Interpretation of clinical trials comparing different drug regimens for Parkinson's disease (PD) is complicated by the different dose intensities used: higher doses of levodopa and, possibly, other drugs produce better symptomatic control but more late complications. To address this problem, conversion factors have been calculated for antiparkinsonian drugs that yield a total daily levodopa equivalent dose (LED). LED estimates vary, so we undertook a systematic review of studies reporting LEDs to provide standardized formulae. Electronic database and hand searching of references identified 56 primary reports of LED estimates. Data were extracted and the mean and modal LEDs calculated. This yielded a standardized LED for each drug, providing a useful tool to express dose intensity of different antiparkinsonian drug regimens on a single scale. Using these conversion formulae to report LEDs would improve the consistency of reporting and assist the interpretation of clinical trials comparing different PD medications.

SummaryBackgroundSurgical intervention for advanced Parkinson's disease is an option if medical therapy fails to control symptoms adequately. We aimed to assess whether surgery and best medical therapy improved self-reported quality of life more than best medical therapy alone in patients with advanced Parkinson's disease.MethodsThe PD SURG trial is an ongoing randomised, open-label trial. At 13 neurosurgical centres in the UK, between November, 2000, and December, 2006, patients with Parkinson's disease that was not adequately controlled by medical therapy were randomly assigned by use of a computerised minimisation procedure to immediate surgery (lesioning or deep brain stimulation at the discretion of the local clinician) and best medical therapy or to best medical therapy alone. Patients were analysed in the treatment group to which they were randomised, irrespective of whether they received their allocated treatment. The primary endpoint was patient self-reported quality of life on the 39-item Parkinson's disease questionnaire (PDQ-39). Changes between baseline and 1 year were compared by use of t tests. This trial is registered with , number ISRCTN34111222.Findings366 patients were randomly assigned to receive immediate surgery and best medical therapy (183) or best medical therapy alone (183). All patients who had surgery had deep brain stimulation. At 1 year, the mean improvement in PDQ-39 summary index score compared with baseline was 5·0 points in the surgery group and 0·3 points in the medical therapy group (difference −4·7, 95% CI −7·6 to −1·8; p=0·001); the difference in mean change in PDQ-39 score in the mobility domain between the surgery group and the best medical therapy group was −8·9 (95% CI −13·8 to −4·0; p=0·0004), in the activities of daily living domain was −12·4 (−17·3 to −7·5; p<0·0001), and in the bodily discomfort domain was −7·5 (−12·6 to −2·4; p=0·004). Differences between groups in all other domains of the PDQ-39 were not significant. 36 (19%) patients had serious surgery-related adverse events; there were no suicides but there was one procedure-related death. 20 patients in the surgery group and 13 in the best medical therapy group had serious adverse events related to Parkinson's disease and drug treatment.InterpretationAt 1 year, surgery and best medical therapy improved patient self-reported quality of life more than best medical therapy alone in patients with advanced Parkinson's disease. These differences are clinically meaningful, but surgery is not without risk and targeting of patients most likely to benefit might be warranted.FundingUK Medical Research Council, Parkinson's UK, and UK Department of Health.

Shade avoidance in higher plants is regulated by the action of multiple phytochrome (phy) species that detect changes in the red/far-red ratio (R/FR) of incident light and initiate a redirection of growth and an acceleration of flowering. The phyB mutant of Arabidopsis is constitutively elongated and early flowering and displays attenuated responses to both reduced R/FR and end-of-day far-red light, conditions that induce strong shade-avoidance reactions in wild-type plants. This indicates that phyB plays an important role in the control of shade avoidance. In Arabidopsis phyB and phyD are the products of a recently duplicated gene and share approximately 80% identity. We investigated the role played by phyD in shade avoidance by analyzing the responses of phyDdeficient mutants. Compared with the monogenic phyB mutant, the phyB-phyD double mutant flowers early and has a smaller leaf area, phenotypes that are characteristic of shade avoidance. Furthermore, compared with the monogenic phyB mutant, the phyB-phyD double mutant shows a more attenuated response to a reduced R/FR for these responses. Compared with the phyA-phyB double mutant, the phyA-phyB-phyD triple mutant has elongated petioles and displays an enhanced elongation of internodes in response to end-ofday far-red light. These characteristics indicate that phyD acts in the shade-avoidance syndrome by controlling flowering time and leaf area and that phyC and/or phyE also play a role.Plant development is strongly influenced by the environment. Of all of the environmental factors, light arguably has the most formative influence on the life history of a plant. Cues from the light environment are involved in the regulation of seed germination, establishment of seedlings, determination of growth habit, and the transition to flowering. Plants have evolved an extensive collection of photoreceptors to perceive information about their light environment.The phytochromes are a family of plant photoreceptors that absorb mainly in the red and far-red regions of the spectrum (Quail, 1993). The phytochrome molecule consists of a dimer of identical, approximately 124-kD protein moieties, each with a covalently linked tetrapyrrole chromophore (Furuya and Song, 1994). Phytochromes are reversibly photochromic, existing in two photointerconvertible isoforms: the biologically inactive form, Pr, and the active form, Pfr (Furuya and Song, 1994).All higher plants examined to date contain multiple, distinct phytochrome species that are the products of a divergent gene family (Mathews and Sharrock, 1997). In Arabidopsis, which has been the subject of the most extensive study, there are five phytochromes; they are known as phyA through phyE (Clack et al., 1994). phyA, the product of the PHYA gene, is light labile and predominates in etiolated seedlings, where it accumulates to relatively high levels. phyB and phyC are more light stable, with phyB predominating in light-grown tissues (Somers et al., 1991). Phylogenetic analysis of the phytochrome genes of higher plants suggests tha...

From a screen of M2 seedlings derived from gamma-mutagenesis of seeds doubly null for phytochromes phyA and phyB, we isolated a mutant lacking phyE. The PHYE gene of the selected mutant, phyE-1, was found to contain a 1-bp deletion at a position equivalent to codon 726, which is predicted to result in a premature stop at codon 739. Immunoblot analysis showed that the phyE protein was undetectable in the phyE-1 mutant. In the phyA- and phyB-deficient background, phyE deficiency led to early flowering, elongation of internodes between adjacent rosette leaves, and reduced petiole elongation. This is a phenocopy of the response of phyA phyB seedlings to end-of-day far-red light treatments. Furthermore, a phyE deficiency attenuated the responses of phyA phyB seedlings to end-of-day far-red light treatments. Monogenic phyE mutants were indistinguishable from wild-type seedlings. However, phyB phyE double mutants flowered earlier and had longer petioles than did phyB mutants. The elongation and flowering responses conferred by phyE deficiency are typical of shade avoidance responses to the low red/far-red ratio. We conclude that in conjunction with phyB and to a lesser extent with phyD, phyE functions in the regulation of the shade avoidance syndrome.

Objective To assess the effectiveness of physiotherapy compared with no intervention in patients with Parkinson's disease.Design Systematic review and meta-analysis of randomised controlled trials.Data sources Literature databases, trial registries, journals, abstract books, and conference proceedings, and reference lists, searched up to the end of January 2012.Review methods Randomised controlled trials comparing physiotherapy with no intervention in patients with Parkinson's disease were eligible. Two authors independently abstracted data from each trial. Standard meta-analysis methods were used to assess the effectiveness of physiotherapy compared with no intervention. Tests for heterogeneity were used to assess for differences in treatment effect across different physiotherapy interventions used. Outcome measures were gait, functional mobility and balance, falls, clinician rated impairment and disability measures, patient rated quality of life, adverse events, compliance, and economic analysis outcomes.

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Background Despite medical therapies and surgical interventions for Parkinson's disease (PD), patients develop progressive disability. The role of physiotherapy is to maximise functional ability and minimise secondary complications through movement rehabilitation within a context of education and support for the whole person. The overall aim is to optimise independence, safety and wellbeing, thereby enhancing quality of life. Trials have shown that physiotherapy has short-term benefits in PD. However, which physiotherapy intervention is most e ective remains unclear. Objectives To assess the e ectiveness of one physiotherapy intervention compared with a second approach in patients with PD. Search methods Relevant trials were identified by electronic searches of numerous literature databases (for example MEDLINE, EMBASE) and trial registers, plus handsearching of major journals, abstract books, conference proceedings and reference lists of retrieved publications. The literature search included trials published up to the end of January 2012. Selection criteria Randomised controlled trials of one physiotherapy intervention versus another physiotherapy intervention in patients with PD. Data collection and analysis Data were abstracted independently from each paper by two authors. Trials were classified into the following intervention comparisons: general physiotherapy, exercise, treadmill training, cueing, dance and martial arts. Main results A total of 43 trials were identified with 1673 participants. All trials used small patient numbers (average trial size of 39 participants); the methods of randomisation and concealment of allocation were poor or not stated in most trials. Blinded assessors were used in just over half of the trials and only 10 stated that they used intention-to-treat analysis.

Background and Purpose-Complications after stroke have been shown to impede rehabilitation, lead to poor functional outcome, and increase cost of care. This inception cohort study sought to investigate the prevalence of immobilityrelated complications during the first year after severely disabling stroke in relation to functional independence and place of residence. Methods-Over a 7-month period, 600 stroke survivors were identified in the hospital through the Nottingham Stroke Register.Those who had a Barthel Index score Յ10 3 months poststroke and did not have a primary diagnosis of dementia were eligible to participate in the study. Assessments of complications were carried out at 3, 6, and 12 months poststroke. Results-Complications were recorded for 122 stroke survivors (mean age, 76 years; 57% male). Sixty-three (52%) had significant language impairment and of the remaining 59 who were able to complete an assessment of cognitive function, 10 (8%) were cognitively impaired. The numbers of reported complications over 12 months, in rank order, were falls, 89 (73%); contracture, 73 (60%); pain, 67 (55%); shoulder pain, 64 (52%); depression, 61 (50%); and pressure sores, 26 (22%). A negative correlation was found between Barthel Index score and the number of complications experienced (low scores on the Barthel Index correlate with a high number of complications). The highest relative percentages of complications were experienced by patients who were living in a nursing home at the time of their last completed assessment. Conclusions-Immobility-related complications are very common in the first year after a severely disabling stroke.Patients who are more functionally dependent in self-care are likely to experience a greater number of complications than those who are less dependent.