Latest from JNNP

1H-MR spectroscopy metabolite levels correlate with executive function in vascular cognitive impairment [CEREBROVASCULAR DISEASE]

Mon, 1 Jul 2013 00:00:00 +0000

Paediatric autoimmune encephalopathies: clinical features, laboratory investigations and outcomes in patients with or without antibodies to known central nervous system autoantigens [NEURO-INFLAMMATION]

Mon, 1 Jul 2013 00:00:00 +0000

Hypogonadism and low bone mineral density in patients on long-term intrathecal opioid delivery therapy [RESEARCH]

Mon, 17 Jun 2013 00:00:00 +0000

ObjectivesThis study aimed to investigate the hypothalamic-pituitary-gonadal axis in a sample of male patients undertaking intrathecal opioid delivery for the management of chronic non-malignant pain and the presence of osteopaenia and/or osteoporosis in those diagnosed with hypogonadism. DesignObservational study using health data routinely collected for non-research purposes. SettingDepartment of Pain Management, Russells Hall Hospital, Dudley, UK. PatientsTwenty consecutive male patients attending follow-up clinics for intrathecal opioid therapy had the gonadal axis evaluated by measuring their serum luteinising hormone, follicle stimulating hormone, total testosterone, sex hormone binding globulin and calculating the free testosterone level. Bone mineral density was measured by DEXA scanning in those patients diagnosed with hypogonadism. ResultsBased on the calculated free testosterone concentrations, 17 (85%) patients had biochemical hypogonadism with 15 patients (75%) having free testosterone <180 pmol/L and 2 patients (10%) between 180 and 250 pmol/L. Bone mineral density was assessed in 14 of the 17 patients after the exclusion of 3 patients. Osteoporosis (defined as a T score [≤]-2.5 SD) was detected in three patients (21.4%) and osteopaenia (defined as a T score between -1.0 and -2.5 SD) was observed in seven patients (50%). Five of the 14 patients (35.7%) were at or above the intervention threshold for hip fracture. ConclusionsThis study suggests an association between hypogonadism and low bone mass density in patients undertaking intrathecal opioid delivery for the management of chronic non-malignant pain. Surveillance of hypogonadism and the bone mineral density levels followed by appropriate treatment may be of paramount importance to reduce the risk of osteoporosis development and prevention of fractures in this group of patients.

Predictors of good functional outcome in counterpulsation-treated recent ischaemic stroke patients [RESEARCH]

Mon, 17 Jun 2013 00:00:00 +0000

ObjectivesExternal counterpulsation (ECP) is a non-invasive method being investigated for ischaemic stroke. We aimed to explore predictors of good functional outcome for ECP-treated ischaemic stroke patients who completed a minimum of 10 sessions. MethodsWe analysed our ECP registry of ischaemic stroke patients with cerebral large artery stenosis who underwent ECP therapy at the Prince of Wales Hospital from 2004 to 2010. We included 155 patients who completed at least 10 sessions of ECP and had 3-month follow-up data as well as 52 medical controls. Functional outcomes were dichotomised into good outcome (modified Rankin Scale (mRS) 0-2) and bad outcome (mRS 3-6). We compared the differences in two groups in terms of demographics, medical history and parameters of ECP treatment. ResultsAt 3 months after stroke, 70.5% of patients who finished the whole course of ECP had a good outcome (only 46.5% in the unfinished group and 38.5% in the medical group). Among all 207 recruited cases, 119 (57.5%) patients had a good outcome at 3 months after stroke. Compared with the bad outcome group, patients in the good outcome group were younger and had a lower baseline National Institutes of Health Stroke Scale (NIHSS) and longer ECP therapy duration. Multivariate logistic regression showed that ECP duration (OR 1.032), baseline NIHSS (OR 0.734) and age (OR 0.961) were independent predictors for a favourable outcome. ConclusionsDuration of ECP therapy is first found to be an important predictor for good outcome of ECP-treated ischaemic stroke patients, in addition to the well-known prognostic factors such as age and NIHSS.

An enhanced exercise and cognitive programme does not appear to reduce incident delirium in hospitalised patients: a randomised controlled trial [RESEARCH]

Mon, 17 Jun 2013 00:00:00 +0000

ObjectiveTo determine if a programme of progressive resistance exercise, mobilisation and orientation, in addition to usual care, was superior to usual care alone in the prevention of incident delirium in older hospitalised patients. DesignA randomised controlled trial. SettingThe study was performed at a secondary referral hospital in Melbourne, Australia between May 2005 and December 2007. Participants648 consecutive medical inpatients aged 65 years or older who had been in hospital for less than 48 h and who did not have delirium. InterventionParticipants were randomly allocated to a twice-daily programme of progressive resistance exercise tailored to individual ability, mobilisation and orientation in addition to usual care or to usual care alone. MeasurementsDelirium was measured using the Confusion Assessment Method at baseline and every 48 h until discharge. Secondary outcome measures were severity and duration of delirium, discharge destination and length of stay. ResultsDelirium occurred in 4.9% (95% CI 2.3% to 7.3%) of the intervention group (15/305) and in 5.9% (20/339; 95% CI 3.8% to 9.2%) of the group receiving usual care. No difference was observed between groups ({chi}2; p=0.5). The intervention had no effect on delirium duration, severity, discharge destination or length of stay. ConclusionA programme of progressive resistance exercise and orientation was not effective in reducing incident delirium in hospitalised elderly patients.

Serum perfluoroalkyl acids concentrations and memory impairment in a large cross-sectional study [RESEARCH]

Mon, 17 Jun 2013 00:00:00 +0000

ObjectivesTo examine the cross-sectional association between serum perfluorooctanate (PFOA), perfuorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA) and perfluorohexane sulfonate (PFHxS) concentrations with self-reported memory impairment in adults and the interaction of these associations with diabetes status. DesignCross-sectional study. SettingPopulation-based in Mid-Ohio Valley, West Virginia following contamination by a chemical plant. ParticipantsThe C8 Health Project collected data and measured the serum level of perfluoroalkyl acids (PFAAs) of 21 024 adults aged 50+ years. Primary outcome measureSelf-reported memory impairment as defined by the question have experienced short-term memory loss?' ResultsA total of 4057 participants self-reported short-term memory impairment. Inverse associations between PFOS and PFOA and memory impairment were highly statistically significant with fully adjusted OR=0.93 (95% CI 0.90 to 0.96) for doubling PFOS and OR=0.96 (95% CI 0.94 to 0.98) for doubling PFOA concentrations. Comparable inverse associations with PFNA and PFHxS were of borderline statistical significance. Inverse associations of PFAAs with memory impairment were weaker or non-existent in patients with diabetes than overall in patients without diabetes. ConclusionsAn inverse association between PFAA serum levels and self-reported memory impairment has been observed in this large population-based, cross-sectional study that is stronger and more statistically significant for PFOA and PFOS. The associations can be potentially explained by a preventive anti-inflammatory effect exerted by a peroxisome proliferator-activated receptor agonist effect of these PFAAs, but confounding or even reverse causation cannot be excluded as an alternative explanation.

MRI and cerebrospinal fluid biomarkers for predicting progression to Alzheimer's disease in patients with mild cognitive impairment: a diagnostic accuracy study [RESEARCH]

Mon, 17 Jun 2013 00:00:00 +0000

ObjectivesTo assess the incremental value of MRI and cerebrospinal fluid (CSF) analysis after a short memory test for predicting progression to Alzheimer's disease from a pragmatic clinical perspective. DesignDiagnostic accuracy study in a multicentre prospective cohort study. SettingAlzheimer Disease Neuroimaging Initiative participants with complete data on neuropsychological assessment, MRI of the brain and CSF analysis. ParticipantsPatients with mild cognitive impairment (MCI; n=181) were included. Mean follow-up was 38.9 months (range 5.5-75.9). Main outcome measuresDiagnostic accuracy of individual instruments and incremental value of entorhinal cortex volume on MRI and p-{tau}/A{beta} ration in CSF after administration of Rey's Auditory Verbal Learning Memory Test are calculated and expressed as the Net Reclassification Improvement' (NRI), which is the change in the percentage of individuals that are correctly diagnosed as Alzheimer or non-Alzheimer case. ResultsTested in isolation, a short memory test, MRI and CSF all substantially contribute to the differentiation of those MCI patients who remain stable during follow-up from those who progress to develop Alzheimer's disease. The memory test, MRI and CSF improved the diagnostic classification by 21% (95% CI 15.1 to 26.9), 22.1% (95% CI 16.1 to 28.1) and 18.8% (95% CI 13.1 to 24.5), respectively. After administration of a short memory test, however, the NRI of MRI is +1.1% (95% CI 0.1 to 3.9) and of CSF is -2.2% (95% CI -5.6 to -0.6). ConclusionsAfter administration of a brief test of memory, MRI or CSF do not substantially affect diagnostic accuracy for predicting progression to Alzheimer's disease in patients with MCI. The NRI is an intuitive and easy to interpret measure for evaluation of potential added value of new diagnostic instruments in daily clinical practice.

Effect of occupation on risk of developing MS: an insurance cohort study [RESEARCH]

Mon, 17 Jun 2013 00:00:00 +0000

ObjectiveThe aim of this study was to estimate the occupational risks in relation to multiple sclerosis (MS). The immediate background for this research was our finding that there had been a high number of critical illness insurance claims by patients diagnosed with MS within the agricultural segment of a Danish pension fund. DesignAn open insurance cohort. All payouts for the critical illness insurance from 2002 to 2011 were continuously registered. SettingsPensionDanmark; one of Denmark's largest pension funds. ParticipantsPensionDanmark insures more than 300 000 members of the Danish Confederation of Trade Unions against critical illness. All members are insured, and all policies are identical. The total exposure is 3.3 million person-years. Primary outcome measuresThe incidence of MS. ResultsDuring the 10-year period, 389 persons were diagnosed with MS. The crude incidence rate for men was 10.2/100 000; the corresponding figure for women was 16.1/100 000. We found signs of an overall effect of occupation on the risk of developing MS, and the high frequency found within the agricultural segment was attributed to dairy operators, who had an incidence of MS 2.0 times higher than the rest of the study's population (95% CI=1.2 to 3.0). ConclusionsOur results indicate some occupational risk factors in MS, and this should be investigated further.

Prognostication of recovery time after acute peripheral facial palsy: a prospective cohort study [RESEARCH]

Mon, 17 Jun 2013 00:00:00 +0000

ObjectiveOwing to a lack of prospective studies, our aim was to evaluate diagnostic factors, in particular, motor and non-motor function tests, for prognostication of recovery time in patients with acute facial palsy (AFP). DesignProspective cohort study. SettingUniversity hospital. Participants259 patients with AFP. MeasurementsClinical data, facial grading, electrophysiological motor function tests and other non-motor function tests were assessed for their contribution to recovery time. ResultsThe predominant origin of AFP was idiopathic (59%) and traumatic (21%). At baseline, the House-Brackmann scale (HB) was >III in 46% of patients. Follow-up time was 5.6{+/-}9.8 months with a complete recovery rate of 49%. The median recovery time was 3.5 months (95% CI 2.2 to 4.7 months). The following variables were associated with faster recovery: Interval between onset of AFP and treatment <6 days versus [≥]6 days (median recovery time in months 2.1 vs 6.5; p<0.0001); HB [≤]III vs >III (2.2 vs 4.6; p=0.001); no versus presence of pathological spontaneous activity in first electromyography (EMG; 2.8 vs probability of recovery <50%; p<0.0001); no versus voluntary activity in EMG (probability of recovery <50% vs 3.1; p<0.0001); normal versus pathological ipsilateral electroneurography (1.9 vs 6.5; p=0.008), normal versus pathological stapedius reflexes (1.6 vs 3.3; p=0.003). ConclusionsStart of treatment and grading, but most importantly EMG evaluated for pathological spontaneous activity and the stapedius reflex test are powerful prognosticators for estimating the recovery time from AFP. These results need confirmation in larger datasets.

Results from the Upper Limb International Spasticity Study-II (ULIS-II): a large, international, prospective cohort study investigating practice and goal attainment following treatment with botulinum toxin A in real-life clinical management [RESEARCH]

Mon, 17 Jun 2013 00:00:00 +0000

The Val158Met COMT polymorphism is a modifier of the age at onset in Parkinson's disease with a sexual dimorphism [MOVEMENT DISORDERS]

Sat, 1 Jun 2013 00:00:00 +0000

The long-term safety and efficacy of bilateral transplantation of human fetal striatal tissue in patients with mild to moderate Huntington's disease [MOVEMENT DISORDERS]

Sat, 1 Jun 2013 00:00:00 +0000

The differential diagnosis of Huntington's disease-like syndromes: 'red flags' for the clinician [MOVEMENT DISORDERS]

Sat, 1 Jun 2013 00:00:00 +0000

Microbleeds as a predictor of intracerebral haemorrhage and ischaemic stroke after a TIA or minor ischaemic stroke: a cohort study [RESEARCH]

Fri, 31 May 2013 00:00:00 +0000

ObjectivesWe examined whether patients with cerebral microbleeds on MRI, who started and continued antithrombotic medication for years, have an increased risk of symptomatic intracerebral haemorrhage (ICH). DesignProspective cohort study. SettingsMulticentre outpatient clinics in the Netherlands. ParticipantsWe followed 397 patients with newly diagnosed transient ischaemic attack (TIA) or minor ischaemic stroke receiving anticoagulants or antiplatelet drugs. 58% were men. The mean age was 65.3 years. 395 (99%) patients were white Europeans. MRI including a T2*-weighted gradient echo was performed within 3 months after start of medication. 48 (12%) patients had one or more microbleeds. They were followed every 6 months by telephone for a mean of 3.8 years. Primary and secondary outcome measuresPrimary outcome was a symptomatic ICH. Secondary outcome were all strokes, ischaemic stroke, myocardial infarct, death from all vascular causes, death from non-vascular causes and death from all causes. ResultsFive patients (1%) suffered from a symptomatic ICH. One ICH occurred in a patient with microbleeds at baseline (adjusted HR 2.6, 95% CI 0.3 to 27). The incidence of all strokes during follow-up was higher in patients with than without microbleeds (adjusted HR 2.3, 95% CI 1.0 to 5.3), with a dose-response relationship. The incidences of ischaemic stroke, vascular death, non-vascular death and death of all causes were higher in patients with microbleeds, but not statistically significant. ConclusionsIn our cohort of patients using antithrombotic drugs after a TIA or minor ischaemic stroke, we found that microbleeds on MRI are associated with an increased risk of future stroke in general, but we did not find an increased risk of symptomatic ICH.

Surgery versus prolonged conservative treatment for sciatica: 5-year results of a randomised controlled trial [RESEARCH]

Tue, 28 May 2013 00:00:00 +0000

ObjectiveThis study describes the 5 years' results of the Sciatica trial focused on pain, disability, (un)satisfactory recovery and predictors for unsatisfactory recovery. DesignA randomised controlled trial. SettingNine Dutch hospitals. ParticipantsFive years' follow-up data from 231 of 283 patients (82%) were collected. InterventionEarly surgery or an intended 6 months of conservative treatment. Main outcome measuresScores from Roland disability questionnaire, visual analogue scale (VAS) for leg and back pain and a Likert self-rating scale of global perceived recovery were analysed. ResultsThere were no significant differences between groups on the 5 years' primary outcome scores. Despite at least 6 months of conservative treatment 46% of the conservatively allocated patients were treated surgically because of severe leg pain and disability. Forty-nine (21%) patients had an unsatisfactory recovery at 5 years and the recovery pattern showed that there was a variable group of 66 patients (31%) with at least one unsatisfactory outcome at 1, 2 or 5 years of follow-up. Multivariate logistic regression showed that age (>40; OR 2.42 (95% CI 1.16 to 5.02)), severity of leg pain (VAS >70; OR 3.32 (95% CI 1.69 to 6.54)) and the Mc Gill affective score (score >3; OR 6.23 (95% CI 2.23 to 17.38)) were the only significant predictors for an unsatisfactory outcome at 5 years. ConclusionsIn the long term, 8% of the patients with sciatica never showed any recovery and in at least 23%, sciatica appears to result in ongoing complaints, which fluctuate over time, irrespective of treatment. Prolonged conservative care might give patients a fair chance for pain and disability to resolve without surgery, but with the risk to receive delayed surgery after prolonged suffering of sciatica. Age above 40 years, severe leg pain at baseline and a higher affective Mc Gill pain score were predictors for unsatisfactory recovery. Trial Registry ISRCT No 26872154.

Mapping the 12-item multiple sclerosis walking scale to the EuroQol 5-dimension index measure in North American multiple sclerosis patients [RESEARCH]

Tue, 28 May 2013 00:00:00 +0000

ObjectiveTo map the 12-item Multiple Sclerosis Walking Scale (MSWS-12) onto the EuroQol 5-dimension (EQ-5D) health-utility index in multiple sclerosis (MS) patients participating in the North American Research Committee on Multiple Sclerosis (NARCOMS) registry. DesignCross-sectional MSWS-12 to EQ-5D cross-walking analysis. SettingNARCOMS registry spring 2010 biannual update and supplemental survey. ParticipantsNorth American patients completing both the MSWS-12 and the EQ-5D randomly split into derivation and validation cohorts. Outcome measuresOrdinary least squares regression was performed within the derivation cohort, with participants' EQ-5D as the dependent variable. Results of the MSWS-12 were input as independent variable(s) into six regression models. Model goodness-of-fit was subsequently assessed in the validation cohort using the mean absolute error (MAE), root mean square error (RMSE) and the adjusted R2. The best performing model was refined in the entire cohort and utilised for additional analyses. ResultsA total of 3505 NARCOMS participants were included. Their mean{+/-}SD EQ-5D and MSWS-12 scores were 0.74{+/-}0.18 and 50.8{+/-}33.5, respectively, and these assessments were found to be moderately correlated (r=-0.553, p<0.001). The model using all individual MSWS-12 item scores as independent variables was found to have the best fit (MAE=0.109{+/-}0.096, RMSE=0.145, adjusted R2=0.329). The percentage of EQ-5D estimates within 0.05 and 0.10 of the actual value were 30% and 61%, respectively. This mapping equation was more precise in patients with moderate mobility impairment (MAE=0.087{+/-}0.061 at patient-determined disease step (PDDS) of 3-6) and less precise in patients with no (MAE=0.141{+/-}0.128 at PDDS of 0-2) or severe mobility impairment (MAE=0.121{+/-}0.049 at PDDS [≥]7). ConclusionsThe EQ-5D scores can be predicted using the MSWS-12 item scores with reasonable precision in North American patients with MS. Prediction estimates were more precise in patients with moderate mobility impairment.

A pragmatic parallel arm multi-centre randomised controlled trial to assess the effectiveness and cost-effectiveness of a group-based fatigue management programme (FACETS) for people with multiple sclerosis [MULTIPLE SCLEROSIS]

Wed, 22 May 2013 00:00:00 +0000

A pragmatic parallel arm multi-centre randomised controlled trial to assess the effectiveness and cost-effectiveness of a group-based fatigue management programme (FACETS) for people with multiple sclerosis [MULTIPLE SCLEROSIS]

Tue, 21 May 2013 00:00:00 +0000

Long-term efficacy and safety of incobotulinumtoxinA injections in patients with cervical dystonia [MOVEMENT DISORDERS]

Sat, 18 May 2013 00:00:00 +0000

Cognitive and motor skills in school-aged children following maternal vitamin A supplementation during pregnancy in rural Nepal: a follow-up of a placebo-controlled, randomised cohort [RESEARCH]

Thu, 9 May 2013 00:00:00 +0000

ObjectiveTo determine the effects of maternal vitamin A supplementation from preconception through postpartum on cognitive and motor development of children at 10-13 years of age in rural Nepal. DesignFollow-up assessment of children born to women randomly assigned by a village to receive either supplemental vitamin A (7000 {micro}g retinol equivalents) or placebo weekly during a continuous 3.5-year period from 1994-1997. The participants came from 12 wards, a subset of 270 wards in the original trial. Trained staff tested children for cognition by the Universal Nonverbal Intelligence Test (UNIT) and motor ability using four subtests from the Movement Assessment Battery for Children (MABC). Data on schooling, home environment and nutritional and socioeconomic status were also collected. SettingSouthern plains district of Sarlahi, Nepal. Participants390 Nepalese children 10-13 years of age. Main outcome measuresRaw scores on UNIT and square-root transformed scores on an abridged version of the MABC tests, expressed as cluster-summarised (mean{+/-}SD) values to account for the design of the original trial. ResultsThere were no differences in UNIT (79.61{+/-}5.99 vs 80.69{+/-}6.71) or MABC (2.64{+/-}0.07 vs 2.49{+/-}0.09) test scores in children whose mothers were exposed to vitamin A vs placebo (mean differences: -1.07, 95% CI -7.10 to 9.26, p=0.78; 0.15, 95% CI 0.43 to -0.08, p=0.15), respectively. More children in the placebo group had repeated a grade in school (28% of placebo vs 16.7% of vitamin A, p=0.01). ConclusionsPreconceptional to postpartum maternal vitamin A supplementation, in an undernourished setting, does not improve cognition or motor development at ages 10-13 years.

Randomised controlled trial of an education and support package for stroke patients and their carers [RESEARCH]

Wed, 8 May 2013 00:00:00 +0000

ObjectiveTailoring stroke information and providing reinforcement opportunities are two strategies proposed to enhance the effectiveness of education. This study aimed to evaluate the effects of an education package which utilised both strategies on the knowledge, health and psychosocial outcomes of stroke patients and carers. DesignMultisite, randomised trial comparing usual care with an education and support package. SettingTwo acute stroke units. ParticipantsPatients and their carers (N=138) were randomised (control n=67, intervention n=71) of which data for 119 participants (control n=59, intervention n=60) were analysed. InterventionThe package consisted of a computer-generated, tailored written information booklet and verbal reinforcement provided prior to, and for 3 months following, discharge. Outcome measuresOutcome measures were administered prior to hospital discharge and at 3-month follow-up by blinded assessors. The primary outcome was stroke knowledge (score range: 0-25). Secondary outcomes were: self-efficacy (1-10), anxiety and depression (0-21), ratings of importance of information (1-10), feelings of being informed (1-10), satisfaction with information (1-10), caregiver burden (carers) (0-13) and quality of life (patients) (1-5). ResultsIntervention group participants reported better: self-efficacy for accessing stroke information (adjusted mean difference (MD) of 1.0, 95% CI 0.3 to 1.7, p=0.004); feeling informed (MD 0.9, 95% CI 0.2 to 1.6, p=0.008); and satisfaction with medical (MD 2.0, 95% CI 1.1 to 2.8, p<0.001); practical (MD 1.1, 95% CI 0.3 to 1.9, p=0.008), services and benefits (MD 0.9, 95% CI 0.1 to 1.8, p=0.036) and secondary prevention information (MD 1.7, 95% CI 0.9 to 2.5, p<0.001). There was no significant effect on other outcomes. ConclusionsIntervention group participants had improved self-efficacy for accessing stroke information and satisfaction with information, but other outcomes were not significantly affected. Evaluation of a more intensive intervention in a trial with a larger sample size is required to establish the value of an educational intervention that uses tailoring and reinforcement strategies. ACTRN12608000469314

Clinical relevance and practical implications of trials of perfusion and angiographic imaging in patients with acute ischaemic stroke: a multicentre cohort imaging study [CEREBROVASCULAR DISEASE]

Fri, 3 May 2013 00:00:00 +0000

Nodding syndrome in Ugandan children--clinical features, brain imaging and complications: a case series [RESEARCH]

Fri, 3 May 2013 00:00:00 +0000

ObjectivesNodding syndrome is a devastating neurological disorder of uncertain aetiology affecting children in Africa. There is no diagnostic test, and risk factors and symptoms that would allow early diagnosis are poorly documented. This study aimed to describe the clinical, electrophysiological and brain imaging (MRI) features and complications of nodding syndrome in Ugandan children. DesignCase series. Participants22 children with nodding syndrome brought to Mulago National Referral Hospital for assessment. Outcome measuresClinical features, physical and functional disabilities, EEG and brain MRI findings and a staging system with a progressive development of symptoms and complications. ResultsThe median age of symptom onset was 6 (range 4-10) years and median duration of symptoms was 8.5 (range 2-11) years. 16 of 22 families reported multiple affected children. Physical manifestations and complications included stunting, wasting, lip changes and gross physical deformities. The bone age was delayed by 2 (range 1-6) years. There was peripheral muscle wasting and progressive generalised wasting. Four children had nodding as the only seizure type; 18 in addition had myoclonic, absence and/or generalised tonic-clonic seizures developing 1-3 years after the onset of illness. Psychiatric manifestations included wandering, aggression, depression and disordered perception. Cognitive assessment in three children demonstrated profound impairment. The EEG was abnormal in all, suggesting symptomatic generalised epilepsy in the majority. There were different degrees of cortical and cerebellar atrophy on brain MRI, but no hippocampal changes. Five stages with worsening physical, EEG and brain imaging features were identified: a prodrome, the development of head nodding and cognitive decline, other seizure types, multiple complications and severe disability. ConclusionsNodding syndrome is a neurological disorder that may be characterised as probably symptomatic generalised epilepsy. Clinical manifestations and complications develop in stages which might be useful in defining treatment and rehabilitation. Studies of risk factors, pathogenesis, management and outcome are urgently needed.

High-sensitivity troponin assay improves prediction of cardiovascular risk in patients with cerebral ischaemia [CEREBROVASCULAR DISEASE]

Wed, 1 May 2013 00:00:00 +0000

The eye response test alone is sufficient to predict stroke outcome--reintroduction of Japan Coma Scale: a cohort study [RESEARCH]

Mon, 29 Apr 2013 00:00:00 +0000

ObjectivesPrompt assessment of consciousness levels is vitally important during the emergency care of stroke patients. The Japan Coma Scale (JCS) is a one-axis coma scale published in 1974 with outstanding simplicity. The hypothesis is that JCS is sufficient to predict stroke outcome. The aim of the study was to verify the predictability of JCS, which should help JCS attain international recognition. DesignA cohort study. SettingA prefectural stroke registry. ParticipantsWe analysed 13 788 stroke patients identified from January 1999 to December 2009 inclusive in the entire Kyoto prefecture and registered in the Kyoto Stroke Registry (KSR). Main outcome measuresWe investigated the relationship between consciousness levels, based on JCS at stroke onset and activities of daily living (ADL) at 30 days or deaths within 30 days in a large population-based stroke registry. We calculated Spearman's coefficient for the correlation between JCS and the ADL scale, generated estimated survival curves by the Kaplan-Meier method and finally compared HRs for death within 30 days after onset, comparing patients with different conscious levels based on JCS. ResultsA total of 13 406 (97.2%) patients were graded based on JCS. JCS correlated to the ADL scale with Spearman's correlation coefficient of 0.61. HRs for death within 30 days were 1 (reference) (95% CIs), 5.55 (4.19 to 7.37), 9.54 (7.16 to 12.71) and 35.21 (26.10 to 44.83) in those scored as JCS0, JCS1, JCS2 and JCS3, respectively. ConclusionsUsing a single test of eye response, JCS has outstanding merits as a coma scale, that is, simplicity and applicability. The present study adds predictability for early outcome in stroke patients. JCS is valuable, especially in an emergency setting, when a prompt assessment of consciousness levels is needed.

Cardiovascular mortality in bipolar disorder: a population-based cohort study in Sweden [RESEARCH]

Thu, 18 Apr 2013 00:00:00 +0000

ObjectiveTo estimate the cardiovascular mortality among persons with bipolar disorder in Sweden compared to the general population. DesignPopulation register-based cohort study with a 20-year follow-up. SettingSweden. ParticipantsThe entire population of Sweden (n=10.6 million) of whom 17 101 persons were diagnosed with bipolar disorder between 1987 and 2006. Main outcome measuresMortality rate ratios (MRR), excess mortality (excess deaths), cardiovascular disorder (CVD) and specifically cerebrovascular disease, coronary heart disease, acute myocardial infarction, sudden cardiac deaths and hospital admission rate ratio (ARR). ResultsPersons with bipolar disorder died of CVD approximately 10 years earlier than the general population. One third (38%) of all deaths in persons with bipolar disorder were caused by CVD and almost half (44%) by other somatic diseases, whereas suicide and other external causes accounted for less than a fifth of all deaths (18%). Excess mortality of both CVD (n=824) and other somatic diseases (n=988) was higher than that of suicide and other external causes (n=675 deaths). MRRs for cerebrovascular disease, coronary heart disease and acute myocardial infarction were twice as high in persons with bipolar disorder compared to the general population. Despite the increased mortality of CVD, hospital admissions (ARR) for CVD treatment were only slightly increased in persons with bipolar disorder when compared to the general population. ConclusionsThe increased cardiovascular mortality in persons with bipolar disorder calls for renewed efforts to prevent and treat somatic diseases in this group. Specifically, our findings further imply that it would be critical to ensure that persons with bipolar disorder receive the same quality care for CVD as persons without bipolar disorder.

An open-label cohort study of the improvement of quality of life and pain in de novo cervical dystonia patients after injections with 500 U botulinum toxin A (Dysport) [RESEARCH]

Thu, 18 Apr 2013 00:00:00 +0000

ObjectivesIt remains to be determined whether the benefits of botulinum toxin type A (BoNT-A) on cervical dystonia (CD) motor symptoms extend to improvements in patient's quality of life (QoL). This analysis of a large, multicentre study was conducted with the aim of investigating changes in QoL and functioning among de novo patients receiving 500 U BoNT-A (abobotulinumtoxinA; Dysport) for the treatment of the two most frequent forms of CD, predominantly torticollis and laterocollis. DesignA prospective, open-label study of Dysport (500 U; Ipsen Biopharm Ltd) administered according to a defined intramuscular injection algorithm. SettingGerman and Austrian outpatient clinics. Participants516 male and female patients (aged [≥]18 years) with de novo CD. The majority of patients had torticollis (78.1%). 35 patients had concomitant depression (MedDRA-defined). Main outcome measuresChange from baseline to weeks 4 and 12 in Craniocervical Dystonia Questionnaire (CDQ-24) total and subscale scores, patient diary items ( day-to-day capacities and activities', pain' and duration of pain') and global assessment of pain. ResultsSignificant improvements were observed in CDQ-24 total and subscale scores at week 4 and were sustained up to week 12 (p<0.001). Changes in CDQ-24 scores did not significantly differ between the torticollis and laterocollis groups or between patients with or without depression. There were also significant reductions in patient diary item scores for activities of daily living, pain and pain duration at weeks 4 and 12 (p<0.001). Pain relief (less or no pain) was reported by 66% and 74.1% of patients at weeks 4 and 12, respectively. Changes in pain parameters demonstrated a positive relationship with change in Tsui score. ConclusionsAfter standardised open-label treatment with Dysport 500 U, improvements in QoL and pain intensity up to 12 weeks in patients with CD were observed.

A novel oral nutraceutical formula of omega-3 and omega-6 fatty acids with vitamins (PLP10) in relapsing remitting multiple sclerosis: a randomised, double-blind, placebo-controlled proof-of-concept clinical trial [RESEARCH]

Wed, 17 Apr 2013 00:00:00 +0000

ObjectiveTo assess whether three novel interventions, formulated based on a systems medicine therapeutic concept, reduced disease activity in patients with relapsing-remitting multiple sclerosis (MS) who were either treated or not with disease-modifying treatment. DesignA 30-month randomised, double-blind, placebo-controlled, parallel design, phase II proof-of-concept clinical study. SettingsCyprus Institute of Neurology and Genetics. Participants80 participants were randomised into four groups of 20 each. A total of 41 (51%) patients completed the 30-month trial. The eligibility criteria were an age of 18-65; a diagnosis of relapsing-remitting MS according to the McDonald criteria; a score of 0.0-5.5 on the Expanded Disability Status Scale (EDSS); MRI showing lesions consistent with MS; at least one documented clinical relapse and either receiving or not a disease-modifying treatment within the 24-month period before enrolment in the study. Patients were excluded because of a recent (<30 days) relapse, prior immunosuppressant or monoclonal antibody therapy, pregnancy or nursing, other severe disease compromising organ function, progressive MS, history of recent drug or alcohol abuse, use of any additional food supplements, vitamins or any form of polyunsaturated fatty acids, and a history of severe allergic or anaphylactic reactions or known specific nutritional hypersensitivity. InterventionsThe first intervention (A) was composed of {Omega}-3 and {Omega}-6 polyunsaturated fatty acids at 1:1 wt/wt. Specifically, the {Omega}-3 fatty acids were docosahexaenoic acid and eicosapentaenoic acid at 3:1 wt/wt, and the {Omega}-6 fatty acids were linoleic acid and {gamma}-linolenic acid at 2:1 wt/wt. This intervention also included minor quantities of other specific polyunsaturated, monounsaturated and saturated fatty acids as well as vitamin A and vitamin E (-tocopherol). The second intervention (B, PLP10) was a combination of A and {gamma}-tocopherol. The third intervention (C) was {gamma}-tocopherol alone. The fourth group of 20 participants received placebo. The interventions were administered per os (by mouth) once daily, 30 min before dinner for 30 months. Main outcome measuresThe primary end point was the annualised relapse rate (ARR) of the three interventions versus the placebo at 2 years. The secondary end point was the time to confirmed disability progression at 2 years. ResultsA total of 41 (51%) patients completed the 30-month trial. Overall, for the per-protocol analysis of the 2-year primary end point, eight relapses were recorded in the PLP10 group (n=10; 0.40 ARR) versus 25 relapses in the placebo group (n=12; 1.04 ARR), representing a 64% adjusted relative rate reduction for the PLP10 group (RRR 0.36, 95% CI 0.15 to 0.87, p=0.024). In a subgroup analysis that excluded patients on monoclonal antibody (natalizumab) treatment, the observed adjusted RRR became stronger (72%) over the 2 years (RRR 0.28, 95% CI 0.10 to 0.79, p=0.016). The per-protocol analysis for the secondary outcome at 2 years, the time to disability progression, was significantly longer only for PLP10. The cumulative probability of disability progression at 2 years was 10% in the PLP10 group and 58% in the placebo group (unadjusted log-rank p=0.019). In a subgroup analysis that excluded patients on natalizumab, the cumulative probability of progression was 10% for the 10 patients in the PLP10 group and 70% for the 12 patients in the placebo group, representing a relative 86% decrease in the risk of the sustained progression of disability in the PLP10 group (unadjusted log-rank p=0.006; adjusted HR, 0.11; 95% CI 0.01 to 0.97, p=0.047). No adverse events were reported. Interventions A (10 patients) and C (9 patients) showed no significant efficacy. ConclusionsIn this small proof-of-concept, randomised, double-blind clinical trial; the PLP10 treatment significantly reduced the ARR and the risk of sustained disability progression without any reported serious adverse events. Larger studies are needed to further assess the safety and efficacy of PLP10. Trial registrationInternational Standard Randomised Controlled Trial, number ISRCTN87818535.

Renal function estimations and dose recommendations for dabigatran, gabapentin and valaciclovir: a data simulation study focused on the elderly [RESEARCH]

Thu, 11 Apr 2013 00:00:00 +0000

ObjectivesThe thrombin inhibitor dabigatran is mainly excreted by the kidneys. We investigated whether the recommended method for estimation of renal function used in the clinical trials, the Cockcroft-Gault (CGold) equation and the estimated glomerular filtration rate (eGFR) modification of diet in renal disease equation 4 (MDRD4), differ in elderly participants, resulting in erroneously higher dose recommendations of dabigatran, which might explain the serious, even fatal, bleeding reported. The renally excreted drugs gabapentin and valaciclovir were also included for comparison. DesignA retrospective data simulation study. ParticipantsParticipants 65 years and older included in six different studies. Main outcome measureEstimated renal function by CG based on uncompensated ( old Jaffe' method) creatinine (CGold) or by MDRD4 based on standardised compensated P-creatinine traceable to isotope-dilution mass spectrometry, and the resulting doses. Results790 participants (432 females), mean age ({+/-}SD) 77.6{+/-}5.7 years. Mean estimated creatinine clearance (eCrCl) by the CGold equation was 44.2{+/-}14.8 ml/min, versus eGFR 59.6{+/-}20.7 ml/min/1.73 m2 with MDRD4 (p<0.001), absolute median difference 13.5, 95% CI 12.9 to 14.2. MDRD4 gave a significantly higher mean dose (valaciclovir +21%, dabigatran +25% and gabapentin +37%) of all drugs (p<0.001). With MDRD4 58% of the women would be recommended a full dose of dabigatran compared with 18% if CGold is used. ConclusionsMDRD4 would result in higher recommended doses of the three studied drugs to elderly participants compared with CG, particularly in women, and thus increased the risk of dose and concentration-dependent adverse reactions. It is important to know which method of estimation of renal function the Summary of Products Characteristics was based on, and use only that one when prescribing renally excreted drugs with narrow safety window. Doses based on recently developed methods for estimation of renal function may be associated with considerable risk of overtreatment in the elderly.

Move it to improve it (Mitii): study protocol of a randomised controlled trial of a novel web-based multimodal training program for children and adolescents with cerebral palsy [PROTOCOL]

Wed, 10 Apr 2013 00:00:00 +0000

IntroductionPersons with cerebral palsy require a lifetime of costly and resource intensive interventions which are often limited by equity of access. With increasing burden being placed on health systems, new methods to deliver intensive rehabilitation therapies are needed. Move it to improve it (Mitii) is an internet-based multimodal programme comprising upper-limb and cognitive training with physical activity. It can be accessed in the client's home at their convenience. The proposed study aims to test the efficacy of Mitii in improving upper-limb function and motor planning. Additionally, this study hopes to further our understanding of the central neurovascular mechanisms underlying the proposed changes and determine the cost effectiveness of Mitii. Methods and analysisChildren with congenital hemiplegia will be recruited to participate in this waitlist control, matched pairs, single-blind randomised trial. Children be matched at baseline and randomly allocated to receive 20 weeks of 30 min of daily Mitii training immediately, or waitlisted for 20 weeks before receiving the same Mitii training (potential total dose=70 h). Outcomes will be assessed at 20 weeks after the start of Mitii, and retention effects tested at 40 weeks. The primary outcomes will be the Assessment of Motor and Process Skills (AMPS), the Assisting Hand Assessment (AHA) and unimanual upper-limb capacity using the Jebsen-Taylor Test of Hand Function (JTTHF). Advanced brain imaging will assess use-dependant neuroplasticity. Measures of body structure and functions, activity, participation and quality of life will be used to assess Mitii efficacy across all domains of the International Classification of Functioning, Disability and Health framework. Ethics and disseminationThis project has received Ethics Approval from the Medical Ethics Committee of The University of Queensland (2011000608) and the Royal Children's Hospital Brisbane (HREC/11/QRCH/35). Findings will be disseminated widely through conference presentations, seminars and peer-reviewed scientific journals. Trial registrationACTRN12611001174976

(123I)FP-CIT SPECT in suspected dementia with Lewy bodies: a longitudinal case study [RESEARCH]

Mon, 8 Apr 2013 00:00:00 +0000

ObjectivesLittle is known regarding the false-negative' or false-positive' striatal dopamine transporter binding on SPECT for the diagnosis of dementia with Lewy bodies (DLB). We explored the clinical course in patients fulfilling the criteria for clinical DLB with a normal (123I)FP-CIT SPECT (ie, SPECT scan negative, clinical features positive (S-CF+)) and patients not fulfilling DLB criteria with an abnormal scan (S+CF-). DesignLongitudinal case study over 2-5 years. SettingConsecutive referrals of patients with mild dementia to dementia clinics in western Norway. Participants50 patients (27 men and 23 women; mean age at baseline of 74 (range 52-88)) with (123I)FP-CIT SPECT images underwent cluster analysis: 20/50 patients allocated to a DLB' and 8 to a non-DLB' cluster were included. Outcome measuresScores on standardised clinical rating scales for hallucinations, parkinsonism, fluctuations, rapid eye movement (REM) sleep behaviour disorder and visually rated (123I)FP-CIT SPECT. ResultsDuring the follow-up period, in the S+CF- group (n=7), frequency and severity of DLB symptoms tended to increase, particularly parkinsonism (7/7) and cognitive fluctuations (7/7), while severity of visual hallucinations and REM sleep behaviour disorder remained stable. The S-CF+ (n=3) fulfilled the operationalised criteria for probable DLB both at baseline and at the end of the follow-up. ConclusionsThe findings suggest that systematic visual analyses of (123I)FP-CIT SPECT can detect people with DLB prior to the development of the full clinical syndrome. In addition, the study indicates that some patients fulfilling clinical criteria for probable DLB have a normal scan, and further studies are required to characterise these patients better.

Executive functioning in children with unilateral cerebral palsy: protocol for a cross-sectional study [PROTOCOL]

Wed, 3 Apr 2013 00:00:00 +0000

IntroductionEarly brain injury, as found in children with unilateral cerebral palsy (CP), may cause deficits in higher-order cognitive tasks known as executive functions (EF). EF has been conceptualised as comprised of four distinct yet inter-related components: (1) attentional control, (2) cognitive flexibility, (3) goal setting and (4) information processing. The aim of this study was to examine EF in children with unilateral CP and compare their performance with a typically developing reference group (TDC). The potential laterality effects of unilateral CP on EF will be explored, as will the relationship between the cognitive measures of EF, behavioural manifestations of EF, psychological functioning and clinical features of unilateral CP. Methods and analysisThis cross-sectional study aims to recruit a total of 42 children with unilateral CP (21 right unilateral CP and 21 left unilateral CP) and 21 TDC aged between 8 and 16 years. Clinical severity will be described for gross motor function and manual ability. Outcomes for cognitive EF measureswill include subtests from the Wechsler Intelligence Scale for Children--Fourth Edition, Delis-Kaplan Executive Function System, Rey Complex Figure Test and the Test of Everyday Attention for Children. Behavioural manifestations of EF will be assessed using the Behaviour Rating Inventory of Executive Function, Parent and Teacher versions. Psychological functioning will be examined using the Strengths and Difficulties Questionnaire. Between-groups differences will be examined in a series of one-way analyses of covariance and followed up using linear comparisons. An overall composite of cognitive EF measures will be created. Bivariate correlations between the EF composite and psychological measures will be calculated. Ethics and disseminationThis protocol describes a study that, to our knowledge, is the first to examine multiple components of EF using a cohort of children with unilateral CP. Exploration of potential laterality effects of EF among children with a congenital, unilateral brain injury is also novel. Possible relationships between EF and psychological functioning will also be investigated. Ethics have been obtained through the University of Queensland School of Psychology Ethics Committee and the Queensland Children's Health Services Human Research Ethics Committee. Results will be disseminated in peer reviewed publications and presentations at national and international conferences. This study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12611000263998).

Juvenile Huntington's disease: a population-based study using the General Practice Research Database [RESEARCH]

Wed, 3 Apr 2013 00:00:00 +0000

BackgroundThe juvenile form of Huntington's disease (HD) is a rare disorder. There are no population-based estimates of either its incidence or prevalence in any population in the world. The present study was undertaken to estimate the frequency of juvenile HD in the UK and to examine the range of pharmacological treatments used in its management. MethodThe records of individuals under the age of 21 who had recorded diagnoses of HD were retrieved from the General Practice Research Database from 1990 through 2010. From these data estimates of incidence and prevalence were made as well as the specific treatments used in the treatment of its physical and psychological manifestations. Results12 incident and 21 prevalent patients with juvenile HD were identified. The 21 prevalent cases included the 12 incident cases. The minimum population-based estimate of incidence is 0.70 (95% CI 0.36 to 1.22) per million patient-years. The minimum estimate of prevalence is 6.77/million (95% CI 5.60 to 8.12) per million patient-years. Patients were most frequently prescribed antidepressants, hypnotics, antipsychotics and treatments for motor abnormalities. ConclusionsIn the UK, juvenile HD is an extremely rare and complex disorder. The prescribing data demonstrate that the clinical management of juvenile HD is undertaken with no formal evidence base for the efficacy or safety of the treatments used. Research into the safety and efficacy of appropriate therapies is urgently required to offset the haphazard nature of prescribing. Multinational collaboration will be necessary to enrol sufficient numbers. Exploratory studies, though, should begin now.

Specificity and sensitivity of transcranial sonography of the substantia nigra in the diagnosis of Parkinson's disease: prospective cohort study in 196 patients [RESEARCH]

Tue, 2 Apr 2013 00:00:00 +0000

ObjectiveNumerous ultrasound studies have suggested that a typical enlarged area of echogenicity in the substantia nigra (SN+) can help diagnose idiopathic Parkinson's disease (IPD). Almost all these studies were retrospective and involved patients with well-established diagnoses and long-disease duration. In this study the diagnostic accuracy of transcranial sonography (TCS) of the substantia nigra in the patient with an undiagnosed parkinsonian syndrome of recent onset has been evaluated. DesignProspective cohort study for diagnostic accuracy. SettingNeurology outpatient clinics of two teaching hospitals in the Netherlands. Patients196 consecutive patients, who were referred to two neurology outpatient clinics for analysis of clinically unclear parkinsonism. Within 2 weeks of inclusion all patients also underwent a TCS and a 123I-ioflupane Single Photon Emission CT (FP-CIT SPECT) scan of the brain (n=176). Outcome measuresAfter 2 years, patients were re-examined by two movement disorder specialist neurologists for a final clinical diagnosis, that served as a surrogate gold standard for our study. ResultsTemporal acoustic windows were insufficient in 45 of 241 patients (18.67%). The final clinical diagnosis was IPD in 102 (52.0%) patients. Twenty-four (12.3%) patients were diagnosed with atypical parkinsonisms (APS) of which 8 (4.0%) multisystem atrophy (MSA), 6 (3.1%) progressive supranuclear palsy (PSP), 6 (3.1%) Lewy body dementia and 4 (2%) corticobasal degeneration. Twenty-one (10.7%) patients had a diagnosis of vascular parkinsonism, 20 (10.2%) essential tremor, 7 (3.6%) drug-induced parkinsonism and 22 (11.2%) patients had no parkinsonism but an alternative diagnosis. The sensitivity of a SN+ for the diagnosis IPD was 0.40 (CI 0.30 to 0.50) and the specificity 0.61 (CI 0.52 to 0.70). Hereby the positive predictive value (PPV) was 0.53 and the negative predictive value (NPV) 0.48. The sensitivity and specificity of FP-CIT SPECT scans for diagnosing IPD was 0.88 (CI 0.1 to 0.95) and 0.68 (CI 0.58 to 0.76) with a PPV of 0.75 and an NPV of 0.84. ConclusionsThe diagnostic accuracy of TCS in early stage Parkinson's disease is not sufficient for routine clinical use. Clinicaltrials.gov identifierNCT0036819

Self-reported feelings of anger and aggression towards others in patients on levetiracetam: data from the UK antiepileptic drug register [RESEARCH]

Tue, 19 Mar 2013 00:00:00 +0000

ObjectivesTo ascertain the frequency of self-reported anger and depression in levetiracetam (LEV). DesignWe compared patients with epilepsy (PWE) taking LEV with PWE taking other antiepileptic drugs (AEDs). SettingAll PWE and controls submitted information to the UK AED register. ParticipantsWe analysed the data of 418 PWE and 41 control participants. 158 participants took LEV in monotherapy or as part of polypharmacotherapy, 260 PWE took other AED. Primary and secondary outcome measuresAll PWE and controls completed the Liverpool Adverse Event Profile (LAEP) which includes items on anger and depression quantified on a four-point Likert scale, with 1 indicating that there was never a problem; 2, rarely a problem; 3, sometimes a problem and 4, always or often a problem. Results49% of PWE on LEV and 39% on AED other than LEV reported anger as sometimes or always being a problem (p=0.042). 48% of PWE on LEV and 45% on AED other than LEV reported depression as sometimes or always being a problem (p=0.584). 7% of control participants reported anger as sometimes being a problem and 93% reported anger as never or rarely being a problem. Depression was never a problem in 75% of controls and rarely a problem in 25%. ConclusionsAnger and depression were more frequently reported as a problem by PWE than by control participants. Our observational register of self-reported symptoms suggested anger being more often a problem in patients taking LEV than in PWE taking other AED. PWE should be informed about this potential problem of LEV.

Upper limb international spasticity study: rationale and protocol for a large, international, multicentre prospective cohort study investigating management and goal attainment following treatment with botulinum toxin A in real-life clinical practice [RESEARCH]

Mon, 18 Mar 2013 00:00:00 +0000

ObjectivesThis article provides an overview of the Upper Limb International Spasticity (ULIS) programme, which aims to develop a common core dataset for evaluation of real-life practice and outcomes in the treatment of upper-limb spasticity with botulinum toxin A (BoNT-A). Here we present the study protocol for ULIS-II, a large, international cohort study, to describe the rationale and steps to ensure the validity of goal attainment scaling (GAS) as the primary outcome measure. Methods and analysis designAn international, multicentre, observational, prospective, before-and-after study, conducted at 84 centres in 22 countries across three continents. Participants468 adults presenting with poststroke upper limb spasticity in whom a decision had already been made to inject BoNT-A (5-12 consecutive participants recruited per centre). InterventionsPhysicians were free to choose targeted muscles, BoNT-A preparation, injected doses/technique and timing of follow-up in accordance with their usual practice and the goals for treatment. Primary outcome measure: GAS. Secondary outcomes: Measurements of spasticity, standardised outcome measures and global benefits. Steps to ensure validity included: (1) targeted training of all investigators in the use of GAS; (2) within-study validation of goal statements and (3) establishment of an electronic case report form with an in-built tracking facility for separation of baseline/follow-up data. AnalysisEfficacy population: all participants who had (1) BoNT-A injection and (2) subsequent assessment of GAS. Primary efficacy variable: percentage (95% CI) achievement of the primary goal from GAS following one BoNT-A injection cycle. Ethics and disseminationThis non-interventional study is conducted in compliance with guidelines for good pharmacoepidemiology practices. Appropriate ethical approvals were obtained according to local regulations. ULIS-II will provide important information regarding treatment and outcomes from BoNT-A in real-life upper limb spasticity management. The results will be published separately. RegistrationClinicalTrials.gov identifier: NCT01020500.

Survival analysis of HDR brachytherapy versus reoperation versus temozolomide alone: a retrospective cohort analysis of recurrent glioblastoma multiforme [RESEARCH]

Fri, 15 Mar 2013 00:00:00 +0000

ObjectivesTumour recurrence of glioblastoma multiforme (GBM) after initial treatment with surgical resection, radiotherapy and chemotherapy is an inevitable phenomenon. This retrospective cohort study compared the efficacy of interstitial high dose rate brachytherapy (HDR-BRT), re-resection and sole dose dense temozolomide chemotherapy (ddTMZ) in the treatment of recurrent glioblastoma after initial surgery and radiochemotherapy. DesignRetropective cohort study. SettingPrimary level of care with two participating centres. The geographical location was central Germany. ParticipantsFrom January 2005 to December 2010, a total of 111 patients developed recurrent GBM after initial surgery and radiotherapy with concomitant temozolomide. The inclusion criteria were as follows: (1) histology-proven diagnosis of primary GBM (WHO grade 4), (2) primary treatment with resection and radiochemotherapy, and (3) tumour recurrence/progression. InterventionsThis study compared retrospectively the efficacy of interstitial HDR-BRT, re-resection and ddTMZ alone in the treatment of recurrent glioblastoma. Primary and secondary outcome measuresMedian survival, progression free survival and complication rate. ResultsMedian survival after salvage therapy of the recurrence was 37, 30 and 26 weeks, respectively. The HDR-BRT group did significantly better than both the reoperation (p<0.05) and the ddTMZ groups (p<0.05). Moderate to severe complications in the HDR-BRT, reoperation and sole chemotherapy groups occurred in 5/50 (10%), 4/36 (11%) and 9/25 (36%) cases, respectively. ConclusionsCT-guided interstitial HDR-BRT attained higher survival benefits in the management of recurrent glioblastoma after initial surgery and radiotherapy with concurrent temozolomide in comparison with the other treatment modalities. The low risk of complications of the HDR-BRT and the fact that it can be delivered percutaneously in local anaesthesia render it a promissing treatment option for selected patients which should be further evaluated.

Assessing fracture risk in people with MS: a service development study comparing three fracture risk scoring systems [RESEARCH]

Fri, 15 Mar 2013 00:00:00 +0000

ObjectivesSuboptimal bone health is increasingly recognised as an important cause of morbidity. Multiple sclerosis (MS) has been consistently associated with an increased risk of osteoporosis and fracture. Various fracture risk screening tools have been developed, two of which are in routine use and a further one is MS-specific. We set out to compare the results obtained by these in the MS clinic population. DesignThis was a service development study. The 10-year risk estimates of any fracture and hip fracture generated by each of the algorithms were compared. SettingThe MS clinic at the Royal London Hospital. Participants88 patients with a confirmed diagnosis of MS. Outcome measuresMean 10-year overall fracture risk and hip fracture risk were calculated using each of the three fracture risk calculators. The number of interventions that would be required as a result of using each of these tools was also compared. ResultsMean 10-year fracture risk was 4.7%, 2.3% and 7.6% using FRAX, QFracture and the MS-specific calculator, respectively (p<0.0001 for difference). The agreement between risk scoring tools was poor at all levels of fracture risk. ConclusionsThe agreement between these three fracture risk scoring tools is poor in the MS population. Further work is required to develop and validate an accurate fracture risk scoring system for use in MS. Trial registrationThis service development study was approved by the Clinical Effectiveness Department at Barts Health NHS Trust (project registration number 156/12).

Cognitive ability and educational level in relation to concussion: a population study of young men [RESEARCH]

Sat, 9 Mar 2013 00:00:00 +0000

ObjectivesTo investigate the association of concussion with cognitive ability (CA) and educational level (EL). DesignEpidemiological--cross-linkage of national computer registers. SettingDenmark. Participants130 420 young men appearing before the Danish draft board during the period 2006-2010. Primary and secondary outcome measuresCA test scores, EL and occurrence of concussion during the period 2004-2009, treated either in an A&E unit or upon admission to a hospital ward. ResultsThe 3067 men who had suffered a concussion had lower CAs (mean=96.5, SD=15, 95% CI 95.0 to 97.0) than the total cohort and they were lower for 1452 who were admitted to a hospital ward (mean CA=95.8, SD=15, 95% CI 95.1 to 96.6) than for 1615 who were treated only at an A&E unit (mean CA=97.1, SD=15, 95% CI 96.3 to 98.0). Multiple logistic regressions revealed that the effects for EL were stronger than those for CA. Among 127 353 men not sustaining a concussion, 48% attended a gymnasium' (sixth-form college), among men treated for a concussion at an A&E unit, this falls to 36% and among men hospitalised for a concussion to 30%. Transfer to a gymnasium, if it happens, almost invariably does so before the 18th birthday. Among 701 men suffering a concussion and admitted to a hospital department after this date, only 26% (n=182) were previously transferred to a gymnasium. Among the 804 men treated at an A&E unit after their 18th birthday, 33% (n=265) had done so. These two percentages are significantly below the corresponding non-concussed population (48%). ConclusionsTaken together, the results suggest that lower CA and, in particular, lower EL are risk factors for sustaining a concussion, the risk increasing with the severity of the injury.

The contribution of stress to the comorbidity of migraine and major depression: results from a prospective cohort study [RESEARCH]

Sat, 9 Mar 2013 00:00:00 +0000

ObjectivesTo assess how much the association between migraine and depression may be explained by various measures of stress. DesignNational Population Health Survey is a prospective cohort study representative of the Canadian population. Eight years of follow-up time were used in the present analyses. SettingCanadian adult population ages 18-64. Participants9288 participants. OutcomeIncident migraine and major depression. ResultsAdjusting for sex and age, depression was predictive of incident migraine (HR: 1.62; 95% CI 1.03 to 2.53) and migraine was predictive of incident depression (HR: 1.55; 95% CI 1.15 to 2.08). However, adjusting for each assessed stressor (childhood trauma, recent marital problems, recent unemployment, recent household financial problems, work stress, chronic stress and change in social support) decreased this association, with chronic stress being a particularly strong predictor of outcomes. When adjusting for all stressors simultaneously, both associations were largely attenuated (depression-migraine HR: 1.30; 95% CI 0.80 to 2.10; migraine-depression HR: 1.19; 95% CI 0.86 to 1.66). ConclusionsMuch of the apparent association between migraine and depression may be explained by stress.

Hypometabolism in the supplementary and anterior cingulate cortices is related to dysphagia in Parkinson's disease: a cross-sectional and 3-year longitudinal cohort study [RESEARCH]

Fri, 1 Mar 2013 00:00:00 +0000

ObjectiveDysphagia is one of the cardinal symptoms of Parkinson's disease (PD). It is closely related to the quality of life and longevity of PD patients. The aim of the study is to clarify the pathophysiological mechanisms responsible for dysphagia in PD. DesignA cross-sectional and longitudinal comparative study. SettingTohoku University Hospital. ParticipantsEight patients with dysphagia, 15 patients without dysphagia and 10 normal control subjects. Main outcome measuresThe time needed for swallowing initiation and changes in brain glucose metabolism at baseline and after a 3-year follow-up period. ResultsThe time needed for swallowing initiation was significantly longer in the patients with dysphagia compared with the patients without dysphagia at baseline and after the 3-year follow-up period (p<0.05). The patients with dysphagia exhibited hypometabolism in the supplementary motor area (SMA) and the anterior cingulate cortex (ACC) compared with the 10 normal control subjects at baseline (uncorrected p<0.001). After the 3-year follow-up period, the number of brain areas showing hypometabolism increased, involving not only the SMA and the ACC but also the bilateral medial frontal lobes, middle cingulate cortex, thalamus and right superior, middle, inferior and orbital frontal gyri (uncorrected p<0.001). In contrast, the patients without dysphagia showed virtually no regional hypometabolism at baseline (uncorrected p<0.001) and only a small degree of hypometabolism in the SMA and ACC after the 3-year follow-up period (uncorrected p<0.001). ConclusionsThese results suggest that dysphagia in PD patients is mainly related to a difficulty in swallowing initiation that is based on a combination of poor movement planning due to SMA dysfunction and impaired cognitive processing due to ACC dysfunction.

Poststroke fatigue and depression are related to mortality in young adults: a cohort study [RESEARCH]

Fri, 1 Mar 2013 00:00:00 +0000

ObjectivesTo investigate the relationship between poststroke fatigue and depression and subsequent mortality in young ischaemic stroke patients in a population-based study. DesignA prospective cohort study. SettingAll surviving young ischaemic stroke patients living in Hordaland County. ParticipantsYoung ischaemic stroke patients aged 15-50 years at the time of the stroke were invited to a follow-up on an average 6 years after the index stroke. Psychosocial factors and risk factors were registered. Fatigue was self-assessed by the Fatigue Severity Scale (FSS). Depression was measured by Montgomery-Asberg Depression Rating Scale (MADRS). InterventionNo intervention was performed. Primary and secondary outcome measureMortality on follow-up. ResultsIn total, 190 patients were included. The mean age on follow-up was 48 years and subsequent follow-up period was 12 years. Cox regression analysis showed that mortality was associated with FSS score (p=0.005) after adjusting for age (p=0.06) and sex (p=0.19). Cox regression analysis showed that mortality was associated with MADRS score (p=0.006) after adjusting for age (p=0.10) and sex (p=0.11). ConclusionsBoth fatigue and depression are associated with long-term mortality in young adults with ischaemic stroke. Depression may be linked to higher mortality because of psychosocial factors and unhealthy lifestyles whereas the link between fatigue and mortality is broader including connection to diabetes mellitus, myocardial infarction and psychosocial factors.

Sympathetic skin response and heart rate variability as diagnostic tools for the differential diagnosis of Lewy body dementia and Alzheimer's disease: a diagnostic test study [RESEARCH]

Fri, 1 Mar 2013 00:00:00 +0000

ObjectiveThe purpose of this study is to investigate the usefulness of sympathetic skin response (SSR) and heart rate variability (HRV) for the differential diagnosis of patients with dementia with Lewy bodies (DLB). DesignA diagnostic test study. SettingSingle centre in Japan. ParticipantsWe examined 20 patients with probable Alzheimer's disease (AD) diagnosed with NINCDS-ADRDA criteria and 20 with probable DLB diagnosed with the criteria of the third international DLB workshop. MethodsFor the SSR measurement, surface electrodes were used: the active recording electrode was placed on the palm of the hand and the reference electrode was placed on the dorsum of the same hand. SSR was induced by a median nerve electrical stimulation at an amplitude of 20 mA. For the HRV measurement, the A-A intervals were measured twice for 2 min with an interval of 5 min in a sitting position after a rest of 5 min. From the low-frequency power (LF; 0.02-0.15 Hz) and high-frequency power (HF; 0.15-0.50 Hz), the ratio of LF to HF power (LF/HF) was calculated using the maximal entropy method. ResultsSSR and HRV could detect the abnormality of autonomic function in patients with DLB at sensitivities of 85% and 90%, respectively. On the other hand, SSR and HRV detected an abnormality of autonomic function in patients with AD at sensitivities of 15% and 25% (p<0.05). The combination of the SSR and the HRV (double-positive) indicated abnormal autonomic function was recorded in only 1 of 20 patients (5%) with AD. In contrast, this combination indicated autonomic abnormality in 15 of 20 patients with DLB by our criteria (75%). ConclusionsSSR and HRV can be applied to differentiate DLB from AD.

Neurological assessment of preterm infants for predicting neuromotor status at 2 years: results from the LIFT cohort [RESEARCH]

Fri, 22 Feb 2013 00:00:00 +0000

ObjectiveTo develop a predictive risk stratification model for the identification of preterm infants at risk of 2-year suboptimal neuromotor status. DesignPopulation-based observational study. SettingRegional preterm infant follow-up programme (Loire Infant Follow-up Team (LIFT) cohort) implemented in 2003. Participants4030 preterm infants were enrolled in the LIFT cohort, and examined by neonatologists using a modified version of the Amiel-Tison neurological assessment tool. Main outcome criteria2 year neuromotor status based on clinical examinations was conducted by trained paediatricians and parents' responses to the Ages and Stages Questionnaire were reported. ResultsAt 2 years of corrected age, 3321 preterm infants were examined, and suboptimal neuromotor status was found in 355 (10.7%). The study population was divided into training and validation sets. In the training set, 13 neonatal neurological items were associated with a 2-year suboptimal neuromotor status. Having at least one abnormal item was defined as an abnormal neurological status at term. In the validation set, these data predicted a 2-year suboptimal neuromotor status with a sensitivity of 0.55 (95% CI 0.47 to 0.62) and a specificity of 0.65 (95% CI 0.62 to 0.67). Two predictive risk stratification trees were built using the training set, which were based on the neurological assessment at term along with either gestational age or severe cranial lesions or birth weight. Using the validation set, the first tree identified a subgroup with a relatively low risk of suboptimal neuromotor status (3%), representing 32% of infants, and the second tree identified a subgroup with a risk of 5%, representing 42% of infants. ConclusionA normal neurological assessment at term allows the identification of a subgroup of preterm infants with a lower risk of non-optimal neuromotor development at 2 years.

The Needs and Provision Complexity Scale: a multicentre prospective cohort analysis of met and unmet needs and their cost implications for patients with complex neurological disability [RESEARCH]

Fri, 22 Feb 2013 00:00:00 +0000

ObjectiveTo provide a brief overview of the Needs and Provision Complexity Scale (NPCS) and report its first application to describe the level of met' and unmet' health/social care needs, and to estimate their costs in community-based patients with complex neurological disability. DesignA multicentre prospective cohort analysis. SettingConsecutive discharges to the community from the nine tertiary specialist inpatient neurorehabilitation units in London over 12 months (2010/2011). ParticipantsPatients responding at follow-up (n=211). Mean age 50.2(SD14) years, males:females 127/84. Diagnosis 157(74%) brain injury, 27(13%) spinal cord injury/peripheral neuropathy; 27(13%) other. Primary outcome measureThe NPCS is a brief, pragmatic, directly costable instrument for measuring both an individual's needs for rehabilitation and support (NPCS-Needs) and the levels of service provided (NPCS-Gets) within a given period. MethodsThe NPCS-Needs' was completed by the treating clinical team at discharge. Patients and/or their carers self-reported NPCS-Gets' after 6 months by a postal/online questionnaire supported by a follow-up telephone interview. ResultsNeeds for medical/nursing care and accommodation were generally well met. Significant shortfalls in provision were identified in the subscales of Rehabilitation (paired t test: t -9.7, p<0.001, effect size (ES)=-0.85), Social support (t -5.8, p<0.001, ES=-0.48) and Equipment (t -5.6, p<0.001, ES=-0.44). Item-level analysis demonstrated that the frequency of Personal care received exceeded predicted needs (Wilcoxon z=-3.3, p<0.001). In 80% of cases, this care was provided/paid for by families. Translated into mean costs/patient/year, the estimated underspends on Rehabilitation (-{pound}2320) and Social support (-{pound}1790) were exceeded >3.5-fold by excess costs of Personal care ({pound}10 313) and Accommodation ({pound}4296). ConclusionsThe results identify underprovision of community-based rehabilitation and support services compared with needs, which may contribute directly to excess care burden and costs to family carers. The NPCS requires further evaluation but has potential use as a simple, directly costable tool to inform both clinical decision-making and population-based service planning and delivery.

UP-BEAT (Upper Limb Baby Early Action-observation Training): protocol of two parallel randomised controlled trials of action-observation training for typically developing infants and infants with asymmetric brain lesions [PROTOCOL]

Thu, 14 Feb 2013 00:00:00 +0000

IntroductionInfants with asymmetric brain lesions are at high risk of developing congenital hemiplegia. Action-observation training (AOT) has been shown to effectively improve upper limb motor function in adults with chronic stroke. AOT is based on action observation, whereby new motor skills can be learnt by observing motor actions. This process is facilitated by the Mirror Neuron System, which matches observed and performed motor actions. This study aims to determine the efficacy of AOT in: (1) influencing the early development of reaching and grasping of typically developing infants and (2) improving the upper limb activity of infants with asymmetric brain lesions. Methods and analysisThis study design comprises two parallel randomised sham-controlled trials (RCTs) in: (1) typically developing infants (cohort I) and (2) infants with asymmetric brain lesions (eg, arterial stroke, venous infarction, intraventricular haemorrhage or periventricular leukomalacia; cohort II). Cohort II will be identified through a neonatal ultrasound or neonatal MRI. A sham control will be used for both RCTs, taking into consideration that it would be unethical to give no intervention to an at-risk population. Based on a two-tailed t test of two independent means, with a significance () level of 0.05, 80% power, predicted effect size of 0.8 and a 90% retention rate, we require 20 participants in each group (total sample of 40) for cohort I. The sample size for cohort II was based on the assumption that the effect size of the proposed training would be similar to that found by Heathcock et al in preterm born infants (n=26) with a mean effect size of 2.4. Given the high effect size, the calculation returned a sample of only four participants per group, on a two-tailed t test, with a significance () level of 0.05 and 80% power. As cohort II will consist of two subgroups of lesion type (ie, arterial stroke and venous infarction), we have quadrupled the sample to include 16 participants in each group (total sample of 32). Infants will be randomised to receive either AOT or standard Toy Observation Training (TOT). Both interventions will be of 4 weeks' duration, from the infant's 9th-13th post-term week of age. Three sessions of 5 min each will be performed each day for 6 days/week (total of 6 h over 28 days). Parents of the AOT group will repeatedly show the infant a grasping action on a set of three toys, presented in random order. Parents of the TOT group will show the infant the same set of three toys, in random order, without demonstrating the grasping action. At 14, 16 and 18 weeks, the quantity and quality of reaching and grasping will be measured using the Grasping and Reaching Assessment of Brisbane; symmetry of reaching and grasping will be measured using the Hand Assessment of Infants (HAI) and pressure of grasping for each hand with a customised pressure sensor. At 6 months' corrected age, the primary outcome measures will be the HAI and Bayley Scales of Infant and Toddler Development (third edition; BSID III), to measure cognitive and motor development. At 8 months, HAI and EEG will be used to measure brain activity and cortical coherence. At 12 months, the primary outcome measures will again be HAI and BSID III. DisseminationThis paper outlines the theoretical basis, study hypotheses and outcome measures for two parallel RCTs comparing the novel intervention Action-observation training with standard TOT in: (1) influencing the early development of reaching and grasping of typically developing infants and (2) improving the upper limb motor activity of infants with asymmetric brain lesions. Trial RegistrationACTRN1261100991910. Web address of trial http://www.ANZCTR.org.au/ACTRN12611000991910.aspx

Diagnosing Mild Cognitive Impairment (MCI) in clinical trials: a systematic review [RESEARCH]

Mon, 4 Feb 2013 00:00:00 +0000

ObjectiveTo describe how criteria for amnestic Mild Cognitive Impairment (aMCI) have been operationalised in randomised controlled clinical trials (RCTs). DesignSystematic review. Information sourcesEMBASE, PubMed and PSYCHInfo were searched from their inception to February 2012. Electronic clinical trial registries were also searched (February 2012). Study selectionRCTs were included where participant selection was made using Petersen et al-defined aMCI. There was no restriction on intervention type or the outcome tested. Data extractionFor each trial, we extracted information on study design, demographics, exclusion criteria and the operationalisation strategy for the five aMCI diagnostic criteria including: (1) memory complaint, (2) normal general cognitive function, (3) memory impairment, (4) no functional impairment and (5) no dementia. Results223 articles and 278 registered trials were reviewed, of which 22 met inclusion criteria. Various methods were applied for operationalising aMCI criteria resulting in variability in participant selection. Memory complaint and assessment of general cognitive function were the most consistently measured criteria. There was large heterogeneity in the neuropsychological methods used to determine memory impairment. It was not possible to assess the impact of these differences on case selection accuracy for dementia prediction. Further limitations include selective and unclear reporting of how each of the criteria was measured. ConclusionsThe results highlight the urgent need for a standardised approach to map aMCI. Lack of uniformity in clinical diagnosis, however, is not exclusively a problem for MCI but also for other clinical states such as dementia including Alzheimer's disease, Lewy Body, frontotemporal or vascular dementia. Defining a uniform approach to MCI classification, or indeed for any classification concept within the field of dementia, should be a priority if further trials are to be undertaken in the older aged population based on these concepts.

A new stratified risk assessment tool for whiplash injuries developed from a prospective observational study [RESEARCH]

Wed, 30 Jan 2013 00:00:00 +0000

ObjectivesAn initial stratification of acute whiplash patients into seven risk-strata in relation to 1-year work disability as primary outcome is presented. DesignThe design was an observational prospective study of risk factors embedded in a randomised controlled study. SettingAcute whiplash patients from units, general practitioners in four Danish counties were referred to two research centres. ParticipantsDuring a 2-year inclusion period, acute consecutive whiplash-injured (age 18-70 years, rear-end or frontal-end car accident and WAD (whiplash-associated disorders) grades I-III, symptoms within 72 h, examination prior to 10 days postinjury, capable of written/spoken Danish, without other injuries/fractures, pre-existing significant somatic/psychiatric disorder, drug/alcohol abuse and previous significant pain/headache). 688 (438 women and 250 men) participants were interviewed and examined by a study nurse after 5 days; 605 were completed after 1 year. A risk score which included items of initial neck pain/headache intensity, a number of non-painful complaints and active neck mobility was applied. The primary outcome parameter was 1-year work disability. ResultsThe risk score and number of sick-listing days were related (Kruskal-Wallis, p<0.0001). In stratum 1, less than 4%, but in stratum 7, 68% were work-disabled after 1 year. Early work assessment (p<0.0001), impact of the event questionnaire (p<0.0006), psychophysical pain measures being McGill pain questionnaire parameters (p<0.0001), pressure pain algometry (p<0.0001) and palpation (p<0.0001) showed a significant relationship with risk stratification. AnalysisFindings confirm previous studies reporting intense neck pain/headache and distress as predictors for work disability after whiplash. Neck-mobility was a strong predictor in this study; however, it was a more inconsistent predictor in other studies. ConclusionsApplication of the risk assessment score and use of the risk strata system may be beneficial in future studies and may be considered as a valuable tool to assess return-to-work following injuries; however, further studies are needed.

Abdominal fat distribution and its relationship to brain changes: the differential effects of age on cerebellar structure and function: a cross-sectional, exploratory study [RESEARCH]

Thu, 24 Jan 2013 00:00:00 +0000

ObjectivesTo investigate whether the metabolically important visceral adipose tissue (VAT) relates differently to structural and functional brain changes in comparison with body weight measured as body mass index (BMI). Moreover, we aimed to investigate whether these effects change with age. DesignCross-sectional, exploratory. SettingUniversity Clinic, Integrative Research and Treatment Centre. ParticipantsWe included 100 (mean BMI=26.0 kg/m{superscript 2}, 42 women) out of 202 volunteers randomly invited by the city's registration office, subdivided into two age groups: young-to-mid-age (n=51, 20-45 years of age, mean BMI=24.9, 24 women) versus old (n=49, 65-70 years of age, mean BMI=27.0, 18 women). Main outcome measuresVAT, BMI, subcutaneous abdominal adipose tissue, brain structure (grey matter density), functional brain architecture (eigenvector centrality, EC). ResultsWe discovered a loss of cerebellar structure with increasing VAT in the younger participants, most significantly in regions involved in motor processing. This negative correlation disappeared in the elderly. Investigating functional brain architecture showed again inverse VAT-cerebellum correlations, whereas now regions involved in cognitive and emotional processing were significant. Although we detected similar results for EC using BMI, significant age interaction for both brain structure and functional architecture was only found using VAT. ConclusionsVisceral adiposity is associated with cerebellar changes of both structure and function, whereas the regions involved contribute to motor, cognitive and emotional processes. Furthermore, these associations seem to be age dependent, with younger adults' brains being adversely affected.

Trends in the prevalence of antipsychotic drug use among patients with Alzheimer's disease and other dementias including those treated with antidementia drugs in the community in the UK: a cohort study [RESEARCH]

Mon, 7 Jan 2013 00:00:00 +0000

ObjectiveTo investigate the pattern and trends of use of antipsychotics, antidepressants, hypnotics and anxiolytics in Alzheimer's disease and other dementias and in patients treated with antidementia medications. DesignCohort study with dementia patients formed in the UK Clinical Practice Research Datalink. Participants Patients with incident dementia, between 1995 and 2011 and a reference non-dementia cohort matched on age, gender and date of dementia diagnosis. Two subcohorts included new users of acetylcholinesterase inhibitors (AChEIs) and memantine. The study endpoint was use of antipsychotics, antidepressants, hypnotics and anxiolytics up to 10 years before and 4 years after dementia diagnosis, and for up to 5 years before and 1 year after first use of AChEI or memantine. Results50 349 patients with incident dementia diagnosis and 50 349 matched controls, 10 794 first-time users of AChEI and 669 of memantine. The mean prevalence of antipsychotic use from 1995 to 2011 on diagnosis of dementia was 12.5%, decreasing from 19.9% in 1995 to 7.4% in 2011. There was an increase in antidepressant use (10.7-26.3%) and a small increase in anxiolytic use. The matched cohort showed a lower use of antipsychotics and anxiolytics but a rise in antidepressants (5.9-13.4%). Both groups showed a decrease in hypnotic use. 10.6% of AChEI and 26.3% of memantine users were prescribed antipsychotics, 34.1% and 26.3% antidepressants, 13.2% and 4.1% anxiolytics and 18.4% and 8.3% hypnotics. The slopes for monthly use of antipsychotics were positive in the year leading up to AChEI and memantine use; after treatment initiation the slope for AChEI users continued to increase but at a reduced rate whereas antipsychotic use declined for memantine users. ConclusionsThe marked reduction in antipsychotic use in dementia is to be welcomed while there was a steady increase in antidepressant use. There was a decline in antipsychotic use after the initiation of memantine.

The effectiveness of smoking cessation interventions in smokers with cerebrovascular disease: a systematic review [RESEARCH]

Thu, 20 Dec 2012 00:00:00 +0000

ObjectiveThe main objective of this study was to determine the effectiveness of smoking cessation interventions (SCIs) for increasing cessation rates in smokers with cerebrovascular disease. DesignSystematic review. Two independent reviewers searched information sources and assessed studies for inclusion/exclusion criteria. Eligibility criteria for included studiesRandomised control trials, conducted prior to the 22 May 2012 investigating SCIs in smokers with cerebrovascular disease, were included. No age or ethnicity limitations were applied in order to be as inclusive as possible. MethodsWe followed the PRISMA statement approach to identify relevant randomised control studies. Due to the variability of interventions used in the reported studies, a meta-analysis was not conducted. ResultsOf 852 identified articles, 4 articles fit the inclusion criteria describing the outcome in 354 patients. The overall cessation rate with an SCI was 23.9% (42 of 176) while without one was 20.8% (37 of 178). ConclusionsThere are a limited number of reported intervention studies that explore this area of secondary stroke prevention. Furthermore, of those intervention studies that were found, only two implemented evidence-based approaches to smoking cessation. A meta-analysis was not conducted because of the variability of interventions in the reported studies. Larger studies with homogeneous interventions are needed to determine how effective SCIs are in increasing cessation in smokers with established cerebrovascular disease.

Restless legs syndrome and all-cause mortality in four prospective cohort studies [RESEARCH]

Wed, 19 Dec 2012 00:00:00 +0000

ObjectivesTo evaluate the association between restless legs syndrome (RLS) and all-cause mortality. DesignFour prospective cohort studies. SettingThe Dortmund Health Study (DHS) and the Study of Health in Pomerania (SHIP) from Germany. The Women's Health Study (WHS) and the Physicians' Health Study (PHS) from the USA. ParticipantsIn DHS: a random sample (n=1 299) from the population of Dortmund; in SHIP: a sample (n=4 291) from residents living in West Pomerania were drawn by multistage random sampling design; in WHS: female healthcare professionals (n=31 370); in PHS: male physicians (n=22 926) Main outcome measuresAll-cause mortality. ResultsThe prevalence of RLS ranged between 7.4% and 11.9% at baseline. During follow-up (ranging between 6 and 11 years) RLS was not associated with increased risk of all-cause mortality in any of the four cohorts. The multivariable-adjusted HRs (95% CI) for all-cause mortality ranged from 0.21 (0.03 to 1.53) to 1.07 (0.93 to 1.23) across the four studies. The HRs for all-cause mortality did not differ according to gender. ConclusionsIn these four independently conducted large prospective cohort studies from Germany and the USA, RLS did not increase the risk of all-cause mortality. These findings do not support the hypothesis that RLS is a risk factor for mortality of any cause.

Carbidopa/levodopa dose elevation and safety concerns in Parkinson's patients: a cross-sectional and cohort design [RESEARCH]

Tue, 11 Dec 2012 00:00:00 +0000

ObjectiveSinemet, a combination drug containing carbidopa and levodopa is considered the gold standard therapy for the treatment of Parkinson's disease (PD). When approved by the Food and Drug Administration (FDA) in 1988, a maximum daily dosage limit of 800 mg (eight tablets) of the 25/100 carbidopa/levodopa formulation was introduced. Overall, the FDA approval was a historic success; however, the pill limit has been hardcoded into many online medical record systems. This study investigates the 800 mg threshold by using a prospectively collected database of patient information. DesignA retrospective cohort study: (Part I) cross-sectional, (Part II) longitudinal. Setting and participantsPD patients at a Movement Disorders Center in a large academic, tertiary medical setting. Outcome measuresAn analysis was performed using carbidopa/levodopa at dosages below and above the 800 mg threshold. A secondary analysis was then performed using two consecutive clinic visits to determine the effects of crossing the 800 mg threshold. Comparisons were made on standardised scales. ResultsThere was no significant difference in motor, mood and quality-of-life scores in patients consuming below and above the 800 mg carbidopa/levodopa threshold, though a mild worsening in dyskinesia duration was noted without worsening in dyskinesia pain and disability. In PD patients who crossed the 800 mg threshold between two consecutive clinic visits, a significant improvement in depressive symptoms and quality-of-life measures was demonstrated, and in these patients there was no worsening of motor fluctuations or dyskinesia. ConclusionsThe data suggest that PD patients have the potential for enhanced clinical benefits when eclipsing the 800 mg carbidopa/levodopa threshold. Many patients will likely need to eclipse the 800 mg threshold and pharmacies and insurance companies should be aware of the requirements that may extend beyond approval limits.

Cause of death in MS: long-term follow-up of a randomised cohort, 21 years after the start of the pivotal IFN{beta}-1b study [RESEARCH]

Fri, 30 Nov 2012 00:00:00 +0000

ObjectivesCompared with controls, multiple sclerosis (MS) patients die, on average, 7-14 years prematurely. Previously, we reported that, 21 years after their participation in the pivotal randomised, controlled trial (RCT) of interferon {beta}-1b, mortality was reduced by 46-47% in the two groups who received active therapy during the RCT. To determine whether the excessive deaths observed in placebo-treated patients was due to MS-related causes, we analysed the causes-of-death (CODs) in these three, randomised, patient cohorts. DesignLong-term follow-up (LTF) of the pivotal RCT of interferon {beta}-1b. SettingEleven North American MS-centres participated. ParticipantsIn the original RCT, 372 patients participated, of whom 366 (98.4%) were identified after a median of 21.1 years from RCT enrolment. InterventionsUsing multiple information sources, we attempted to establish COD and its relationship to MS in deceased patients. Primary outcomeAn independent adjudication committee, masked to treatment assignment and using prespecified criteria, determined the likely CODs and their MS relationships. ResultsAmong the 366 MS patients included in this LTF study, 81 deaths were recorded. Mean age-at-death was 51.7 ({+/-}8.7) years. COD, MS relationship, or both were determined for 88% of deaths (71/81). Patients were assigned to one of nine COD categories: cardiovascular disease/stroke; cancer; pulmonary infections; sepsis; accidents; suicide; death due to MS; other known CODs; and unknown COD. Of the 69 patients for whom information on the relationship of death to MS was available, 78.3% (54/69) were adjudicated to be MS related. Patients randomised to receive placebo during the RCT (compared with patients receiving active treatment) experienced an excessive number of MS-related deaths. ConclusionsIn this long-term, randomised, cohort study, MS patients receiving placebo during the RCT experienced greater all-cause mortality compared to those on active treatment. The excessive mortality in the original placebo group was largely from MS-related causes, especially, MS-related pulmonary infections.

Timing of gastrostomy insertion in children with a neurodisability: a cross-sectional study of early versus late intervention [RESEARCH]

Wed, 21 Nov 2012 00:00:00 +0000

ObjectivesThe aim of the study was to assess whether gastrostomy placement before 18 months of age results in a greater increase in z-score for weight and to assess whether admission rates were reduced postgastrostomy in this age group. DesignRetrospective cross-sectional study. SettingSingle-centre secondary care District General Hospital. ParticipantsAll children with a neurodisability with a gastrostomy in situ in September 2011 were included. Those with primary neoplasia and undergoing chemo or radiotherapy or being palliated for an aggressive neurodegenerative disorder were excluded. Those with cystic fibrosis, primary congenital heart disease or Inflammatory bowel disease were also excluded. Forty-one children underwent final analysis. Twenty-four children underwent gastrostomy insertion less than 18 months and 17 children were older than 18 months. Primary and secondary outcome measuresPrimary outcome was z-scores for weight immediately pregastrostomy and 12 months postgastrostomy. Secondary outcomes were hospital admission rates pregastrostomy and postgastrostomy. Values were compared for those with gastrostomy insertion less than or equal to 18 months against those older than 18 months at insertion. ResultsZ-score for weight increased significantly in both age groups. There was significantly increased mean difference in the z-score for weight of +1.33 pregastrostomy and postgastrostomy in the less than 18 months age group as compared with an increased mean difference in the z-score for weight of +0.45 in the older age group (p=0.021). There was no significant difference in the admission rates postgastrostomy insertion in either age group. ConclusionsGastrostomy insertion before 18 months of age results in greater z-score for weight gain in children with a neurodisability. This conclusion is limited by the lack of height and skin-fold thickness measurements. Further long-term matched control studies are required to determine the neurodevelopmental and clinical benefit of early gastrostomy placement in such children.

Does mild cognitive impairment affect the occurrence of radiographic knee osteoarthritis? A 3-year follow-up in the ROAD study [RESEARCH]

Mon, 19 Nov 2012 00:00:00 +0000

ObjectiveTo determine whether mild cognitive impairment (MCI) increases the risk of occurrence or progression of radiographic knee osteoarthritis (KOA) in a general population. DesignPopulation-based cohort study. SettingResidents in mountain and seaside areas of Wakayama Prefecture, Japan. Participants1690 participants (596 men, 1094 women; mean age 65.2 years old) were enrolled from the large-scale cohort for the Research on Osteoarthritis (OA)/osteoporosis Against Disability (ROAD) study initiated in 2005 to investigate epidemiological features of OA in Japan. Of these, 1384 individuals (81.9%; 466 men, 918 women) completed the second survey including knee radiography 3 years later. Primary outcome measuresRadiographic KOA was defined as Kellgren-Lawrence (KL) grade [≥] 2 using paired x-ray films. Incidence of KOA during follow-up defined on radiographs as KL grade [≥]2, progression of KOA defined as a higher KL grade (either knee) at follow-up compared with baseline. MCI defined as a summary mini-mental state examination (MMSE) score [≤]23. Associations between MCI and incidence or progression of KOA were analysed. ResultsThe annual cumulative incidence of KOA was 3.3%; for progression of OA it was 8.0%. On logistic regression analysis adjusted for age, gender, regional differences, body mass index, grip strength (worse side), smoking, alcohol consumption, regular exercise and history of knee injury, baseline MMSE summary score was significantly associated with the incidence of KOA (+1 MMSE score; OR 0.83, p=0.010). Baseline MCI was also significantly associated with the incidence of KOA (vs non-occurrence of KOA; OR 4.90, p=0.027). There was no significant association between MMSE scores, the presence of MCI and progression of KOA (+1 MMSE score; OR 0.96, p=0.232; vs non-progression of KOA; OR 1.38, p=0.416). ConclusionsMCI significantly increases the risk of incident radiographic KOA, but not the progression of KOA.

Comparing the validity of the Modified Modified Ashworth Scale (MMAS) and the Modified Tardieu Scale (MTS) in the assessment of wrist flexor spasticity in patients with stroke: protocol for a neurophysiological study [PROTOCOL]

Mon, 19 Nov 2012 00:00:00 +0000

IntroductionReliable and valid tools must be used to assess spasticity in clinical practise and research settings. There is a paucity of literature regarding the validity of the Modified Modified Ashworth Scale (MMAS) and the Modified Tardieu Scale (MTS). No study, to date, has been performed to compare the validity of the MMAS and the MTS. This neurophysiological study protocol will compare the validity of the MMAS and the MTS in the assessment of poststroke wrist flexor spasticity. Methods and analysisThirty-two patients with stroke from the University Rehabilitation clinics will be recruited to participate in this cross-sectional, non-interventional study. All measurements will be taken in the Physical Medicine and Rehabilitation Department of Shafa University Hospital in Tehran, Iran. First, wrist flexor spasticity will be assessed clinically using the MMAS and MTS. The tests will be applied randomly. For the MTS, the components of R1, R2, R2-R1 and quality of muscle reaction will be measured. Second, neurophysiological measures of H-reflex latency, Hmax/Mmax ratio, Hslp and Hslp/Mslp ratio will be collected from the affected side. The results will be analysed using Spearman's {rho} test or Pearson's correlation test to determine the validity of the MMAS and the MTS as well as to compare the validity between the MMAS and the MTS. Ethics and disseminationThe Research Council, School of Rehabilitation and the Ethics Committee of Tehran University of Medical Sciences (TUMS) approved the study protocol. The study results will be disseminated in peer-reviewed publications and presented at international congresses.

The PREVENT study: a prospective cohort study to identify mid-life biomarkers of late-onset Alzheimer's disease [PROTOCOL]

Mon, 19 Nov 2012 00:00:00 +0000

IntroductionEpidemiological studies indicate that significant decreases in the incidence of Alzheimer's disease (AD) may be obtained by targeting multiple middle-age risk factors. However, as dementia is unlikely to be diagnosed for decades, short-term outcome measures are required. AD biomarker changes precede clinical symptoms by many years, but their sensitivity to mid-life change remains unknown. Methods and analysisPREVENT is a prospective cohort study examining biomarker status at mid-life in at least 150 individuals genetically at high, medium or low risk of late-onset AD. Participants are children of individuals with or without a diagnosed AD allocated to high, medium and low-risk groups according to parental clinical status and ApoE genotype. The biomarkers examined over 2 years are plasma and CSF A{beta}42 amyloid, Tau and pTau, proinflammatory cytokines, acute-phase proteins, medial temporal-lobe atrophy, white matter lesion volume, cognitive performance related to transentorhinal and hippocampal functioning and hypothalamic-pituitary-adrenal and sympathetic axes regulation. Ethics and disseminationDetected pathologies are communicated to the participant's general practitioner with their permission. Risk status by genotype would not be revealed. The results of the study would be published in peer-reviewed journals and validated biomarkers used to construct a randomised controlled intervention study.

The natural history of early-onset dementia: the Artemis Project [RESEARCH]

Wed, 10 Oct 2012 00:00:00 +0000

ObjectivesThe natural history of early-onset Alzheimer's disease (AD) and fronto-temporal dementia (FTD) remains to be described in detail. We seek to describe the natural history of early onset AD and FTD in terms of changes in cognitive assessment and staging, medical history and survival. DesignLongitudinal prospective cohort analysis. SettingNeurodegenerative disorders research clinic. ParticipantsIn total, 155 consecutive patients with clinically confirmed sporadic early-onset AD or FTD at a neurodegenerative disorders research clinic in Subiaco, Western Australia (The Artemis Project). MethodsA detailed history was recorded from the patients at baseline, including education, family history and medical history. Mini-mental state exam (MMSE), Global Deterioration Scale (GDS) and total functional capacity (TFC) were determined at each visit from 1994 until 2011. Kaplan-Meier survival analysis was performed. ResultsPatients with FTD were more likely to have a family history of dementia (p=0.026), to develop at least one cerebrovascular risk factor (p=0.003), manifest depression (Fisher's exact p=0.007) and to die during the follow-up period (Pearson {chi}2 8.97, p=0.003). Kaplan-Meier survival estimates revealed a highly significant difference in the proportion of patients surviving the follow-up period (log rank 7.25, p=0.007) with FTD patients experiencing poorer survival than those with AD. The mean MMSE and TFC were consistently lower in those with FTD compared with those with AD over a decade of follow-up; mean GDS was consistently higher in those with FTD over the follow-up period. ConclusionsWe believe that the difference in survival in patients with AD and FTD in our cohort might relate to the development of one or more cerebrovascular risk factors in FTD patients and the severity of the underlying pathology.

Does low-dose acetylsalicylic acid prevent cognitive decline in women with high cardiovascular risk? A 5-year follow-up of a non-demented population-based cohort of Swedish elderly women [RESEARCH]

Wed, 3 Oct 2012 00:00:00 +0000

ObjectiveThe aim of this study was to examine whether low-dose acetylsalicylic acid (ASA) influences the rate of cognitive change in elderly women. DesignProspective, population-based cohort study. SettingThe city of Gothenburg, Sweden, including those living in private households as well as in residential care. ParticipantsThe sample was derived from the Prospective Population Study of Women and from the H70 Birth Cohort Study in Gothenburg, Sweden. Both samples were obtained from the Swedish Population Register, based on birth date, and included 789 (response rate 71%) women aged 70-92 years. After the exclusion of individuals with dementia and users of warfarin, clopidogrel or heparin at baseline, 681 women were examined. Among all participants, 95.4% (N=601) had a high cardiovascular risk (CVD), defined as 10% or higher 10-year risk of any CVD event according to the Framingham heart study and 129 used low-dose ASA (75-160 mg daily) at baseline. After 5 years a follow-up was completed by 489 women. Primary outcome and secondary outcome measuresCognitive decline and dementia incidence in relation to the use of low-dose ASA and cardiovascular risk factors. Cognition was measured using the Mini Mental State Examination (MMSE), word fluency, naming ability and memory word tests. Dementia was diagnosed according to the DSM-III-R criterion. As secondary outcome incidence of stroke and peptic ulcer in relation to low-dose ASA use was studied. ResultsWomen on regular low-dose ASA declined less on MMSE at follow-up than those not on ASA. This difference was even more pronounced in those who had ASA at both examinations (p=0.004 compared with never users; n=66 vs n=338). All other cognitive tests showed the same trends. There were no differences between the groups regarding short-term risk for dementia (N=41). ConclusionLow-dose ASA treatment may have a neuroprotective effect in elderly women at high cardiovascular risk.

Derivation and validation of a clinical prediction rule for delirium in patients admitted to a medical ward: an observational study [RESEARCH]

Fri, 14 Sep 2012 00:00:00 +0000

ObjectivesTo develop and validate a simple clinical prediction rule, based on variables easily measurable at admission, to identify patients at high risk of developing delirium during their hospital stay on an internal medicine ward. DesignProspective study of two cohorts of patients admitted between 1 May and 30 June 2008 (derivation cohort), and between 1 May and 30 June 2009 (validation cohort). SettingA tertiary hospital in Donostia-Gipuzkoa (Spain). ParticipantsIn total 397 patients participated in the study. The mean age and incidence of delirium were 75.9 years and 13%, respectively, in the derivation cohort, and 75.8 years and 25% in the validation cohort. Main outcome measuresThe predictive variables analysed and finally included in the rule were: being aged 85 years old or older, being dependent in five or more activities of daily living, and taking two or more psychotropic drugs (antipsychotics, benzodiazepines, antidepressants, anticonvulsant and/or antidementia drugs). The variable of interest was delirium as defined by the short Confusion Assessment Method, which assesses four characteristics: acute onset and fluctuating course, inattention, disorganised thinking and altered level of consciousness. ResultsWe developed a rule in which the individual risk of delirium is obtained by adding one point for each criterion met (age[≥]85, high level of dependence, and being on psychotropic medication). The result is considered positive if the score is [≥]1. The rule accuracy was: sensitivity=93.4% (95% CI 85.5% to 97.2%), specificity=60.6% (95% CI 54.1% to 66.8%), positive predictive value=44.4% (95% CI 36.9% to 52.1%) and negative predictive value=96.5% (95% CI: 92% to 98.5%). The area under the receiver operator characteristic (ROC) curve was 0.85 for the validation cohort. ConclusionsThe presence or absence of any of the three predictive factors (age[≥]85, high level of dependence and psychotropic medication) allowed us to classify patients on internal medicine wards according to the risk of developing delirium. The simplicity of the variables in our clinical prediction rule means that the data collection required is feasible in busy medicine units.

Relevance of anxiety in clinical practice of Guillain-Barre syndrome: a cohort study [RESEARCH]

Fri, 24 Aug 2012 00:00:00 +0000

ObjectivesIllness is often associated with anxiety, but few data exist about the prognostic significance of this phenomenon. To address this issue, we assessed whether patient anxiety is associated with subsequent need for intubation in Guillain-Barre syndrome (GBS). DesignIncident case-cohort study. SettingAcute secondary care in a teaching hospital (France) from 2006 to 2010. Participants110 adult GBS patients. Either language barrier or cognitive decline that precluded understanding was considered as exclusion criteria. Primary outcomeAcute respiratory failure. InterventionsAt admission, anxiety and clinical factors (including known predictors of respiratory failure: delay between GBS onset and admission, inability to lift head, vital capacity (VC)) were assessed and related to subsequent need for mechanical ventilation (MV). Anxiety was assessed using a Visual Analogical Scale (VAS), the State Anxiety Inventory form Y1 (STAI-Y1) score and a novel-specific questionnaire, evaluating fears potentially triggered by GBS. Patients were asked to choose which they found most stressful from weakness, pain, breathlessness and uncertainty. Results23 (22%) were subsequently ventilated. Mean STAI-Y1 was 47.2 (range 22-77) and anxiety VAS 5.2 (range 0-10). STAI was above 60/80 in 22 (21%) patients and anxiety VAS above 7/10 in 28 (27%) patients. Fear of remaining paralysed, uncertainty as to how the disease would progress and fear of intubation were the most stressful. Factors significantly associated with anxiety were weakness and bulbar dysfunction. STAI-Y1 was higher and uncertainty more frequent in subsequently ventilated patients, who had shorter onset-admission delay and greater weakness but not a lower VC. Uncertainty was independently associated with subsequent MV. ConclusionsEarly management of patients with GBS should evaluate anxiety and assess its causes both to adjust psychological support and to anticipate subsequent deterioration.

Seasonality, incidence and prognosis in atrial fibrillation and stroke in Denmark and New Zealand [RESEARCH]

Fri, 24 Aug 2012 00:00:00 +0000

ObjectivesThere are relatively few large studies of seasonal variation in the occurrence of stroke in patients with atrial fibrillation (AF). We investigated the seasonal variation in incidence rates of hospitalisation with stroke in patients from Denmark and New Zealand. DesignCohort study. SettingNationwide hospital discharge data from Denmark and New Zealand. Participants243 381 (median age 75) subjects having a first-time hospitalisation with AF in Denmark and 51 480 (median age 76) subjects in New Zealand constituted the study population. Subjects with previous hospitalisation with stroke were excluded. Primary and secondary effect measuresPeak-to-trough ratio of the seasonal variation in incidence rates of stroke in AF patients adjusted for an overall trend was primary effect measure and was assessed using a log-linear Poisson regression model. Secondary effect measures were incidence rate ratios of AF and 30-day case fatality for stroke patients. ResultsIncidence rates of AF per 1000 person-years in Denmark increased by 5.4% (95% CI 5.3% to 5.7%) for patients aged <65 and 5% (95% CI 4.9% to 5.1%) for patients aged [≥]65, whereas the increase was 0.2% (95% CI -0.2% to 0.6%) for patients aged <65 and 2.6% (95% CI 2.4% to 2.8%) for patients aged [≥]65 in New Zealand. In Denmark 36 088 subjects were hospitalised with stroke, and 7518 subjects in New Zealand, both showing peaks during winter with peak-to-trough ratios of 1.22 and 1.27, respectively and a decreasing trend. The 30-day case fatality risk for stroke patients having AF is now (2000-2008) about 20% in both countries. ConclusionsAlthough incidence rates of hospitalisation with stroke in patients with AF have decreased in recent years, stroke remains a common AF complication with a high case fatality risk. The marked winter peak in incidence rates of hospitalisation with stroke in AF patients suggests that there are opportunities to reduce this complication. Further studies are necessary to identify how to optimise treatment of AF and prevention of stroke.

Prospective analysis of neutralising antibody titres in secondary non-responders under continuous treatment with a botulinumtoxin type A preparation free of complexing proteins--a single cohort 4-year follow-up study [RESEARCH]

Wed, 22 Aug 2012 00:00:00 +0000

ObjectivesIn long-term botulinum neurotoxin treatment, loss of therapeutic efficacy may occur due to neutralising antibody formation. Preliminary results with incobotulinumtoxinA, a preparation free of complexing/accessory proteins, have indicated a low antigenicity. We hypothesised that continuous treatment with this botulinum neurotoxin preparation would not result in an increase in neutralising antibody titres (NABTs) in patients with pre-existing NABTs. DesignProspective, blinded cohort study. SettingSingle centre in Germany. ParticipantsThirty-seven cervical dystonia patients with NABTs and partial secondary non-responsiveness to their previous botulinum neurotoxin type A treatment. InterventionThree-monthly intramuscular injections of incobotulinumtoxinA with a constant dose of 200 MU per injection during the first year; thereafter up to 500 MU for the next 36 months. Outcome measuresPrimary outcome measure: number of patients in whom NABTs declined below the initial titre after 48 months of incobotulinumtoxinA treatment or in whom titres had become negative within the 48 months. Secondary outcome measure: steepness of changes in NABT. NABTs were determined by mouse hemidiaphragm assay. Findings were compared to long-term data from 24 cervical dystonia patients who had developed NABTs and in whom treatment had been discontinued. ResultsFollowing a transient increase in the first 24 months under incobotulinumtoxinA treatment in some patients, NABTs declined well below the initial titre in the majority of patients. Test assay results were negative in most of the patients followed for more than 36 months. NABTs seemed to decline into the negative detection range as rapidly under incobotulinumtoxinA treatment as after cessation of botulinum neurotoxin therapy. ConclusionsThe reduction of NABTs despite continuous treatment with incobotulinumtoxinA indicates low antigenicity of incobotulinumtoxinA. This might have implications on restrictions such as minimum injection intervals of [≥]10 weeks currently in place for maintaining successful long-term application of botulinum neurotoxin.

Longitudinal cohort protocol study of oropharyngeal dysphagia: relationships to gross motor attainment, growth and nutritional status in preschool children with cerebral palsy [PROTOCOL]

Thu, 16 Aug 2012 00:00:00 +0000

IntroductionThe prevalence of oropharyngeal dysphagia (OPD) in children with cerebral palsy (CP) is estimated to be between 19% and 99%. OPD can impact on children's growth, nutrition and overall health. Despite the growing recognition of the extent and significance of health issues relating to OPD in children with CP, lack of knowledge of its profile in this subpopulation remains. This study aims to investigate the relationship between OPD, attainment of gross motor skills, growth and nutritional status in young children with CP at and between two crucial age points, 18-24 and 36 months, corrected age. Methods and analysisThis prospective longitudinal population-based study aims to recruit a total of 200 children with CP born in Queensland, Australia between 1 September 2006 and 31 December 2009 (60 per birth-year). Outcomes include clinically assessed OPD (Schedule for Oral Motor Assessment, Dysphagia Disorders Survey, Pre-Speech Assessment Scale, signs suggestive of pharyngeal phase impairment, Thomas-Stonell and Greenberg Saliva Severity Scale), parent-reported OPD on a feeding questionnaire, gross motor skills (Gross Motor Function Measure, Gross Motor Function Classification System and motor type), growth and nutritional status (linear growth and body composition) and dietary intake (3 day food record). The strength of relationship between outcome and exposure variables will be analysed using regression modelling with ORs and relative risk ratios. Ethics and disseminationThis protocol describes a study that provides the first large population-based study of OPD in a representative sample of preschool children with CP, using direct clinical assessment. Ethics has been obtained through the University of Queensland Medical Research Ethics Committee, the Children's Health Services District Ethics Committee, and at other regional and organisational ethics committees. Results are planned to be disseminated in six papers submitted to peer reviewed journals, and presentations at relevant international conferences.

Stroke and mortality in patients with incident heart failure: the Diet, Cancer and Health (DCH) cohort study [RESEARCH]

Sat, 7 Jul 2012 00:00:00 +0000

ObjectiveThe objective was to test the hypothesis that the risk of stroke, death and the composite of stroke and death' would be increased among patients with incident heart failure (HF). While HF increases the risk of mortality, stroke and thromboembolism in general, the extreme high-risk' nature of incident HF is perhaps under-recognised in everyday clinical practice. DesignProspective cohort study. SettingLarge Danish prospective epidemiological cohort. ParticipantsSubjects in the Diet, Cancer and Health study. Outcome measuresStroke, death and the composite of stroke and death' among patients with incident cases of HF, without concomitant atrial fibrillation. ResultsFrom the original cohort, 1239 patients with incident HF were identified. Incidence rates show a higher incidence in the initial period following the diagnosis of HF, with a markedly higher rate of death and stroke (ischaemic or haemorrhagic) in the initial 30 days following the diagnosis of incident HF. While lower than the risk at 0-30 days, the higher risk did not return to normal at 6+ months after the diagnosis of incident HF. This risk increase was apparent for the end points of stroke (ischaemic or haemorrhagic or both) whether or not a vitamin K antagonist (VKA) was used. With VKA use, there was a lower adjusted HR for death and the composite of death or stroke' compared to non-VKA use at the three time intervals following diagnosis of HF, whether 0-30 days, 30 days to 6 months and 6+ months. On multivariate analysis, previous stroke/transient ischaemic attack/thromboembolism was a predictor of higher risk of stroke, death and the composite of stroke and death', while VKA treatment was a highly significant predictor of a lower risk for death (adjusted HR 0.46, 95% CI 0.28 to 0.74, p<0.001) and the combined end point of death or stroke (adjusted HR 0.64, 95% CI 0.43 to 0.96, p=0.003). ConclusionsBased on relative hazards, incident HF is clearly a major risk factor for stroke, death and the composite of stroke and death', especially in the initial 30 days following initial diagnosis. The use of VKA therapy was associated with a lower risk of these end points. These findings would have major implications for the approach to management of patients presenting with incident HF, given the high risk of this population for death and stroke, which may be ameliorated by VKA therapy.

Multigene interactions and the prediction of depression in the Wisconsin Longitudinal Study [RESEARCH]

Mon, 2 Jul 2012 00:00:00 +0000

ObjectivesSingle genetic loci offer little predictive power for the identification of depression. This study examined whether an analysis of gene-gene (G x G) interactions of 78 single nucleotide polymorphisms (SNPs) in genes associated with depression and age-related diseases would identify significant interactions with increased predictive power for depression. DesignA retrospective cohort study. SettingA survey of participants in the Wisconsin Longitudinal Study. ParticipantsA total of 4811 persons (2464 women and 2347 men) who provided saliva for genotyping; the group comes from a randomly selected sample of Wisconsin high school graduates from the class of 1957 as well as a randomly selected sibling, almost all of whom are non-Hispanic white. Primary outcome measureDepression as determine by the Composite International Diagnostic Interview-Short-Form. ResultsUsing a classification tree approach (recursive partitioning (RP)), the authors identified a number of candidate G x G interactions associated with depression. The primary SNP splits revealed by RP (ANKK1 rs1800497 (also known as DRD2 Taq1A) in men and DRD2 rs224592 in women) were found to be significant as single factors by logistic regression (LR) after controlling for multiple testing (p=0.001 for both). Without considering interaction effects, only one of the five subsequent RP splits reached nominal significance in LR (FTO rs1421085 in women, p=0.008). However, after controlling for G x G interactions by running LR on RP-specific subsets, every split became significant and grew larger in magnitude (OR (before) [->] (after): men: GNRH1 novel SNP: (1.43 [->] 1.57); women: APOC3 rs2854116: (1.28 [->] 1.55), ACVR2B rs3749386: (1.11 [->] 2.17), FTO rs1421085: (1.32 [->] 1.65), IL6 rs1800795: (1.12 [->] 1.85)). ConclusionsThe results suggest that examining G x G interactions improves the identification of genetic associations predictive of depression. 4 of the SNPs identified in these interactions were located in two pathways well known to impact depression: neurotransmitter (ANKK1 and DRD2) and neuroendocrine (GNRH1 and ACVR2B) signalling. This study demonstrates the utility of RP analysis as an efficient and powerful exploratory analysis technique for uncovering genetic and molecular pathway interactions associated with disease aetiology.

Increase in self-reported migraine prevalence in the Danish adult population: a prospective longitudinal population-based study [RESEARCH]

Mon, 2 Jul 2012 00:00:00 +0000

ObjectiveIt is uncertain whether migraine prevalence has increased in modern society. The aim of this study was to assess any change in migraine prevalence over an 8-year period among the adult population in Denmark. DesignProspective longitudinal population-based study. Setting30 000 twin individuals were invited to participate in two cross-sectional questionnaire surveys containing validated questions to diagnose migraine in 1994 and 2002. The twins are representative of the Danish population with regard to migraine and other somatic diseases. ParticipantsThe 1994 cohort comprised 28 571 twin individuals aged 12-41 years and the 2002 cohort 31 865 twin individuals aged 20-71 years. Outcome measuresSex-, age- and subtype-specific incidence and lifetime prevalence as well as 1-year prevalence of migraine. Results1-year prevalence in 2002 was 12.3% for migraine, 4.1% for migraine with aura and 8.2% for migraine without aura. Lifetime prevalence of migraine was 16.1% in 1994 (aged 12-41 years) and 25.2% in 2002 (aged 20-71 years). Lifetime prevalence of migraine for age 20-41 was increased from 1994 to 2002 (18.5% vs 24.5%) by 32.2% (95% CI 27.0% to 37.3%; p<0.001). The difference was primarily seen in the population older than 32 years. The increase was especially evident in migraine with aura (5.6% vs 9.4%, p<0.001) but also a significant increase in migraine without aura was found (13.0% vs 15.1%, p<0.001). Eight-year period incidence rate of migraine was 0.141 corresponding to an average annual incidence rate of 17.6 per 1000 person-years. ConclusionsLifetime prevalence of migraine in Denmark increased substantially from 1994 to 2002. Part of the increase may be due to increased medical consultation resulting in increased rate of physician diagnosis or awareness due to previously participation in the 1994 survey. It is pertinent to study the environmental causes of the increase and to implement preventive measures.

Micrographia and related deficits in Parkinson's disease: a cross-sectional study [RESEARCH]

Mon, 25 Jun 2012 00:00:00 +0000

ObjectivesTo determine the prevalence and clinical features associated with micrographia in Parkinson's Disease (PD). SettingThis study was conducted at a Movement Disorders clinic located in a Veteran Administration Hospital. ParticipantsPD subjects were included only if they satisfied UK Parkinson's Disease Society criteria for diagnosis. Subjects with history of severe tremors, dystonia, dyskinesia, strokes, peripheral neuropathy and dementia were excluded. DesignThis was a case-control study where PD subjects were prospectively enrolled and their demographics, Hoehn & Yahr stage, Unified Parkinson's Disease Rating Scale and Mini Mental Status examination (MMSE) scores were recorded. All subjects were specifically asked for micrographia on history and the handwritings were quantitatively documented. Bradykinesia was determined by history and quantified by a finger tap, Purdue pegboard and a timed walk test. Similarly, hypophonia was determined by history and the volume of speech quantified using a decibel meter. Controls were enrolled for validation of handwriting test scores and decibel meter recordings. Primary outcome measuresPrevalence of micrographia in the PD cohort and the clinical factors that correlate with micrographia. Results68 subjects with PD were enrolled (68 men; mean age 72.3 years). Micrographia was identified in 63.2% of the cohort on verbal history and in 50% of the cohort when the handwriting test was used for ascertainment. Micrographia ascertained on history correlated significantly with disease severity (Hoehn & Yahr stage), motor impairment (Unified Parkinson's Disease Rating Scale), cognitive impairment (MMSE) and both bradykinesia and hypophonia determined by history and quantitative testing. Micrographia on handwriting test correlated with age (p=0.02), MMSE testing (p=0.04), hypophonia by history (p=0.01) and bradykinesia by quantitative testing (p=0.04). ConclusionMicrographia was found in nearly half of the PD cohort. Disease severity and impaired cognition were important clinical correlates. Micrographia had a significant relationship with bradykinesia and hypophonia, suggesting a possible overlap in their pathophysiology.

Factors influencing response to Botulinum toxin type A in patients with idiopathic cervical dystonia: results from an international observational study [RESEARCH]

Thu, 14 Jun 2012 00:00:00 +0000

ObjectivesReal-life data on response to Botulinum toxin A (BoNT-A) in cervical dystonia (CD) are sparse. An expert group of neurologists was convened with the overall aim of developing a definition of treatment response, which could be applied in a non-interventional study of BoNT-A-treated subjects with CD. DesignInternational, multicentre, prospective, observational study of a single injection cycle of BoNT-A as part of normal clinical practice. Setting38 centres across Australia, Belgium, Czech Republic, France, Germany, The Netherlands, Portugal, Russia and the UK. Participants404 adult subjects with idiopathic CD. Most subjects were women, aged 41-60 years and had previously received BoNT-A. Outcome measuresPatients were classified as responders if they met all the following four criteria: magnitude of effect ([≥]25% improvement Toronto Western Spasmodic Torticollis Rating Scale), duration of effect ([≥]12-week interval between the BoNT-A injection day and subject-reported waning of treatment effect), tolerability (absence of severe related adverse event) and subject's positive Clinical Global Improvement (CGI). ResultsHigh rates of response were observed for magnitude of effect (73.6%), tolerability (97.5%) and subject's clinical global improvement (69.8%). The subjective duration of effect criterion was achieved by 49.3% of subjects; 28.6% of subjects achieved the responder definition. Factors most strongly associated with response were age (<40 years; OR 3.9, p<0.05) and absence of baseline head tremor (OR 1.5; not significant). ConclusionsThree of four criteria were met by most patients. The proposed multidimensional definition of response appears to be practical for routine practice. Unrealistically high patient expectation and subjectivity may influence the perception of a quick waning of effect, but highlights that this aspect may be a hurdle to response in some patients. Clinical registration number(NCT00833196; ClinicalTrials.gov).

Memantine and cholinesterase inhibitor combination therapy for Alzheimer's disease: a systematic review [NEUROLOGY]

Mon, 11 Jun 2012 00:00:00 +0000

BackgroundMemantine is licensed for moderate-to-severe Alzheimer's disease (AD). National Institute for Clinical Excellence (NICE) guidance does not recommend the use of memantine in combination with cholinesterase inhibitors (acetylcholinesterase inhibitor (AChEI)). The underpinning meta-analysis was disputed by the manufacturer. ObjectivesTo compare the efficacy of AChEI monotherapy with combination memantine and AChEI therapy in patients with moderate-to-severe AD and to examine the impact of including unpublished data on the results. DesignSystematic review and meta-analysis of randomised controlled trials. Data sourcesThe Cochrane Dementia Group trial register, ALOIS, searched for the last time on 3 May 2011. Data synthesisData from four domains (clinical global, cognition, function, behaviour and mood) were pooled. Sensitivity analyses examined the impact on the NICE-commissioned meta-analysis of restricting data to patients with moderate-to-severe AD and of including an unpublished trial of an extended release preparation of memantine. ResultsPooled data from the trials, which were included in the NICE-commissioned meta-analysis but which were restricted to moderate-to-severe AD only, showed a small effect of combination therapy on cognition (standardised mean difference (SMD)=-0.29, 95% CI -0.45 to -0.14). Adding data from an unpublished trial of an extended release memantine (total three trials, 1317 participants) showed a small benefit of combination therapy on global scores (SMD=-0.20, 95% CI -0.31 to -0.09), cognition (SMD=-0.25, 95% CI -0.36 to -0.14) and behaviour and mood (SMD=-0.17, 95% CI -0.32 to -0.03) but not on function (SMD=-0.04, 95% CI -0.21 to 0.13) at 6 months. No clinical data have been reported from a 1-year trial, although this found no significant benefit' on any clinical measures at 1 year. ConclusionsThese results suggest that there may be a small benefit at 6 months of adding memantine to AChEIs. However, the impact on clinical global impression depends on exactly which studies are included, and there is no benefit on function, so its clinical relevance is not robustly demonstrated. Currently available information from randomised controlled trails indicates no benefit of combination therapy over monotherapy at 1 year. Legislation on the form and content of registry posted results is needed in Europe.

Ambient temperature and spontaneous intracerebral haemorrhage: a cross-sectional analysis in Tainan, Taiwan [RESEARCH]

Fri, 8 Jun 2012 00:00:00 +0000

ObjectivesAmbient temperature has been reported to play a role in the occurrence of spontaneous intracerebral haemorrhage (ICH). This study aimed to investigate the relation between ambient temperature of onset time and ICH and the effect of hourly temperature within 72 h before ICH. DesignThis is a cross-sectional case-only study and a retrospective analysis of a prospective database. SettingTwo medical centres in Southern Taiwan participating a prospective stroke registry. ParticipantsA total of 933 patients with ICH registered from August 2006 to July 2008. Primary and secondary outcome measuresThe hourly temperature was collected, and patients were grouped according to the deciles of hourly temperature at onset. Primary outcome was the association between the number of ICH cases and mean temperature (or temperature variation). Secondary outcome was the difference of onset temperature and hourly temperature before onset in patients with known onset time. ResultsWinter (n=282) had significant higher ICH cases than other seasons (n=651; p=0.002). Of those patients with an exact time of onset, the results showed 13% patients occurred at the lowest decile temperature group (<17.4{degrees}C) and 8% patients occurred at the highest decile temperature group (>30.8{degrees}C). It showed a significant temperature change before onset for these patients (p<0.005). ConclusionsThis study showed that lower ambient temperature and variation of temperatures precipitated ICH in southern Taiwan. Better protecting vulnerable people from cold temperatures may prevent the occurrences of ICH.

The relationship between executive dysfunction and post-stroke mortality: a population-based cohort study [RESEARCH]

Wed, 9 May 2012 00:00:00 +0000

ObjectivesTo study the associations of pre-stroke cognitive performance with mortality after first-ever stroke or transient ischaemic attack (TIA). DesignA prospective cohort study. Setting and participantsIn participants having first-ever stroke or TIA during up to 14 years of post-test follow-up (n=155), we investigated the associations of pre-stroke variables and cognitive test results with post-stroke survival. The study is based on those participants of the Uppsala Longitudinal Study of Adult Men who performed cognitive function tests at approximately age 70 (n=919). Primary outcome measuresMortality after first-ever stroke or TIA related to pre-stroke executive performance. ResultsEighty-four (54%) of the first-ever stroke/TIA patients died under a median follow-up of 2.5 years after the event. In Cox proportional hazard analyses adjusting for age, education, social group and traditional stroke risk factors, poor performance in Trail Making Test (TMT)-A was related to mortality (HR 1.88 per SD, 95% CI 1.31 to 2.71, p=0.001). The risk of mortality was approximately threefold higher in the highest tertile compared with the lowest tertile (HR TMT-A= 2.90 per SD, 95% CI 1.24 to 6.77, p=0.014). A similar pattern was seen for TMT-B, but Mini-Mental State Examination results were not related to risk of post-stroke mortality. ConclusionExecutive performance measured by TMT-A and -B before stroke was independently associated with long-term risk of mortality, after first-ever stroke or TIA in a population-based study of older men.

Grey and white matter abnormalities in chronic obstructive pulmonary disease: a case-control study [RESEARCH]

Tue, 24 Apr 2012 00:00:00 +0000

ObjectivesThe irreversible airflow limitation characterised by chronic obstructive pulmonary disease (COPD) causes a decrease in the oxygen supply to the brain. The aim of the present study was to investigate brain structural damage in COPD. DesignRetrospective case-control study. Patients with COPD and healthy volunteers were recruited. The two groups were matched in age, gender and educational background. SettingA hospital and a number of communities: they are all located in southern Fujian province, China. Participants25 stable patients and 25 controls were enrolled from December 2009 to May 2011. MethodsUsing voxel-based morphometry and tract-based spatial statistics based on MRI to analyse grey matter (GM) density and white matter fractional anisotropy (FA), respectively, and a battery of neuropsychological tests were performed. ResultsPatients with COPD (vs controls) showed decreased GM density in the limbic and paralimbic structures, including right gyrus rectus, left precentral gyrus, bilateral anterior and middle cingulate gyri, bilateral superior temporal gyri, bilateral anterior insula extending to Rolandic operculum, bilateral thalamus/pulvinars and left caudate nucleus. Patients with COPD (vs controls) had decreased FA values in the bilateral superior corona radiata, bilateral superior and inferior longitudinal fasciculus, bilateral optic radiation, bilateral lingual gyri, left parahippocampal gyrus and fornix. Lower FA values in these regions were associated with increased radial diffusivity and no changes of longitudinal diffusivity. Patients with COPD had poor performances in the Mini-Mental State Examination, figure memory and visual reproduction. GM density in some decreased regions in COPD had positive correlations with arterial blood Po2, negative correlations with disease duration and also positive correlations with visual tasks. ConclusionThe authors demonstrated that COPD exhibited loss of regional GM accompanied by impairment of white matter microstructural integrity, which was associated with disease severity and may underlie the pathophysiological and psychological changes of COPD.

Inclusion criteria provide heterogeneity in baseline profiles of patients with mild cognitive impairment: comparison of two prospective cohort studies [RESEARCH]

Tue, 24 Apr 2012 00:00:00 +0000

BackgroundMild cognitive impairment (MCI) is considered to represent a transitional stage between ageing and Alzheimer's disease (AD). To aim at identifying neuroimaging measures associated with cognitive changes in healthy elderly and MCI patients, longitudinal multicentre studies are ongoing in several countries. The patient profiles of each study are based on unique inclusion criteria. ObjectivesThe purpose of the study is to clarify differences in baseline profiles of MCI patients between Studies on Diagnosis of Early Alzheimer's Disease--Japan (SEAD-J) and Alzheimer's Disease Neuroimaging Initiative (ADNI) and to examine the association between baseline profiles and risk of early conversion to AD. DesignProspective cohort study. Setting and participantsSEAD-J recruited 114 patients from nine facilities in Japan. A total of 200 patients in ADNI with fluorodeoxyglucose-positron emission tomography (FDG-PET) were enrolled from the USA. MethodsBaseline profiles were statistically analysed. For FDG-PET at a time of inclusion, associations between each profile and cerebral metabolic rate for glucose (CMRgl) were examined using SPM5 software. In each study, the ratio of conversion to AD within the 1-year and 2-year period after inclusion was investigated and differences in baseline profiles between AD converters and non-converters were analysed. ResultsSEAD-J included MCI patients with more severe verbal memory deficits and extracted patients with higher depressive tendencies. These differences were likely to be associated with criteria. SEAD-J exhibited a higher rate of conversion within 1 year compared with ADNI (24.5% vs 13.5%). In FDG-PET analyses of SEAD-J, AD converters within 1 year showed more severe decrease of FDG uptake in bilateral inferior parietal regions compared with non-converters. ConclusionsDifferent inclusion criteria provided differences in baseline profiles. The severity of memory deficit might cause increase of the AD conversion within 1 year. Clinical outcomes of multicentre studies for early diagnosis of AD should be interpreted carefully considering profiles of patients.

Knowledge about epilepsy among health professionals: a cross-sectional survey in Sao Paulo, Brazil [RESEARCH]

Thu, 19 Apr 2012 00:00:00 +0000

ObjectiveTo evaluate the epilepsy knowledge among health professionals in Sao Paulo, Brazil. DesignThis is a cross-sectional study. ParticipantsProfessionals with academic degrees in physical education (n=134), nutrition (n=116), medicine (n=100), psychology (n=53), nursing (n=122) and physiotherapy (n=99) who lived in Sao Paulo City, Brazil. Primary and secondary outcome measuresKnowledge of health professionals about epilepsy. MethodsProfessionals with academic degrees in physical education (n=134), nutrition (n=116), medicine (n=100), psychology (n=53), nursing (n=122) and physiotherapy (n=99) who lived in Sao Paulo City, Brazil, were invited to participate in the study. The subjects (n=624) answered a questionnaire composed of 25 simple closed-ended questions from three areas: personal, educational and knowledge. ResultsOut of all subjects, 88.5% (n=552) had a postgraduate education, while 11.5% (n=72) had only an undergraduate degree. The authors found that physical educators, nutritionists and physiotherapists received lower scores on their epilepsy knowledge than other health professionals. ConclusionsHealth professionals are considered better-educated group inside the society, especially with regards to healthcare issues. Thus, it is important they also have an accurate and correct knowledge about epilepsy. The findings of the present study indicate an imperative improvement in education about epilepsy, as well as an inclusion of formal programmes for epilepsy education especially for non-medical professionals. An improvement in epilepsy education might contribute to an improvement in epilepsy care and management.

A meta-analysis to determine the effect on survival of platelet transfusions in patients with either spontaneous or traumatic antiplatelet medication-associated intracranial haemorrhage [RESEARCH]

Thu, 5 Apr 2012 00:00:00 +0000

ObjectivesThe aim of this study was to evaluate by meta-analysis the current level of evidence in order to establish the impact of a platelet transfusion on survival in patients on pre-injury antiplatelet agents who sustain an intracranial haemorrhage (either spontaneous or traumatic). DesignThis was a meta-analysis; the MEDLINE Database was searched using the PubMed interface and the Ovid interface. CINAHL and EMBASE Databases were also searched. The search was performed to identify randomised controlled trials (RCT)'s case-controlled studies or nested case-controlled studies. Comparing the outcome (death or survival) of patients with intracranial haemorrhage (ICH) and pre-injury antiplatelet agents who received a platelet transfusion against a similar cohort of patients who did not receive a platelet transfusion. Results499 citations were obtained from the PubMed search. 31 full articles were reviewed from 34 abstracts. 6 studies were found suitable for the meta-analysis. No randomised controlled studies were identified. 2 of the six studies were in patients with spontaneous ICH. The remaining four studies were in patients with traumatic intracranial haemorrhage. Significant heterogeneity was present between the studies, I2=58.276. The random effects model was therefore the preferred model, this produced a pooled OR for survival of 0.773 (95% CI 0.414 to 1.442). ConclusionsThe results of this meta-analysis has shown, based upon six small studies, that there was no clear benefit in terms of survival in the administration of a platelet transfusion to patients with antiplatelet-associated ICH. Further work is required in order to establish any potential benefit in the administration of a platelet transfusion in patients with spontaneous or traumatic intracranial haemorrhage who were on pre-injury antiplatelet agents.

Changing trends in incidence and aetiology of childhood acute non-traumatic coma over a period of changing malaria transmission in rural coastal Kenya: a retrospective analysis [RESEARCH]

Sun, 1 Apr 2012 00:00:00 +0000

ObjectivesRecent changes in malaria transmission have likely altered the aetiology and outcome of childhood coma in sub-Saharan Africa. The authors conducted this study to examine change in incidence, aetiology, clinical presentation, mortality and risk factors for death in childhood non-traumatic coma over a 6-year period. DesignRetrospective analysis of prospectively collected data. SettingSecondary level health facility: Kilifi, Coast, Kenya. ParticipantsChildren aged 9 months to 13 years admitted with acute non-traumatic coma (Blantyre Coma Score =2) between January 2004 and December 2009 to Kilifi District Hospital, Kenya. Exclusion criteria: delayed development, epilepsy and sickle cell disease. ResultsDuring the study period, 665 children (median age 32 (IQR 20-46) months; 46% were girls) were admitted in coma. The incidence of childhood coma declined from 93/100 000 children in 2004 to 44/100 000 children in 2009. There was a 64% overall drop in annual malaria-positive coma admissions and a 272% overall increase in annual admissions with encephalopathies of undetermined cause over the study period. There was no change in case death of coma. Vomiting, breathing difficulties, bradycardia, profound coma (Blantyre Coma Score=0), bacteraemia and clinical signs of meningitis were associated with increased risk of death. Seizures within 24 h prior to admission, and malaria parasitaemia, were independently associated with survival, unchanging during the study period. ConclusionThe decline in the incidence and number of admissions of childhood acute non-traumatic coma is due to decreased malaria transmission. The relative and absolute increase in admissions of encephalopathy of undetermined aetiology could represent aetiologies previously masked by malaria or new aetiologies.

Restless legs syndrome and risk of incident cardiovascular disease in women and men: prospective cohort study [RESEARCH]

Fri, 23 Mar 2012 00:00:00 +0000

ObjectivesTo evaluate the association between restless legs syndrome (RLS) and incident cardiovascular disease (CVD). DesignProspective cohort study. SettingWomen's Health Study (WHS) and Physicians' Health Study (PHS), USA. Participants29 756 female health professionals aged [≥]45 years and 19 182 male physicians aged [≥]40 years at baseline. Main outcome measuresMain outcome was incidence of major CVD; secondary outcomes were first incidence of myocardial infarction, stroke, death due to CVD or coronary revascularisation. Results3487 (11.7%) women and 1373 (7.2%) men met International Restless Legs Study Group criteria for RLS. In the WHS 450 major CVD events occurred and 1064 major CVD events were confirmed in the PHS. In both cohorts, RLS was not associated with increased risk of major CVD, stroke, myocardial infarction, CVD death or coronary revascularisation. After adjustment for major vascular risk factors, the HRs (95% CI) for major CVD were 1.15 (0.88 to 1.50) in women and 1.01 (0.81 to 1.25) in men. Highest multivariable-adjusted HRs were 1.29 (0.91 to 1.82) for total stroke in women and 1.22 (0.87 to 1.70) for CVD death in men. Excluding participants with comorbidities potentially leading to RLS did not substantially change the effect estimates. ConclusionsIn these large prospective studies of female and male health professionals, RLS was not associated with an increased risk of any incident CVD event. The data do not support the hypothesis that RLS is a marker of increased risk of vascular disease.

Laterality, hand control and scholastic performance: a British birth cohort study [RESEARCH]

Thu, 22 Mar 2012 00:00:00 +0000

ObjectivesTo use simple measures of laterality and hand control that can identify a greater risk of poorer scholastic ability, potentially signalling suboptimal hemispheric lateralisation. DesignAnalysis of material from a birth cohort study. SettingMembers of the National Child Development Study, a British birth cohort study following people born in 1958. Participants10 612 children who undertook tests at age 11 years. Primary outcome measuresTeacher-administered tests of non-verbal general ability, verbal general ability, reading comprehension and mathematics. ResultsLinear regression produced associations (and 95% CIs) with tests of verbal general ability, non-verbal general ability, reading comprehension and mathematics scores for the lowest third (compared with highest) of a left-hand control test involving picking up matches of -1.21 (-1.73 to -0.68; p<0.001), -0.72 (-1.14 to -0.29; p=0.001), -0.70 (-1.06 to -0.35; p<0.001) and -1.32 (-1.90 to -0.73; p<0.001). Among those in the lowest third of the right-hand control test score, mixed-handedness compared with right-handedness was associated with poorer scholastic performance, with regression coefficients (and 95% CIs; p values) of 1.90 (-3.01 to -0.80; p=0.001), -1.25 (-2.15 to -0.35; p=0.007), -1.28 (2.04 to -0.53; p=0.001) and -1.33 (-2.53 to -0.13; p=0.030). The estimates are for a point change in the scholastic test scores, after adjustment for sex, left-hand motor function and social class. Statistically significant associations with mixed-handedness were only observed for the lowest third of right-hand motor function. ConclusionsMeasures involving poorer left-hand motor function may represent useful markers of reduced cognitive function possibly reflecting suboptimal hemispheric lateralisation. Crude measures of laterality such as reported non-right-handedness may be more useful for research when combined with measures of motor function.

A case-control study examining whether neurological deficits and PTSD in combat veterans are related to episodes of mild TBI [RESEARCH]

Sun, 18 Mar 2012 00:00:00 +0000

BackgroundMild traumatic brain injury (mTBI) is a common injury among military personnel serving in Iraq or Afghanistan. The impact of repeated episodes of combat mTBI is unknown. ObjectiveTo evaluate relationships among mTBI, post-traumatic stress disorder (PTSD) and neurological deficits (NDs) in US veterans who served in Iraq or Afghanistan. MethodsThis was a case-control study. From 2091 veterans screened for traumatic brain injury, the authors studied 126 who sustained mTBI with one or more episodes of loss of consciousness (LOC) in combat. Comparison groups: 21 combat veterans who had definite or possible episodes of mTBI without LOC and 21 veterans who sustained mTBI with LOC as civilians. ResultsAmong combat veterans with mTBI, 52% had NDs, 66% had PTSD and 50% had PTSD and an ND. Impaired olfaction was the most common ND, found in 65 veterans. The prevalence of an ND or PTSD correlated with the number of mTBI exposures with LOC. The prevalence of an ND or PTSD was >90% for more than five episodes of LOC. Severity of PTSD and impairment of olfaction increased with number of LOC episodes. The prevalence of an ND for the 34 combat veterans with one episode of LOC (4/34=11.8%) was similar to that of the 21 veterans of similar age and educational background who sustained civilian mTBI with one episode of LOC (2/21=9.5%, p-NS). ConclusionsImpaired olfaction was the most frequently recognised ND. Repeated episodes of combat mTBI were associated with increased likelihood of PTSD and an ND. Combat setting may not increase the likelihood of an ND. Two possible connections between mTBI and PTSD are (1) that circumstances leading to combat mTBI likely involve severe psychological trauma and (2) that altered cerebral functioning following mTBI may increase the likelihood that a traumatic event results in PTSD.

Presymptomatic cerebral blood flow changes in CHMP2B mutation carriers of familial frontotemporal dementia (FTD-3), measured with MRI [RESEARCH]

Thu, 15 Mar 2012 00:00:00 +0000

ObjectivesTo assess functional changes measured by cerebral blood flow (CBF) in the presymptomatic stage of frontotemporal dementia linked to chromosome 3 (FTD-3) caused by a truncating mutation in CHMP2B. DesignCase-control study. SettingA memory clinic and tertiary referrals centre for dementia and inherited neurodegenerative disorders. ParticipantsThe authors included 11 presymptomatic CHMP2B mutation carriers and seven first-degree-related family non-carriers. Participants were MRI scanned twice with an interval of 15 months. Primary and secondary outcome measuresLocal functional changes in brain tissue perfusion were measured as CBF with two different MR techniques, gradient echo (GRE) and spin echo (SE), focusing on CBF in all cerebral vessels (GRE) and cerebral capillaries (SE), respectively. As planned, data analysis included co-registration of perfusion images to structural T1 images. Perfusion data were then extracted from seven regions-of-interest, normalised to white matter and statistically compared between carriers and non-carriers. ResultsFor SE, contrasts between carriers and non-carriers showed significant differences in temporal, occipital and parietal lobes and in hippocampus. There was no evidence of changes from baseline to follow-up. For GRE, there were no significant differences between carriers and non-carriers. ConclusionsSignificantly decreased CBF was found in presymptomatic CHMP2B mutation carriers in occipital-and parietal lobes. Comparing SE with GRE, data indicate that FTD-3 vascular pathology might primarily affect brain capillaries.

A systematic review with meta-analysis of comprehensive interventions for preschool children with autism spectrum disorder (ASD): study protocol [PROTOCOL]

Tue, 6 Mar 2012 00:00:00 +0000

IntroductionThe aims of this study are to (1) conduct a systematic review of the intervention literature in preschool children with autism spectrum disorder (ASD), including types of interventions that are tested and the classification of outcome measures used and (2) to undertake a meta-analysis of the studies, allowing for the first time the comparison of different approaches to intervention using comparative outcomes. There are a number of alternative modalities of intervention for preschool children with ASD in use with different theoretical background and orientation, each of which tend to use different trial designs and outcome measures. There is at this time an urgent need for comprehensive systematic review and meta-analyses of intervention studies for preschool children with ASD, covering studies of adequate quality across different intervention types and measurement methods, with a view to identifying the best current evidence for preschool interventions in the disorder. Methods and analysisThe authors will perform a systematic review of randomised controlled trials for preschool children with ASD aged 0-6 years, along with a meta-analysis of qualifying studies across intervention modality. The authors will classify the interventions for preschool children with ASD under three models: behaviour, multimodal developmental and communication focused. First, the authors will perform a systematic review. Then, the authors will conduct a meta-analysis by comparing the three models with various outcomes using an inverse variance method in a random effect model. The authors will synthesise each outcome of the studies for the three models using standardised mean differences. Dissemination and ethicsThis study will identify each intervention's strengths and weaknesses. This study may also suggest what kinds of elements future intervention programmes for children with ASD should have. The authors strongly believe those findings will be able to translated into the clinical practices and patients and their family benefits. Review registration: PROSPERO CRD42011001349.

HIV-associated neurocognitive disorders (HAND) in a South Asian population - contextual application of the 2007 criteria [RESEARCH]

Mon, 13 Feb 2012 00:00:00 +0000

ObjectivesTo estimate the prevalence of HIV-associated neurocognitive disorders (HAND) among HIV patients in a multiethnic South Asian population, describe the pattern of neurocognitive impairment in HAND and the factors associated with HAND. DesignA cross-sectional survey of HIV-positive outpatients and inpatients. SettingThe sole referral centre for HIV/AIDS treatment in Singapore. ParticipantsInclusion criteria were HIV positive, age between 21 and 80 years old and at least 3 years of education. Exclusion criteria included concomitant delirium, serious systemic disease or major psychiatric illness. 265 patients did not meet criteria or declined to participate. The final sample size was 132. Outcome measuresThe primary outcome measure was cognitive impairment based on performance on the Montreal Cognitive Assessment, International HIV Dementia Scale and Instrumental Activities of Daily Living. The secondary outcome measure was the classification of impairment based on the 2007 updated research nosology for HAND. ResultsThe prevalence of HAND was 22.7% of which 70% (15.9% of total) were asymptomatic neurocognitive impairment, 23.3% (5.3% of total) were mild neurocognitive disorder and 6.7% (1.5% of total) were HIV-associated dementia. Increasing age (OR 1.104, 95% CI 1.054 to 1.155, p<0.001), less education (OR 0.78, 95% CI 0.69 to 0.89, p<0.001) and low baseline CD4 count (OR 0.15, 95% CI 0.03 to 0.74, p=0.019) were associated with HAND. Delayed recall, language and abstract thinking were the domains most commonly affected, but impairment in visuospatial ability (RC 3.013, 95% CI 1.954 to 4.073, p<0.001) and attention (RC 2.205, 95% CI 1.043 to 3.367, p<0.001) were most strongly associated with HAND. ConclusionHAND is common among HIV patients in a South Asian sample, most of whom are asymptomatic. Older patients with less education and severe illness at diagnosis are at highest risk of HAND. Delayed recall is most commonly affected, but visuospatial dysfunction is most strongly associated with prevalent HAND.

Comparison of cognitive decline between dementia with Lewy bodies and Alzheimer's disease: a cohort study [RESEARCH]

Wed, 8 Feb 2012 00:00:00 +0000

ObjectivesDementia with Lewy bodies (DLB) accounts for 10%-15% of dementia cases at autopsy and has distinct clinical features associated with earlier institutionalisation and a higher level of carer distress than are seen in Alzheimer's disease (AD). At present, there is on-going debate as to whether DLB is associated with a more rapid cognitive decline than AD. An understanding of the rate of decline of cognitive and non-cognitive symptoms in DLB may help patients and carers to plan for the future. DesignIn this cohort study, the authors compared 100 AD and 58 DLB subjects at baseline and at 12-month follow-up on cognitive and neuropsychiatric measures. SettingPatients were recruited from 40 European centres. ParticipantsSubjects with mild-moderate dementia. Diagnosis of DLB or AD required agreement between consensus panel clinical diagnosis and visual rating of 123I-FP-CIT (dopamine transporter) single photon emission computed tomography neuroimaging. Outcome measuresThe Cambridge Cognitive Examination including Mini-Mental State Examination and Neuropsychiatric Inventory (NPI). ResultsThe AD and DLB groups did not differ at baseline in terms of age, gender, Clinical Dementia Rating score and use of cholinesterase inhibitors or memantine. NPI and NPI carer distress scores were statistically significantly higher for DLB subjects at baseline and at follow-up, and there were no differences between AD and DLB in cognitive scores at baseline or at follow-up. There was no significant difference in rate of progression of any of the variables analysed. ConclusionsDLB subjects had more neuropsychiatric features at baseline and at follow-up than AD, but the authors did not find any statistically significant difference in rate of progression between the mild-moderate AD and DLB groups on cognitive or neuropsychiatric measures over a 12-month follow-up period.

A prospective follow-up study of the association of radiation exposure with fatal and non-fatal stroke among atomic bomb survivors in Hiroshima and Nagasaki (1980-2003) [RESEARCH]

Fri, 3 Feb 2012 00:00:00 +0000

ObjectiveUse of medical radiotherapy has increased markedly in recent decades. Whether the consequence includes an increased risk of cardiovascular disease remains to be determined. The purpose of this study was to examine the association between radiation exposure and the incidence of stroke among Japanese atomic bomb survivors. DesignA prospective follow-up study. Setting and participantsRadiation exposure from the atomic bombing was assessed in 9515 subjects (34.8% men) with 24-year follow-up from 1980. Subjects were free of prevalent stroke when follow-up began. Outcome measuresStroke events and the underlying cause of death were reviewed to confirm the first-ever stroke. Subtypes (ischaemic and haemorrhagic events) were categorised based on established criteria according to the definitions of typical/atypical stroke symptoms. ResultsOverall mean radiation dose ({+/-}SD) in units of gray (Gy) was 0.38{+/-}0.58 (range: 0-3.5). During the study period, 235 haemorrhagic and 607 ischaemic events were identified. For men, after adjusting for age and concomitant risk factors, the risk of haemorrhagic stroke rose consistently from 11.6 to 29.1 per 10 000 person-years as doses increased from <0.05 to [≥]2 Gy (p=0.009). Incidence also rose within the dose range <1 Gy (p=0.004) with no dose threshold. In women, the risk of haemorrhagic stroke rose with increasing radiation exposure but not until doses reached a threshold of 1.3 Gy (95% CI 0.5 to 2.3). Among women, for doses <1.3 Gy, differences in stroke risk were modest (13.5 per 10 000 person-years), while it increased to 20.3 per 10 000 person-years for doses that ranged from 1.3 to <2.2 Gy and to 48.6 per 10 000 person-years for doses that were higher (p=0.002). In both sexes, dose was unrelated to ischaemic stroke. ConclusionWhile the risk of haemorrhagic stroke increases with rising radiation exposure for both sexes, effects in women are less apparent until doses exceed a threshold at 1.3 Gy.

Multicentre multiobserver study of diffusion-weighted and fluid-attenuated inversion recovery MRI for the diagnosis of sporadic Creutzfeldt-Jakob disease: a reliability and agreement study [RESEARCH]

Mon, 30 Jan 2012 00:00:00 +0000

ObjectivesTo assess the utility of the display standardisation of diffusion-weighted MRI (DWI) and to compare the effectiveness of DWI and fluid-attenuated inversion recovery (FLAIR) MRI for the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD). DesignA reliability and agreement study. SettingThirteen MRI observers comprising eight neurologists and five radiologists at two universities in Japan. ParticipantsData of 1.5-Tesla DWI and FLAIR were obtained from 29 patients with sCJD and 13 controls. Outcome measuresStandardisation of DWI display was performed utilising b0 imaging. The observers participated in standardised DWI, variable DWI (the display adjustment was observer dependent) and FLAIR sessions. The observers independently assessed each MRI for CJD-related lesions, that is, hyperintensity in the cerebral cortex or striatum, using a continuous rating scale. Performance was evaluated by the area under the receiver operating characteristics curve (AUC). ResultsThe mean AUC values were 0.84 (95% CI 0.81 to 0.87) for standardised DWI, 0.85 (95% CI 0.82 to 0.88) for variable DWI and 0.68 (95% CI 0.63 to 0.72) for FLAIR, demonstrating the superiority of DWI (p<0.05). There was a trend for higher intraclass correlations of standardised DWI (0.74, 95% CI 0.66 to 0.83) and variable DWI (0.72, 95% CI 0.62 to 0.81) than that of FLAIR (0.63, 95% CI 0.53 to 0.74), although the differences were not statistically significant. ConclusionsStandardised DWI is as reliable as variable DWI, and the two DWI displays are superior to FLAIR for the diagnosis of sCJD. The authors propose that hyperintensity in the cerebral cortex or striatum on 1.5-Tesla DWI but not FLAIR can be a reliable diagnostic marker for sCJD.

Factors associated with depressive state in patients with myasthenia gravis: a multicentre cross-sectional study [RESEARCH]

Mon, 19 Dec 2011 00:00:00 +0000

ObjectivesThe objective of this study was to examine clinical factors associated with depressive state in patients with myasthenia gravis (MG). DesignCross-sectional study. Setting and participantsWe evaluated 287 consecutive cases of MG seen at six neurological centres located in Eastern Japan. Outcome measuresAll MG patients completed the Japanese version of the Beck Depression Inventory-Second Edition (BDI-II). Disease severity was determined according to the MG Foundation of America (MGFA) quantitative MG score, MG activities of daily living scale and MG composite scale (MG composite). Clinical state following treatment was categorised according to MGFA postintervention status. Associations between detailed clinical parameters of MG and BDI-II score were then examined statistically. ResultsMean BDI-II score for patients with MG (11.0{+/-}8.1) did not differ substantially from and overlapped with that reported as the Japanese standard (8.7{+/-}6.4). The mean +2 SDs for the Japanese standard is 21.5, approximately equal to the cut-off level indicative of moderate or worse depression (>20 points) in the original English version. We thus defined BDI-II >21.5 as depressive state, with a frequency of 13.6% in patients with MG. Multivariate logistic regression analysis revealed current dose of oral prednisolone (OR 1.09, 95% CI 1.02 to 1.17; p=0.01), unchanged MGFA postintervention status (OR 3.55, 95% CI 1.18 to 10.71; p=0.02), time since onset (OR 0.93, 95% CI 0.87 to 0.99; p=0.03) and MG composite (OR 1.16, 95% CI 1.00 to 1.34; p=0.046) as factors independently associated with depressive state in MG. ConclusionsDose of oral corticosteroids appears to represent the major factor associated with depressive state in MG. Unchanged status despite treatment and early disease stage are also significant background factors for depressive state, along with disease severity.

A botulinum toxin A treatment algorithm for de novo management of torticollis and laterocollis [RESEARCH]

Sun, 27 Nov 2011 00:00:00 +0000

ObjectivesFew studies have investigated the injection patterns for botulinum toxin type A for the treatment of heterogeneous forms of cervical dystonia (CD). This large, prospective, open-label, multicentre study aimed to evaluate the effectiveness and safety of 500 U botulinum toxin A for the initial treatment according to a standardised algorithm of the two most frequent forms of CD, predominantly torticollis and laterocollis. DesignPatients (aged [≥]18 years) with CD not previously treated with botulinum neurotoxin therapy were given one treatment with 500 U Dysport, according to a defined intramuscular injection algorithm based on clinical assessment of direction of head deviation, occurrence of shoulder elevation, occurrence of tremor (all evaluated using the Tsui rating scale) and hypertrophy of the sternocleidomastoid muscle. ResultsIn this study, 516 patients were enrolled, the majority of whom (95.0%) completed treatment. Most patients had torticollis (78.1%). At week 4, mean Tsui scores had significantly decreased by -4.01, -3.76 and -4.09 points in the total, torticollis and laterocollis populations, respectively. Symptom improvement was equally effective between groups. Tsui scores remained significantly below baseline at week 12 in both groups. Treatment was well tolerated; the most frequent adverse events were muscular weakness (13.8%), dysphagia (9.9%) and neck pain (6.6%). ConclusionsDysport 500 U is effective and well tolerated for the de novo management of a range of heterogeneous forms of CD, when using a standardised regimen that allows tailored dosing based on individual symptom assessment. Clinical trials information(NCT00447772; clinicaltrials.gov)

Obesity, orbitofrontal structure and function are associated with food choice: a cross-sectional study [RESEARCH]

Sun, 27 Nov 2011 00:00:00 +0000

ObjectivesObesity is on the rise in the US and is linked to the development of type 2 diabetes and cardiovascular disease. Emerging evidence over the last decade suggests that obesity may also adversely affect executive function and brain structure. Although a great deal of research focuses on how diet affects the brain and cognitive performance, no study focuses on how food choice may be associated with brain integrity. Here we investigated how lean and overweight/obese (o/o) adults differed in their food choices and how brain structure and cognition may be associated with those choices. DesignAs part of an ongoing study on diabetes and the brain, participants had routine blood work and a research MRI, received a battery of neurocognitive tests, and were instructed to keep a 3-day food diary. Results and conclusionsThe lean group ate more high quality foods and less low quality foods compared to the o/o group. In the o/o group, high quality food choices were associated with orbitofrontal cortex volume. The lean group performed better than the o/o group on neurocognitive measures of executive function, such as the Stroop Interference Test, the Wisconsin Card Sort Test and the Trail Making Test B-A, and on attention and concentration tasks such as the Digit Symbol Substitution Test. Taken together, these preliminary data suggest that in obesity poor food choices may be associated with frontal cognitive impairments that may be the result of, or contribute to, decreases in orbitofrontal cortex volume. Therefore, longitudinal studies are warranted to investigate a causal link between food choice and executive functioning.

Asymptomatic coronary heart disease in patients with type 2 diabetes with vascular complications: a cross-sectional study [RESEARCH]

Sun, 27 Nov 2011 00:00:00 +0000

BackgroundRecent studies have suggested that microvascular and macrovascular diseases are associated with coronary events. ObjectiveTo test the hypothesis that asymptomatic coronary heart disease (CHD) may be present in many patients with diabetes with vascular complications. DesignFrom April 2009 to August 2010, the authors conducted a cross-sectional study to assess the prevalence of asymptomatic CHD among patients with type 2 diabetes with vascular complications at a national diabetes centre in Japan. Eligibility criteria included patients with type 2 diabetes with no known CHD and one or more of the following four criteria: (1) proliferative diabetic retinopathy or after photocoagulation; (2) estimated glomerular filtration rate <30 ml/min/1.73 m2 or an estimated glomerular filtration rate <45 ml/min/1.73 m2 plus albuminuria; (3) peripheral arterial disease; and (4) cerebrovascular disease. Each patient underwent a stress single-photon emission computed tomography; patients with myocardial perfusion abnormalities then underwent coronary angiography. ResultsA total of 1008 patients with type 2 diabetes were screened, and 122 eligible patients consented to participate. Stress single-photon emission computed tomography revealed myocardial perfusion abnormalities in 96 (79%) patients. Of the 112 patients who completed the study protocol, 59 (53%) had asymptomatic CHD with [≥]50% diameter stenosis. Additionally, 35 (31%) patients had multivessel disease or left main disease, and 42 (38%) had a coronary artery with [≥]75% diameter stenosis. In the multivariate logistic-regression analysis to identify coronary risk factors associated with asymptomatic CHD, the only significant predictor was male sex (OR 6.18; 95% CI 2.30 to 16.64; p<0.001). ConclusionsAsymptomatic CHD with [≥]50% diameter stenosis and myocardial perfusion abnormalities was detected in more than half of the patients with type 2 diabetes with vascular complications.

A nationwide prospective cohort study on return to gainful occupation after stroke in Denmark 1996-2006 [RESEARCH]

Sun, 27 Nov 2011 00:00:00 +0000

BackgroundReturn to work is an important outcome factor for working-age patients poststroke. Previous epidemiological studies on this topic have been small (on average 125 patients per study). Their estimated effects are therefore associated with a tremendous statistical uncertainty. The present study estimates the effect of various predictors on the odds of returning to work after stroke in the total population of 20-57-year-old previously employed hospital treated patients with stroke in Denmark 1996-2006 (N=19 985). Methods and resultsThe patients were followed through national registers; 62% were gainfully occupied 2 years after stroke. The odds of returning to work were higher among people with intracerebral infarction, OR 1.0 (the reference group), than they were among people with subarachnoid haemorrhage, OR 0.79 (95% CI 0.71 to 0.88), and intracerebral haemorrhage, OR 0.39 (0.35 to 0.43). The odds of returning to work were lower among workers in elementary occupations OR 1.0 (reference group) than they were among workers in occupations that require skills at a basic level, OR 1.50 (1.38 to 1.64), technicians and associate professionals, OR 2.33 (2.05 to 2.65) and professionals, OR 3.04 (2.70 to 3.43). Patients in municipalities with a brain-injury rehabilitation centre did not have a better prognosis than patients in other municipalities, OR 0.91 (0.78 to 1.06). Being a woman, OR 0.79 (0.74 to 0.84), self-employed, OR 0.87 (0.78 to 0.96), or [≥]50 years, OR 0.61 (0.57 to 0.65), was associated with an adverse prognosis. ConclusionFurther research is needed to explain the gender inequality, which suggests either a potential to improve return-to-work rates among the females or a tendency among the males to return too early.

Voxel-based analysis of apparent diffusion coefficient in perihaematomal oedema: associated factors and outcome predictive value for intracerebral haemorrhage [RESEARCH]

Thu, 3 Nov 2011 00:00:00 +0000

ObjectivesThe pathophysiology of perihaematomal oedema (PO) surrounding a primary intracerebral haemorrhage (ICH) is complicated and incompletely understood. We prospectively investigated the components of PO with voxel-based analysis of the apparent diffusion coefficient (ADC) value and assessed its predictive value for functional outcome. DesignForty-six patients with ICH who were enrolled for clinical evaluation underwent MRI scans within 24 h after ICH. Based on the ADC value of the ipsilateral voxels divided by the mean ADC value of the contralateral mirror region of interest, the voxels with oedema were classified into three categories: cytotoxic, vasogenic and undetermined. The percentages of cytotoxic and vasogenic oedema were then calculated and correlated with clinical outcome according to the modified Rankin Scale (mRS) at 6 months after ICH. The intraobserver and interobserver reliability of this method were examined using intraclass correlation coefficients. ResultsThe intraclass correlation coefficients showed that analysis using the voxel-based method is highly reliable. Among the clinical variables tested, age and serum creatinine levels were positively correlated with percentage of cytotoxic oedema. Age, history of coronary artery disease, National Institutes of Health Stroke Scale score and percentage of cytotoxic oedema were all associated with mRS at 6 months after ICH. ConclusionsThe pathophysiological processes within PO are complicated. Voxel-based analysis of ADC values may help to identify the components of PO and may be beneficial for decision making and predicting outcome.

Differences in coronary heart disease, stroke and cancer mortality rates between England, Wales, Scotland and Northern Ireland: the role of diet and nutrition [RESEARCH]

Thu, 3 Nov 2011 00:00:00 +0000

IntroductionIt is unclear how much of the geographical variation in coronary heart disease (CHD), stroke and cancer mortality rates within the UK is associated with diet. The aim of this study is to estimate how many deaths from CHD, stroke and cancer would be delayed or averted if Wales, Scotland and Northern Ireland adopted a diet equivalent in nutritional quality to the English diet. MethodsMortality data for CHD, stroke and 10 diet-related cancers for 2007-2009 were used to calculate the mortality gap (the difference between actual mortality and English mortality rates) for Wales, Scotland and Northern Ireland. Estimates of mean national consumption of 10 dietary factors were used as baseline and counterfactual inputs in a macrosimulation model (DIETRON). An uncertainty analysis was conducted using a Monte Carlo simulation with 5000 iterations. ResultsThe mortality gap in the modelled scenario (achieving the English diet) was reduced by 81% (95% credible intervals: 62% to 108%) for Wales, 40% (33% to 51%) for Scotland and 81% (67% to 99%) for Northern Ireland, equating to approximately 3700 deaths delayed or averted annually. For CHD only, the mortality gap was reduced by 88% (69% to 118%) for Wales, 58% (47% to 72%) for Scotland, and 88% (70% to 111%) for Northern Ireland. ConclusionImproving the average diet in Wales, Scotland and Northern Ireland to a level already achieved in England could have a substantial impact on reducing geographical variations in chronic disease mortality rates in the UK. Much of the mortality gap between Scotland and England is explained by non-dietary risk factors.

A survey on self-assessed well-being in a cohort of chronic locked-in syndrome patients: happy majority, miserable minority [RESEARCH]

Fri, 2 Sep 2011 00:00:00 +0000

ObjectivesLocked-in syndrome (LIS) consists of anarthria and quadriplegia while consciousness is preserved. Classically, vertical eye movements or blinking allow coded communication. Given appropriate medical care, patients can survive for decades. We studied the self-reported quality of life in chronic LIS patients. Design168 LIS members of the French Association for LIS were invited to answer a questionnaire on medical history, current status and end-of-life issues. They self-assessed their global subjective well-being with the Anamnestic Comparative Self-Assessment (ACSA) scale, whose +5 and -5 anchors were their memories of the best period in their life before LIS and their worst period ever, respectively. Results91 patients (54%) responded and 26 were excluded because of missing data on quality of life. 47 patients professed happiness (median ACSA +3) and 18 unhappiness (median ACSA -4). Variables associated with unhappiness included anxiety and dissatisfaction with mobility in the community, recreational activities and recovery of speech production. A longer time in LIS was correlated with happiness. 58% declared they did not wish to be resuscitated in case of cardiac arrest and 7% expressed a wish for euthanasia. ConclusionsOur data stress the need for extra palliative efforts directed at mobility and recreational activities in LIS and the importance of anxiolytic therapy. Recently affected LIS patients who wish to die should be assured that there is a high chance they will regain a happy meaningful life. End-of-life decisions, including euthanasia, should not be avoided, but a moratorium to allow a steady state to be reached should be proposed.

A multicentre RCT on community occupational therapy in Alzheimer's disease: 10 sessions are not better than one consultation [RESEARCH]

Fri, 2 Sep 2011 00:00:00 +0000

ObjectiveTo compare the benefits and harms of a Dutch 10-session Community Occupational Therapy programme for patients with Alzheimer's disease with the impact of a one session consultation at home in German routine healthcare. DesignA seven-centre, parallel group, active controlled randomised controlled trial. Patients and carers were not masked. Assessors were fully blind for treatment allocation for one of two primary-outcome measurements. SettingPatients' homes. ParticipantsPatients with mild to moderate Alzheimer's disease (Mini-Mental State Examination 14-24), living in the community with primary carer available and without severe depression or behavioural symptoms, were eligible. InterventionsExperimental 10 home visits within 5 weeks by an occupational therapist, educating patients in the performance of simplified daily activities and in the use of aids to compensate for cognitive decline; and educating carers in coping with behaviour of the patient and in giving supervision to the patient. Control one home visit including individual counselling of patient and carer and explanation of a leaflet on coping with dementia in daily life. Outcome measuresThe primary outcome was the patient's daily functioning measured with the Interview of Deterioration in Daily activities in Dementia and the Perceive, Recall, Plan and Perform System of Task Analysis. Assessments were at baseline, 6, 16 and 26 weeks, with a postal assessment at 52 weeks. Results141 patients were 1:1 randomised to the experimental (N=71) and control group (N=70). Data for 54 and 50 participants were analysed. Patients' daily functioning did not differ significantly between the experimental and control group at week 6, 16, 26 or 52 and remained stable over 26 weeks in both groups. No adverse events were associated with the interventions. ConclusionsIn German healthcare, a Dutch 10-session community occupational therapy was not better than a one-session consultation for the daily functioning of patients with Alzheimer's disease. Further research on the transfer of complex psychosocial is needed. International Clinical Trials Registry PlatformDRKS00000053; Funded by the German Federal Ministry of Health.

Systematic review of genome-wide expression studies in multiple sclerosis [RESEARCH]

Fri, 2 Sep 2011 00:00:00 +0000

BackgroundAlthough recent genome-wide association studies have identified several genetic variants contributing to the complex aetiology of multiple sclerosis (MS), expression and functional studies are required to further understand its molecular basis. ObjectivesTo identify genes and pathways with differential expression in MS. DesignThe authors conducted a systematic review of seven microarray studies, in which expression in immune cells was compared between MS patients and controls. These studies include a previously unpublished study, which is described here in detail. Results and conclusionAlthough in general the overlap between studies was poor, 229 genes were found to be differentially expressed in MS in at least two studies, of which 11 were in three studies and HSPA1A in four studies. After excluding the authors' unpublished experiment which may have been affected by certain confounding factors and inclusion of treated subjects, 135 genes were identified in at least two studies. The differentially expressed genes were significantly associated with several immunological pathways, including interleukin (IL)-4, IL-6, IL-17 and glucocorticoid receptor signalling pathways. 15 of the 229 loci have shown some association with MS in published genome-wide association studies (p<0.0001), including three loci with confirmed MS risk variants.

Why did an effective Dutch complex psycho-social intervention for people with dementia not work in the German healthcare context? Lessons learnt from a process evaluation alongside a multicentre RCT [RESEARCH]

Fri, 2 Sep 2011 00:00:00 +0000

BackgroundThe positive effects of the Dutch Community Occupational Therapy in Dementia programme on patients' daily functioning were not found in a multicentre randomised controlled trial (RCT) in Germany. ObjectivesTo evaluate possible effect modification on the primary outcome within the German RCT with regard to (1) participant characteristics, (2) treatment performance and (3) healthcare service utilisation; and (4) to compare the design and primary outcome between the German and the original Dutch study. Methods(1) The impact of participant baseline data on the primary outcome was analysed in exploratory ANCOVA and regression analyses. (2) Therapists completed questionnaires on context and performance problems. The main problems were identified by a qualitative content analysis and focus-group discussion. Associations of the primary outcome with scores of participant adherence and treatment performance were evaluated by regression analysis. (3) Utilisation rates of healthcare services were controlled for significant group differences. (4) Differences in the Dutch and German study design were identified, and the primary outcome was contrasted at the item level. Results(1) Participant characteristics could not explain more than 5% of outcome variance. (2) The treatment performance of some active intervention components was poor but not significantly associated with the primary outcome. (3) There were no significant group differences in the utilisation of healthcare resources. (4) In contrast to the Dutch waiting-control group, the active intervention in the German control group may have reduced group differences in the current RCT. The German patients demonstrated a higher independence at baseline and less improvement in instrumental activities of daily living. ConclusionThe differences in outcome may be explained by a more active control treatment, partially poor experimental treatment and less room for improvement in the German sample. Future cross-national transfers should be prepared by pilot studies assessing the applicability of the intervention and patient needs specific to the target country. Trial registrationInternational Clinical Trials Registry Platform, DRKS00000053.

Magnetic resonance spectroscopy in the prediction of early conversion from amnestic mild cognitive impairment to dementia: a prospective cohort study [RESEARCH]

Fri, 2 Sep 2011 00:00:00 +0000

BackgroundMild cognitive impairment (MCI) of an amnestic type is a common condition in older people and highly predictive of Alzheimer's disease (AD). To date, there is no clear consensus regarding the best antecedent biomarker to predict early conversion to AD. ObjectiveThe aim of the study is to demonstrate that 1H magnetic resonance spectroscopy (MRS) of the brain in MCI patients may predict early conversion to dementia within the 2-year period after baseline assessment. MethodsA cohort of patients fulfilling the criteria of amnestic MCI were enrolled consecutively. At baseline the patients underwent neuropsychological examination, standard blood tests and APOE genotype. 1H-MRS (1.5 T) of the brain was carried out by exploring two areas: the posteromedial bilateral parietal lobe and left medial occipital lobe. The patients were followed up to detect conversion to probable AD according to the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association group criteria. ResultsAfter a 2-year follow-up, 27 (38%) patients converted to AD. The mean N-acetyl-aspartate/creatine (NAA/Cr) ratio in the posteromedial bilateral parietal cortex was 1.38 in converters versus 1.49 in non-converters (p<0.0001). An NAA/Cr ratio equal to or lower than 1.43 in this area predicted conversion to probable AD at 74.1% sensitivity and 83.7% specificity (area under the curve: 0.84; 95% CI 0.73 to 0.92). The cross-validated accuracy of classification was 82%, which reaches 85% when the APOE4 genotype and memory test are included in the analysis. In the left medial occipital lobe, the predictive value was somewhat lower with 85.2% sensitivity and 61.4% specificity (area under the curve: 0.8; 95% CI 0.69 to 0.89). Neither the APOE4 genotype nor leuco-araiosis was predictive of conversion to dementia. ConclusionMRS is a valuable biomarker to predict early conversion to dementia in patients with amnestic MCI.

Electrical modulation of the sympathetic nervous system in order to augment cerebral blood flow: a protocol for an experimental study [PROTOCOL]

Fri, 2 Sep 2011 00:00:00 +0000

IntroductionCerebral blood flow (CBF) is regulated by several mechanisms. Neurogenic control has been a matter of debate, even though several publications reported the effects of changes in sympathetic tone on CBF. Transcutaneous electrical nerve stimulation and spinal-cord stimulation have been shown to influence peripheral and cerebral blood flow through a sympathetic pathway. The authors hypothesise that certain pathological conditions result in a relative increase in the neurogenic regulation of CBF and that this regulation can be modulated electrically. Methods and analysisPatients with cerebral vasospasm after subarachnoid haemorrhage will be included. The experimental set-up measures several parameters that are involved in cerebral blood flow regulation in patients with cerebral vasospasm after subarachnoid haemorrhage. Measurements are taken at baseline and with stimulation in several frequencies. An ad hoc statistical analysis is used to evaluate different settings of the electrical stimulation. Autoregulation is evaluated with transfer function analysis and autoregulatory index calculations. Ethics and disseminationEthical registration was granted by Medical Review Ethics Committee Groningen (ID METc 2010.123). All participants provide written informed consent on participation. Upon finishing a pilot study to investigate feasibility and effect, either future prospective (randomised) studies will be designed, or other modalities of electrical stimulation will be explored using the same set-up. Trial RegistrationDutch Trial Registry: NTR2358.