Workforce unavailability in Parkinson's disease.

OBJECTIVES: Individuals with Parkinson's disease (PD) become unavailable in the workforce earlier than comparable members of the general population. This may result in significant social insurance expenses, but as workforce participation can be a source for social interaction and a vital part of the personal identity, there are likely to be personal implications extending far beyond the economic aspects. This study aimed to identify aspects that may contribute to workforce unavailability in people with PD. MATERIALS & METHODS: This was a cross-sectional registry study using data from the Swedish national quality registry for PD and included persons with PD in Skåne County, Sweden who were younger than 65 years. Variables were selected from the registry based on earlier studies and clinical experience and were tested for association with unavailability in the workforce: first in a series of simple regression analyses and then in a multiple logistic regression analysis. RESULTS: A total of 99 persons with PD-of whom 59 were available and 40 were unavailable in the workforce-were included in the study. Age (OR per year: 1.47, 95% CI: 1.18-1.85; P < 0.01) and anxiety (OR: 6.81, 95% CI: 1.20-38.67; P = 0.03) were significant contributing factors for unavailability in the workforce. CONCLUSIONS: Based on the findings in this exploratory study, anxiety-a potentially modifiable factor-and age may be contributing factors for workforce unavailability in PD. However, prospective studies are warranted to confirm the findings and the causation of the association between anxiety and workforce unavailability needs to be clarified.

Is excessive daytime sleepiness a separate manifestation in Parkinson's disease?

BACKGROUND: Excessive daytime sleepiness (EDS) is common in Parkinson's disease (PD), but its role and relation to other PD features is less well understood. OBJECTIVE: To investigate potential predictors of EDS in PD and to explore how EDS relates to other motor and non-motor PD features. METHODS: 118 consecutive persons with PD (54% men; mean age, 64) were assessed regarding EDS using the Epworth Sleepiness Scale (ESS) and a range of motor and non-motor symptoms. Variables significantly associated with ESS scores in bivariate analyses were used in multiple regression analyses with ESS scores as the dependent variable. Principal component analysis (PCA) was conducted to explore the interrelationships between ESS scores and other motor and non-motor PD aspects. RESULTS: Among 114 persons with complete ESS data, significant independent associations were found between ESS scores and axial/postural/gait impairment, depressive symptoms, and pain (R2, 0.199). ESS scores did not load significantly together with any other PD features in the PCA. CONCLUSIONS: Only a limited proportion of the variation in EDS could be accounted for by other symptoms, and EDS did not cluster together with any other PD features in PCAs. This suggests that EDS is a separate manifestation differing from, for example, poor sleep quality and fatigue.

Interim analysis of long-term intraduodenal levodopa infusion in advanced Parkinson disease.

BACKGROUND: This interim 12-month analysis is a part of an open-label, observational, prospective study on health outcomes and cost impact of levodopa/carbidopa intestinal gel (LCIG, Duodopa) in Parkinson disease (PD). The specific aim was to investigate clinical and health-related quality of life (HRQoL) effects in routine care. METHODS: Unified PD rating scale (UPDRS) was the primary efficacy measurement. PD QoL questionnaire 39 (PDQ-39) assessed HRQoL. Subjects were assessed at baseline, ≥3 months after surgery, and then every 3 months. RESULTS: Twenty-seven treatment-naïve subjects when started with LCIG showed a decrease in UPDRS score that was statistically significant throughout the year: UPDRS total score (mean ± SD), baseline = 52.1 ± 16.1, N = 27, month 0 (first visit; at least 3 months after permanent LCIG) = 43.1 ± 16.7, N = 27, P = 0.003; month 12 = 42.5 ± 22.6, n = 25, P = 0.017. PDQ-39 results also showed a tendency for improvement: PDQ-39 (mean ± SD), baseline = 33.6 ± 10.8, N = 27, month 0 = 27.1 ± 11.8, N = 27, P = 0.001; 12 months = 28.8 ± 12.8, n = 23, P = 0.126. CONCLUSIONS: LCIG provides functional improvement beginning at first visit that is sustained for 12 months.

A Swedish version of the 16-item Parkinson fatigue scale (PFS-16).

BACKGROUND: The PFS-16 is a 16-item fatigue scale for Parkinson's disease (PD) developed in the UK. However, documented translations and psychometric evaluations are sparse. AIM: To translate the PFS-16 into Swedish and conduct initial testing of its psychometric properties. METHODS: Following translation, the PFS-16 was administered twice (2 weeks apart) to 30 people with PD (18 men; mean age/PD duration, 60/6.4 years). The PFS-16 uses five response categories (1 = strongly disagree, 5 = strongly agree), and the total score is the mean over item scores (1-5; 5 = more fatigue). An alternative, dichotomised scoring method has also been suggested (total score, 0-16; 16 = more fatigue). Scaling assumptions, floor/ceiling effects, reliability, and correlations with other variables including the generic fatigue scale Functional Assessment of Chronic Illness Therapy - Fatigue scale (FACIT-F) were tested. RESULTS: Scaling assumptions were generally supported for the original scoring [range of mean (SD) item scores, 2.1-3.3 (1-1.4); corrected item-total correlations, ≥0.40], but not for dichotomised scoring [range of mean (SD) item scores, 0.1-0.6 (0.3-0.5); corrected item-total correlations, ≥0.16]. Reliabilities were ≥0.88. Floor effects were absent (original scoring) and >23% (dichotomised scoring); there were no ceiling effects. Correlations with other variables followed expectations (e.g. -0.88 with FACIT-F scores). CONCLUSIONS: These observations support the psychometric properties of the Swedish PFS-16, but cautions against dichotomised scoring.

Depressive illness in Parkinson's disease--indication of a more advanced and widespread neurodegenerative process?

OBJECTIVE: The aims were to study if the type and complexity of Parkinsonian symptoms, as well as treatment, could be related to the occurrence and severity of later depressive symptoms. Furthermore, the aim was to study if there is a different depressive symptomatology in Parkinson's disease (PD) patients compared with depressive illness in an age-matched group of patients with major depression but without Parkinson's disease. METHODS: Eleven PD-patients with major depression (MD) were compared to 14 PD-patients without depression and to 12 MD patients without PD. RESULTS: PD patients who later developed a depressive illness were younger at the debut of PD than patients without depression (P < 0.05). At inclusion the depressed PD patients were more disabled than PD patients without depression with higher level in the H&Y scale (P<0.05), and they had more involuntary movements according to Unified Parkinson's Disease Rating Scale (UPDRS IV) (P < 0.01). A family history of depression was found in one third of the depressed non-parkinsonian patients but in none of the PD groups. Sleep disturbances were significantly more common among depressed PD patients than in PD patients without depression but even more common in depressed patients without PD. CONCLUSIONS: Depressed PD patients had a longer duration of PD and more severe motor symptoms than PD patients without depression, although tremor as an initial symptom seemed to be more common in PD without a later depression. It cannot be excluded that depression in PD reflects a more advanced and widespread neurodegeneration, including serotonergic as well as dopaminergic neurons. Sleep disturbances is common and could be overlooked as an expression of depression.

Outcome prediction of enteral levodopa/carbidopa infusion in advanced Parkinson's disease.

Two studies comparing intraduodenal infusion of a levodopa/carbidopa gel with oral treatments in advanced PD patients demonstrated improvement in UPDRS scores and in frequent clinical ratings on a global treatment response scale. Further analysis of data from these studies was performed to find predictive factors related to degree of improvement with infusion. Pearson's correlation coefficients between measures of improvement and baseline variables were calculated. Using data from one study, a prediction model was designed and was then evaluated using the other study's data. Correlations were found indicating that patients with more severe symptoms at baseline were most improved after infusion.

Selegiline slows the progression of the symptoms of Parkinson disease.

OBJECTIVE: To study the long-term effects of selegiline in monotherapy and in combination with levodopa in the early phase of Parkinson disease (PD). METHODS: One hundred fifty-seven de novo PD patients were randomized in a double-blind, placebo-controlled study of 7 years' duration. In the monotherapy part, selegiline significantly delayed the initiation of levodopa therapy vs placebo. The authors now report the results from the combination part of the study, in which 140 patients received selegiline or placebo in addition to individually tailored levodopa therapy. RESULTS: Compared with placebo, selegiline slowed the progression of disease disability as measured by the Unified Parkinson Disease Rating Scale (UPDRS) total score (p = 0.003) or by motor (p = 0.002) and Activities of Daily Living (p = 0.0002) subscores. After 5 years in combination therapy, the mean difference in the UPDRS total score was nearly 10 points, with patients receiving placebo having 35% higher scores. Simultaneously, patients receiving placebo needed progressively higher doses of levodopa than patients receiving selegiline; after 5 years, the mean dosage of levodopa was 19% higher with placebo than with selegiline (p = 0.0002). Considering the entire (monotherapy and combination therapy) 7-year study time, there was a trend for selegiline to delay the start of wearing-off fluctuations (hazard ratio 0.55, p = 0.08). In both phases of the study, selegiline was safe and well tolerated. CONCLUSIONS: The results of this long-term study confirm earlier findings indicating that selegiline delays the progression of the signs and symptoms of Parkinson disease.

Does L-dopa treatment contribute to reduction in body weight in elderly patients with Parkinson's disease?

OBJECTIVE: Many patients with Parkinson's disease (PD) lose weight also early during the disease. The objective of the study was to investigate possible causative factors for this loss. MATERIALS AND METHODS: In this report, 28 PD patients and 28 age- and sex-matched controls were repeatedly assessed with the focus on body weight, body fat mass, dysphagia, olfaction, physical activity, PD symptomatology and drug treatment. RESULTS: Weight loss was seen in PD patients both before and during L-dopa treatment. CONCLUSION: The underlying disease could play a role, but our results also suggest that L-dopa per se could contribute to the weight loss.

Factors of importance for weight loss in elderly patients with Parkinson's disease.

OBJECTIVE: Weight loss is reported frequently in patients with Parkinson's disease (PD). The objective of this study was to find the underlying factors of this phenomenon. PARTICIPANTS AND METHODS: Twenty-six L-dopa-treated patients with PD and 26 age- and sex-matched healthy controls were assessed twice within a 1-year interval. Body weight, body fat mass, resting energy expenditure, physical activity, energy intake, thyroid hormones and cognitive function were investigated. RESULTS: Nineteen (73%) of the PD patients lost body weight, although energy intake and the time for rest increased. Weight loss was most marked in patients with more severe PD symptoms and in whom cognitive function had decreased. Multiple regression analyses showed that determinants for weight loss were female gender, age and low physical activity. CONCLUSION: Weight loss was common in PD patients, in spite of the increased energy intake and was most obvious in patients with increased PD symptoms and decreased cognitive function.

Rufinamide: a double-blind, placebo-controlled proof of principle trial in patients with epilepsy.

OBJECTIVE: This was the first proof of principle clinical trial assessing the efficacy and safety of rufinamide as adjunctive therapy in epileptic patients. The pharmacokinetic (PK) profile of rufinamide was also determined. METHODS: Fifty patients with diagnoses of partial or primary generalized tonic-clonic seizures were enrolled in this 28-day double-blind, placebo-controlled, weekly rising dose (400-1600 mg/day) trial. PK profiles were obtained after administration of single-dose rufinamide prior to and after the Double-blind phase. RESULTS: In the evaluable patient population, seizure frequency decreased by 41% in the rufinamide group and increased by 52% in the placebo group (P=0.040). Thirty-nine percent (39%) of rufinamide-treated and 16% of placebo-treated patients experienced reduction in seizure frequency of at least 50% relative to baseline (P=0.096). SAFETY: Treatment-emergent adverse events (AEs) consisted mainly of neurologic signs and symptoms commonly associated with antiepileptic drugs (AEDs). PHARMACOKINETICS: At steady state, rufinamide reached a peak plasma concentration with a mean time (Tmax) of 3.4 h and a mean half-life (t1/2) of 7.3 h. No autoinduction of rufinamide metabolism occurred. Rufinamide did not influence the plasma concentration of carbamazepine, phenytoin or valproate when added to these single AED regimens. CONCLUSION: Rufinamide has been shown, in this proof of principle trial, to be safe and effective in reducing seizure frequency in epileptic patients with no relevant influence on the metabolism of other AEDs.

Effect of selegiline on mortality in patients with Parkinson's disease: a meta-analysis.

INTRODUCTION: The Parkinson's Disease Research Group of the United Kingdom (PDRG-UK) reported increased mortality in PD patients treated with levodopa plus selegiline compared with those treated with levodopa alone. METHODS: We performed a meta-analysis on five long-term, prospective, randomized trials of selegiline in patients with untreated PD. Included in the analysis were four randomized, double-blind, placebo-controlled studies and one randomized, double-blind, placebo-controlled study of 2 years' duration followed by long-term, open follow-up. RESULTS: The mean duration of follow-up was 4.1 +/- 1.8 years. There were 14 deaths in 297 selegiline-treated patients (4.7%) and 17 deaths in 292 non-selegiline-treated patients (5.8%). The hazard ratio for mortality was 1.02 (95% CI 0.44 to 2.37; p = 0.96). An analysis restricted to patients receiving only levodopa with or without selegiline noted 11 deaths in 257 levodopa/selegiline-treated patients (4.3%) and 11 deaths in 254 patients treated with levodopa alone (4.3%). The hazard ratio was 1.06 (95% CI 0.44 to 2.55; p = 0.90). Death rate per 1,000 patient years was 11.4 in the selegiline group and 14.2 in the nonselegiline group. Kaplan-Meier survival curves reflecting pooled survival data showed no significant difference in duration of survival. The hazard ratio was 0.84 (95% CI 0.41 to 1.70; p = 0.63) for selegiline- versus non-selegiline-treated patients and 1.05 (95% CI 0.46 to 2.43; p = 0.91) for selegiline/levodopa- versus levodopa-treated patients. CONCLUSION: These results contrast with those of the PDRG-UK study and demonstrate no increase in mortality associated with selegiline treatment whether or not patients also received levodopa.

Selegiline delays the onset of disability in de novo parkinsonian patients. Swedish Parkinson Study Group.

OBJECTIVE: The objective of this study was to investigate the effect of selegiline first as monotherapy and then in combination with levodopa in the early phase of PD. METHODS: A total of 157 de novo PD patients were randomized to receive either selegiline or placebo in a double-blind study until levodopa therapy became necessary. Thereafter, the drugs were withdrawn for an 8-week washout period to evaluate the possible symptomatic effect of selegiline. RESULTS: Analysis of Kaplan-Meier survival curves for each group showed that selegiline delayed significantly the need for levodopa therapy (p = 0.028). The semiannual rate of disability progression was slowed down significantly in the selegiline group analyzed with the Unified Parkinson's Disease Rating Scale (total and motor scores; p < 0.001). Selegiline had a "wash-in" effect (i.e., an initial symptomatic amelioration of PD at 6 weeks and 3 months). However, after the 8-week washout period, no significant differences in the deterioration of disability between the groups was revealed in any of the scales, suggesting that besides having a slight symptomatic effect, selegiline may also have neuroprotective effects. Similarly, the progression of symptoms from baseline to the end of the washout period was significantly slower (p = 0.033) in the selegiline group when the progression was adjusted by the time to reach the end point. Selegiline was well tolerated. CONCLUSIONS: Selegiline delayed significantly the need to start levodopa in early PD. After a 2-month washout period (before the start of levodopa therapy) no significant symptomatic effect of selegiline was seen in comparison with the placebo group, supporting the concept of neuroprotective properties of the drug.

Multiple sclerosis and exposure to solvents, ionizing radiation and animals.

Earlier studies have indicated an association between multiple sclerosis and environmental factors, especially occupational exposure to solvents. The present study examined such relationships further. From medical files of hospitals in Kalmar and Jönköping, 91 cases of multiple sclerosis, diagnosed in 1983-1988, were identified from population registers corresponding to the catchment areas of the hospitals, and 348 referents were randomly drawn. The cases and referents answered a questionnaire concerning occupational exposure and animal contacts. The men had significantly elevated risks, determined from logistic odds ratios, for solvent exposure, occupational contact with dogs or cats, and leisure-time contact with caged birds. X-ray treatment and previous diseases were risk indicators among the women. For the men and women together, solvent exposure, radiological work, and previous diseases were associated with clearly elevated risks. Although the study concerned rather few subjects, the findings indicate that several exogenous factors might contribute to the development of multiple sclerosis.

Metoprolol and propranolol in migraine prophylaxis: a double-blind multicentre study.

In a double-blind, cross-over multicentre trial, the prophylactic antimigraine effect of the beta 1-selective beta-blocker metoprolol was evaluated and compared with that of the non-selective beta-blocker propranolol. Metoprolol was used in a dosage of 50 mg b.i.d. and propranolol in 40 mg b.i.d. 56 patients with classical or common migraine were included in the double-blind part of the investigation. 3 patients withdrew, but none because of side-effects. The data suggest that metoprolol is clinically equivalent in effectiveness to propranolol in migraine prophylaxis regarding parameters such as attack frequency, improvement in sum of severity score and subjective evaluation. Both drugs were generally well tolerated and the number of reported side-effects was similar to those reported during the run-in period (placebo).