Identification of the Neural Correlates Underlying Conflict Resolution Performance Using a Rodent Analogue of the Stroop Tests.

The Stroop test is a widely used neuropsychological test measuring attention and conflict resolution, which shows sensitivity across a range of diseases, including Alzheimer's, Parkinson's and Huntington's diseases. A rodent analogue of the Stroop test, the Response-Conflict task (rRCT), allows for systematic investigation of the neural systems underpinning performance in this test. Little is known about the involvement of the basal ganglia in this neural process. The aim of this study was to use the rRCT to determine whether striatal subregions are recruited during conflict resolution processing. To achieve this, rats were exposed to Congruent or Incongruent stimuli in the rRCT and the expression patterns of the immediate early gene Zif268 were analysed throughout cortical, hippocampal and basal ganglia subregions. The results confirmed the previously reported involvement of prefrontal cortical and hippocampal regions, as well as identifying a specific role for the dysgranular (but not granular) retrosplenial cortex in conflict resolution. Finally, performance accuracy correlated significantly with reduced neural activation in the dorsomedial striatum. Involvement of the basal ganglia in this neural process has not previously been reported. These data demonstrate that the cognitive process of conflict resolution requires not only prefrontal cortical regions, but also recruits the dysgranular retrosplenial cortex and the medial region of the neostriatum. These data have implications for understanding the neuroanatomical changes that underpin impaired Stroop performance in people with neurological disorders.

Repeated cardiopulmonary performance measurements in young competitive handball players with and without SARS-CoV-2 infection.

BACKGROUND: The SARS-CoV-2 virus and its long-term consequences in adolescents have a global impact on upcoming medical issues. The aim of this study was to investigate the effects of a SARS-CoV-2 infection on cardiorespiratory parameters in young athletes. METHODS: In a cohort study involving repeated measurements during a six-month period, cardiorespiratory parameters were assessed in infected (SCoV) and non-infected (noSCoV) athletes. We evaluated handball players (17.2 ± 1.0 years) via performance diagnostics and a specific examination after a SARS-CoV-2 infection or without. RESULTS: We observed no significant differences between the two groups at the first visit. But between the first and second visit, the SCoV group's maximum power output was significantly lower than the noSCoV group's (- 48.3 ± 12.5; p ≤ 0.01 vs. - 15.0 ± 26.0 W; p = 0.09). At the second visit, lung diffusion capacity (DLCO/VA, %predicted) did not differ between groups (111.6 ± 11.5 vs. 116.1 ± 11.8%; p = 0.45). HR during comparative stress showed no group differences. The SCoV group's mean oxygen uptake during incremental exercise was lower (Two-way-ANOVA: 1912 vs. 2106 ml; p ≤ 0.01; mean difference: - 194 ml; 95% CI - 317 to - 71); we also noted a significantly lower stroke volume course during exercise (Two-way-ANAOVA: 147.5 vs. 169.5 ml; mean difference: - 22 ml; p ≤ 0.01; 95% CI - 34.2 to - 9.9). The probability of premature ventricular complexes after a SARS-CoV-2 infection yielded an odds ratio of 1.6 (95% CI 0.24-10.81). CONCLUSIONS: The physical performance of young athletes infected with SARS-CoV-2 was impaired. This decreased performance is probably due to cardiac and/or peripheral deconditioning. Studies with larger cohorts are needed to make more profound conclusions.

Multi-Scale Investigation of Human Renal Tissue in Three Dimensions.

Histopathology as a diagnostic mainstay for tissue evaluation is strictly a 2D technology. Combining and supplementing this technology with 3D imaging has been proposed as one future avenue towards refining comprehensive tissue analysis. To this end, we have developed a laboratory-based X-ray method allowing for the investigation of tissue samples in three dimensions with isotropic volume information. To assess the potential of our method for micro-morphology evaluation, we selected several kidney regions from three patients with cystic kidney disease, obstructive nephropathy and diabetic glomerulopathy. Tissue specimens were processed using our in-house-developed X-ray eosin stain and investigated with a commercial microCT and our in-house-built NanoCT. The microCT system provided overview scans with voxel sizes of [Formula: see text] and the NanoCT was employed for higher resolutions including voxel sizes from [Formula: see text] to 210 nm. We present a methodology allowing for a precise micro-morphologic investigation in three dimensions which is compatible with conventional histology. Advantages of our methodology are its versatility with respect to multi-scale investigations, being laboratory-based, allowing for non-destructive imaging and providing isotropic volume information. We believe, that after future developmental work this method might contribute to advanced multi-modal tissue diagnostics.

Effects of surgical face masks on cardiopulmonary parameters during steady state exercise.

Wearing face masks reduce the maximum physical performance. Sports and occupational activities are often associated with submaximal constant intensities. This prospective crossover study examined the effects of medical face masks during constant-load exercise. Fourteen healthy men (age 25.7 ± 3.5 years; height 183.8 ± 8.4 cm; weight 83.6 ± 8.4 kg) performed a lactate minimum test and a body plethysmography with and without masks. They were randomly assigned to two constant load tests at maximal lactate steady state with and without masks. The cardiopulmonary and metabolic responses were monitored using impedance cardiography and ergo-spirometry. The airway resistance was two-fold higher with the surgical mask (SM) than without the mask (SM 0.58 ± 0.16 kPa l-1 vs. control [Co] 0.32 ± 0.08 kPa l-1; p < 0.01). The constant load tests with masks compared with those without masks resulted in a significantly different ventilation (77.1 ± 9.3 l min-1 vs. 82.4 ± 10.7 l min-1; p < 0.01), oxygen uptake (33.1 ± 5 ml min-1 kg-1 vs. 34.5 ± 6 ml min-1 kg-1; p = 0.04), and heart rate (160.1 ± 11.2 bpm vs. 154.5 ± 11.4 bpm; p < 0.01). The mean cardiac output tended to be higher with a mask (28.6 ± 3.9 l min-1 vs. 25.9 ± 4.0 l min-1; p = 0.06). Similar blood pressure (177.2 ± 17.6 mmHg vs. 172.3 ± 15.8 mmHg; p = 0.33), delta lactate (4.7 ± 1.5 mmol l-1 vs. 4.3 ± 1.5 mmol l-1; p = 0.15), and rating of perceived exertion (6.9 ± 1.1 vs. 6.6 ± 1.1; p = 0.16) were observed with and without masks. Surgical face masks increase airway resistance and heart rate during steady state exercise in healthy volunteers. The perceived exertion and endurance performance were unchanged. These results may improve the assessment of wearing face masks during work and physical training.

Effects of surgical and FFP2/N95 face masks on cardiopulmonary exercise capacity.

BACKGROUND: Due to the SARS-CoV2 pandemic, medical face masks are widely recommended for a large number of individuals and long durations. The effect of wearing a surgical and a FFP2/N95 face mask on cardiopulmonary exercise capacity has not been systematically reported. METHODS: This prospective cross-over study quantitated the effects of wearing no mask (nm), a surgical mask (sm) and a FFP2/N95 mask (ffpm) in 12 healthy males (age 38.1 ± 6.2 years, BMI 24.5 ± 2.0 kg/m2). The 36 tests were performed in randomized order. The cardiopulmonary and metabolic responses were monitored by ergo-spirometry and impedance cardiography. Ten domains of comfort/discomfort of wearing a mask were assessed by questionnaire. RESULTS: The pulmonary function parameters were significantly lower with mask (forced expiratory volume: 5.6 ± 1.0 vs 5.3 ± 0.8 vs 6.1 ± 1.0 l/s with sm, ffpm and nm, respectively; p = 0.001; peak expiratory flow: 8.7 ± 1.4 vs 7.5 ± 1.1 vs 9.7 ± 1.6 l/s; p < 0.001). The maximum power was 269 ± 45, 263 ± 42 and 277 ± 46 W with sm, ffpm and nm, respectively; p = 0.002; the ventilation was significantly reduced with both face masks (131 ± 28 vs 114 ± 23 vs 99 ± 19 l/m; p < 0.001). Peak blood lactate response was reduced with mask. Cardiac output was similar with and without mask. Participants reported consistent and marked discomfort wearing the masks, especially ffpm. CONCLUSION: Ventilation, cardiopulmonary exercise capacity and comfort are reduced by surgical masks and highly impaired by FFP2/N95 face masks in healthy individuals. These data are important for recommendations on wearing face masks at work or during physical exercise.

[Application and effects of blood flow restriction training]. / Anwendung und Effekte des "blood flow restriction training".

Blood flow restriction (BFR) limits arterial and venous blood flow and leads to blood pooling, which could increase exercise-induced training effects. Strength training at lower intensities (20-30% of maximum strength) in combination with BFR showed similar effects on muscle hypertrophy as training with 70% without BFR. Low-intensity cycling endurance training with BFR improves muscle hypertrophy and endurance performance and activates angiogenesis. After determination of the complete occlusion pressure on the corresponding extremity, it is recommended that BFR training should be performed with 40-80% of the measured occlusion pressure. During strength training of the upper extremities, an occlusion of 60-80% leads to a reduction in the arterial blood flow by 20-50%. Local ischemia and hypoxia, a stronger metabolic stimulus, swelling of the muscle cells and the increased oxidative stress are discussed as causes for the increased training effects due to BFR. In short-term studies, comparable adjustments to parameters of fibrinolytic activity, coagulation and inflammation could be observed for strength training with and without BFR. So far, thromboses after BFR have been described only rarely but need to be further clarified by appropriate studies. The BFR training leads to a stronger activation of the muscular metabolic reflex and thus to a relatively greater increase in exercise blood pressure, so that cardiovascular parameters should be controlled during BFR training. First meta-analyses with small numbers of healthy people and patients indicate the effectiveness of BFR training. Standardization or guidelines for clinical use are still lacking.

Revealing the Microscopic Structure of Human Renal Cell Carcinoma in Three Dimensions.

For fully characterizing renal cell carcinoma (RCC), information about the 3D tissue microstructure is essential. Histopathology, which represents the current diagnostic gold standard, is destructive and only provides 2D information. 3D X-ray histology endeavors to overcome these limitations by generating 3D data. In a laboratory environment, most techniques struggle with limited resolution and the weak X-ray attenuation contrast of soft tissue. We recently developed a laboratory-based method combining nanoscopic X-ray CT with a cytoplasm-specific X-ray stain. Here, we present the application of this method to human RCC biopsies. The NanoCT slices enable pathological characterization of crucial structures by reproducing tissue morphology with a similar detail level as corresponding histological light microscopy images. Beyond that, our data offer deeper insights into the 3D configuration of the tumor. By demonstrating the compatibility of the X-ray stain with standard pathological stains, we highlight the feasibility of integrating staining based NanoCT into the pathological routine.

Automated Assessment of Movement Impairment in Huntington's Disease.

Quantitative assessment of movement impairment in Huntington's disease (HD) is essential to monitoring of disease progression. This paper aimed to develop and validate a novel low cost, objective automated system for the evaluation of upper limb movement impairment in HD in order to eliminate the inconsistency of the assessor and offer a more sensitive, continuous assessment scale. Patients with genetically confirmed HD and healthy controls were recruited to this observational study. Demographic data, including age (years), gender, and unified HD rating scale total motor score (UHDRS-TMS), were recorded. For the purposes of this paper, a modified upper limb motor impairment score (mULMS) was generated from the UHDRS-TMS. All participants completed a brief, standardized clinical assessment of upper limb dexterity while wearing a tri-axial accelerometer on each wrist and on the sternum. The captured acceleration data were used to develop an automatic classification system for discriminating between healthy and HD participants and to automatically generate a continuous movement impairment score (MIS) that reflected the degree of the movement impairment. Data from 48 healthy and 44 HD participants was used to validate the developed system, which achieved 98.78% accuracy in discriminating between healthy and HD participants. The Pearson correlation coefficient between the automatic MIS and the clinician rated mULMS was 0.77 with a p-value < 0.01. The approach presented in this paper demonstrates the possibility of an automated objective, consistent, and sensitive assessment of the HD movement impairment.

Size-dependent loss of aboveground animals differentially affects grassland ecosystem coupling and functions.

Increasing evidence suggests that community-level responses to human-induced biodiversity loss start with a decrease of interactions among communities and between them and their abiotic environment. The structural and functional consequences of such interaction losses are poorly understood and have rarely been tested in real-world systems. Here, we analysed how 5 years of progressive, size-selective exclusion of large, medium, and small vertebrates and invertebrates-a realistic scenario of human-induced defaunation-impacts the strength of relationships between above- and belowground communities and their abiotic environment (hereafter ecosystem coupling) and how this relates to ecosystem functionality in grasslands. Exclusion of all vertebrates results in the greatest level of ecosystem coupling, while the additional loss of invertebrates leads to poorly coupled ecosystems. Consumer-driven changes in ecosystem functionality are positively related to changes in ecosystem coupling. Our results highlight the importance of invertebrate communities for maintaining ecological coupling and functioning in an increasingly defaunated world.

Alterations in the metabolic and cardiorespiratory response to exercise in Huntington's Disease.

BACKGROUND: Limited data suggests that an altered metabolic and cardiorespiratory exercise response may affect exercise performance in individuals with Huntington's disease (HD). There is no clear exploration of the response in individuals at different stages of the disease or in relation to genetic markers. This study aimed to examine the exercise response and recovery of HD participants, and the relationship to genetic and clinical markers. METHOD: HD gene-positive participants (n = 31; 9 pre-manifest; 22 manifest HD) and a healthy control group (n = 29) performed an incremental exercise test until exhaustion. Performance, cardiorespiratory, metabolic and perceptual responses to exercise were determined from a maximal cycle ergometer test throughout the exercise test and during a recovery period. RESULTS: During sub-maximal exercise, metabolic (lactate levels, oxygen uptake) and cardiorespiratory markers (heart rate) were elevated in HD participants compared to controls. Lactate elevation was specific to pre-manifest HD participants. Work capacity was reduced in both pre-manifest and manifest HD participants with tests terminated with no difference in metabolic, perceptual or cardiorespiratory markers. Submaximal oxygen uptake was correlated with motor score, whilst peak measures were unrelated to genetic or clinical markers. Heart rate recovery was attenuated in pre-manifest and manifest HD participants. CONCLUSIONS: Our findings confirm metabolic and cardiorespiratory deficits reduce exercise performance and affect recovery from an early stage in HD, with submaximal deficits related to phenotypic expression. Exercise capacity appears to be limited by an altered movement economy, thus clinicians should consider an altered exercise response and recovery may affect prescription in HD.

The societal cost of Huntington's disease: are we underestimating the burden?

BACKGROUND AND PURPOSE: Approximately 9000 people in the UK are affected by Huntington's disease (HD). People with HD require ongoing health and social care support. There is a knowledge gap about costs of health and social care use associated with HD in the UK. This paper estimates the economic cost in the UK. METHODS: Data on UK patients for the year 2013 were extracted from the European Huntington's Disease Network REGISTRY study, a full clinical dataset, including the full medical history and medication history for patients with HD. National unit costs for the price year 2013 were applied to health and social care services. RESULTS: Data were available for 131 people. The mean annual cost per person with HD was £21 605. The largest proportion of this cost (65%) was due to informal care (£14 085). CONCLUSIONS: Informal care was the largest driver of costs across all stages of HD; thus there is a need to also consider the needs of carers when planning services for people with HD.

Exercise testing and training in people with Huntington's disease.

OBJECTIVE: To explore exercise response in people with Huntington's disease (HD). DESIGN: Experimental observational study with a randomly allocated subgroup before/after interventional study. SETTING: Community. SUBJECTS: People with HD (n=30) and a healthy comparator group (n=20). Thirteen people from the HD group were randomly allocated to an exercise training program. MAIN MEASURES: Heart rate (HR) and perceived exertion on the Borg-CR10 scale (RPE) during a submaximal cycle ergometer exercise test (three minute unloaded and nine minute 65%-75%HRmaximum phase). Expired air and lactate measures were available for 8 people with HD during the exercise. INTERVENTION: A 12 week gym and home walking exercise programme (n=13). RESULTS: People with HD achieved a lower work rate at nine minutes (82±42(0-195) v 107±35(50 -185) Watts (p<0.05)), but higher RPE at both three (3±2(0-7) v 1±1(0-4)) and nine minutes (7±3(1-10) v 5± 2(2-9)) both p<0.01, compared to the healthy group and did not achieve a steady state HR during unloaded cycling. People with HD also demonstrated higher than expected lactate at three 2.5±2.5(1.1-8)mmo.L-1 and nine 3.8±1.9(1.2-6.6)mmo.L-1 minutes and respiratory exchange ratio at three 0.78±0.03 (0.74-0.81) and nine minutes 0.94±0.11(0.81-1.15). After exercise training there were no changes observed in HR or RPE responses during the exercise test. CONCLUSIONS: There was a large variability in the observed metabolic and physiological responses to exercise in people with HD. The observed exercise responses suggest that altered exercise prescription parameters may be required for people with HD and that exercise response and factors' affecting this requires further investigation.

Long-term safety and sustained efficacy of extended-release pramipexole in early and advanced Parkinson's disease.

BACKGROUND AND PURPOSE: To assess the long-term safety and efficacy of pramipexole as a once-daily (q.d.) extended-release oral formulation in early or advanced Parkinson's disease (PD). METHODS: In two double-blind (DB) studies of early PD and one of advanced PD,active-treatment arms received pramipexole immediate release (IR) or extended release (ER), with exposure lasting up to 33 weeks. In open-label (OL) extensions that followed immediately, subjects took ER q.d. for up to 80 weeks, with dosage adjustment permitted (range 0.375-4.5 mg q.d.). RESULTS: Of 590 subjects completing an early-PD DB study, 511 entered the early-PD OL extension; 408 completed it. Reported adverse events (AEs) with incidence ≥10.0% were somnolence (15.1%), peripheral edema (11.7%) and back pain (10.6%). Of 465 subjects completing the advanced-PD DB study, 391 entered the advanced-PD OL extension; 329 completed it. Reported AEs with incidence ≥10.0%were dyskinesia (27.4%) and somnolence (13.6%). Impulse control disorders were identified by semi-structured interview in 13 subjects (1.4% of 902). In exploratory analyses, adjusted mean Unified Parkinson's Disease Rating Scale (UPDRS) PartsII + III scores (excluding ex-placebo recipients) remained substantially improved from DB baseline scores prior to pramipexole introduction, at -6.6 and -6.3 points amongst ex-DB-ER and ex-DB-IR recipients after 113 weeks of pramipexole (33 DB plus 80 OL) in early PD, and -11.5 and -9.1 after up to 113 weeks (up to 33 DB plus 80 OL) in advanced PD. CONCLUSIONS: These results support the long-term safety and efficacy of pramipexole ER in early and advanced PD. AEs were typical for dopaminergic medications, and UPDRS scores suggested sustained symptomatic benefit.

Patient-reported convenience of once-daily versus three-times-daily dosing during long-term studies of pramipexole in early and advanced Parkinson's disease.

BACKGROUND AND PURPOSE: In chronic diseases including Parkinson's disease (PD), complex pharmacotherapy dosing schedules are reported to reduce adherence, perhaps leading to less-effective symptom control and, in PD, more erratic stimulation of dopamine receptors. However, blinded clinical-trial designs preclude direct comparisons of adherence to various schedules. METHODS: In two double-blind (DB) studies of early PD and one of advanced PD, subjects received three-times-daily (t.i.d.) pramipexole or placebo. In open-label (OL) extensions, subjects took extended-release, once-daily (q.d.) pramipexole. At 24 or 32 OL weeks, q.d. versus t.i.d. dosing preference was surveyed by questionnaire. RESULTS: Of 590 DB-trial completers with early PD, 511 entered the OL extension. Of 374 survey respondents, 94.4% preferred q.d. dosing (72.2% of them found it 'very much more convenient' and 27.8%'more convenient'), 2.7% preferred t.i.d., and 2.9% chose 'no difference'. Of 465 DB-trial completers with advanced PD, 391 entered its OL extension. Of 334 survey respondents, 88.9% preferred q.d. dosing (59.9% of them found it 'very much more convenient' and 40.1%'more convenient'), 5.7% preferred t.i.d., and 5.4% chose 'no difference'. Results excluding DB-placebo recipients were highly similar. CONCLUSIONS: In this first direct comparison of patient preference for q.d. versus t.i.d. dopamine-agonist dosing, patients with early or advanced PD had a strong preference for q.d. rather than t.i.d. pramipexole. The high proportion of advanced-PD patients declaring this preference indicates that it does not depend on whether a patient is taking concomitant PD medications dosed more frequently than q.d.

Success rate, efficacy, and safety/tolerability of overnight switching from immediate- to extended-release pramipexole in advanced Parkinson's disease.

BACKGROUND AND PURPOSE: For Parkinson's disease (PD), an extended-release (ER) pramipexole formulation taken once daily, has shown efficacy, safety, and tolerability resembling those of immediate-release (IR) pramipexole taken three times daily. The present study assessed, in advanced PD, the success of an overnight switch from adjunctive IR to ER. METHODS: Levodopa users experiencing motor fluctuations were randomized to adjunctive double-blind (DB) placebo, IR, or ER. Amongst completers of ≥18 weeks, ER recipients were kept on DB ER, whilst IR recipients were switched overnight to DB ER at unchanged daily dosage. After a DB week, switch success was assessed. During the next 5 weeks, all patients underwent ER titration to optimal open-label maintenance dosage. RESULTS: One week post-switch, 86.2% of 123 IR-to-ER and 83.8% of 105 ER-to-ER patients had ≤15% (or ≤3-point, for pre-switch scores ≤20) increase on UPDRS Parts II + III, and 77.9% (of 122) and 70.2% (of 104) had ≤1-h increase in daily OFF-time. At 32 weeks, the groups showed comparable improvements from DB baseline (pramipexole inception), including, on UPDRS II + III, adjusted mean (SE) changes of -14.8 (1.5) for IR-to-ER and -13.3 (1.6) for ER-to-ER. Rates of premature discontinuation owing to adverse events were 6.5% for IR-to-ER and 4.9% for ER-to-ER. CONCLUSIONS: By OFF-time and UPDRS criteria, majorities of patients with advanced PD were successfully switched overnight from pramipexole IR to ER at unchanged daily dosage. During subsequent maintenance, pramipexole showed sustained efficacy, safety, and tolerability, regardless of formulation (IR or ER) in the preceding DB trial.

Management of respiratory problems in people with neurodegenerative conditions: a narrative review.

BACKGROUND: Respiratory failure and dysfunction are common problems in many neurodegenerative conditions. Although physiotherapists manage these problems, it is not known which treatments have been studied and their efficacy. OBJECTIVE: To review evidence on the management of respiratory problems in people with neurodegenerative conditions using the PRISMA approach. DATA SOURCES: Comprehensive searches were conducted using the following electronic databases from inception to May 2010: HUGEnet, SIGLE, British Library Direct, CINAHL, Medline, AMED and Web of Knowledge. Bibliographies of all studies and systematic reviews were searched by hand. STUDY SELECTION: Studies were selected based on: self-ventilating participants with neurodegenerative conditions; interventions aimed at improving respiratory function; and any valid and reliable measures of respiratory function as outcomes. STUDY APPRAISAL: Studies were appraised by one reviewer using the Critical Appraisal Skills Programme. Data were synthesised using a narrative approach. RESULTS: Thirty-five studies were included in the review. The strongest evidence was for the use of non-invasive ventilation for people with amyotrophic lateral sclerosis, although this was weak. The evidence for the use of respiratory muscle training and methods to increase peak cough flow showed a positive effect, but was also weak. CONCLUSION: There is weak evidence for the positive effects of physiotherapeutic interventions for respiratory problems in people with neurodegenerative conditions. Further work is necessary in specific neurodegenerative conditions to identify why respiratory problems occur, and larger scale studies should be undertaken to investigate management of these problems.

Extended-release pramipexole in advanced Parkinson disease: a randomized controlled trial.

BACKGROUND: In advanced Parkinson disease (PD), immediate-release pramipexole, taken 3 times daily, improves symptoms and quality of life. A once-daily extended-release formulation may be an effective and simple alternative therapy. METHODS: For a multicenter randomized, double-blind, parallel trial of extended- and immediate-release pramipexole vs placebo, patients experiencing motor fluctuations while taking levodopa underwent flexible study drug titration and then maintenance at optimized dosage (0.375-4.5 mg/day). The primary endpoint was a change in the Unified Parkinson's Disease Rating Scale (UPDRS) part II+III score at 18 weeks, with further assessments at 33 weeks in a subset of patients. Adverse events were recorded throughout. RESULTS: Among 507 patients in the 18-week analyses, UPDRS II+III scores decreased (from baseline means of 40.0-41.7) by an adjusted mean of -11.0 for extended-release pramipexole and -12.8 for immediate-release pramipexole vs -6.1 for placebo (p = 0.0001 and p < 0.0001) and off-time decreased (from baseline means of 5.8-6.0 hours/day) by an adjusted mean of -2.1 and -2.5 vs -1.4 hours/day (p = 0.0199 and p < 0.0001). Other outcomes were largely corroborative, including a significant improvement in early morning off symptoms. Among 249 pramipexole patients completing 33 weeks, UPDRS II+III and off-time findings showed ≤10.1% change from 18-week values. Both formulations were well-tolerated. CONCLUSIONS: Extended-release pramipexole significantly improved UPDRS score and off-time compared with placebo, with similar efficacy, tolerability, and safety of immediate-release pramipexole compared with placebo. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that the extended-release form of pramipexole, taken once daily, is efficacious as an adjunct to levodopa in advanced PD.

What treatment packages do UK physiotherapists use to treat postural control and mobility problems after stroke?

OBJECTIVE: The aim of this study was to identify the treatment packages (combinations of interventions) used to treat postural control and mobility problems for patients with stroke. METHOD: A convenience sample of 74 physiotherapists from 34 National Health Service hospitals recorded the interventions used to treat postural control and mobility problems for 251 patients with stroke in 1156 treatment sessions using the Stroke Physiotherapy Intervention Recording Tool (Tyson and Selley, Disabil Rehabil 2004;26:1184 - 1188). Descriptive statistics assessed the frequency with which the interventions were used and geometric coding identified treatment packages. RESULTS: The most frequently used interventions involved facilitation, practice of activities and their components and mobilisations. The least frequently used interventions involved the provision of equipment, teaching carers or professionals and exercise. Two treatment packages were identified; one involving the facilitation (of activities and their components) and the other involving whole activities (facilitation and practice). CONCLUSIONS: Interventions are often combined in two treatment packages to treat postural control and mobility problems after stroke. One involved facilitation (of whole and component activities) and the other involved practice and facilitation of whole activities. Future research in which conventional or standard UK stroke physiotherapy is delivered should focus on these interventions and exclude atypically used interventions.