Erratum: Author Correction: Using a smartphone-based self-management platform to support medication adherence and clinical consultation in Parkinson's disease.

[This corrects the article DOI: 10.1038/s41531-016-0003-z.].

Using a smartphone-based self-management platform to support medication adherence and clinical consultation in Parkinson's disease.

The progressive nature of Parkinson's disease, its complex treatment regimens and the high rates of comorbid conditions make self-management and treatment adherence a challenge. Clinicians have limited face-to-face consultation time with Parkinson's disease patients, making it difficult to comprehensively address non-adherence. Here we share the results from a multi-centre (seven centres) randomised controlled trial conducted in England and Scotland to assess the impact of using a smartphone-based Parkinson's tracker app to promote patient self-management, enhance treatment adherence and quality of clinical consultation. Eligible Parkinson's disease patients were randomised using a 1:1 ratio according to a computer-generated random sequence, stratified by centre and using blocks of variable size, to intervention Parkinson's Tracker App or control (Treatment as Usual). Primary outcome was the self-reported score of adherence to treatment (Morisky medication adherence scale -8) at 16 weeks. Secondary outcomes were Quality of Life (Parkinson's disease questionnaire -39), quality of consultation for Parkinson's disease patients (Patient-centred questionnaire for Parkinson's disease), impact on non-motor symptoms (Non-motor symptoms questionnaire), depression and anxiety (Hospital anxiety and depression scale) and beliefs about medication (Beliefs about Medication Questionnaire) at 16 weeks. Primary and secondary endpoints were analysed using a generalised linear model with treatment as the fixed effect and baseline measurement as the covariate. 158 patients completed the study (Parkinson's tracker app = 68 and TAU = 90). At 16 weeks Parkinson's tracker app significantly improved adherence, compared to treatment as usual (mean difference: 0.39, 95%CI 0.04-0.74; p = 0.0304) with no confounding effects of gender, number of comorbidities and age. Among secondary outcomes, Parkinson's tracker app significantly improved patients' perception of quality of consultation (0.15, 95% CI 0.03 to 0.27; p = 0.0110). The change in non-motor symptoms was -0.82 (95% CI -1.75 to 0.10; p = 0.0822). 72% of participants in the Parkinson's tracker app group continued to use and engage with the application throughout the 16-week trial period. The Parkinson's tracker app can be an effective and novel way of enhancing self-reported medication adherence and quality of clinical consultation by supporting self-management in Parkinson's disease in patients owning smartphones. Further work is recommended to determine whether the benefits of the intervention are maintained beyond the 16 week study period.

The role of the amygdala during emotional processing in Huntington's disease: from pre-manifest to late stage disease.

BACKGROUND: Deficits in emotional processing can be detected in the pre-manifest stage of Huntington's disease and negative emotion recognition has been identified as a predictor of clinical diagnosis. The underlying neuropathological correlates of such deficits are typically established using correlative structural MRI studies. This approach does not take into consideration the impact of disruption to the complex interactions between multiple brain circuits on emotional processing. Therefore, exploration of the neural substrates of emotional processing in pre-manifest HD using fMRI connectivity analysis may be a useful way of evaluating the way brain regions interrelate in the period prior to diagnosis. METHODS: We investigated the impact of predicted time to disease onset on brain activation when participants were exposed to pictures of faces with angry and neutral expressions, in 20 pre-manifest HD gene carriers and 23 healthy controls. On the basis of the results of this initial study went on to look at amygdala dependent cognitive performance in 79 Huntington's disease patients from a cross-section of disease stages (pre-manifest to late disease) and 26 healthy controls, using a validated theory of mind task: "the Reading the Mind in the Eyes Test" which has been previously been shown to be amygdala dependent. RESULTS: Psychophysiological interaction analysis identified reduced connectivity between the left amygdala and right fusiform facial area in pre-manifest HD gene carriers compared to controls when viewing angry compared to neutral faces. Change in PPI connectivity scores correlated with predicted time to disease onset (r=0.45, p<0.05). Furthermore, performance on the "Reading the Mind in the Eyes Test" correlated negatively with proximity to disease onset and became progressively worse with each stage of disease. CONCLUSION: Abnormalities in the neural networks underlying social cognition and emotional processing can be detected prior to clinical diagnosis in Huntington's disease. Connectivity between the amygdala and other brain regions is impacted by the disease process in pre-manifest HD and may therefore be a useful way of identifying participants who are approaching a clinical diagnosis. Furthermore, the "Reading the Mind in the Eyes Test" is a surrogate measure of amygdala function that is clinically useful across the entire cross-section of disease stages in HD.

Which patients with Parkinson's disease participate in clinical trials? One centre's experiences with a new cell based therapy trial (TRANSEURO).

BACKGROUND: There is currently little evidence regarding the selection of patients for clinical trials in Parkinson's Disease (PD), especially those involving experimental therapies delivered using invasive techniques. OBJECTIVE: Understanding which patients are recruited will increase awareness of issues regarding parity of access to clinical trials and have an impact on the wider applicability of results, as well as provoking discussion regarding future improvements in the enrolment process. METHODS: TRANSEURO is an open label multi-centre surgical transplant trial which seeks to investigate the feasibility and efficacy of grafts of human foetal ventral mesencephalic tissue in patients with PD. The Cambridge based cohort of TRANSEURO participants (n = 26) was compared with a population representative sample of patients with PD eligible for, but not enrolled in, TRANSEURO (n = 33). Measurements were available in both populations for demographics, neuropsychological tests, tests of motor and non-motor function and quality of life. RESULTS: Patients enrolled in TRANSEURO were younger and had significantly more years of education with higher scores on the revised Addenbrooke's Cognitive Examination. This difference was accounted for by memory, fluency and visuospatial subscores. There were significant differences in the Movement Disorder Society Unified PD Rating Scale scores with better motor function but more motor complications in the enrolled group. Those enrolled were also more likely to be under the care of the principal investigator of the study. CONCLUSIONS: In this trial our population was younger and more educated with higher cognitive scores and better motor function than eligible PD patients not enrolled. This raises interesting questions about the parity of access to clinical trials of this nature amongst patients with PD.

Long-term safety and tolerability of ProSavin, a lentiviral vector-based gene therapy for Parkinson's disease: a dose escalation, open-label, phase 1/2 trial.

BACKGROUND: Parkinson's disease is typically treated with oral dopamine replacement therapies; however, long-term treatment leads to motor complications and, occasionally, impulse control disorders caused by intermittent stimulation of dopamine receptors and off-target effects, respectively. We aimed to assess the safety, tolerability, and efficacy of bilateral, intrastriatal delivery of ProSavin, a lentiviral vector-based gene therapy aimed at restoring local and continuous dopamine production in patients with advanced Parkinson's disease. METHODS: We undertook a phase 1/2 open-label trial with 12-month follow-up at two study sites (France and UK) to assess the safety and efficacy of ProSavin after bilateral injection into the putamen of patients with Parkinson's disease. All patients were then enrolled in a separate open-label follow-up study of long-term safety. Three doses were assessed in separate cohorts: low dose (1·9×10(7) transducing units [TU]); mid dose (4·0×10(7) TU); and high dose (1×10(8) TU). Inclusion criteria were age 48-65 years, disease duration 5 years or longer, motor fluctuations, and 50% or higher motor response to oral dopaminergic therapy. The primary endpoints of the phase 1/2 study were the number and severity of adverse events associated with ProSavin and motor responses as assessed with Unified Parkinson's Disease Rating Scale (UPDRS) part III (off medication) scores, at 6 months after vector administration. Both trials are registered at ClinicalTrials.gov, NCT00627588 and NCT01856439. FINDINGS: 15 patients received ProSavin and were followed up (three at low dose, six mid dose, six high dose). During the first 12 months of follow-up, 54 drug-related adverse events were reported (51 mild, three moderate). Most common were increased on-medication dyskinesias (20 events, 11 patients) and on-off phenomena (12 events, nine patients). No serious adverse events related to the study drug or surgical procedure were reported. A significant improvement in mean UPDRS part III motor scores off medication was recorded in all patients at 6 months (mean score 38 [SD 9] vs 26 [8], n=15, p=0·0001) and 12 months (38 vs 27 [8]; n=15, p=0·0001) compared with baseline. INTERPRETATION: ProSavin was safe and well tolerated in patients with advanced Parkinson's disease. Improvement in motor behaviour was observed in all patients. FUNDING: Oxford BioMedica.

The Addenbrooke's Cognitive Examination-Revised accurately detects cognitive decline in Huntington's disease.

Cognitive features, which begin before manifestation of the motor features, are an integral part of Huntington's disease and profoundly affect quality of life. A number of neuropsychological batteries have been used to assess this aspect of the condition, many of which are difficult to administer and time consuming, especially in advanced disease. We, therefore, investigated a simple and practical way to monitor cognition using the Addenbrooke's Cognitive Examination-Revised (ACE-R) in 126 manifest Huntington's disease patients, 28 premanifest gene carriers and 21 controls. Using this test, we demonstrated a selective decrease in phonemic, but not semantic, fluency in premanifest participants Cognitive decline in manifest Huntington's disease varied according to disease severity with extensive cognitive decline observed in early-stage Huntington's disease patients, indicating that this would be an optimal stage for interventions designed to halt cognitive decline, and lesser changes in the advanced cases. We next examined cognitive performance in patients prescribed antidopaminergic drugs as these drugs are known to decrease cognition when administered to healthy volunteers. We paradoxically found that these drugs may be beneficial, as early-stage Huntington's disease participants in receipt of them had improved attention and Mini-Mental State Examination scores. In conclusion, this is the first study to test the usefulness of the ACE-R in a Huntington's disease population and demonstrates that this is a brief, inexpensive and practical way to measure global cognitive performance in clinical practice with potential use in clinical trials.

A pilot study of self-esteem as a mediator between family factors and depressive symptoms in young adult university students.

The aim of this study was to examine whether self-esteem mediates the relationship between family factors and depressive symptoms in young adults. Participants completed self-report questionnaires about overall family environment, conflict with mother or father, parental rearing, self esteem, and depressive symptoms. Self-esteem was found to mediate the relationship between the combined family factors and depressive symptoms. When examined simultaneously, none of the individual family variables uniquely predicted depressive symptoms or self-esteem. However, separate analysis of each of the three family factors provided evidence for self-esteem mediating the relationship between parental conflict and depressive symptoms, and the relationship between parental care and depressive symptoms. Self-esteem may play a role in the mechanism underlying the link between parent-offspring relationship factors and depressive symptoms.