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.

Challenges integrating skin sensitization data for assessment of difficult to test substances.

Difficult to test substances, including poorly soluble, mildly irritating, or UVCBs (unknown or variable composition complex reaction products or biological materials), producing weak or borderline in vivo results, face additional challenges in in vitro assays that often necessitate data integration in a weight of evidence (WOE) approach to inform skin sensitization potential. Here we present several case studies on difficult to test substances and highlight the utility of the toxicological priority index (ToxPi) as a data visualization tool to compare skin sensitization biological activity. The case study test substances represent two poorly soluble substances, tetrakis (2-ethylbutyl) orthosilicate and decyl palmitate, and two UVCB substances, alkylated anisole and hydrazinecarboximidamide, 2-[(2-hydroxyphenyl)methylene]-, reaction products with 2 undecanone. Data from key events within the skin sensitization adverse outcome pathway were gathered from publicly available sources or specifically generated. Incorporating the data for these case study test substances as well as data on chemicals of a known sensitization class (sensitizer, irritating non-sensitizer, and non-sensitizer) into ToxPi produced biological activity profiles which were grouped using unsupervised hierarchical clustering. Three of the case study test substances concluded to lack skin sensitization potential by traditional WOE produced biological activity profiles most consistent with non-sensi­tizing substances, whereas the prediction was less definitive for a substance considered positive by traditional WOE. Visualizing the data using bioactivity profiles can provide further support for WOE conclusions in certain circumstances but is unlikely to replace WOE as a stand-alone prediction due to limitations of the method including the impact of missing data points.

Non-animal test methods to detect chemicals that cause skin allergies are accepted alternatives to animal testing for this purpose. However, some chemicals are difficult to test using these methods, e.g., substances that cause skin irritation, are not water soluble or are mixtures of different compo­nents. We compiled existing and new data on how four such chemicals activate key elements of the biological pathway leading to allergic skin reactions and compared the resulting patterns with respective patterns of many chemicals confirmed to cause skin allergy, skin irritation or neither. The patterns were visualized and analyzed with a computer software tool. The tool confirmed that three substances were non-sensitizers but did not confirm that the fourth substance was a skin sensitizer as predicted by the standard assessment. This approach, which incorporates all available data types into the assessment of difficult to test chemicals, may further reduce unnecessary animal testing.

Identifying epilepsy surgery candidates with natural language processing: A systematic review.

INTRODUCTION: Epilepsy surgery is an underutilised, efficacious management strategy for selected individuals with drug-resistant epilepsy. Natural language processing (NLP) may aid in the identification of patients who are suitable to undergo evaluation for epilepsy surgery. The feasibility of this approach is yet to be determined. METHOD: In accordance with the PRISMA guidelines, a systematic review of the databases PubMed, EMBASE and Cochrane library was performed. This systematic review was prospectively registered on PROSPERO. RESULTS: 6 studies fulfilled inclusion criteria. The majority of included studies reported on datasets from only a single centre, with one study utilising data from two centres and one study six centres. The most commonly employed algorithms were support vector machines (5/6), with only one study utilising NLP strategies such as random forest models and gradient boosted machines. However, the results are promising, with all studies demonstrating moderate to high levels of performance in the identification of patients who may be suitable to undergo epilepsy surgery evaluation. Furthermore, multiple studies demonstrated that NLP could identify such patients 1-2 years prior to the treating clinicians instigating referral. However, no studies were identified that have evaluated the influence of implementing such algorithms on healthcare systems or patient outcomes. CONCLUSIONS: NLP is a promising approach to aid in the identification of patients that may be suitable to undergo epilepsy surgery evaluation. Further studies are required examining diverse datasets with additional analytical methodologies. Studies evaluating the impact of implementation of such algorithms would be beneficial.

Rapid infusion of infliximab biosimilars and the incidence and severity of infusion-related reactions in patients with inflammatory bowel disease.

WHAT IS KNOWN AND OBJECTIVE: Infliximab is an anti-tumour necrosis factor agent used in the treatment of inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis. While the use of infliximab is well established in the treatment of IBD, there are now four recently FDA-approved infliximab biosimilars that are increasingly used due to their cost-benefit for patients, institutions and payors. In addition, shortening the length of infliximab infusions from 120 min (standard infusion) to 60 min or less (rapid infusion) has been shown to safely provide further cost-benefit while also improving patient convenience. The safety of rapid infusions has been well-established for the infliximab reference product, however, there are limited data available regarding the safety of rapid infusions for infliximab biosimilars. The purpose of this study was to compare the incidence and severity of infusion reactions among patients with IBD receiving rapid infusion of infliximab reference product compared with infliximab biosimilar. METHODS: This was a retrospective analysis of electronic health record data of patients with a diagnosis of IBD receiving an infliximab reference product or infliximab biosimilar infusion between December 2020 and December 2021. Patient-level variables included demographics, immunomodulator use, IBD-related hospitalization and infliximab trough concentration and antibody levels. Infusion-related variables of interest included total number of infusions, drug, dose, dosing interval, infusion time and use of pre-medications. Infusion-related reactions were defined as safety concerns documented by the administering nurse (anaphylaxis, shortness of breath, hypotension, swelling, rash, pruritus, hives, flushing, chest pain, muscle pain, joint pain, fevers, chills, headache or hypertension) or administration of emergency medications. Fisher's exact test was used to compare reaction rates. RESULTS AND DISCUSSION: A total of 188 patients met inclusion criteria for analysis, and a total of 1124 infusions were administered during the study period. There were no statistically significant differences among any of the pre-specified outcomes. There were no differences in the incidence of infusion reactions among rapid infusion (60 min) infliximab and infliximab biosimilars (p = 0.863). Additionally, there were no differences in the incidence of infusion reactions among standard infusion (120 min) infliximab and infliximab biosimilars (p = 0.993). Finally, there were no differences among the rate of infusion reactions between rapid infusion of infliximab biosimilars and standard infusion of infliximab biosimilars (p = 0.536). Eight patients experienced safety issues, with three patients requiring emergency medications (1.6% of 188 patients). WHAT IS NEW AND CONCLUSIONS: Rapid infusions of infliximab biosimilars were not associated with an increase in the incidence of infusion reactions compared with: rapid infusion of infliximab reference product, standard infusion of infliximab biosimilars, or standard infusion of infliximab reference product. This should reassure clinicians that rapid infusions of infliximab biosimilars are safe in clinical practice.

Efficacy and tolerability of adjuvant perampanel: an Australian multicenter real-world observational study in refractory focal and generalized epilepsy syndromes.

PURPOSE: To explore the efficacy and tolerability of adjuvant perampanel (PER) and their associated risk factors in late add-on drug-resistant epilepsy. METHOD: Retrospective multicenter 'real-world' observational study. Consecutively identified patients commenced on PER, with mixed epilepsy syndromes, from nine Australian epilepsy centers. Primary efficacy endpoints were at least 50% reduction in seizure frequency (responders), seizure freedom, and retention at 6 and 12 months, following a 3-month titration period. Tolerability endpoints were cessation of PER for any reason, cessation of PER due to treatment-emergent adverse events (TEAE), or cessation due to inefficacy. Outcomes were assessed for a-priori risk factors associated with efficacy and tolerability. RESULTS: Three-hundred and eighty seven adults were identified and followed up for a median of 12.1 months (IQR 7.0-25.2). Focal epilepsy accounted for 79.6% (FE), idiopathic generalized epilepsy (IGE), 10.3% and developmental epileptic encephalopathy (DEE) 10.1%, of the cohort. All patients had drug-resistant epilepsy, 71.6% had never experienced six months of seizure freedom, and the mean number of antiepileptic medications (AEDs) prior to starting PER was six. At 12 months, with missing cases classified as treatment failure, retention was 40.0%, responder 21.7%, and seizure freedom 9.0%, whereas, using last outcome carried forward (LOCF), responder and seizure freedom rates were 41.3% and 14.7%, respectively. Older age of epilepsy onset was associated with a marginal increase in the likelihood of seizure freedom at 12-month maintenance (OR 1.04, 95% CI 1.02, 1.06). Male sex (adjusted OR [aOR] 2.06 95% CI 1.33, 3.19), lower number of prior AEDs (aOR 0.84, 95% CI 0.74, 0.96) and no previous seizure-free period of at least 6-month duration (aOR 2.04 95% CI 1.21, 3.47) were associated with retention. Perampanel combined with a GABA receptor AED was associated with a lower responder rate at 12 months but reduced cessation of PER. The most common TEAEs were neuropsychiatric (18.86%), followed by dizziness (13.70%), and sleepiness (5.68%). CONCLUSIONS: Adjuvant PER treatment, even in late-add on drug-resistant epilepsy is an effective and well-tolerated treatment for drug-resistant epilepsy.

Fatal Aortoesophageal Fistula Complicating Placement of a 20-mm Lumen-Apposing Metal Stent for Refractory Esophagojejunal Anastomotic Stricture.

We report the case of a patient with a benign refractory esophagojejunal anastomotic stricture for which a 20-mm lumen-apposing metal stent was placed, resulting in a fatal aortoenteric fistula. We report this case to alert others to this potential complication of LAMS placement for esophageal strictures and recommend caution when using the 20-mm LAMS in similar settings.

Epilepsy and Seizure-Related Hospital Admissions to an Australian Neurology Unit: A Prospective Observational Study.

This study provides contemporary data on patients admitted to a Neurology unit with seizures, the majority of whom have a diagnosis of epilepsy. There were 278 hospital presentations with seizure during the 6-month study period, with 60 admissions to the Neurology unit included for analysis. Provoking factors were identified in 40%, with poor medication adherence the commonest precipitant. CT-brain had low diagnostic yield in patients with epilepsy presenting with seizure and should be reserved for those with further indications for imaging. Patients with drug-resistant epilepsy comprised 54% of admissions suggesting management strategies in this cohort can be further optimized.

Measuring disease activity and predicting response to intravenous immunoglobulin in chronic inflammatory demyelinating polyneuropathy.

Chronic inflammatory demyelinating polyneuropathy (CIDP) is characterised by significant clinical heterogeneity and as such reliable biomarkers are required to measure disease activity and assess treatment response. Recent advances in our understanding of disease pathogenesis and the discovery of novel serum-based, electrophysiologic and imaging biomarkers allow clinicians to make more informed decisions regarding individualised treatment regimes. As a chronic immune-mediated process typified by relapse following withdrawal of immunomodulatory therapy, a substantial proportion of patients with CIDP require long term treatment with intravenous immunoglobulin (IVIg), a scarce and expensive donor-derived resource. The required duration and intensity of immunoglobulin treatment vary widely between individuals, highlighting both the heterogeneous nature of the underlying disease process as well as the variable pharmacologic properties of IVIg. This review outlines the use of multimodal biomarkers in the longitudinal evaluation of nerve injury and how recent developments have impacted our ability to predict both response to immunoglobulin administration and its withdrawal.

Psychology of learning: a new approach to study behavior of Rhodnius prolixus stal under laboratory conditions.

Conditioning methodologies associated with the psychology of learning are suggested as a new strategy to investigate behavior of the assassin bug Rhodnius prolixus, which is the main vector of Chagas disease in Venezuela. Chagas disease is the fourth leading cause of death in Latin America, as it causes severe chronic illness and approximately 43,000 deaths per year. To illustrate this strategy, two preliminary experiments are reported. In the first, Pavlovian conditioning was examined by pairing an olfactory conditioned stimulus with a temperature unconditioned stimulus. A temperature of 42 degrees C elicits a complex behavioral sequence in R. prolixus consisting of proboscis extension and crawling. Over the course of 12 training trials, this behavioral sequence was not elicited by an olfactory conditioned stimulus. In the second experiment, a latent inhibition paradigm was used to pre-expose R. prolixus to an olfactory conditioned stimulus before pairing the odor with temperature. Over the course of training, an effect of pre-exposure was found. Suggestions for research are discussed and potential conditioned and unconditioned stimuli identified.