmonary exercise testing

BackgroundWe aimed to test the differences in peak VO2 between males and females in patients diagnosed with heart failure (HF), using combined stress echocardiography (SE) and cardiopulmonary exercise testing (CPET).MethodsPatients who underwent CPET and SE for evaluation of dyspnea or exertional intolerance at our institution, between January 2013 and December 2017, were included and retrospectively assessed. Patients were divided into three groups: HF with preserved ejection fraction (HFpEF), HF with mildly reduced or reduced ejection fraction (HFmrEF/HFrEF), and patients without HF (control). These groups were further stratified by sex.ResultsOne hundred seventy-eight patients underwent CPET-SE testing, of which 40% were females. Females diagnosed with HFpEF showed attenuated increases in end diastolic volume index (P = 0.040 for sex × time interaction), significantly elevated E/e' (P < 0.001), significantly decreased left ventricle (LV) end diastolic volume:E/e ratio (P = 0.040 for sex × time interaction), and lesser increases in A-VO2 difference (P = 0.003 for sex × time interaction), comparing to males with HFpEF. Females diagnosed with HFmrEF/HFrEF showed diminished increases in end diastolic volume index (P = 0.050 for sex × time interaction), mostly after anaerobic threshold was met, comparing to males with HFmrEF/HFrEF. This resulted in reduced increases in peak stroke volume index (P = 0.010 for sex × time interaction) and cardiac output (P = 0.050 for sex × time interaction).ConclusionsCombined CPET-SE testing allows for individualized non-invasive evaluation of exercise physiology stratified by sex. Female patients with HF have lower exercise capacity compared to men with HF. For females diagnosed with HFpEF, this was due to poorer LV compliance and attenuated peripheral oxygen extraction, while for females diagnosed with HFmrEF/HFrEF, this was due to attenuated increase in peak stroke volume and cardiac output. As past studies have shown differences in clinical outcomes between females and males, this study provides an essential understanding of the differences in exercise physiology in HF patients, which may improve patient selection for targeted therapeutics

The Vascular Impairment of Cognition Classification Consensus Study

H. Jokinen työryhmän jäsenenä.Introduction: Numerous diagnostic criteria have tried to tackle the variability in clinical manifestations and problematic diagnosis of vascular cognitive impairment (VCI) but none have been universally accepted. These criteria have not been readily comparable, impacting on clinical diagnosis rates and in turn prevalence estimates, research, and treatment. Methods: The Vascular Impairment of Cognition Classification Consensus Study (VICCCS) involved participants (81% academic researchers) from 27 countries in an online Delphi consensus study. Participants reviewed previously proposed concepts to develop new guidelines. Results: VICCCS had a mean of 122 (98-153) respondents across the study and a 67% threshold to represent consensus. VICCCS redefined VCI including classification of mild and major forms of VCI and subtypes. It proposes new standardized VCI-associated terminology and future research priorities to address gaps in current knowledge. Discussion: VICCCS proposes a consensus-based updated conceptualization of VCI intended to facilitate standardization in research. (C) 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.Peer reviewe

A panel of induced pluripotent stem cells from chimpanzees: A resource for comparative functional genomics

Comparative genomics studies in primates are restricted due to our limited access to samples. In order to gain better insight into the genetic processes that underlie variation in complex phenotypes in primates, we must have access to faithful model systems for a wide range of cell types. To facilitate this, we generated a panel of 7 fully characterized chimpanzee induced pluripotent stem cell (iPSC) lines derived from healthy donors. To demonstrate the utility of comparative iPSC panels, we collected RNA-sequencing and DNA methylation data from the chimpanzee iPSCs and the corresponding fibroblast lines, as well as from 7 human iPSCs and their source lines, which encompass multiple populations and cell types. We observe much less withinspecies variation in iPSCs than in somatic cells, indicating the reprogramming process erases many inter-individual differences. The low within-species regulatory variation in iPSCs allowed us to identify many novel inter-species regulatory differences of small magnitude