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Background: The optimal time to commence anticoagulation in patients with atrial fibrillation (AF) after ischaemic stroke or transient ischaemic attack (TIA) is unclear, with guidelines differing in recommendations. A limitation of previous studies is the focus on clinically overt stroke, rather than radiologically obvious diffusion-weighted imaging ischaemic lesions. We aimed to quantify silent ischaemic lesions and haemorrhages on MRI at 1 month in patients commenced on early (<4 days) vs late (≥4 days) anticoagulation. We hypothesised that there would be fewer ischaemic lesions and more haemorrhages in the early anticoagulant group at 1-month MRI., Methods: A prospective multicentre, observational cohort study was performed at 11 Australian stroke centres. Clinical and MRI data were collected at baseline and follow-up, with blinded imaging assessment performed by two authors. Timing of commencement of anticoagulation was at the discretion of the treating stroke physician., Results: We recruited 276 patients of whom 208 met the eligibility criteria. The average age was 74.2 years (SD±10.63), and 79 (38%) patients were female. Median National Institute of Health Stroke Scale score was 5 (IQR 1-12). Median baseline ischaemic lesion volume was 5 mL (IQR 2-17). There were a greater number of new ischaemic lesions on follow-up MRI in patients commenced on anticoagulation ≥4 days after index event (17% vs 8%, p=0.04), but no difference in haemorrhage rates (22% vs 32%, p=0.10). Baseline ischaemic lesion volume of ≤5 mL was less likely to have a new haemorrhage at 1 month (p=0.02). There was no difference in haemorrhage rates in patients with an initial ischaemic lesion volume of >5 mL, regardless of anticoagulation timing., Conclusion: Commencing anticoagulation <4 days after stroke or TIA is associated with fewer ischaemic lesions at 1 month in AF patients. There is no increased rate of haemorrhage with early anticoagulation. These results suggest that early anticoagulation after mild-to-moderate acute ischaemic stroke associated with AF might be safe, but randomised controlled studies are needed to inform clinical practice., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hyperglycemia in acute ischemic stroke reduces the efficacy of stroke thrombolysis and thrombectomy, with worse clinical outcomes. Insulin-based therapies are difficult to implement and may cause hypoglycemia. We investigated whether exenatide, a GLP-1 (glucagon-like peptide-1) receptor agonist, would improve stroke outcomes, and control poststroke hyperglycemia with minimal hypoglycemia., Methods: The TEXAIS trial (Treatment With Exenatide in Acute Ischemic Stroke) was an international, multicenter, phase 2 prospective randomized clinical trial (PROBE [Prospective Randomized Open Blinded End-Point] design) enrolling adult patients with acute ischemic stroke ≤9 hours of stroke onset to receive exenatide (5 µg BID subcutaneous injection) or standard care for 5 days, or until hospital discharge (whichever sooner). The primary outcome (intention to treat) was the proportion of patients with ≥8-point improvement in National Institutes of Health Stroke Scale score (or National Institutes of Health Stroke Scale scores 0-1) at 7 days poststroke. Safety outcomes included death, episodes of hyperglycemia, hypoglycemia, and adverse event., Results: From April 2016 to June 2021, 350 patients were randomized (exenatide, n=177, standard care, n=173). Median age, 71 years (interquartile range, 62-79), median National Institutes of Health Stroke Scale score, 4 (interquartile range, 2-8). Planned recruitment (n=528) was stopped early due to COVID-19 disruptions and funding constraints. The primary outcome was achieved in 97 of 171 (56.7%) in the standard care group versus 104 of 170 (61.2%) in the exenatide group (adjusted odds ratio, 1.22 [95% CI, 0.79-1.88]; P =0.38). No differences in secondary outcomes were observed. The per-patient mean daily frequency of hyperglycemia was significantly less in the exenatide group across all quartiles. No episodes of hypoglycemia were recorded over the treatment period. Adverse events of mild nausea and vomiting occurred in 6 (3.5%) exenatide patients versus 0 (0%) standard care with no withdrawal., Conclusions: Treatment with exenatide did not reduce neurological impairment at 7 days in patients with acute ischemic stroke. Exenatide did significantly reduce the frequency of hyperglycemic events, without hypoglycemia, and was safe to use. Larger acute stroke trials using GLP-1 agonists such as exenatide should be considered., Registration: URL: www.australianclinicaltrials.gov.au; Unique identifier: ACTRN12617000409370. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03287076., Competing Interests: Disclosures The authors declare no competing interests for the TEXAIS trial (Treatment With Exenatide in Acute Ischemic Stroke). Dr Grimley declares travel support from Boehringer Ingleheim. Dr Meretoja declares research funding support from Monash University. Dr Davis declares research funding support from Medtronic, Amgen, CSL Behring, AstraZeneca, and Boehringer Ingelheim. Dr Ekinci is a consultant in Eli Lilly, Australia and reports research funding support from Eli Lilly, Australia, Amgen, Boehringer Ingelheim, and Bayer. Dr Thijs is a consultant in Bayer, Boehringer Ingelheim, Medtronic, and Novo Nordisk. Dr Lee-Archer declares research funding support from Clifford Craig Foundation. The other authors report no conflicts.

Creutzfeldt-Jakob disease is a rare and incurable form of rapidly progressive neurodegenerative disease. The disease is fatal, and most patients die within 1 year of diagnosis. Clinical features include progressive cognitive dysfunction, delusions or hallucinations, cerebellar ataxia, myoclonus, visual disturbances, extrapyramidal signs and eventually akinetic mutism. Most patients present with varied clinical presentation, hence making it difficult to diagnose at an early stage. We report five cases of sporadic Creutzfeldt-Jakob disease presenting to a Tasmanian hospital in Australia over a period of 52 months. We highlight significant clinical features in all our patients including few atypical presentations, emphasise on relevant clinical biomarkers and illustrate characteristic abnormalities on electroencephalogram and neuroimaging.

Adult-onset cerebellar ataxias are a group of neurodegenerative conditions that challenge both genetic discovery and molecular diagnosis. In this study, we identified an intronic (GAA) repeat expansion in fibroblast growth factor 14 (FGF14). Genetic analysis of 95 Australian individuals with adult-onset ataxia identified four (4.2%) with (GAA) >300 and a further nine individuals with (GAA) >250 . PCR and long-read sequence analysis revealed these were pure (GAA) repeats. In comparison, no control subjects had (GAA) >300 and only 2/311 control individuals (0.6%) had a pure (GAA) >250 . In a German validation cohort, 9/104 (8.7%) of affected individuals had (GAA) >335 and a further six had (GAA) >250 , whereas 10/190 (5.3%) control subjects had (GAA) >250 but none were (GAA) >335 . The combined data suggest (GAA) >335 are disease causing and fully penetrant (p = 6.0 × 10 -8 , OR = 72 [95% CI = 4.3-1,227]), while (GAA) >250 is likely pathogenic with reduced penetrance. Affected individuals had an adult-onset, slowly progressive cerebellar ataxia with variable features including vestibular impairment, hyper-reflexia, and autonomic dysfunction. A negative correlation between age at onset and repeat length was observed (R 2 = 0.44, p = 0.00045, slope = -0.12) and identification of a shared haplotype in a minority of individuals suggests that the expansion can be inherited or generated de novo during meiotic division. This study demonstrates the power of genome sequencing and advanced bioinformatic tools to identify novel repeat expansions via model-free, genome-wide analysis and identifies SCA50/ATX-FGF14 as a frequent cause of adult-onset ataxia., Competing Interests: Declaration of interests The authors declare no competing interests., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

Introduction: Kidney stone disease (KSD) has a lifetime prevalence of up to 14% in the United Kingdom. Primary and secondary prevention of KSD via dietary intervention is a low-cost public health intervention and remains the best preventative strategy against urolithiasis., Material and Methods: This prospective study was conducted on kidney stone patients attending a stone clinic at our tertiary endourology centre. Patients were taken through a questionnaire, which was completed in the clinic by a trained specialist endourology nurse., Results: A total of 259 patients completed the questionnaire. 141 (54.4%) had an active stone during the clinic visit with the remaining 118 (45.6%) with a history of stone treatment. Regarding barriers to fluid intake, 43 (16.6%) patients did not have a habit of drinking water or felt too bloated, 36 (13.9%) did not like the taste, 17 (6.6%) were not thirsty, 10 (3.9%) of patients were too busy. Of those who answered, 108 (46.8%) patients did not believe there was a link between fluid intake and stone formation. A belief of a link between fluid intake and stone formation significantly predicted fluid intake (p = 0.024) with people who did believe in this drinking less water., Conclusions: There are numerous perceived barriers to adequate fluid intake, with almost half of all patients not believing that there is a link between fluid intake and stone formation. This misunderstanding may predict a lower fluid intake. More attention should therefore be focussed on patient education and primary prevention aspects to avoid kidney stone recurrence., Competing Interests: The authors declare no conflicts of interest., (Copyright by Polish Urological Association.)

Introduction/aims: Immune-mediated neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP) and multifocal motor neuropathy (MMN) produce significant disability and often require maintenance treatment. There is a paucity of epidemiological data on these conditions in Australia., Methods: We undertook a prevalence study of CIDP and MMN in North Queensland and Tasmania, coinciding with a national census. Diagnoses were classified against the diagnostic criteria of the European Federation of Neurological Societies/Peripheral Nerve Society. Case ascertainment was undertaken via multiple methods, including survey of local neurologists across public and private clinics, search of neurophysiology, neurology and hospital databases, search of admitted hospital database collections using ICD codes and through immunoglobulin therapy prescription lists., Results: The crude prevalence of CIDP was 5.00 per 100,000 (95% confidence interval [CI] 3.79-6.62) and the crude prevalence of MMN was 1.33 per 100,000 (95% CI 0.78-2.27). Prevalence was also investigated using National Blood Authority numbers of cases prescribed immunoglobulin therapy, indicating a CIDP prevalence of 5.72 per 100,000 (95% CI 4.41-7.43) and MMN prevalence of 1.94 per 100,000 (95% CI 1.24-3.03). There was no significant difference between these numbers and those calculated through access of patient records locally. There was no significant difference in prevalence between Tasmania and North Queensland for any category., Discussion: This study updates the prevalence of CIDP and MMN in Australia. Understanding the distribution of CIDP and MMN patients and their need for treatment is essential for future resource planning and to enable monitoring and coordination of therapies such as immunoglobulin., (© 2022 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)

Objectives: We aimed to investigate whether sedative medications are associated with adverse outcomes in people with dementia, and whether specific characteristics of these medications predict a higher risk of harm., Design: Retrospective cohort study., Setting and Participants: 15,210 patients diagnosed with dementia between 2008 and 2017 in South London., Methods: From recorded medications at dementia diagnosis, we ascertained those with drowsiness listed as a side effect (termed "sedative" hereafter) and subdivided them by frequency and strength of sedation, receptor profile, half-life, and whether they were psychotropics. Multivariable Cox regression models were applied to determine risk of mortality and emergency hospitalization, and generalized estimating equations to investigate cognitive decline. Final models were adjusted for 19 potential confounders, including measures of physical and mental health, functioning, and central anticholinergic burden., Results: At diagnosis, 70.4% of patients with dementia were receiving at least 1 sedative medication. Median survival time was 4.0 years and median time to first hospitalization 1.4 years. After controlling for potential confounders, receipt of any sedative medication at dementia diagnosis was associated with accelerated cognitive decline and a higher hospitalization risk, but only medications with a cautionary warning yielded an increased mortality hazard. Medications acting through γ-aminobutyric acid agonism, psychotropic sedatives, and those with a short half-life were associated with a higher risk of mortality. γ-aminobutyric acid agonists, N-methyl-d-aspartate receptor antagonists, and nonpsychotropic sedatives were associated with an increased hospitalization risk. α 1 antagonist, antihistamines, N-methyl-d-aspartate receptor antagonists, psychotropic sedatives, and those with the shortest or longest half-life were associated with accelerated cognitive decline., Conclusions and Implications: Receipt of any sedative agent was associated with hospitalization and accelerated cognitive decline. Differences in hazard appear to exist between frequency and strength of sedation, receptor profiles, half-life, and prescribing indication. These differences should be taken into consideration in medication reviews at the time of dementia diagnosis., (Copyright © 2022 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: We introduced a nurse-led telephone-based virtual stone clinic (VSC) follow-up for the surveillance of patients with asymptomatic renal calculi or those at a high risk of recurrent kidney stone disease (KSD). The aim of this study was to look at the outcomes of VSC and its role in the post-COVID era. Methods: Prospective outcomes audit was done for all patients referred to the VSC for a 6-year period (March 2014-April 2020). VSC is led by specialist stone nurses for on-going surveillance of KSD patients. Results: A total of 290 patients were seen (468 individual appointments; 1.6 ± 1.0 per patient), with a mean age of 57.0 ± 15.8 years (range: 17-92) and a men-women ratio of 3:2. The referral was for surveillance of asymptomatic small renal stones (230, 79.3%); history of recurrent stone disease (45, 15.5%); solitary kidneys (5, 1.7%); cystine stones; young age; and other conditions (10, 3.4%). The mean stone size was 5.0 ± 2.7 mm, followed up with kidney, ureter, and bladder radiograph (225, 77.6%) and ultrasound scan (USS) (65, 22.4%), for median duration of 12 months (range: 3-24 months). At the end, 132 patients (45.6%) remained in VSC, 106 (36.6%) were discharged, 47 (16.2%) returned to face-to-face clinic or treatment, and 5 (1.7%) had emergency admissions. Of 47 patients who returned, 23 (48.9%) developed new symptoms, 21 (44.6%) had stone growth, and 3 defaulted to face-to-face appointment. Thirty-five patients needed surgical intervention (URS-21, SWL-13, and PCNL-1) and 10 were managed conservatively. VSC reduced the cost per clinic appointment from £27.9 to £2 per patient (93% reduction), equating to a total saving of £12,006 for the study period. Conclusion: Nurse-led VSC not only provided a safe follow-up but also allowed to substantially reduce the cost of treatment by allowing patients to be either discharged or return to a face-to-face clinic or surgical intervention if needed. Post-COVID, this model using telemedicine will have a much wider uptake and further help to optimize health care resources.

Introduction: Several studies have examined the link between temperature or monthly seasonal variations and urolithiasis. The majority of these studies have demonstrated a link between higher ambient monthly temperatures and the incidence of renal colic and kidney stone disease (KSD). However, a worldwide trend on this association has not been explored and we perform a systematic review to examine the effect of seasonal variations on renal colic and KSD., Materials and Methods: A systematic review of the literature for a 26-year period (1990-2017) was conducted on all studies reporting on the effect of seasonal variations and its link to KSD. Two reviewers independently extracted the data from each study, which were analyzed using SPSS version 24., Results: A total of 59 studies were identified, and after screening, 13 were included in this review. The studies ranged in duration from 1 to 9 years (mean: 5.5 years) and included seasonal/monthly variations for proven stones or lithotripsy treatments or emergency department presentations with renal colic. Except for one study, there was a statistically significant association between higher monthly mean temperatures and the incidence of KSD-related events reported from the United Kingdom, South Korea, the United States, Saudi Arabia, Italy, Spain, Taiwan, Japan, and New Zealand., Conclusions: Worldwide trends on the incidence of renal colic and KSD seem be affected by seasonal variation favoring warmer months, with data suggesting that higher ambient temperature has an association with KSD.

We report the case of an 11-year-old boy presenting with a type III tibial eminence fracture. The fracture fragment was reduced arthroscopically. Two 1.6 mm retrograde K-wires were inserted from the tibial metaphysis across the physis and into the fracture fragment using a standard anterior cruciate ligament tibial tunnel guide. Once the wires were clearly visible within the joint the tips were bent over by ∼120°. The wires were then tensioned around a single small fragment screw inserted into the tibial metaphysis. An exceptionally strong fixation was achieved. The boy was mobilised without a brace. The wires were removed at 12 weeks and he returned to full activity at 14 weeks., (2016 BMJ Publishing Group Ltd.)

Objective: There is little evidence to guide treatment strategies for intracerebral hemorrhage on vitamin K antagonists (VKA-ICH). Treatments utilized in clinical practice include fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC). Our aim was to compare case fatality with different reversal strategies., Methods: We pooled individual ICH patient data from 16 stroke registries in 9 countries (n = 10 282), of whom 1,797 (17%) were on VKA. After excluding 250 patients with international normalized ratio < 1.3 and/or missing data required for analysis, we compared all-cause 30-day case fatality using Cox regression., Results: We included 1,547 patients treated with FFP (n = 377, 24%), PCC (n = 585, 38%), both (n = 131, 9%), or neither (n = 454, 29%). The crude case fatality and adjusted hazard ratio (HR) were highest with no reversal (61.7%, HR = 2.540, 95% confidence interval [CI] = 1.784-3.616, p < 0.001), followed by FFP alone (45.6%, HR = 1.344, 95% CI = 0.934-1.934, p = 0.112), then PCC alone (37.3%, HR = 1.445, 95% CI = 1.014-2.058, p = 0.041), compared to reversal with both FFP and PCC (27.8%, reference). Outcomes with PCC versus FFP were similar (HR = 1.075, 95% CI = 0.874-1.323, p = 0.492); 4-factor PCC (n = 441) was associated with higher case fatality compared to 3-factor PCC (n = 144, HR = 1.441, 95% CI = 1.041-1.995, p = 0.027)., Interpretation: The combination of FFP and PCC might be associated with the lowest case fatality in reversal of VKA-ICH, and FFP may be equivalent to PCC. Randomized controlled trials with functional outcomes are needed to establish the most effective treatment., (© 2015 The Authors Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.)