How is the updated Ticket of Referral doing?

Introduction: The outpatient interface is important for patient care. An updated Ticket of Referral (TOR) was introduced end 2013; our study reviewed its usage in referrals from primary to secondary care, using Medical Consultant (MCC)/Schedule V clinics as an exemplar. Methods: Prospective study of consecutive new case referrals with all personal data anonymised. Completeness of field completion, established quality criteria, and legibility were assessed, and whether written or printed. Results: Of 103 consecutive referrals, 3 exclusions were due to an older version submitted, resulting in n=100. Identity card number, name, address, reasons for referral and referring doctor signature were completed in 100%; with 'date' in 98% and 'referring doctor' name, and 'registration number' in 96%. 88% had a rubber stamp; 79% completed 'age', 76% 'telephone', 47% 'mobile'; date of birth completes in 10 out of 66 possible, (due to differing versions of the TOR). 19% completed 'Next of Kin' - with telephone number (13%) and mobile numbers (18 %). 22% were noted to have investigations and 1% attendance at other clinics. Quality criteria included past history (54%), current treatment (71%) and blood pressure (34%); 100% were written, with 19% containing illegible areas. Conclusion: Data completion was high for patient and doctor details and reasons for referral, whilst fields related to 'Next of Kin' were mainly omitted. Quality criteria were variably completed - notably current treatment was absent in over a quarter - with implications for patient safety. Legibility was an issue in 19%.peer-reviewe

Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) might theoretically reduce post‐stroke disability by direct effects on the brain. This Cochrane Review was first published in 2012 and last updated in 2019. OBJECTIVES: To determine if SSRIs are more effective than placebo or usual care at improving outcomes in people less than 12 months post‐stroke, and to determine whether treatment with SSRIs is associated with adverse effects. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (last searched 7 January 2021), Cochrane Controlled Trials Register (CENTRAL, Issue 7 of 12, 7 January 2021), MEDLINE (1946 to 7 January 2021), Embase (1974 to 7 January 2021), CINAHL (1982 to 7 January 2021), PsycINFO (1985 to 7 January 2021), and AMED (1985 to 7 January 2021). PsycBITE had previously been searched (16 July 2018). We searched clinical trials registers. SELECTION CRITERIA: We included randomised controlled trials (RCTs) recruiting stroke survivors within the first year. The intervention was any SSRI, at any dose, for any period, and for any indication. The comparator was usual care or placebo. Studies reporting at least one of our primary (disability score or independence) or secondary outcomes (impairments, depression, anxiety, quality of life, fatigue, cognition, healthcare cost, death, adverse events and leaving the study early) were included in the meta‐analysis. The primary analysis included studies at low risk of bias. DATA COLLECTION AND ANALYSIS: We extracted data on demographics, stroke type and, our pre‐specified outcomes, and bias sources. Two review authors independently extracted data. We used mean difference (MD) or standardised mean differences (SMDs) for continuous variables, and risk ratios (RRs) for dichotomous variables, with 95% confidence intervals (CIs). We assessed bias risks and applied GRADE criteria. MAIN RESULTS: We identified 76 eligible studies (13,029 participants); 75 provided data at end of treatment, and of these two provided data at follow‐up. Thirty‐eight required participants to have depression to enter. The duration, drug, and dose varied. Six studies were at low risk of bias across all domains; all six studies did not need participants to have depression to enter, and all used fluoxetine. Of these six studies, there was little to no difference in disability between groups SMD ‐0.0; 95% CI ‐0.05 to 0.05; 5 studies, 5436 participants, high‐quality evidence) or in independence (RR 0.98; 95% CI 0.93 to 1.03; 5 studies, 5926 participants; high‐quality evidence) at the end of treatment. In the studies at low risk of bias across all domains, SSRIs slightly reduced the average depression score (SMD 0.14 lower, 95% CI 0.19 lower to 0.08 lower; 4 studies; 5356 participants, high‐quality evidence) and there was a slight reduction in the proportion with depression (RR 0.75, 95% CI 0.65 to 0.86; 3 studies, 5907 participants, high‐quality evidence). Cognition was slightly better in the control group (MD ‐1.22, 95% CI ‐2.37 to ‐0.07; 4 studies, 5373 participants, moderate‐quality evidence). Only one study (n = 30) reported neurological deficit score (SMD ‐0.39, 95% CI ‐1.12 to 0.33; low‐quality evidence). SSRIs resulted in little to no difference in motor deficit (SMD 0.03, ‐0.02 to 0.08; 6 studies, 5518 participants, moderate‐quality evidence). SSRIs slightly increased the proportion leaving the study early (RR 1.57, 95% CI 1.03 to 2.40; 6 studies, 6090 participants, high‐quality evidence). SSRIs slightly increased the outcome of a seizure (RR 1.40, 95% CI 1.00 to 1.98; 6 studies, 6080 participants, moderate‐quality evidence) and a bone fracture (RR 2.35, 95% CI 1.62 to 3.41; 6 studies, 6080 participants, high‐quality evidence). One study at low risk of bias across all domains reported gastrointestinal side effects (RR 1.71, 95% CI 0.33, to 8.83; 1 study, 30 participants). There was no difference in the total number of deaths between SSRI and placebo (RR 1.01, 95% CI 0.82 to 1.24; 6 studies, 6090 participants, moderate quality evidence). SSRIs probably result in little to no difference in fatigue (MD ‐0.06; 95% CI ‐1.24 to 1.11; 4 studies, 5524 participants, moderate‐quality of evidence), nor in quality of life (MD 0.00; 95% CI ‐0.02 to 0.02, 3 studies, 5482 participants, high‐quality evidence). When all studies, irrespective of risk of bias, were included, SSRIs reduced disability scores but not the proportion independent. There was insufficient data to perform a meta‐analysis of outcomes at end of follow‐up. Several small ongoing studies are unlikely to alter conclusions. AUTHORS' CONCLUSIONS: There is high‐quality evidence that SSRIs do not make a difference to disability or independence after stroke compared to placebo or usual care, reduced the risk of future depression, increased bone fractures and probably increased seizure risk

Fluoxetine for stroke recovery: Meta-analysis of randomized controlled trials

Objective: To determine whether fluoxetine, at any dose, given within the first year after stroke to patients who did not have to have mood disorders at randomisation led to a reduction in disability, dependency, neurological deficits and fatigue; improved motor function, mood, and cognition at the end of treatment and follow-up, with the same number or fewer adverse effects. Methods: Searches in July 2018 included several databases, trials registers, reference lists, contact with experts. We excluded RCTs requiring patients to have mood disorder at randomisation. Co-primary outcomes were dependence and disability. Dichotomous data were synthesised using risk ratios (RR) and continuous data using standardised mean differences (SMD). Quality was appraised using Cochrane risk of bias methods. Sensitivity analyses explored influence of study quality. Results: The searches identified 3412 references of which 491 full texts were assessed for eligibility. Six new completed RCTs (n=3710) were eligible, making a total of 13 trials (n=4145). There was no difference in the proportion independent at the end of treatment (3 trials, n=3249, 36·6% fluoxetine vs 36·7% control; RR 1·00, 95% confidence interval 0·91 to 1.09, p=0·99, I2 78%) and no difference in disability (7 trials n=3404, SMD 0·05, -0·02 to 0·12 p=0·15, I2=81%). Fluoxetine was associated with better neurological scores and less depression but more seizures. Among the four (n=3283) high quality RCTs, the only difference between groups was lower depression scores with fluoxetine. Conclusion: Fluoxetine does not reduce disability and dependency after stroke. It improves depression scores but increases seizures. Ongoing RCTs will determine its effects in stroke vary depending on ethnicity, background treatment and other factors. Classification of evidence: meta-analysi

RAB32 Ser71Arg in autosomal dominant Parkinson's disease:linkage, association, and functional analyses

BACKGROUND: Parkinson's disease is a progressive neurodegenerative disorder with multifactorial causes, among which genetic risk factors play a part. The RAB GTPases are regulators and substrates of LRRK2, and variants in the LRRK2 gene are important risk factors for Parkinson's disease. We aimed to explore genetic variability in RAB GTPases within cases of familial Parkinson's disease.METHODS: We did whole-exome sequencing in probands from families in Canada and Tunisia with Parkinson's disease without a genetic cause, who were recruited from the Centre for Applied Neurogenetics (Vancouver, BC, Canada), an international consortium that includes people with Parkinson's disease from 36 sites in 24 countries. 61 RAB GTPases were genetically screened, and candidate variants were genotyped in relatives of the probands to assess disease segregation by linkage analysis. Genotyping was also done to assess variant frequencies in individuals with idiopathic Parkinson's disease and controls, matched for age and sex, who were also from the Centre for Applied Neurogenetics but unrelated to the probands or each other. All participants were aged 18 years or older. The sequencing and genotyping findings were validated by case-control association analyses using bioinformatic data obtained from publicly available clinicogenomic databases (AMP-PD, GP2, and 100 000 Genomes Project) and a private German clinical diagnostic database (University of Tübingen). Clinical and pathological findings were summarised and haplotypes were determined. In-vitro studies were done to investigate protein interactions and enzyme activities.FINDINGS: Between June 1, 2010, and May 31, 2017, 130 probands from Canada and Tunisia (47 [36%] female and 83 [64%] male; mean age 72·7 years [SD 11·7; range 38-96]; 109 White European ancestry, 18 north African, two east Asian, and one Hispanic] underwent whole-exome sequencing. 15 variants in RAB GTPase genes were identified, of which the RAB32 variant c.213C&gt;G (Ser71Arg) cosegregated with autosomal dominant Parkinson's disease in three families (nine affected individuals; non-parametric linkage Z score=1·95; p=0·03). 2604 unrelated individuals with Parkinson's disease and 344 matched controls were additionally genotyped, and five more people originating from five countries (Canada, Italy, Poland, Turkey, and Tunisia) were identified with the RAB32 variant. From the database searches, in which 6043 individuals with Parkinson's disease and 62 549 controls were included, another eight individuals were identified with the RAB32 variant from four countries (Canada, Germany, UK, and USA). Overall, the association of RAB32 c.213C&gt;G (Ser71Arg) with Parkinson's disease was significant (odds ratio [OR] 13·17, 95% CI 2·15-87·23; p=0·0055; I2=99·96%). In the people who had the variant, Parkinson's disease presented at age 54·6 years (SD 12·75, range 31-81, n=16), and two-thirds had a family history of parkinsonism. RAB32 Ser71Arg heterozygotes shared a common haplotype, although penetrance was incomplete. Findings in one individual at autopsy showed sparse neurofibrillary tangle pathology in the midbrain and thalamus, without Lewy body pathology. In functional studies, RAB32 Arg71 activated LRRK2 kinase to a level greater than RAB32 Ser71.INTERPRETATION: RAB32 Ser71Arg is a novel genetic risk factor for Parkinson's disease, with reduced penetrance. The variant was found in individuals with Parkinson's disease from multiple ethnic groups, with the same haplotype. In-vitro assays show that RAB32 Arg71 activates LRRK2 kinase, which indicates that genetically distinct causes of familial parkinsonism share the same mechanism. The discovery of RAB32 Ser71Arg also suggests several genetically inherited causes of Parkinson's disease originated to control intracellular immunity. This shared aetiology should be considered in future translational research, while the global epidemiology of RAB32 Ser71Arg needs to be assessed to inform genetic counselling.FUNDING: National Institutes of Health, the Canada Excellence Research Chairs program, Aligning Science Across Parkinson's, the Michael J Fox Foundation for Parkinson's Research, and the UK Medical Research Council.</p

Cobalt Cardiomyopathy Secondary to Hip Arthroplasty: An Increasingly Prevalent Problem

A forty-year-old man experienced worsening heart failure four years following bilateral complicated total hip replacement. His condition was extensively worked up but no underlying pathology was immediately evident. Given the cobalt-chromium alloy component present in the hip arthroplasties, the raised cobalt blood levels, and a fitting clinical picture coupled with radiological findings, the patient underwent right hip revision. Evidence of biotribocorrosion was present on direct visualisation intraoperatively. The patient subsequently experienced symptomatic improvement (NYHA class III to class I) and echocardiography showed recovery of ejection fraction. Cobalt exists as a bivalent and trivalent molecule in circulation and produces a cytotoxicity profile similar to nanoparticles, causing neurological, thyroid, and cardiological pathology. Blood levels are not entirely useful as there is no identifiable conversion factor for levels in whole blood, serum, and erythrocytes which seem to act independently of each other. Interestingly cobalt cardiomyopathy is frequently compounded by other possible causes of cardiomyopathy such as alcohol and a link has been postulated. Definitive treatment is revision of the arthroplasty as other treatments are unproven

Selective Serotonin Reuptake Inhibitors for Stroke Recovery

Stroke is a major cause of adult disability. Selective serotonin reuptake inhibitors (SSRIs) have been used for many years to manage depression and other mood disorders after stroke. Small studies suggested that SSRIs might also promote motor recovery by direct effects on the brain. In this Cochrane review, we aimed to determine the effects of SSRIs in improving outcomes in people <12 months after stroke and to determine whether treatment with SSRIs is associated with adverse effects