Rebecca Woolley

Physiotherapy and Occupational Therapy vs No Therapy in Mild to Moderate Parkinson Disease: A Randomized Clinical Trial.

IMPORTANCE It is unclear whether physiotherapy and occupational therapy are clinically effective and cost-effective in Parkinson disease (PD). OBJECTIVE To perform a large pragmatic randomized clinical trial to evaluate the clinical effectiveness of individualized physiotherapy and occupational therapy in PD. DESIGN, SETTING, AND PARTICIPANTS The PD REHAB Trial was a multicenter, open-label, parallel group, controlled efficacy trial. A total of 762 patients with mild to moderate PD were recruited from 38 sites across the United Kingdom. Recruitment took place between October 2009 and June 2012, with 15 months of follow-up. INTERVENTIONS Participants with limitations in activities of daily living (ADL) were randomized to physiotherapy and occupational therapy or no therapy. MAIN OUTCOMES AND MEASURES The primary outcome was the Nottingham Extended Activities of Daily Living (NEADL) Scale score at 3 months after randomization. Secondary outcomes were health-related quality of life (assessed by Parkinson Disease Questionnaire-39 and EuroQol-5D); adverse events; and caregiver quality of life. Outcomes were assessed before trial entry and then 3, 9, and 15 months after randomization. RESULTS Of the 762 patients included in the study (mean [SD] age, 70 [9.1] years), 381 received physiotherapy and occupational therapy and 381 received no therapy. At 3 months, there was no difference between groups in NEADL total score (difference, 0.5 points; 95% CI, -0.7 to 1.7; P = .41) or Parkinson Disease Questionnaire-39 summary index (0.007 points; 95% CI, -1.5 to 1.5; P = .99). The EuroQol-5D quotient was of borderline significance in favor of therapy (-0.03; 95% CI, -0.07 to -0.002; P = .04). The median therapist contact time was 4 visits of 58 minutes over 8 weeks. Repeated-measures analysis showed no difference in NEADL total score, but Parkinson Disease Questionnaire-39 summary index (diverging 1.6 points per annum; 95% CI, 0.47 to 2.62; P = .005) and EuroQol-5D score (0.02; 95% CI, 0.00007 to 0.03; P = .04) showed small differences in favor of therapy. There was no difference in adverse events. CONCLUSIONS AND RELEVANCE Physiotherapy and occupational therapy were not associated with immediate or medium-term clinically meaningful improvements in ADL or quality of life in mild to moderate PD. This evidence does not support the use of low-dose, patient-centered, goal-directed physiotherapy and occupational therapy in patients in the early stages of PD. Future research should explore the development and testing of more structured and intensive physical and occupational therapy programs in patients with all stages of PD. TRIAL REGISTRATION isrctn.org Identifier: ISRCTN17452402.

Headache determines quality of life in idiopathic intracranial hypertension.

BackgroundThe effect of idiopathic intracranial hypertension (IIH) on quality of life (QOL) is poorly understood. Our objectives were to compare QOL in IIH to the normal UK population; to investigate QOL changes with treatment of IIH, using a weight loss intervention, and to determine which clinical factors influence QOL.MethodsThis was a prospective cohort evaluation of QOL, using the 36-Item Short Form (SF-36) Health Survey questionnaire, before and after a therapeutic dietary intervention which resulted in significant reduction in body mass index (BMI), intracranial pressure (ICP), papilloedema, visual acuity, perimetric mean deviation (Humphrey 24–2) and headache (six-item headache impact test (HIT-6) and headache diary). Baseline QOL was compared to an age and gender matched population. The relationship between each clinical outcome and change in QOL was evaluated.ResultsAt baseline, QOL was significantly lower in IIH compared to an age and gender matched population in most domains, p < 0.001. Therapeutic weight loss led to a significant improvement in 10 out of 11 QOL domains in conjunction with the previously published data demonstrating significant improvement in papilloedema, visual acuity, perimetry and headache (p < 0.001) and large effect size. Despite significant improvement in clinical measures only headache correlated significantly (p < 0.001) with improving QOL domains.ConclusionsQOL in IIH patients is significantly reduced. It improved with weight loss alongside significant improvement in clinical measures and headache. However, headache was the only clinical outcome that correlated with enhanced QOL. Effective headache management is required to improve QOL in IIH.

Safety and Efficacy of Antiviral Therapy for Prevention of Cytomegalovirus Reactivation in Immunocompetent Critically Ill Patients: A Randomized Clinical Trial

Importance Latent cytomegalovirus (CMV) infection is present in more than half the adult population, and a viral reactivation (ie, when the virus becomes measurable in body fluids such as blood) can occur in up to one-third of these individuals during episodes of critical illness. Objective To determine whether antiviral therapy is safe and effective for preventing CMV reactivation in a general population of critically ill patients. Design, Setting, and Participants A single-center, open-label, randomized, controlled clinical trial recruited 124 CMV-seropositive patients undergoing mechanical ventilation for at least 24 hours in the intensive care unit between January 1, 2012, and January 31, 2014. The mean baseline Acute Physiology and Chronic Health Evaluation II score of all patients was 17.6. Interventions Patients were randomized to receive anti-CMV prophylaxis with valacyclovir hydrochloride (n = 34) or low-dose valganciclovir hydrochloride (n = 46) for up to 28 days to suppress viral reactivation, or to a control group with no intervention (n = 44). Main Outcomes and Measures Time to first CMV reactivation in blood within the 28-day follow-up period following initiation of the study drug. Results Among the 124 patients in the study (46 women and 78 men; mean [SD] age, 56.9 [16.9] years), viral reactivation in the blood occurred in 12 patients in the control group, compared with 1 patient in the valganciclovir group and 2 patients in the valacyclovir group (combined treatment groups vs control: hazard ratio, 0.14; 95% CI 0.04-0.50). Although this trial was not powered to assess clinical end points, the valacyclovir arm was halted prematurely because of higher mortality; 14 of 34 patients (41.2%) had died by 28 days, compared with 5 of 37 (13.5%) patients in the control arm at the point of the decision to halt this arm. Other safety end points showed similar outcomes between groups. Conclusions and Relevance Antiviral prophylaxis with valacyclovir or low-dose valganciclovir suppresses CMV reactivation in patients with critical illness. However, given the higher mortality, a large-scale trial would be needed to determine the clinical efficacy and safety of CMV suppression. Trial Registration clinicaltrials.gov Identifier: NCT01503918

Idiopathic Intracranial Hypertension

Idiopathic intracranial hypertension (IIH) is an uncommon condition where loss of vision is the predominant morbid factor. The primary objectives of this research have been to study the population aspects of the disease, to make original observations on associated ocular motility abnormalities, to present new data on visual field survival in a cohort of patients followed prospectively and to present data on the clinical outcomes on the same cohort of patients. This constitutes the first in-depth and largest prospective study of visual function and epidemiology for the condition of IIH in the UK. Thirty-four patients have been followed over a four year period with comprehensive documentation of presentation, associated factors and conditions, assessment of visual function, ocular motility and neurological status. Risk factors for poor visual outcome have been determined for the patients in this study. The incidence figures for occurrence of IIH exist only for the USA and Libya. Only hospital based recruitment figures exist for UK studies and one of the objectives of this research has been to provide original epidemiological data for IIH in a defined UK population. The incidence of IIH in this UK population has been calculated as 0.70 per 100,000 persons and 1.38 for females. An age standardised adjustment to the national UK population provides an estimated incidence of 0.71 per 100,000 for the overall population and 1.39 for females. The incidence rates were also adjusted for the population of obese individuals and rose significantly to 12.25 per 100,000 for adult females with a body mass index of 30 or more. The diagnosis of a number of asymptomatic cases raised concerns regarding incidence calculations generally with lack of complete ascertainment of cases. This is the first study to prospectively assess overweight and obesity in a population of IIH. Obesity has been confirmed as a common association with this condition and has been identified as having a high relative risk factor in this study particularly those with a body mass index of 40 or more. Analysis of serial weight measurements demonstrate no correlation between weight change and visual outcome. When reviewing the aetiology of this condition, the association of obesity should be taken into consideration as this may play a role in the disruption of the cerebrospinal fluid absorption mechanism and development of cerebral oedema. Ocular motility disturbances have not been assessed in a prospective study and this study aims to cast light on the types of ocular motility disturbances that occur in association with the condition and those that are directly caused by the raised intracranial pressure. Ocular motility assessment was normal in 23 patients. Eleven patients, however, had an ocular motility defect and not all were due to the classic non localising sixth cranial nerve palsy associated with raised intracranial pressure. Two patients had long-standing strabismus, two had transient ocular motility restrictions following optic nerve sheath fenestration procedures, one developed a secondary exotropia following visual loss and optic atrophy, and six patients had acquired cranial nerve palsies including third and sixth nerves. The level of intracranial pressure was not significantly associated with the development of acquired ocular motility disorders. The prognosis for visual outcome is generally good with a favourable outcome achieved in most cases (82%). A significant improvement was found from initial to last assessment of visual function and the pattern of improvement was also significant over the period of follow up. It was noted that patients treated surgically responded more quickly, with improvement in visual status, than those patients treated medically. However, there was no difference in the final outcome or level of visual function between these two treatment groups. Serious loss of visual function occurs in a minority of cases and appears to relate to poor visual function prior to presentation, a high degree of obesity and features of long-standing optic nerve pathology including optic atrophy. However, in general, patients who are appropriately evaluated at regular intervals and those who are treated promptly and effectively have a favourable outcome. The recommendation for visual assessment in this study includes documentation of visual acuity, visual field assessment with automated or Goldmann perimetry with sensitive testing strategies, full Orthoptic investigation as indicated and fundus examination, and close liaison with the neurology and neurosurgery departments. The use of this regime enabled the detection of insidious and asymptomatic visual loss and therefore was of considerable prognostic value. The Humphrey 24-2 programme and a new testing strategy for Goldmann perimetry were employed for the first time in this prospective study as was the Pelli-Robson contrast sensitivity assessment. Visual field assessments using the above methods were identified as suitable and reliable testing techniques. This thesis, in addition to the clinical study, provides a review of the literature relating to papilloedema and IIH, and the pathogenesis of visual loss in IIH. Observations are made regarding the clinical data of this study and the proposed mechanisms involved in the condition and its associated visual dysfunction.

Randomised controlled trial of bariatric surgery versus a community weight loss programme for the sustained treatment of idiopathic intracranial hypertension: the Idiopathic Intracranial Hypertension Weight Trial (IIH:WT) protocol

Introduction Effective treatments are lacking for idiopathic intracranial hypertension (IIH), a condition characterised by raised intracranial pressure (ICP) and papilloedema, and found primarily in obese women. Weight loss and lowering body mass index (BMI) have been shown to lower ICP and improve symptoms in IIH; however, weight loss is typically not maintained, meaning IIH symptoms return. The Idiopathic Intracranial Hypertension Weight Trial (IIH:WT) will assess whether bariatric surgery is an effective long-term treatment for patients with IIH with a BMI over 35 kg/m2. The National Institute for Health and Care Excellence recommends bariatric surgery in people with a BMI over 35 kg/m2 and a qualifying comorbidity; currently IIH does not qualify as a comorbidity. Methods and analysis IIH:WT is a multicentre, open-label, randomised controlled clinical trial of 64 participants with active IIH and a BMI over 35 kg/m2. Participants will be randomised in a 1:1 ratio to bariatric surgery or a dietary weight loss programme and followed up for 5 years. The primary outcome measure is ICP at 12 months. Secondary outcome measures include ICP at 24 and 60 months, and IIH symptoms, visual function, papilloedema, headache, quality of life and cost-effectiveness at 12, 24 and 60 months. Trial registration number IIH:WT is registered as ISRCTN40152829 and on ClinicalTrials.gov as NCT02124486 and is in the pre-results stage.

Clinical effectiveness and cost-effectiveness of physiotherapy and occupational therapy versus no therapy in mild to moderate Parkinson's disease: a large pragmatic randomised controlled trial (PD REHAB).

BACKGROUND Cochrane reviews of physiotherapy (PT) and occupational therapy (OT) for Parkinsons disease found insufficient evidence of effectiveness, but previous trials were methodologically flawed with small sample size and short-term follow-up. OBJECTIVES To evaluate the clinical effectiveness and cost-effectiveness of individualised PT and OT in Parkinsons disease. DESIGN Large pragmatic randomised controlled trial. SETTING Thirty-eight neurology and geriatric medicine outpatient clinics in the UK. PARTICIPANTS Seven hundred and sixty-two patients with mild to moderate Parkinsons disease reporting limitations in activities of daily living (ADL). INTERVENTION Patients were randomised online to either both PT and OT NHS services (n = 381) or no therapy (n = 381). Therapy incorporated a patient-centred approach with individual assessment and goal setting. MAIN OUTCOME MEASURES The primary outcome was instrumental ADL measured by the patient-completed Nottingham Extended Activities of Daily Living (NEADL) scale at 3 months after randomisation. Secondary outcomes were health-related quality of life [Parkinsons Disease Questionnaire-39 (PDQ-39); European Quality of Life-5 Dimensions (EQ-5D)], adverse events, resource use and carer quality of life (Short Form questionnaire-12 items). Outcomes were assessed before randomisation and at 3, 9 and 15 months after randomisation. RESULTS Data from 92% of the participants in each group were available at the primary time point of 3 months, but there was no difference in NEADL total score [difference 0.5 points, 95% confidence interval (CI) -0.7 to 1.7; p = 0.4] or PDQ-39 summary index (0.007 points, 95% CI -1.5 to 1.5; p = 1.0) between groups. The EQ-5D quotient was of borderline significance in favour of therapy (-0.03, 95% CI -0.07 to -0.002; p = 0.04). Contact time with therapists was for a median of four visits of 58 minutes each over 8 weeks (mean dose 232 minutes). Repeated measures analysis including all time points showed no difference in NEADL total score, but PDQ-39 summary index (curves diverging at 1.6 points per annum, 95% CI 0.47 to 2.62; p = 0.005) and EQ-5D quotient (0.02, 95% CI 0.00007 to 0.03; p = 0.04) showed significant but small differences in favour of the therapy arm. Cost-effective analysis showed that therapy was associated with a slight but not significant gain in quality-adjusted life-years (0.027, 95% CI -0.010 to 0.065) at a small incremental cost (£164, 95% CI -£141 to £468), resulting in an incremental cost-effectiveness ratio of under £4000 (£3493, 95% -£169,371 to £176,358). There was no difference in adverse events or serious adverse events. CONCLUSIONS NHS PT and OT did not produce immediate or long-term clinically meaningful improvements in ADL or quality of life in patients with mild to moderate Parkinsons disease. This evidence does not support the use of low-dose, patient-centred, goal-directed PT and OT in patients in the early stages of Parkinsons disease. Future research should include the development and testing of more structured and intensive PT and OT programmes in patients with all stages of Parkinsons disease. TRIAL REGISTRATION Current Controlled Trials ISRCTN17452402. FUNDING This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 63. See the NIHR Journals Library website for further project information. The Birmingham Clinical Trials Unit, University of Birmingham, received support from the UK Department of Health up to March 2012. Catherine Sackley was supported by a NIHR senior investigator award, Collaboration for Leadership in Applied Health Research and Care East of England and West Midlands Strategic Health Authority Clinical Academic Training award.

Coding accuracy for Parkinson's disease hospital admissions: implications for healthcare planning in the UK

OBJECTIVES Hospital Episode Statistics data are used for healthcare planning and hospital reimbursements. Reliability of these data is dependent on the accuracy of individual hospitals reporting Secondary Uses Service (SUS) which includes hospitalisation. The number and coding accuracy for Parkinsons disease hospital admissions at a tertiary centre in Birmingham was assessed. STUDY DESIGN Retrospective, routine-data-based study. METHODS A retrospective electronic database search for all Parkinsons disease patients admitted to the tertiary hospital over a 4-year period (2009-2013) was performed on the SUS database using International Classification of Disease codes, and on the local inpatient electronic prescription database, Prescription and Information Communications System, using medication prescriptions. Capture-recapture methods were used to estimate the number of patients and admissions missed by both databases. RESULTS From the two databases, between July 2009 and June 2013, 1068 patients with Parkinsons disease accounted for 1999 admissions. During these admissions, the Parkinsons disease was coded as a primary or secondary diagnosis. Ninety-one percent of these admissions were recorded on the SUS database. Capture-recapture methods estimated that the number of Parkinsons disease patients admitted during this period was 1127 patients (95% confidence interval: 1107-1146). A supplementary search of both SUS and Prescription and Information Communications System was undertaken using the hospital numbers of these 1068 patients. This identified another 479 admissions. SUS database under-estimated Parkinsons disease admissions by 27% during the study period. CONCLUSION The accuracy of disease coding is critical for healthcare policy planning and must be improved. If the under-reporting of Parkinsons disease admissions on the SUS database is repeated nationally, expenditure on Parkinsons disease admissions in England is under-estimated by approximately £61 million per year.

PD REHAB: a large pragmatic randomised controlled trial of physiotherapy and occupational therapy versus no therapy in mild to moderate Parkinson's disease

Objective: To explore the association between striatal dopaminergic deficits and cognitive impairment within a large cohort of early, drug-naive Parkinson’s disease patients and to test the hypothesis that executive dysfunction in Parkinson’s disease is caused by striatal dopaminergic depletion. Background: Cognitive impairment in Parkinson’s disease is common and influences patients’ everyday functioning, but the mechanisms of early cognitive decline are not known. Understanding of these mechanisms is important for the development of methods preventing cognitive decline in Parkinson’s disease. Previous studies suggest that the dopaminergic system influences cognition in PD. Methods: Neuropsychological and cerebral dopamine transporter SPECT imaging data of 339 Parkinson’s disease patients and 158 Healthy controls of the Parkinson’s Progression Markers Initiative study were analysed. Neuropsychological evaluation consisted of standardized tests of memory, visuospatial and executive function. SPECT imaging was performed with [123I]FP-CIT and specific binding ratios in left and right putamen and caudate nucleus were calculated. The association between specific binding ratios and cognition was performed using a cognitive composite z-score, domain z-scores and individual test scores. Multivariate general linear model regression analyses were performed including age, gender, education, and laterality as predictors and specific binding ratios as dependent variables. Results: Uncorrected analysis showed no associations between dopamine transporter imaging and memory and visuospatial domains. A small but significant positive association between specific binding ratios and the attention/executive domain was found, which was not significant after adjusting for age. However, in a moderated mediation model, we found that cognitive executive differences between controls and patients with Parkinson’s disease were mediated by an age-moderated dopaminergic deficit in the left caudate nucleus. Conclusions: Our findings support the hypothesis that nigrostriatal dopaminergic deficit contributes to executive impairment, but not to memory or visuospatial impairment in early Parkinson’s disease.Objective: To investigate whether spirography-based objective measures of motor dysfunctions are able to discriminate between Parkinson’s disease (PD) patients with different motor states (Off and ...Objective: This study aims to determine PPN’s electrophysiological activities in rats to help future studies and to investigate the effect of subthalamic nucleus stimulation on PPN. Background: Long-duration medical treatment of Parkinson patients causes complications and morbidity. Risks in destructive surgery are releatively high, new treatment methods such as stereotactic functional surgery has been proposed recently. While sensory and behavioral processes of pedunculopontine nucleus (PPN) are well known as a locomotor center, its role on initiating and sustaining motion function in primates or rats has been also demonstrated. All functions of PPN are not fully known yet, and its DBS has been proposed as an alternative therapeutic target in treating gait problems of Parkinson’s disease recently. Methods: In this study, 14 male wistar type healthy rats with average 292 (284-317) gram weight and with the same age group were used. In the sham group, two probes were inserted, one to the STN bilaterally and the other to the right PPN to record PPN’s electrophysiological activities. In the experiment group, in addition to the same procedures used in the sham group, STN was stimulated bilaterally at 0.5 Hz, 10 Hz, 60 Hz ve 130 Hz and PPN’s electrophysiological activities were recorded before and after bilateral STN stimulations. Results: Analyzing the neural activity after the 60 Hz stimulation, it revealed that STN has a stimulus effect on PPN neurons increasing the firing rate. The PPN neurons demonstrated three different patterns of firing, burst random and regular. The majority of the neurons (68%) exhibited a regular pattern of firing in the sham group. After bilateral STN stimulation with very low (0,5 Hz and 10 Hz) and high (130 Hz) frequencies the PPN neurons maintained their firing patterns. However, after 60 Hz stimulation of STN a significant percentage of neurons (82,1 %) fired with a more regular pattern. Conclusions: The results of this study provides additional information to our understanding on PPN’s electrophysiological activities. 60 Hz STN stimulation can increase the firing rates and changes the behaviour of the PPN neurons.Objective: To analyze the relationship between the electric field and the volume of tissue activated (VTA) during model-based investigations of deep brain stimulation (DBS).Background: An important ...This journal suppl. entitled: Supplement: Abstracts of the Eighteenth International Congress of Parkinsons Disease and Movement Disorders / Poster Presentation