Short-wavelength free-electron laser sources and science: a review.

This review is focused on free-electron lasers (FELs) in the hard to soft x-ray regime. The aim is to provide newcomers to the area with insights into: the basic physics of FELs, the qualities of the radiation they produce, the challenges of transmitting that radiation to end users and the diversity of current scientific applications. Initial consideration is given to FEL theory in order to provide the foundation for discussion of FEL output properties and the technical challenges of short-wavelength FELs. This is followed by an overview of existing x-ray FEL facilities, future facilities and FEL frontiers. To provide a context for information in the above sections, a detailed comparison of the photon pulse characteristics of FEL sources with those of other sources of high brightness x-rays is made. A brief summary of FEL beamline design and photon diagnostics then precedes an overview of FEL scientific applications. Recent highlights are covered in sections on structural biology, atomic and molecular physics, photochemistry, non-linear spectroscopy, shock physics, solid density plasmas. A short industrial perspective is also included to emphasise potential in this area.

Novel insights into early neuroanatomical evolution in penguins from the oldest described penguin brain endocast.

Digital methodologies for rendering the gross morphology of the brain from X-ray computed tomography data have expanded our current understanding of the origin and evolution of avian neuroanatomy and provided new perspectives on the cognition and behavior of birds in deep time. However, fossil skulls germane to extracting digital endocasts from early stem members of extant avian lineages remain exceptionally rare. Data from early-diverging species of major avian subclades provide key information on ancestral morphologies in Aves and shifts in gross neuroanatomical structure that have occurred within those groups. Here we describe data on the gross morphology of the brain from a mid-to-late Paleocene penguin fossil from New Zealand. This most basal and geochronologically earliest-described endocast from the penguin clade indicates that described neuroanatomical features of early stem penguins, such as lower telencephalic lateral expansion, a relatively wider cerebellum, and lack of cerebellar folding, were present far earlier in penguin history than previously inferred. Limited dorsal expansion of the wulst in the new fossil is a feature seen in outgroup waterbird taxa such as Gaviidae (Loons) and diving Procellariiformes (Shearwaters, Diving Petrels, and allies), indicating that loss of flight may not drastically affect neuroanatomy in diving taxa. Wulst enlargement in the penguin lineage is first seen in the late Eocene, at least 25 million years after loss of flight and cooption of the flight stroke for aquatic diving. Similar to the origin of avian flight, major shifts in gross brain morphology follow, but do not appear to evolve quickly after, acquisition of a novel locomotor mode. Enlargement of the wulst shows a complex pattern across waterbirds, and may be linked to sensory modifications related to prey choice and foraging strategy.

Development and application of an urban solar photovoltaic opportunity mapping tool.

A Geospatial Opportunity Mapping (GOMap) tool was created to identify policy unconstrained land in urban cities that is technically feasible for the deployment of solar photovoltaic power stations; and identify buildings with north- or south-facing orientation for the installation of building integrated PV (BIPV). Collaboration with a local Governing authority and a local electricity provider enabled the process to elicit comprehensive policy and technical aspect information respectively that would impact the site selection process. Five policy and four technical aspects are comprised of a total of 36 individual factors displayable by GOMap on a high-resolution city grid with a scoring system implemented to distinguish between factors that encourage or inhibits solar PV deployment. Weightings can be applied, and different scenarios explored including alternative policy changes and infrastructure upgrades. GOMap generates opportunity maps in the form of available land estimates which can be extrapolated by an in-built solar PV model to quantify annual energy generation based on local weather data, array spacing, panel type and array tilt angle. Three scenarios were devised to identify unconstrained land for solar PV deployment with varying levels of policy and technical factor relaxation, and a fourth scenario to identify dwellings for potential BIPV. These scenarios aim to tackle Glasgow City's growing energy demand and fuel poverty issue, the latter of which can supply energy to dwellings categorised as 'hard-to-heat' once heating is electrified due to the Scottish Government's Energy Strategy commitment.

Vetting of medical imaging referrals: A scoping review of the radiographers' role.

INTRODUCTION: Vetting and treatment verification, are now an expectation of threshold radiography competencies at qualification. Radiographer-led vetting contributes to the expedition of patients' treatment and management. However, the current state and the role of the radiographer in vetting medical imaging referrals remains unclear. This review aims to explore the current state and associated challenges to a radiographer-led vetting and offer directions for future research by addressing knowledge gaps. METHOD: The Arksey and O'Malley methodological framework was employed for this review. This includes a comprehensive search using key terms relating to radiographer-led vetting across relevant databases: Medline, PubMed, AMED and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Articles were screened for eligibility and information extracted and analysed descriptively to map the available evidence. RESULTS: 1149 studies were identified with 12 articles included for this review after duplicates were removed. The findings indicate existence of some radiographer-led vetting activities in practice; however, the scope of this practice is associated with a large variance across settings. Key challenges relating to radiographer-led vetting include referral selectivity, medical professional dominance, and lack of clinical indication on referrals. CONCLUSION: Radiographers vet various categories of referrals depending on jurisdictional policies and more clarity in regulation, advanced practice training and change in workplace culture is needed to support radiographer-led vetting. IMPLICATION FOR PRACTICE: Radiographer-led vetting should be championed across settings through formalised training to widen the scope of advance practice and career progression pathways for radiographers as a means of ensuring optimal use of resources.

Demonstration of a high-field short-period superconducting helical undulator suitable for future TeV-scale linear collider positron sources.

The first demonstration of a full-scale working undulator module suitable for future TeV-scale positron-electron linear collider positron sources is presented. Generating sufficient positrons is an important challenge for these colliders, and using polarized e(+) would enhance the machine's capabilities. In an undulator-based source polarized positrons are generated in a metallic target via pair production initiated by circularly polarized photons produced in a helical undulator. We show how the undulator design is developed by considering impedance effects on the electron beam, modeling and constructing short prototypes before the successful fabrication, and testing of a final module.

Traction for low-back pain with or without sciatica.

BACKGROUND: Traction is used to treat low-back pain (LBP), often with other treatments. OBJECTIVES: To determine traction's effectiveness, compared to reference treatments, placebo, sham traction or no treatment for LBP. SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library 2006, issue 4), MEDLINE, EMBASE, and CINAHL to October 2006, references in relevant reviews and personal files. SELECTION CRITERIA: Randomized controlled trials (RCTs) involving traction to treat acute (less than four weeks duration), sub-acute (four to 12 weeks) or chronic (more than 12 weeks) non-specific LBP with or without sciatica. DATA COLLECTION AND ANALYSIS: Study selection, methodological quality assessment and data extraction were done independently by two authors. As there were insufficient data for statistical pooling, we performed a qualitative analysis. MAIN RESULTS: We included 25 RCTs (2206 patients; 1045 receiving traction). Five trials were considered high quality. For patients with mixed symptom patterns (acute, sub-acute and chronic LBP with and without sciatica) there is: strong evidence of no statistically significant difference in outcomes between traction as a single treatment and placebo, sham or no treatment; moderate evidence that traction as a single treatment is no more effective than other treatments; limited evidence of no significant difference in outcomes between a standard physical therapy program with or without continuous traction. For LBP patients with sciatica (with acute, sub-acute or chronic pain), there is conflicting evidence in several comparisons: autotraction compared to placebo, sham or no treatment; other forms of traction compared to other treatments; different forms of traction. In other comparisons, there were no statistically significant differences; the evidence is moderate for continuous or intermittent traction compared to placebo, sham or no treatment, and limited for light versus normal force traction. IMPLICATIONS FOR PRACTICE: The results of the available studies involving mixed groups of acute, sub-acute and chronic patients with LBP with and without sciatica were quite consistent, indicating that continuous or intermittent traction as a single treatment for LBP is not likely effective for this group. Traction for patients with sciatica cannot be judged effective at present either, due to inconsistent results and methodological problems in most studies. We conclude that traction as a single treatment for LBP is probably not effective. IMPLICATIONS FOR RESEARCH: Any future research on traction for patients with LBP should distinguish between symptom pattern and duration, and should be carried out according to the highest methodological standards.

Traction for low-back pain with or without sciatica.

BACKGROUND: Various types of traction are used in the treatment of low-back pain (LBP), often in conjunction with other treatments. OBJECTIVES: To determine the effectiveness of traction in the management of LBP. SEARCH STRATEGY: We searched The Cochrane Library 2004, Issue 4, MEDLINE, EMBASE, and CINAHL to November 2004, references in relevant reviews, and our personal files. SELECTION CRITERIA: Randomized controlled trials (RCTs) examining any type of traction for the treatment of acute (less than four weeks duration), sub-acute (four to 12 weeks) or chronic (more than 12 weeks) non-specific LBP with or without sciatica. DATA COLLECTION AND ANALYSIS: Study selection, methodological quality assessment and data extraction were done independently by sets of two reviewers. As available studies did not provide sufficient data for statistical pooling, a qualitative analysis was performed. MAIN RESULTS: Twenty-four RCTs, involving 2177 patients (1016 receiving traction) were included in the review. Five trials were considered high quality. There is strong evidence that there is no significant difference in short or long-term outcomes between either continuous or intermittent traction and placebo, sham, or other treatments for patients with a mixed duration of LBP, with or without sciatica. There is moderate evidence that: autotraction is more effective other forms of traction are no more effective than placebo, sham or no treatment for patients with a mixed duration of LBP with sciatica. There is limited evidence that: there is no significant difference in outcomes between a standard physical therapy program with continuous traction and the same program without traction, for patients with a mixed duration of LBP, with or without sciatica autotraction on its own is more effective than a physical therapy program that includes Tru-Trac traction for patients with a mixed duration of LBP with sciatica. There is conflicting evidence regarding the short-term effectiveness of either continuous or intermittent traction compared to placebo, sham or other treatments, in the management of patients who have either chronic LBP or a mixed duration of LBP with sciatica. AUTHORS' CONCLUSIONS: The evidence suggests that traction is probably not effective. Neither continuous nor intermittent traction by itself was more effective in improving pain, disability or work absence than placebo, sham or other treatments for patients with a mixed duration of LBP, with or without sciatica. Although trials studying patients with sciatica had methodological limitations and inconsistent results, there was moderate evidence that autotraction was more effective than mechanical traction for global improvement in this population.

Carotid chemoreceptor function and structure in the atherosclerotic rabbit: respiratory and cardiovascular responses to hyperoxia, hypoxia and hypercapnia.

We tested the following hypothesis: if carotid body blood flow, and hence the relationship of the frequency of discharge in chemoreceptor afferent fibres to arterial PO2, were affected by atherosclerotic change, then a modification of the control of the respiratory and cardiovascular systems might result. Carotid body reflexes were therefore studied in conscious atherosclerotic rabbits and a control group of normal animals breathing 100% O2, three hypoxic gas mixtures to which was added sufficient CO2 to maintain the arterial PCO2 constant, and 2% and 4% CO2 in 21% O2 and N2. When breathing room air, the atherosclerotic rabbits breathed at a higher respiratory frequency and lower tidal volume than the normal animals, although there was no difference in the respiratory minute volume. The respiratory and cardiovascular responses to hyperoxia, isocapnic hypoxia and hypercapnia were essentially the same in both groups of animals. Serial sections of the carotid bodies showed pathological changes including interstitial fibrosis in the caudal part with interstitial haemorrhages. The proximal part of the ascending pharyngeal artery, the vessel supplying the organ, and its origin from the external carotid, and the arterioles in the caudal part of the carotid body were nearly always occluded to a varying extent by atheromatous plaques. The capillaries appeared normal under light microscopy. The rostral-caudal lengths of the carotid bodies were similar in the two groups. We conclude that the peripheral arterial chemoreceptor responses in atherosclerotic rabbits are relatively normal even though the arteries to, and arterioles within, the carotid body are partly occluded.

Monokine products as predictors of AIDS dementia.

OBJECTIVE: To determine whether or not soluble factors produced by peripheral blood mononuclear cells (PBMC) can predict AIDS dementia. DESIGN AND METHODS: PBMC were isolated from individuals with and without AIDS dementia complex (ADC) to determine if the levels of cytokines tumour necrosis factor (TNF)-alpha and interleukin (IL)-6, or the production of a neurotoxic substance, were significantly different. PBMC were studied after determining that the numbers of monocyte-derived macrophages isolated by adherence were highly variable from patients with ADC compared with individuals without ADC. We prospectively studied 16 AIDS dementia patients, 13 healthy HIV-seropositive individuals, and eight sero-negative controls. Supernatants from PBMC were assayed for TNF-alpha, IL-6 and alone for neurotoxicity on human neural cells in vitro. RESULTS: We observed a trend towards worse cognitive and motor performance in patients suffering from ADC but who had no opportunistic infections ('pure dementia'; n = 8). Levels of PBMC IL-6 were significantly higher in 'pure dementia' patients. There was a trend towards lower levels of PBMC TNF-alpha in the group of patients who had both dementia and opportunistic infections compared with "pure dementia' patients. Supernatant from PBMC of ADC patients was significantly more neurotoxic than that from healthy HIV-seropositive individuals. CONCLUSIONS: Macrophage isolation from PBMC of patients with ADC was altered. Soluble factors produced from PBMC were significantly more neurotoxic than soluble factors from PBMC of healthy HIV-seropositive individuals. PBMC production of TNF-alpha and IL-6 was not a significant predictor of ADC.

Respiratory and cardiovascular responses to hyperoxia, hypoxia and hypercapnia in the renal hypertensive rabbit: role of carotid body chemoreceptors.

We tested the hypothesis that in renal hypertension the increased peripheral vascular resistance of neurogenic origin might be due to a reflex through resetting of the carotid body chemoreceptors. The reflex respiratory and cardiovascular functions of the carotid bodies were studied in a one-kidney wrapped hypertension model in conscious rabbits, and compared with a control group of animals, by breathing 100% oxygen, three hypoxic gas mixtures to which were added sufficient CO2 to maintain the PaCO2 constant, and 2 and 4% CO2 in 21% O2 and N2. In the control state (breathing room air) the renal hypertensive animals had a slightly higher respiratory minute volume, a higher level of arterial blood pressure and increased calculated systemic vascular resistance, compared with the normal group, but there was no difference in cardiac output. Hyperoxia had no consistent effect on respiration, heart rate or arterial blood pressure. Increasing degrees of isocapnic hypoxia caused the same degree of hyperventilation and bradycardia in both groups of animals. The arterial blood pressure did not change in either group but there was a transient increase in systemic vascular resistance in the renal hypertensives breathing 9 and 7.5% O2. The respiratory responses to 2 and 4% CO2 were similar in the two groups of animals. In the renal hypertensive animals, serial sections of the carotid bodies showed pathological changes, including subendothelial proliferation in vessels supplying the carotid bodies with narrowing of their lumens, fragmentation of the elastic laminae of the media, hypertrophy of the smooth muscle and extensive fibrosis with occasional haemorrhages. The capillaries, however, were normal. The rostral-caudal lengths of the carotid bodies were similar in the two groups. In view of our findings we conclude that the relatively normal carotid chemoreceptor responses in renal hypertensive rabbits may, in part at least, be the result of the carotid body blood flow through the partially occluded vessels being maintained at near normal levels by the elevated blood pressure.

Assessment of adherence to renal dosing guidelines in long-term care facilities.

OBJECTIVE: We determined whether dosing guidelines based on creatinine clearance (Ccr) for renally excreted drugs are being applied when prescribing to long-term care residents DESIGN: A cross sectional chart review for the month of May 1999. PARTICIPANTS: Long-term care residents more than 65 years of age from four long-term care facilities in Southern Ontario who were prescribed a medication from a list of renally excreted drugs commonly prescribed in long-term care facilities. RESULTS: Approximately one in three prescriptions (34.1%) were considered inappropriate for the calculated Ccr of the residents. Overall, 42.3% of the residents who were prescribed a drug under review received at least one inappropriate prescription based on creatinine clearance. Logistic regression found that age (odds ratio (OR) = 1.06 per year; 95% confidence interval (CI) 1.03-1.09, P = .001), weight (OR = 0.96 per kg; 95% CI 0.94-0.98, P < .001), the total number of prescribed medications (OR = 1.10; 95% CI 1.04-1.17, P = .001), and the number of physicians prescribing in the facility (OR 1.02; 95% CI, 1.003-1.044, P = .03) were predictive for receiving an inappropriate prescription based on Ccr. CONCLUSIONS: Renal function is often overlooked when prescribing renally excreted drugs to older long-term care residents. These findings emphasize the need for consideration of Ccr when prescribing such drugs in this population.

New method for detecting changes in the surface appearance of human red blood cells.

A new method for examining the surface of blood cells, using the Stereoscan electron microscope, is described. Some of the cellular appearances revealed by this technique are illustrated. The potentialities and limitations of scanning electron microscopy are discussed.

Utility of Scottish morbidity and mortality data for epidemiological studies of motor neuron disease.

OBJECTIVES: To determine the accuracy of (1) hospital discharge data and (2) death certificates, coded as motor neuron disease (MND). DESIGN: Comparison of data from The Scottish Motor Neuron Disease Register (SMNDR) with routinely collected Scottish Hospital In-Patient Statistics (SHIPS) and death certificate coding. SETTING: Scotland UK. PATIENTS: 1) 379 adults (> 15 years) discharged for the first time from a Scottish hospital in 1989-90 and (2) 281 deaths in the same period assigned to the International Classification of Diseases (ICD)-9, category 335 (MND). MAIN OUTCOME MEASURES: The sensitivity and positive predictive value of a diagnosis of MND as retrieved by (1) the Information and Statistics Division of the Common Services Agency for the Scottish Health Service for morbidity data and (2) the Registrar General's office for mortality data, using the SMNDR as the 'gold standard'. RESULTS: (1) Thirty per cent of adult patients identified as having MND by SHIPS did not have this disease and 23% of patients with MND did not appear on SHIPS. The sensitivity of a diagnosis of MND, as retrieved by SHIPS, was 84% and the positive predictive value was 70% overall. Miscoding of patients with pseudobulbar palsy caused by cerebrovascular disease was the major source of false positive error. The incidence of adult onset sporadic MND was over estimated by SHIPS by a factor of 1.6. (2) Mortality data were more accurate, with a false negative rate of 6% and a positive predictive value of 90%. CONCLUSIONS: Coded hospital discharge data are an inaccurate record of a diagnosis of MND and cannot, in their present form, be used as a reliable measure of disease incidence in Scotland. Greater care is required in the preparation of discharge summaries and coding if these data are to be useful for health care planning and epidemiological research. SHIPS is, however, an important source of information to achieve a complete sample of patients with MND. There is also a problematic false positive rate for mortality data but this source more closely approximates true incidence.

Comments on dietary intake of drug-dependent persons.

Interviews by means of a questionnaire were used to study the food habits and estimate the nutritional value of food eaten by forty clients in a methadone maintenance program and nineteen clients in a drug detoxification program in a drug treatment center, Marin Open House, San Rafael, California. Although responses to the questionnaires were highly varied, many subjects reported that drugs did affect appetite or cause craving for certain foods. Patients in the detoxification program tended to eat meals either once or twice a day, whereas one-third of those in the methadone program ate three or more meals daily. Over 90 per cent of the clients reported eating snacks. Foods consumed in inadequate amounts included fruits and vegetables high in either vitamin A or ascorbic acid, liver and other meats, and whole grain and enriched cereals or bread. Food consumed as reported on a 24-hr. recall was evaluated by a computer program, and the tabulation was compared with the Recommended Dietary Allowances. Diets were considered to be inadequate if nutrient intakes were below two-thirds of the allowances. In general, the clients in the detoxification program consumed less adequate amounts of the nutrients studied than the methadone group. The females in both groups consumed less adequate diets than the males. About two-fifths of the men of both groups and about three-fourths of the women had diets inadequate in three or more nutrients by the standards chosen. In spite of the limitations of this study, the results do point to the existence and type of nutritional problems likely to be encountered in drug-dependent persons and in those undergoing treatment. The need for nutrition counseling is evident.

The volume of the carotid body and periadventitial type I and type II cells in the carotid bifurcation region of the fetal cat and kitten.

The bilateral distribution of carotid body type I cells was investigated in 6 fetuses (gestational age 95%) and 9 newborn kittens (aged 1 day to 4 days) by serially sectioning the carotid bifurcation regions. In most specimens type I cells occurred in close proximity to the wall of the occipital artery or one of its small proximal branches within a division of connective tissue with definable but irregular borders. This combination of type I cells and connective tissue constituted the principal mass of the carotid body. Using an interacting image analysis system, the area of the carotid body in each serial section was measured by accurately contouring its perimeter. The volume of the carotid body was calculated by multiplying the sum of the areas of the serial sections by the thickness of the section. The volume of the carotid body was 0.052 +/- 0.018 mm3 in the fetuses and 0.025-0.117 mm3 in the 1-4 day old kittens. A degree of symmetry in the values for the volume of the right and left carotid body was found. Caudally, and separate from the principal mass of carotid body type I cells, isolated groups of periadventitial type I cells were noted in the connective tissues around the occipito-ascending pharyngeal trunk, origin of the occipital artery and rostral end of the common carotid artery in 7 out of 12 specimens from fetal cats and 11 out of 18 specimens in newborn kittens. The volumes of the periadventitial groups of cells ranged between 25-1,365 micron3 in fetuses and 10-1,351 micron3 in kittens.

Distribution of carotid body type I cells and other periadventitial type I cells in the carotid bifurcation regions of the cat.

The bilateral distribution of carotid body type I cells was investigated in five non-pedigree cats by serially sectioning the carotid bifurcation regions. Carotid body type I cells occurred bilaterally in close proximity to the wall of the occipital artery or one of its proximal branches, and less frequently the ascending pharyngeal artery within a division of connective tissue with definable but irregular borders. Caudally, and separate from the principal mass of carotid body type I cells, isolated groups of periadventitial type I cells were found in seven out of ten specimens lying freely in the connective tissues around the occipito-ascending pharyngeal trunk and the origin of the occipital artery immediately rostral to the carotid bifurcation. Periadventitial type I cells were not observed at the level of the carotid bifurcation but on one occasion these cells were noted caudal to the carotid bifurcation lying adjacent to the wall of the rostral end of the common carotid artery. From our data on four specimens, reconstructions were made of the carotid body. The occurrence and significance of the periadventitial type I cells is discussed.

The carotid body of the harbour seal (Phoca vitulina richardsi).

The bilateral distribution of carotid body type 1 and 11 cells was investigated in five harbour seals (Phoca vitulina richardsi), by serially sectioning the carotid bifurcation regions. The cells occurred bilaterally in the animals and were also present in one specimen from a sixth animal available for study. The type 1 and 11 cells were located in the space between the internal and external carotid arteries and had a varied relationship to the occipital and condyloid arteries. They lay within a division of connective tissue with irregular but defineable borders and this combination of connective tissue and type 1 and 11 cells constituted the principal mass of the carotid body. The carotid body occurred in a variety of forms: wedge-shaped, crescentic or horse-shoe shaped, or as a discrete oval structure. In some specimens the carotid body had a central 'neurovascular' core of small blood vessels and nerves. The artery to the organ originated from either the external carotid, internal carotid or common carotid arteries. Using an interactive image analysis system in eight specimens, which had been perfusion-fixed at a normal arterial pressure, the mean volume of the carotid body was 1.666 +/- 0.45 (SD) mm3. Caudally and separate from the principal mass of the carotid body periadventitial type 1 and 11 cells were noted in 4 out of 11 specimens in the connective tissues adjacent to the external carotid artery, origin of the occipital, and the rostral part of the common carotid artery and its bifurcation.

A critical appraisal of "out-of-hours" radiography in a major teaching hospital.

The use of plain radiography performed outside normal working hours was studied at the Manchester Royal Infirmary to determine the costs of the service and where possible financial savings could be made. The annual cost of "out-of-hours" radiography was estimated to be in order of 250,000 pounds. During a selected 2-week period, 84% and 76% of all examinations performed on Accident and Emergency patients and inpatients, respectively, were found to be normal. Previous reports suggest that the number of radiographs requested in the Accident and Emergency department can be reduced without detriment to patients by the implementation of appropriate clinical guidelines. We consider that if similar guidelines were developed and applied to the use of out-of-hours radiography, substantial savings could be made. We estimate that in our hospital these savings could amount to 18% of the current expenditure on this service.

Pramipexole versus bromocriptine for levodopa-induced complications in Parkinson's disease.

OBJECTIVES: To compare the efficacy and safety of adjuvant pramipexole versus bromocriptine therapy in patients with Parkinson's disease, already established on levodopa and suffering from motor complications. SEARCH STRATEGY: Electronic searches of MEDLINE, EMBASE and the Cochrane Controlled Trials Register. Handsearching of the neurology literature as part of the Cochrane Movement Disorders Group's strategy. Examination of the reference lists of identified studies and other reviews. Contact with Pharmacia Upjohn and Boehringer Ingelheim. SELECTION CRITERIA: Randomised controlled trials of pramipexole versus bromocriptine in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy. DATA COLLECTION AND ANALYSIS: Data was abstracted independently by the authors and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, 'off' time measurements and the frequency of drop outs and adverse events. MAIN RESULTS: One randomised controlled trial has compared pramipexole with bromocriptine using a double-blind, parallel group, multicentre design. It was not powered to examine differences between active treatment arms. There was a larger reduction in off time with pramipexole therapy compared with bromocriptine (weighted mean difference 1.4 hours; 0, 2.8, 95% CI). No differences occurred in dyskinesia rating scale, dyskinesia as an adverse event or UPDRS complication score. The UPDRS ADL and motor scores showed similar improvements compared to placebo with both agonists. Levodopa dose reduction was similar with both agonists. Subscales of the Functional Status Questionnaire showed significant improvements compared to placebo with both agonists. The finding that the EuroQol improved significantly compared with placebo with pramipexole but not bromocriptine should be treated with caution. Dopaminergic adverse events were similar with each agonist, as was the all cause withdrawal rate. REVIEWER'S CONCLUSIONS: Although pramipexole and bromocriptine improved off time and reduced parkinsonian motor impairments and disability compared with placebo, no conclusions regarding their comparative effectiveness and safety can be drawn as this single trial did not have adequate power to assess such differences. Further larger trials are required to examine this issue in the future.

Pramipexole for levodopa-induced complications in Parkinson's disease.

OBJECTIVES: To compare the efficacy and safety of adjuvant pramipexole therapy versus inactive placebo in patients with Parkinson's disease, already established on levodopa. SEARCH STRATEGY: Electronic searches of MEDLINE, EMBASE and the Cochrane Controlled Trials Register. Handsearching of the neurology literature as part of the Cochrane Movement Disorders Group's strategy. Examination of the reference lists of identified studies and other reviews. Contact with Pharmacia Upjohn and Boehringer Ingelheim. SELECTION CRITERIA: Randomised controlled trials of pramipexole versus placebo in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy. DATA COLLECTION AND ANALYSIS: Data was abstracted independently by the authors and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, 'off' time measurements and the frequency of drop outs and adverse events. MAIN RESULTS: Four randomised controlled trials have compared pramipexole with placebo in 669 patients with later Parkinson's disease. Two phase III studies were medium term (24 weeks maintenance period) and 2 phase II studies were short term (4 weeks maintenance period). The reduction in off time was significantly greater with pramipexole compared with placebo (weighted mean difference 1.8 hours; 1.2, 2.3 95% CI). No significant changes were noted in a dyskinesia rating scale in any of the 4 studies, but dyskinesia as an adverse event was reported more frequently with pramipexole. A significant improvement occurred in UPDRS complication score (part IV) in 2 studies but not in the remaining trials. Statistically significant improvements in UPDRS ADL score occurred with pramipexole in all studies. Significant improvements in UPDRS motor scores in the on state were reported in 3 of the 4 studies. Levodopa dose reduction was allowed in 3 studies and meta-analysis shows a significant difference in favour of pramipexole (weighted mean difference 115 mg; 87, 143 95% CI). Trends toward a higher incidence of dopaminergic adverse events with pramipexole only reached statistical significance regarding hallucinations. There were significantly fewer withdrawals from pramipexole. REVIEWER'S CONCLUSIONS: Pramipexole can be used to reduce off time, improve motor impairments and disability and reduce levodopa dose at the expense of increased dyskinetic adverse events. This conclusion is based on short and medium term trials (up to 24 weeks). Further trials are required to directly compare the newer with the older dopamine agonists.