Subcutaneous sodium valproate in palliative care: A systematic review.

BACKGROUND: Seizures are an important palliative symptom, the management of which can be complicated by patients' capacity to swallow oral medications. In this setting, and the wish to avoid intravenous access, subcutaneous infusions may be employed. Options for antiseizure medications that can be provided subcutaneously may be limited. Subcutaneous sodium valproate may be an additional management strategy. AIM: To evaluate the published experience of subcutaneous valproate use in palliative care, namely with respect to effectiveness and tolerability. DESIGN: A systematic review was registered (PROSPERO CRD42023453427), conducted and reported according to PRISMA reporting guidelines. DATA SOURCES: The databases PubMed, EMBASE and Scopus were searched for publications until August 11, 2023. RESULTS: The searches returned 429 results, of which six fulfilled inclusion criteria. Case series were the most common study design, and most studies included <10 individuals who received subcutaneous sodium valproate. There were three studies that presented results on the utility of subcutaneous sodium valproate for seizure control, which described it to be an effective strategy. One study also described it as an effective treatment for neuropathic pain. The doses were often based on presumed 1:1 oral to subcutaneous conversion ratios. Only one study described a local site adverse reaction, which resolved with a change of administration site. CONCLUSIONS: There are limited data on the use of subcutaneous sodium valproate in palliative care. However, palliative symptoms for which subcutaneous sodium valproate have been used successfully are seizures and neuropathic pain. The available data have described few adverse effects, supporting its use with an appropriate degree of caution.

Pre-stroke anticoagulation for atrial fibrillation in primary English speakers and non-primary English speakers: a multicentre retrospective cohort study.

BACKGROUND: Anticoagulation can prevent most strokes in individuals with atrial fibrillation (AF); however, many people presenting with stroke and known AF are not anticoagulated. Language barriers and poor health literacy have previously been associated with decreased patient medication adherence. The association between language barriers and initiation of anticoagulation therapy for AF is uncertain. AIMS: The aims of this study were to determine whether demographic factors, including non-English primary language, were (1) associated with not being initiated on anticoagulation for known AF prior to admission with stroke, and (2) associated with non-adherence to anticoagulation in the setting of known AF prior to admission with stroke. METHODS: A multicentre retrospective cohort study was conducted for consecutive individuals admitted to the three South Australian tertiary hospitals with stroke units over a 5-year period. RESULTS: There were 6829 individuals admitted with stroke. These cases included 5835 ischaemic stroke patients, 1333 of whom had pre-existing AF. Only 40.0% presenting with ischaemic stroke in the setting of known pre-existing AF were anticoagulated. When controlling for demographics, socioeconomic status and past medical history (including the components of the CHADS2VASC score and anticoagulation contraindications), having a primary language other than English was associated with a lower likelihood of having been commenced on anticoagulant for known pre-stroke AF (odds ratio: 0.52, 95% confidence interval: 0.36-0.77, P = 0.001), but was not associated with a differing likelihood of anticoagulation adherence. CONCLUSIONS: A significant proportion of patients with stroke have pre-existing unanticoagulated AF; these rates are substantially higher if the primary language is other than English. Targeted research and interventions to minimise evidence-treatment gaps in this cohort may significantly reduce stroke burden.

Resuscitation orders demonstrate differences by gender, stroke type and intervention.

BACKGROUND AND PURPOSE: Resuscitation orders describe individual preferences and types of intervention, such as suitability for cardiopulmonary resuscitation (CPR), that may provide benefit in the event of critical deterioration. The purpose of this study was to examine stroke inpatient resuscitation order completion and content. METHODS: This retrospective cohort study examined resuscitation orders in consecutive individuals admitted to a tertiary stroke centre over a 21-month period. Multivariable logistic regression was used to identify factors associated with resuscitation order completion and content. RESULTS: 1924 individuals were included in the study. The proportion of individuals who had resuscitation orders completed was 37.4%. Several factors were associated with an increased likelihood of resuscitation order completion including having received endovascular thrombectomy (p=0.013) and having intracerebral haemorrhage (p=0.001). Females were more likely to have a resuscitation order that is not for CPR (p=0.021, OR 95%CI 1.080-2.542). Patients with intracerebral haemorrhage were also more likely to be not for CPR (p=0.037, OR 95%CI 1.039-3.353). CONCLUSIONS: Disparities exist in resuscitation order completion and content based on demographic and stroke characteristics. Further research is required to identify the reasons for these differences and to optimise resuscitation order completion.

Intravenous immunoglobulin alteration in response to adverse reactions in neurological conditions: A retrospective cohort study.

INTRODUCTION: Intravenous immunoglobulin (IVIg) is an important treatment in a range of neurological conditions. There is currently limited evidence regarding the frequency and management of IVIg-associated adverse reactions (AR) in neurological disorders. METHODS: A single-centre 18-month retrospective cohort study was conducted for all patients at a single tertiary hospital receiving IVIg as an inpatient or the medical day unit. Electronic medical record AR and alerts were reviewed for entries relating to IVIg, and prescribing records associated with recent IVIg administration were reviewed for the use of premedications. Case note review was undertaken to identify AR associated with alterations in IVIg treatment (such as reduction in rate, use of premedications or cessation of IVIg). Demographic, patient, and treatment factors were analysed for associations with AR necessitating alteration in IVIg treatment. RESULTS: This study included 98 individuals who received IVIg during the study period. Of these, 12 (12.1%) patients required an alteration in their IVIg treatment. In total, 3 (3.1%) of the 98 included patients required a reduced rate of IVIg, and 10 (10.2%) patients received premedication. The most common premedications were normal saline at the time of the infusion, cetirizine, and hydrocortisone. No demographic factors, indications or comorbidities were found to be associated with an increased likelihood of AR. However, an IVIg daily dose of >35 g and >45 g were associated with an increased likelihood of requiring IVIg treatment alteration due to AR. CONCLUSIONS: Alterations to IVIg treatment due to AR are commonly required in neurology patients, and may be associated with higher daily doses of IVIg.

Factors associated with delay to carotid endarterectomy for acute ischaemic stroke in South Australia: A multicentre retrospective cohort study.

BACKGROUND: The greatest benefits of carotid endarterectomy (CEA) accrue when performed within two weeks of acute ischaemic stroke (AIS) due to symptomatic carotid stenosis. Previous studies have identified multiple factors contributing to CEA delay. AIMS: To determine factors associated with delayed CEA in patients admitted to tertiary stroke centres within a major metropolitan region with AIS METHODS: In a retrospective cohort study, consecutive patients admitted to the tertiary hospitals with stroke units within South Australia (Lyell McEwin Hospital, Royal Adelaide Hospital and Flinders Medical Centre) between 2016 to 2020 were included. Univariable and multivariable logistic regression were used to identify individual factors associated with time from symptom onset to CEA of over two weeks. RESULTS: A total of 174 patients were included. The median time to CEA was 5 days (IQR 3-9.75). Delayed CEA beyond 14 days occurred in 28/174 (16%). Factors most associated with delayed CEA included presentation to a tertiary hospital without onsite Vascular Surgical Unit (OR 3.71, 95%CI 1.31-10.58), history of previous stroke (OR 3.38, 95% CI 1.11-9.84) and presenting NIHSS above 6 (OR 5.16, 95% CI 1.60-16.39). CONCLUSION: This study identified that presentation to a tertiary hospital without a Vascular Surgery Unit, history of previous stroke and presenting NIHSS above 6 were associated with delay to CEA in AIS patients in South Australia. Interventional studies aiming to improve the proportion of patients that receive CEA within 14 days are required.

Implementation of the South Australian Regional Telestroke service is associated with improved care quality and lower stroke mortality: A retrospective cohort study.

INTRODUCTION: Stroke in Regional Australia may have worse outcomes due to difficulties accessing optimal care. The South Australian Regional Telestroke service aimed to improve telestroke neurologist access, supported by improved ambulance triage. OBJECTIVE: To assess stroke care quality and patient mortality pre- and postimplementation of a vascular neurologist-led Telestroke service. DESIGN: Historically controlled mixed methods cohort study comparing key quality indicators and patient mortality (6 months pre- vs. 18 months postimplementation date [4 June 2018]) at the three major South Australian regional stroke centres. The primary outcome was 13 care quality indicators as a combined composite risk-adjusted score, and the secondary outcome was risk-adjusted mortality at 12-month postadmission. FINDINGS: On an annualised basis, of 189 patients with stroke, more were admitted postintervention to the regional stroke centres than in the control period (158 [annualised rate 105.3, 95% CI 86.2-127.4] vs. 31 [annualised rate 62.0, 95% CI 47.5-79.5]) Baseline patient characteristics were similar in both periods. Post-implementation, median last-known-well time to presentation (3.5 h [IQR 1.6-17] vs. 2.0 [IQR 1-14]; p = 0.46) and door to needle times (121 min [IQR 97-144] vs. 90 [IQR 75-138]; p = 0.65) were not significantly lower but an improvement in the combined composite quality score was observed (0.069 [95% CI 0.004-0.134; p = 0.04]), reflecting individual improvements in some quality indicators. Mortality at 12-month postimplementation was substantially lower postimplementation (prechange 23% vs. postchange 13% [hazard ratio 0.58 (95% CI 0.44-0.76; p < 0.001)]). CONCLUSION: Implementation of a South Australian Regional Telestroke service was associated with improved care metrics and lower mortality.

Endovascular thrombectomy for large vessel occlusion acute ischemic stroke after cardiac surgery.

INTRODUCTION: Acute ischemic stroke (AIS) can be a catastrophic complication of cardiac surgery previously without effective treatment. Endovascular thrombectomy (EVT) is a potentially life-saving intervention. We examined patients at our institution who had EVT to treat AIS post cardiac surgery. METHODS: We retrospectively reviewed a stroke database from January 1, 2016 to October 31, 2021 to identify patients who had undergone EVT to treat AIS following cardiac surgery. Demographic data, operation type, stroke severity, imaging features, management and outcomes (mortality and modified Rankin Score (mRS)) were assessed. RESULTS: Of 5022 consecutive patients with AIS, 870 underwent EVT. Seven patients (0.8%) had EVT following cardiac surgery. Operations varied: two coronary artery bypass grafting (CABG), two transcatheter AVR, one redo surgical aortic valve replacement (AVR), one mitral valve repair and one patient with combined aortic and mitral valve replacements and CABG. Meantime postsurgery to stroke symptoms onset was 3 days (range 0-9 days). Median NIHSS was 26 (range 10-32). Five patients had middle cerebral artery occlusion and two internal carotid artery (n = 2). Median time between onset of symptoms and recanalization was 157 min (range 97-263). Two patients received Intra-arterial Thrombolysis. All patients survived and were discharged to another hospital (n = 3), home (n = 2), or rehabilitation facility (n = 2). Median 3-month mRS was 3 (range 0-6). CONCLUSION: We report the largest case series of EVT after cardiac surgery. EVT can be associated with excellent outcomes in these patients. Close neurological monitoring postoperatively to identify patients who may benefit from intervention is key.

Disseminated Aspergillosis with Mediastinal Invasion Causing Fatal Stroke in an Immunocompetent Young Man.

Introduction: Aspergillus flavus is a common cause of aspergillosis. Case Presentation: A previously fit and well, immunocompetent 27-year-old male living in Australia developed disseminated A. flavus complex infection with mediastinal and cardiac invasion, superior vena cava obstruction and stroke, with fatal haemorrhagic transformation. Conclusion: Aspergillus Flavus is a rare but important cause of serious disease in the immunocompetent.

Metamorphopsia with SMART Syndrome: A Case Report.

Introduction: SMART syndrome is a rare complication of brain radiotherapy. This is the first described presentation of SMART syndrome with metamorphopsia, which responded to aspirin, verapamil, and high-dose L-arginine therapy. Case Presentation: A 43-year-old man presented with 3 weeks of migraine headaches with metamorphopsia and complex visual hallucinations affecting the left lower quadrant of both visual fields. This occurred on a background of high-dose radiotherapy for right cerebellar astrocytoma 32 years ago. MRI brain demonstrated unilateral gyriform enhancement and FLAIR hyperintense cortical swelling in the right occipital lobe consistent with SMART syndrome. Conclusion: Unusual presentations of SMART syndrome exist and require consideration in all patients with focal neurological deficit post-brain radiotherapy. Validated diagnostic and treatment modalities for SMART syndrome are urgently required.

Sensorineural hearing loss after cardiac surgery: a systematic review.

BACKGROUND: Sensorineural hearing loss (SNHL) may occur following cardiac surgery. Although preventing post-operative complications is vitally important in cardiac surgery, there are few guidelines regarding this issue. This review aimed to characterize SNHL after cardiac surgery. METHOD: This systematic review was registered on PROSPERO and conducted in accordance with PRISMA guidelines. A systematic search of the PubMed, Embase and Cochrane Library were conducted from inception. Eligibility determination, data extraction and methodological quality analysis were conducted in duplicate. RESULTS: There were 23 studies included in the review. In the adult population, there were six cohort studies, which included 36 cases of hearing loss in a total of 7135 patients (5.05 cases per 1000 operations). In seven cohort studies including paediatric patients, there were 88 cases of hearing loss in a total of 1342 operations. The majority of cases of hearing loss were mild in the adult population (56.6%). In the paediatric population 59.2% of hearing loss cases had moderate or worse hearing loss. The hearing loss most often affected the higher frequencies, over 6000 Hz. There have been studies indicating an association between hearing loss and extracorporeal circulation, but cases have also occurred without this intervention. CONCLUSION: SNHL is a rare but potentially serious complication after cardiac surgery. This hearing loss affects both paediatric and adult populations and may have significant long-term impacts. Further research is required, particularly with respect to the consideration of screening for SNHL in children after cardiac surgery.

Vital sign measurements demonstrate terminal digit bias and boundary effects.

OBJECTIVE: The measurement and recording of vital signs may be impacted by biases, including preferences for even and round numbers. However, other biases, such as variation due to defined numerical boundaries (also known as boundary effects), may be present in vital signs data and have not yet been investigated in a medical setting. We aimed to assess vital signs data for such biases. These parameters are clinically significant as they influence care escalation. METHODS: Vital signs data (heart rate, respiratory rate, oxygen saturation and systolic blood pressure) were collected from a tertiary hospital electronic medical record over a 2-year period. These data were analysed using polynomial regression with additional terms to assess for underreporting of out-of-range observations and overreporting numbers with terminal digits of 0 (round numbers), 2 (even numbers) and 5. RESULTS: It was found that heart rate, oxygen saturation and systolic blood pressure demonstrated 'boundary effects', with values inside the 'normal' range disproportionately more likely to be recorded. Even number bias was observed in systolic heart rate, respiratory rate and blood pressure. Preference for multiples of 5 was observed for heart rate and blood pressure. Independent overrepresentation of multiples of 10 was demonstrated in heart rate data. CONCLUSION: Although often considered objective, vital signs data are affected by bias. These biases may impact the care patients receive. Additionally, it may have implications for creating and training machine learning models that utilise vital signs data.

Identifying epilepsy surgery referral candidates with natural language processing in an Australian context.

OBJECTIVE: Epilepsy surgery is known to be underutilized. Machine learning-natural language processing (ML-NLP) may be able to assist with identifying patients suitable for referral for epilepsy surgery evaluation. METHODS: Data were collected from two tertiary hospitals for patients seen in neurology outpatients for whom the diagnosis of "epilepsy" was mentioned. Individual case note review was undertaken to characterize the nature of the diagnoses discussed in these notes, and whether those with epilepsy fulfilled prespecified criteria for epilepsy surgery workup (namely focal drug refractory epilepsy without contraindications). ML-NLP algorithms were then developed using fivefold cross-validation on the first free-text clinic note for each patient to identify these criteria. RESULTS: There were 457 notes included in the study, of which 250 patients had epilepsy. There were 37 (14.8%) individuals who fulfilled the prespecified criteria for epilepsy surgery referral without described contraindications, 32 (12.8%) of whom were not referred for epilepsy surgical evaluation in the given clinic visit. In the prediction of suitability for epilepsy surgery workup using the prespecified criteria, the tested models performed similarly. For example, the random forest model returned an area under the receiver operator characteristic curve of 0.97 (95% confidence interval 0.93-1.0) for this task, sensitivity of 1.0, and specificity of 0.93. SIGNIFICANCE: This study has shown that there are patients in tertiary hospitals in South Australia who fulfill prespecified criteria for epilepsy surgery evaluation who may not have been referred for such evaluation. ML-NLP may assist with the identification of patients suitable for such referral. PLAIN LANGUAGE SUMMARY: Epilepsy surgery is a beneficial treatment for selected individuals with drug-resistant epilepsy. However, it is vastly underutilized. One reason for this underutilization is a lack of prompt referral of possible epilepsy surgery candidates to comprehensive epilepsy centers. Natural language processing, coupled with machine learning, may be able to identify possible epilepsy surgery candidates through the analysis of unstructured clinic notes. This study, conducted in two tertiary hospitals in South Australia, demonstrated that there are individuals who fulfill criteria for epilepsy surgery evaluation referral but have not yet been referred. Machine learning-natural language processing demonstrates promising results in assisting with the identification of such suitable candidates in Australia.

Renal disease is not associated with delays in hyperacute stroke management in South Australia.

OBJECTIVE: The aims of the present study were to determine how renal disease is associated with the time to receive hyperacute stroke care. METHODS: The present study involved a 5-year cohort of all patients admitted to stroke units in South Australia. RESULTS: In those with pre-existing renal disease there were no significant differences in the time taken to receive a scan, thrombolysis or endovascular thrombectomy. CONCLUSIONS: The present study shows that in protocolised settings there were no significant delays in hyperacute stroke management for patients with renal disease.

Meeting medical emergency response criteria for hypertension is not associated with an increased likelihood of in-hospital mortality in a tertiary referral center.

Backgrounds: Rapid response team or medical emergency team (MET) calls are typically activated by significant alterations of vital signs in inpatients. However, the clinical significance of a specific criterion, blood pressure elevations, is uncertain. Objectives: The aim of this study was to evaluate the likelihood ratios associated with MET-activating vital signs, particularly in-patient hypertension, for predicting in-hospital mortality among general medicine inpatients who met MET criteria at any point during admission in a South Australian metropolitan teaching hospital. Results: Among the 15,734 admissions over a two-year period, 4282 (27.2%) met any MET criteria, with a positive likelihood ratio of 3.05 (95% CI 2.93 to 3.18) for in-hospital mortality. Individual MET criteria were significantly associated with in-hospital mortality, with the highest positive likelihood ratio for respiratory rate ≤ 7 breaths per minute (9.83, 95% CI 6.90 to 13.62), barring systolic pressure ≥ 200 mmHg (LR + 1.26, 95% CI 0.86 to 1.69). Conclusions: Our results show that meeting the MET criteria for hypertension, unlike other criteria, was not significant associated with in-hospital mortality. This observation warrants further research in other patient cohorts to determine whether blood pressure elevations should be routinely included in MET criteria.

Prognostic significance of paramagnetic rim lesions in multiple sclerosis: A systematic review.

The diagnostic potential of paramagnetic rim lesions (PRLs) has been previously established; however, the prognostic significance of these lesions has not previously been consistently described. This study aimed to establish the prognostic role of PRLs in MS with respect to the Expanded Disability Status Scale (EDSS) and rates of disability progression. Databases of PubMed, EMBASE, Scopus and reference lists of selected articles were searched up to 29/04/2023. The review was conducted in accordance with PRISMA guidelines and was registered prospectively on PROSPERO (CRD42023422052). 7 studies were included in the final review. All of the eligible studies found that patients with PRLs tend to have higher baseline EDSS scores. Longitudinal assessments revealed greater EDSS progression in patients with PRLs over time in most studies. However, the effect of location of PRLs within the central nervous system were not assessed across the studies. Only one study investigated progression independent of relapse activity (PIRA) and showed that this clinical entity occurred in a greater proportion in patients with PRLs. This review supports PRLs as a predictor of EDSS progression. This measure has widespread applicability, however further multicentre studies are needed. Future research should explore the impact of PRLs on silent disability, PIRA, take into account different MS phenotypes and the topography of PRLs in prognosis.

Large language models can effectively extract stroke and reperfusion audit data from medical free-text discharge summaries.

INTRODUCTION: Audits are an integral part of effective modern healthcare. The collection of data for audits can be resource intensive. Large language models (LLM) may be able to assist. This pilot study aimed to assess the feasibility of using a LLM to extract stroke audit data from free-text medical documentation. METHOD: Discharge summaries from a one-month retrospective cohort of stroke admissions at a tertiary hospital were collected. A locally-deployed LLM, LLaMA3, was then used to extract a variety of routine stroke audit data from free-text discharge summaries. These data were compared to the previously collected human audit data in the statewide registry. Manual case note review was undertaken in cases of discordance. RESULTS: Overall, there was a total of 144 data points that were extracted (9 data points for each of the 16 patients). The LLM was correct in 135/144 (93.8%) of individual datapoints. This performance included binary categorical, multiple-option categorical, datetime, and free-text extraction fields. CONCLUSIONS: LLM may be able to assist with the efficient collection of stroke audit data. Such approaches may be pursued in other specialties. Future studies should seek to examine the most effective way to deploy such approaches in conjunction with human auditors and researchers.

Rational clinical approach to transient ischaemic attack, stroke and associated mimics: A retrospective cohort study.

OBJECTIVE: The present study was performed to identify the individual clinical features and risk factors most strongly associated with the diagnosis of transient neurological symptoms with a cerebrovascular cause (transient ischaemic attack (TIA) or stroke), as compared to common TIA mimics (including retinal ischaemia, migraine and seizure). METHODS: In a retrospective cohort study, consecutive patients presenting with transient neurological symptoms to TIA clinic in Royal Adelaide Hospital were included. Clinical features and risk factors were recorded in a standardised form, categorised into subgroups, and analysed using descriptive statistics and diagnostic performance indicators, such as sensitivity, specificity and likelihood ratios. RESULTS: For 218/1273 individuals diagnosed with stroke, the three features with the highest positive likelihood ratio were the presence of diffusion weighted imaging positive lesion on magnetic resonance imaging (23.66, 95% confidence interval (CI) 14.35-51.08), extracranial carotid atherosclerosis (3.98, 95% CI 1.19-6.87) and a history of peripheral vascular disease (3.33, 95% CI 1.64-6.27). For TIA, the three features with the highest positive likelihood ratio were extracranial carotid atherosclerosis (3.98, 95% CI 1.19-8.27), presence of atrial fibrillation (2.43, 95% CI 1.54-3.46) and pre-existing anticoagulant therapy (2.39, 95% CI 1.61-3.29). For stroke and TIA, the respective features with the lowest negative likelihood ratios were limb weakness (0.71, 95% CI 0.65-0.77) and hypertension (0.66, 95% CI 0.49-0.84). CONCLUSIONS: The present study demonstrated that specific clinical features and risk factors were associated with the final diagnosis at TIA clinic. These clinical features may assist with diagnosis of TIA in centres without access to a vascular neurologist.

Delays in the diagnosis of ischaemic stroke presenting with persistent reduced level of consciousness: A systematic review.

INTRODUCTION: Stroke presenting with a reduced level of consciousness (RLOC) may result in diagnostic error and/or delay. Missed or delayed diagnosis of acute ischaemic stroke may preclude otherwise applicable hyperacute stroke interventions. The frequency, reasons for, and consequences of diagnostic error and delay due to RLOC are uncertain. METHOD: The databases PubMed, EMBASE, and Cochrane library were searched in adherence with the PRISMA guidelines. The systematic review was prospectively registered on PROSPERO. RESULTS: Initial searches returned 1162 results, of which 6 fulfilled inclusion criteria. The majority of identified studies show that ischaemic stroke presenting with RLOC is at increased risk of missed or delayed diagnosis. Hyperacute stroke interventions may also be delayed. There is limited evidence regarding the reason for these delays; however, the delays may result from neuroimaging delay associated with diagnostic uncertainty. There is also limited evidence regarding the outcomes of patients with stroke and RLOC who experience diagnostic delay; however, the available literature suggests that outcomes may be poor, including motor and cognitive impairment, as well as long-term impaired consciousness. The included studies did not evaluate, but have suggested urgent MRI access, educational interventions, and protocolisation of the evaluation of RLOC as means to reduce poor outcomes. CONCLUSIONS: Ischaemic stroke patients with RLOC are at risk of diagnostic delay and error. These patients may have poor outcomes. Additional research is required to identify the contributing factors more clearly and to provide amelioration strategies.