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Functional dependency in basic activities of daily living (ADLs) is a key outcome in Parkinson's disease (PD). We aimed to define dependency in PD, using the original and MDS versions of the Unified Parkinson's Disease Rating Scale (UPDRS).We developed two algorithms to define dependency from items of UPDRS Part 2 and MDS-UPDRS Part 2 relating to basic ADLs (feeding, dressing, hygiene and walking, and getting out of a chair). We validated both algorithms using data from 1110 patients from six community-based PD incidence cohorts, testing concurrent validity, convergent validity, and predictive validity.Our optimal algorithm showed high specificity and moderate to high sensitivity versus SchwabEngland80% (specificity 95% [95% confidence interval (CI) 93-97] and sensitivity 65% [95% CI 55-73] at baseline; 88% [95% CI 85-91] and 85% [95% CI 79-97] respectively at five-years follow-up). Convergent validity was demonstrated by strong associations between dependency defined by the algorithm and cognition (MMSE), quality of life (PDQ39), and impairment (UPDRS part 3) (all p 0.001). Algorithm-defined dependency status also predicted mortality: HR for mortality in those dependent vs independent at baseline was 1.6 (95%CI 1.2-2.1) and in those dependent vs independent at five-years' follow-up was 2.2 (1.6-3.0).We have demonstrated the concurrent validity, convergent validity, and predictive validity of a UPDRS-/MDS-UPDRS-based algorithm to define functional dependency in PD. This can be used for studying dependency in any study where UPDRS or MDS-UPDRS part 2 data have been collected.

Objective To describe, and explore heterogeneity in, age at onset/diagnosis in Parkinson's disease (PD) and compare mean age at onset/diagnosis in incidence studies with that in general PD research studies. Methods We systematically reviewed studies of PD incidence. We meta-analysed mean age at onset/diagnosis and age-stratum-specific incidence rates. We compared age-specific incidence rates in screening studies in the elderly with whole-population studies. We collated mean ages at onset/diagnosis in clinical studies of PD in five journals July–December 2016. Results In 17 studies reporting sufficient data to pool, mean age at onset/diagnosis was 69.6 years (95% CI 68.2–71.1), but heterogeneity was high (I2 = 96%). In ten of these studies reporting age at diagnosis specifically, the pooled mean age at diagnosis was slightly higher (71.6 [95% CI 70.6–72.6]) with lower, but still high, heterogeneity (I2 = 84%). In twelve whole-population studies reporting age-specific incidence rates, these peaked in age 70–79 (pooled incidence rate per 100,000 = 93.8 [95% CI 80.3–107.4]). Heterogeneity increased with each increase in age stratum (0% in youngest to 88% in oldest age stratum). Pooled age-specific incidence rates in five population-based screening studies of older age groups were several-fold higher than in whole-population studies. The mean of the reported mean ages at onset/diagnosis in recently published research studies was 60.8 (SD 5.6). Conclusion The mean age of onset/diagnosis PD is about 70, although this may be an underestimate due to under-diagnosis in the elderly. Many published studies use age-unrepresentative subjects: the effect of this selection bias deserves further study.

Objectives To assess the efficacy of comprehensive geriatric assessment (CGA) in prevention of delirium after hip fracture. Design Systematic review and metaanalysis. Setting Ward based models on geriatrics wards and visiting team based models on orthopaedics wards were included. Participants Four trials (three European, one U.S.; 973 participants) were identified. Two assessed ward-based, and two assessed team-based interventions. Measurements MEDLINE, EMBASE, CINAHL and PsycINFO databases; Clinicaltrials.gov; and the Central Register of Controlled Trials were searched. Reference lists from full-text articles were reviewed. Incidence of delirium was the primary outcome. Length of stay, delirium severity, institutionalization, long-term cognition and mortality were predefined secondary outcomes. Duration of delirium was included as a post hoc outcome. Results There was a significant reduction in delirium overall (relative risk (RR) = 0.81, 95% confidence interval (CI) = 0.69–0.94) in the intervention group. Post hoc subgroup analysis found this effect to be preserved in the team-based intervention group (RR = 0.77, 95% CI = 0.61–0.98) but not the ward-based group. No significant effect was observed on any secondary outcome. Conclusion There was a reduction in the incidence of delirium after hip fracture with CGA. This is in keeping with results of non-randomized controlled trials and trials in other populations. Team-based interventions appeared superior in contrast to the Ellis CGA paper, but it is likely that heterogeneity in interventions and population studied affected this.

There have been few incidence studies of vascular parkinsonism (VP), progressive supranuclear palsy (PSP), and parkinsonian-type multiple system atrophy (MSA-P). We measured the age-, gender- and socioeconomic-specific incidence rates for these conditions in north-east Scotland.Incident non drug-induced parkinsonian patients were identified prospectively over three years by several overlapping methods from a baseline primary care population of 311,357. Parkinsonism was diagnosed if patients had two or more cardinal motor signs. Patients had yearly follow-up to improve diagnostic accuracy. Incidence rates using the diagnosis by established research criteria at latest follow-up were calculated for each condition by age, gender, and socioeconomic status.Of 377 patients identified at baseline with possible or probable parkinsonism, 363 were confirmed as incident patients after median follow-up of 26 months (mean age 74.8 years, SD 9.8; 61% men). The crude annual incidence was 3.2 per 100,000 (95% confidence interval (CI) 2.2-4.3) for VP, 1.7 per 100,000 (95% CI 1.0-2.4) for PSP, and 1.4 per 100,000 (95% CI 0.8-2.1) for MSA-P. VP and MSA-P were more common in men (age-adjusted male to female ratios 2.58 (95% CI 1.65-3.83) and 8.65 (95% CI 4.73-14.5) respectively). Incidence did not vary with socioeconomic status.This is the first community-based, prospective study to report the incidence of vascular parkinsonism and the third to report the incidence of PSP and MSA-P. Further follow-up and comparison with similar studies in different populations will yield valuable prognostic and aetiological information on these conditions.

Optimizing drug therapy is an essential part of caring for an older person. Prescribing in this group has unique challenges because of the high interindividual variability in pharmacological response and the fact that frailty, rather than age, predicts physiological responses to external stimuli. The effects of drugs and how they are handled by the body change in a number of ways with increasing age. With decreasing life expectancy, drugs used for secondary prevention might not be appropriate, particularly where their adverse effects lead to a reduction in short-term quality of life. The issue of polypharmacy is of particular concern in older people who, compared with younger individuals, tend to have more disease conditions for which therapies are prescribed. A number of drugs and combinations of drugs are particularly likely to cause harm to the older person with frailty, and these should be prescribed only where there is clear benefit. Unfortunately, the process of weighing the benefits and risks of drugs in this group is made more difficult by a paucity of directly relevant evidence. Formal criteria to identify potentially inappropriate medications have been developed, but can be cumbersome to apply and suffer from a lack of flexibility. Regular medication review is an important part of management of this patient group. Suggested strategies for this are discussed.

Purpose The purpose of this study was to show the viability and performance of a shape-based pattern recognition technique applied to I-N-omega-fluoropropyl-2-beta-carbomethoxy-3beta-(4-iodophenyl) nortropane single-photon emission computed tomography (FP-CIT SPECT) in patients with parkinsonism. Methods A fully automated pattern recognition tool, based on the shape of FP-CIT SPECT images, was written using Java. Its performance was evaluated and compared with QuantiSPECT, a region-of-interest-based quantitation tool, and observer performance using receiver operating characteristic analysis and kappa statistics. The techniques were compared using a sample of patients and controls recruited from a prospective community-based study of first presentation of parkinsonian symptoms with longitudinal follow up (median 3 years). Results The shape-based technique as well as the conventional semiquantitative approach was performed by experienced observers. The technique had a high level of automation, thereby avoiding observer/operator variability. Conclusion A pattern recognition approach is a viable alternative to traditional methods of analysis in FP-CIT SPECT and has additional advantages.

Background: Accurate diagnosis of the cause of parkinsonism during life can be difficult, particularly at presentation but few studies have described changes in clinical diagnosis over time and the effect of applying strict research criteria. Methods: Incident patients with a possible/probable diagnosis of degenerative or vascular parkinsonism had a standardised assessment at diagnosis and at yearly intervals thereafter at which the most likely clinical diagnosis was recorded without strict application of research criteria. Four years after the beginning of the incident period, formal research criteria were applied retrospectively using patients’ records at baseline and latest yearly follow-up. Results: Of 82 incident patients, 66 underwent at least one year of follow-up. After a median follow-up of 29 months, clinical diagnosis had changed in 22 (33%). Most (82%) changes occurred in the first year and were due to the development of atypical clinical features, particularly early cognitive impairment; the results of brain imaging; responsiveness to levodopa; and the rate of disease progression. Diagnosis on research criteria differed from latest clinical diagnosis in eight participants (12%). Research criteria gave a “probable” diagnosis in 71% of parkinsonian patients at follow-up but only 15% at initial assessment. Discussion: The clinical diagnosis of the cause of parkinsonism at presentation was often incorrect, even when made by those with a special interest. In particular, Parkinson’s disease was overdiagnosed. Research criteria were often unhelpful in clarifying the diagnosis even after a median of 29 months follow-up. Further research is required to identify factors that may be used to improve the accuracy of diagnosis at initial assessment.

In their paper Arri and colleagues1 describe a small, randomised, crossover study that appears to demonstrate dramatic, if temporary, improvement in camptocormia in people with Parkinson's disease (PD) as a result of repetitive trans-spinal magnetic stimulation (rTSMS). While it is hard to argue that this treatment does not bear further investigation, it is not the effect of the treatment, but the lack of effect of the sham intervention that bears further discussion. One of the factors that has made trials in repetitive magnetic stimulation, usually applied transcranially (rTMS), difficult …

Background: The issue of whether to adopt a “wait and watch” strategy or to initiate drug therapy soon after diagnosis in Parkinson’s disease (PD) has been the subject of some debate. A recent observational study supported early treatment by demonstrating deterioration in self-reported health status in those left untreated, but not those who received therapy. We aimed to replicate this observation. Methods: People with PD from a prospective incidence study underwent follow-up with yearly clinical assessment of parkinsonian impairment (Unified Parkinson’s Disease Rating Scale (UPDRS)) and self-reported health status (Parkinson’s Disease Questionnaire (PDQ-39)). Two year outcomes were compared with those who started treatment within 1 year of diagnosis and those left untreated. Results: 42 patients with PD were followed-up for 2 years, of whom 26 started treatment during the first year and 16 remained untreated. Those receiving treatment had significantly higher UPDRS and PDQ-39 scores at baseline. There was no significant deterioration in PDQ-39 score in either group (median change untreated 0.8 vs treated 4.0; p = 0.47), despite a significant difference in the change in motor UPDRS scores (untreated 6.0 vs treated −6.0; p = 0.03). Conclusion: Given the lack of significant deterioration in the PDQ-39 in untreated patients, we believe a “wait and watch” strategy for the treatment of newly diagnosed PD remains a credible approach unless randomised trials prove otherwise.

There have been few high quality incidence studies of Parkinson's disease (PD). We measured age-, gender- and socioeconomic-specific incidence rates for parkinsonism and PD in north-east Scotland, and compared our results with those of previous high quality studies. Incident patients were identified prospectively over three years by several overlapping methods from primary care practices (total population 311,357). Parkinsonism was diagnosed if patients had two or more cardinal motor signs. Drug-induced parkinsonism was excluded. Patients had yearly follow-up to improve diagnostic accuracy. Incidence rates using clinical diagnosis at latest follow-up were calculated for all parkinsonism and for PD by age, gender and socioeconomic status. Meta-analysis with similar studies was performed. Of 377 patients identified at baseline with possible or probable parkinsonism, 363 were confirmed as incident patients after median follow-up of 26 months (mean age 74.8 years, SD 9.8; 61% men). The crude annual incidence of parkinsonism was 28.7 per 100,000 (95% confidence interval (CI) 25.7-31.8) and PD 17.9 per 100,000 (95% CI 15.5-20.4). PD was more common in men (age-adjusted male to female ratio 1.87:1, 95% CI 1.55-2.23) but there was no difference by socioeconomic status. Meta-analysis of 12 studies showed an incidence of PD (adjusted to the 1990 Scottish population) of 14.6 per 100,000 (95% CI 12.2-17.3) with considerable heterogeneity (I(2) 95%), partially explained by population size and recruitment duration. The incidence of PD was similar to other high quality studies. The incidence of PD was not affected by socioeconomic status.

Background: Cognitive decline is common in Parkinson’s disease (PD) but may not be adequately identified by the mini-mental state examination (MMSE), which is better suited to Alzheimer’s disease. The mini-mental Parkinson (MMP) examination is a cognitive screening tool designed in French specifically for PD. We aimed to establish the validity and reliability of the English language version of the MMP compared with the MMSE. Methods: People with various stages of PD underwent testing with the MMP and MMSE, which was then compared with a reference standard battery of neuropsychological tests to identify those with significant cognitive impairment. Results: Forty-nine patients were recruited. Both the MMP and MMSE were significantly correlated with scores on all the neuropsychological tests in the validation battery. The median MMP score was proportionally lower (80% of maximum) than the MMSE (90% of maximum) in PD patients with cognitive impairment and those with prior neuropsychiatric complications but there was no difference between the MMP and MMSE in areas under the curves (0.84) for detecting cognitive impairment. Test-retest reliability of the MMP was good (intra-class correlation coefficient 0.793). An MMP of 28 or lower out of 32 detected cognitive impairment with 87% sensitivity and 76% specificity. Discussion: The English language version of the MMP has now been validated. It detects more cognitive deficits in PD patients than the MMSE and identifies significant cognitive impairment in those with PD at least as well as the MMSE.

Background It has been postulated that monoamine oxidase B (MAO-B) inhibitors alter disease progression in Parkinson's disease (PD) but trials have produced conflicting results. Objectives To assess the effectiveness and safety of long-term use of MAO-B inhibitors compared with other dopaminergic agents in early PD. Search strategy We searched several electronic databases including: the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2009), MEDLINE (January 1950 to February 2009) and EMBASE (January 1980 to February 2009). We also handsearched neurology and movement disorders conference proceedings, checked reference lists of relevant studies and contacted other researchers. Selection criteria We included all randomised controlled trials that compared a MAO-B inhibitor with other dopaminergic agents (presently levodopa or dopamine agonists) in patients with early PD, where treatment and follow up lasted at least one year. Data collection and analysis Two reviewers independently selected trials for inclusion, assessed the methodological quality, and extracted the data. Additional data were provided by the original authors. Random-effects models were used to analyse results, where appropriate. Main results Only two eligible trials were included (593 patients), both of reasonable quality although one was unblinded. Both trials compared selegiline with a dopamine agonist, whilst one also compared selegiline with levodopa. MAO-B inhibitors were not associated with a significant increase or decrease in deaths compared with levodopa (odds ratio (OR) 0.96; 95% confidence interval (CI) 0.52 to 1.76) or dopamine agonists (OR 1.30; 95% CI 0.69 to 2.45). Those receiving MAO-B inhibitors were more likely to require add-on therapy during follow-up than those receiving levodopa (OR 12.02; 95% CI 6.78 to 21.31) or dopamine agonist (OR 2.00; 95% CI 1.05 to 3.81). There was a reduction in motor fluctuations with MAO-B inhibitors compared with levodopa (OR 0.55; 95% CI 0.32 to 0.94) but not dopamine agonists (OR 1.15; 95% CI 0.65 to 2.05). Withdrawals due to adverse events were less common with MAO-B inhibitors than with dopamine agonists (OR 0.11; 95% CI 0.01 to 0.99). Authors' conclusions MAO-B inhibitors are one option for the early treatment of PD although they have weaker symptomatic effects than levodopa and dopamine agonists. They may reduce the rate of motor fluctuations compared with initial levodopa therapy and may have fewer significant adverse effects than the older agonists but data are too few to provide reliable conclusions.

Parkinson’s disease (PD) is a neurodegenerative disease, the clinical features of which are usually asymmetrical at presentation. This can lead to difficulty in differentiating it from other asymmetric neurological disorders. We present two cases where idiopathic PD was initially misdiagnosed as stroke, leading to a delay in appropriate symptomatic therapy. Physicians involved in diagnosis and treatment of people with strokes should consider PD when formulating their differential diagnosis.

Background It has been postulated that monoamine oxidase B (MAO-B) inhibitors alter disease progression in Parkinson's disease (PD). Clinical trials have produced conflicting results. Objectives To assess the evidence from randomized controlled trials for the effectiveness and safety of long-term use of MAO-B inhibitors in early PD. Search strategy We searched the following electronic databases: Cochrane Central Register of Controlled trials (CENTRAL) (The Cochrane Library Issue 2, 2004), MEDLINE (last searched 18th August 2004) and EMBASE (last searched 18th August 2004). We also handsearched neurology and movement disorders conference proceedings, checked reference lists of relevant studies and contacted other researchers. Selection criteria We sought to include all unconfounded randomized controlled trials that compared a MAO-B inhibitor with control, in the presence or absence of levodopa or dopamine agonists, in patients with early PD and where treatment and follow up lasted at least one year. Data collection and analysis Two reviewers independently selected trials for inclusion, assessed the methodological quality, and extracted the data. A small amount of additional data was provided by the original authors. Random-effects models were used to analyse results, where appropriate. Main results Ten trials were included (a total of 2422 patients), nine using selegiline, one using lazabemide. The methodological quality was reasonable although concealment of allocation was definitely adequate in only four trials. The mean follow up was for 5.8 years. MAO-B inhibitors were not associated with a significant increase in deaths (odds ratio (OR) 1.15; 95% confidence interval (CI) 0.92 to 1.44). They provided small benefits over control in impairment (weighted mean difference (WMD) for change in motor UPDRS score was 3.81 points less with MAO-B inhibitors; 95% CI 2.27 to 5.36) and disability (WMD for change in UPDRS ADL score was 1.50 less; 95% CI 0.48 to 2.53) at one year which, although statistically significant, were not clinically significant. There was a marked levodopa-sparing effect with MAO-B inhibitors which was associated with a significant reduction in motor fluctuations (OR 0.75; 95% CI 0.59 to 0.94) but not dyskinesia (OR 0.97; 95% CI 0.76 to 1.25). The reduction in motor fluctuations was, however, not robust in sensitivity analyses. Although adverse events were generally mild and infrequent, withdrawals due to side-effects were higher (OR 2.36; 95% CI 1.32 to 4.20) with MAO-B inhibitors. Authors' conclusions MAO-B inhibitors do not appear to delay disease progression but may have a beneficial effect on motor fluctuations. There was no statistically significant effect on deaths although the confidence interval does not exclude a small increase with MAO-B inhibitors. At present we do not feel these drugs can be recommended for routine use in the treatment of early Parkinson's disease but further randomized controlled trials should be carried out to clarify, in particular, their effect on deaths and motor complications.

Colorectal cancer is a major health problem in the western world and is associated with significant morbidity and mortality. Diet makes a significant contribution to the disease, with high fat, low fibre diets correlating positively with a high incidence of colorectal cancer. Intracellular polyamine concentrations and ornithine decarboxylase activity are both increased in colorectal cancer tissue and in premalignant polyps. Measurement of the polyamine content of serum and urine of individuals has been proposed as a diagnostic marker of malignancy but a number of false positives make this idea untenable. There may, however, still be a role for the measurement of urinary polyamine content as a means of monitoring the efficacy of therapy. Inhibition of polyamine metabolism by polyamine analogues or by non-steroidal anti-inflammatory drugs may be useful in the chemotherapy and/or chemoprevention of colorectal cancer. Preliminary results suggest that a low polyamine diet might be helpful as part of a health care plan for cancer patients.

Background There have been few high-quality incidence studies of parkinsonism/Parkinson9s disease (PD) worldwide and none from Scotland. Methods We performed a population-based prospective incidence study of degenerative or vascular parkinsonian disorders from 37 general practices (population 317 884) in and around Aberdeen over 3 years. Patients were identified by direct referral by GPs or hospital physicians/psychiatrists, by searching referral letters, and by searching GP databases and hospital discharge data. Incident patients had to have two or more of the cardinal motor symptoms. The most likely clinical diagnosis was made after assessment by a movement disorder expert. Incidence rates were calculated for all parkinsonism combined and for PD specifically and were also compared by age, sex and socioeconomic status. Results By August 2009, 250 incident patients with parkinsonism had been identified (mean age 74 years, 152 men), 151 (88 men) with a baseline clinical diagnosis of PD. The crude annual incidence of parkinsonism was 26 per 100 000 (95% CI 23 to 29.5) and PD 16 per 100 000 (95% CI 13 to 18). Incidence increased over the age of 60 with a peak between 80 and 89 years (PD 137 per 100 000). PD was more common in men (1.9:1) but there was no difference by socioeconomic status. Conclusion The incidence of parkinsonism/PD in north-east Scotland is similar to other high-quality studies but with a significantly higher mean age of diagnosis.