From compliance to concordance: meeting the needs of patients?

Abstract of a pharmacy practice research paper presented at the British Pharmaceutical Conference, Glasgow, 23-26 Sep 2001. Interviews with 21 English speakers of Pakistani origin with type 2 diabetes. Results suggest that it may be more appropriate to link concordance to an approach which seeks to sensitively elicit patient narratives as a basis for shared understanding

The motor prodromes of parkinson's disease: from bedside observation to large-scale application

There is sufficient evidence that the pathological process that causes Parkinson's disease begins years before the clinical diagnosis is made. Over the last 15 years, there has been much interest in the existence of a prodrome in some patients, with a particular focus on non-motor symptoms such as reduced sense of smell, REM-sleep disorder, depression, and constipation. Given that the diagnostic criteria for Parkinson's disease depends on the presence of bradykinesia, it is somewhat surprising that there has been much less research into the possibility of subtle motor dysfunction as a pre-diagnostic pointer. This review will focus on early motor features and provide some advice on how to detect and measure them

Age-specific effects of childhood body mass index on multiple sclerosis risk

OBJECTIVE: Higher body mass index (BMI) during early life is thought to be a causal risk factor for multiple sclerosis (MS). We used longitudinal Mendelian randomisation (MR) to determine whether there is a critical window during which BMI influences MS risk. METHODS: Summary statistics for childhood BMI (n ~ 28,000 children) and for MS susceptibility were obtained from recent large genome-wide association studies (GWAS) (n = 14,802 MS, 26,703 controls). We generated exposure instruments for BMI during four non-overlapping age epochs (< 3 months, 3 months–1.5 years, 2–5 years, and 7–8 years) and performed MR using the inverse variance weighted method with standard sensitivity analyses. Multivariable MR was used to account for effects mediated via later-life BMI. RESULTS: For all age epochs other than birth, genetically determined higher BMI was associated with an increased liability to MS: Birth [Odds Ratio (OR) 0.81, 95% Confidence Interval (CI) 0.50–1.31, Number of Single-Nucleotide Polymorphisms (N(SNPs)) = 7, p = 0.39], Infancy (OR 1.18, 95% CI 1.04–1.33, N(SNPs) = 18, p = 0.01), Early childhood (OR 1.31, 95% CI 1.03–1.66, N(SNPs) = 4, p = 0.03), Later childhood (OR 1.34, 95% CI 1.08–1.66, N(SNPs) = 4, p = 0.01). Multivariable MR suggested that these effects may be mediated by effects on adult BMI. CONCLUSION: We provide evidence using MR that genetically determined higher BMI during early life is associated with increased MS risk. This effect may be driven by shared genetic architecture with later-life BMI. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00415-022-11161-4

Motor Dysfunction as a Prodrome of Parkinson's Disease

BACKGROUND: Recognition of motor signs in the prodromal stage could lead to best identify populations at risk for developing Parkinson's disease (PD). OBJECTIVE: This study identified motor symptoms and signs in individuals suspected of having PD but who did not have a progressive reduction in the speed and amplitude of finger tapping or other physical signs indicative of bradykinesia. METHODS: 146 patients, who had symptoms or signs suggestive of PD, were serially evaluated by a movement disorder specialist, using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III and video recordings. If the patients 'converted' to PD during follow-up, they were categorized as cases and compared with those who did not meet PD criteria during follow-up (non-cases). RESULTS: The 82 cases were more likely to have action dystonia or postural/action/rest tremor of a limb (OR 2.8; 95% CI 1.10-7.09; p = 0.02), a reduced blink rate at rest (OR 2.32; 95% CI 1.18-4.55; p = 0.01), anxiety (OR 8.91; 95% CI 2.55-31.1; p <  0.001), depression (OR 7.03; 95% CI 2.86-17.2; p <  0.001), or a frozen shoulder (OR 3.14; 95% CI 1.58-6.21) than the 64 'non-cases'. A reduction of the fast blink rate was common in patients who met the criteria for PD (p <  0.001). CONCLUSIONS: This study emphasizes that motor dysfunction is a component of the clinical prodrome seen in some patients with PD

Challenges of Incorporating Digital Health Technology Outcomes in a Clinical Trial: Experiences from PD STAT

\ua9 2022 - The authors. Published by IOS Press.Digital health technologies (DHTs) have great potential for use as clinical trial outcomes; however, practical issues need to be addressed in order to maximise their benefit. We describe our experience of incorporating two DHTs as secondary/exploratory outcome measures in PD STAT, a randomised clinical trial of simvastatin in people with Parkinson\u27s disease. We found much higher rates of missing data in the DHTs than the traditional outcome measures, in particular due to technical and software difficulties. We discuss methods to address these obstacles in terms of protocol design, workforce training and data management

Challenges of Incorporating Digital Health Technology Outcomes in a Clinical Trial: Experiences from PD STAT.

Digital health technologies (DHTs) have great potential for use as clinical trial outcomes; however, practical issues need to be addressed in order to maximise their benefit. We describe our experience of incorporating two DHTs as secondary/exploratory outcome measures in PD STAT, a randomised clinical trial of simvastatin in people with Parkinson's disease. We found much higher rates of missing data in the DHTs than the traditional outcome measures, in particular due to technical and software difficulties. We discuss methods to address these obstacles in terms of protocol design, workforce training and data management

Developing and assessing a new web-based tapping test for measuring distal movement in Parkinson's disease: a Distal Finger Tapping test

Disability in Parkinson's disease (PD) is measured by standardised scales including the MDS-UPDRS, which are subject to high inter and intra-rater variability and fail to capture subtle motor impairment. The BRadykinesia Akinesia INcoordination (BRAIN) test is a validated keyboard tapping test, evaluating proximal upper-limb motor impairment. Here, a new Distal Finger Tapping (DFT) test was developed to assess distal upper-limb function. Kinetic parameters of the test include kinesia score (KS20, key taps over 20 s), akinesia time (AT20, mean dwell-time on each key) and incoordination score (IS20, variance of travelling time between key taps). To develop and evaluate a new keyboard-tapping test for objective and remote distal motor function in PD patients. The DFT and BRAIN tests were assessed in 55 PD patients and 65 controls. Test scores were compared between groups and correlated with the MDS-UPDRS-III finger tapping sub-scores. Nine additional PD patients were recruited for monitoring motor fluctuations. All three parameters discriminated effectively between PD patients and controls, with KS20 performing best, yielding 79% sensitivity for 85% specificity; area under the receiver operating characteristic curve (AUC) = 0.90. A combination of DFT and BRAIN tests improved discrimination (AUC = 0.95). Among three parameters, KS20 showed a moderate correlation with the MDS-UPDRS finger-tapping sub-score (Pearson's r = - 0.40, p = 0.002). Further, the DFT test detected subtle changes in motor fluctuation states which were not reflected clearly by the MDS-UPDRS-III finger tapping sub-scores. The DFT test is an online tool for assessing distal movements in PD, with future scope for longitudinal monitoring of motor complications

A population scale analysis of rare SNCA variation in the UK Biobank

Parkinson's disease (PD) is a complex neurodegenerative disease with a variety of genetic and environmental factors contributing to disease. The SNCA gene encodes for the alpha-synuclein protein which plays a central role in PD, where aggregates of this protein are one of the pathological hallmarks of disease. Rare point mutations and copy number gains of the SNCA gene have been shown to cause autosomal dominant PD, and common DNA variants identified using Genome-Wide Association Studies (GWAS) are a moderate risk factor for PD. The UK Biobank is a large-scale population prospective study including ~500,000 individuals that has revolutionized human genetics. Here we assessed the frequency of SNCA variation in this cohort and identified 30 subjects carrying variants of interest including duplications (n = 6), deletions (n = 6) and large complex likely mosaic events (n = 18). No known pathogenic missense variants were identified. None of these subjects were reported to be a PD case, although it is possible that these individuals may develop PD at a later age, and whilst three had known prodromal features, these did not meet defined clinical criteria for being considered ‘prodromal’ cases. Seven of the 18 large complex carriers showed a history of blood based cancer. Overall, we identified copy number variants in the SNCA region in a large population based cohort without reported PD phenotype and symptoms. Putative mosaicism of the SNCA gene was identified, however, it is unclear whether it is associated with PD. These individuals are potential candidates for further investigation by performing SNCA RNA and protein expression studies, as well as promising clinical trial candidates to understand how duplication carriers potentially escape PD