Citations

Objective To assess the cost-effectiveness of management strategies for patients presenting with chest pain and suspected coronary heart disease (CHD): (1) cardiovascular magnetic resonance (CMR); (2) myocardial perfusion scintigraphy (MPS); and (3) UK National Institute for Health and Care Excellence (NICE) guideline-guided care. Methods Using UK data for 1202 patients from the Clinical Evaluation of Magnetic Resonance Imaging in Coronary Heart Disease 2 trial, we conducted an economic evaluation to assess the cost-effectiveness of CMR, MPS and NICE guidelines. Health outcomes were expressed as quality-adjusted life-years (QALYs), and costs reflected UK pound sterling in 2016–2017. Cost-effectiveness results were presented as incremental cost-effectiveness ratios and incremental net health benefits overall and for low, medium and high pretest likelihood of CHD subgroups. Results CMR had the highest estimated QALY gain overall (2.21 (95% credible interval 2.15, 2.26) compared with 2.07 (1.92, 2.20) for NICE and 2.11 (2.01, 2.22) for MPS) and incurred comparable costs (overall £1625 (£1431, £1824) compared with £1753 (£1473, £2032) for NICE and £1768 (£1572, £1989) for MPS). Overall, CMR was the cost-effective strategy, being the dominant strategy (more effective, less costly) with incremental net health benefits per patient of 0.146 QALYs (−0.18, 0.406) compared with NICE guidelines at a cost-effectiveness threshold of £15 000 per QALY (93% probability of cost-effectiveness). Results were similar in the pretest likelihood subgroups. Conclusions CMR-guided care is cost-effective overall and across all pretest likelihood subgroups, compared with MPS and NICE guidelines.

AbstractEpilepsy is a heterogeneous condition with disparate etiologies and phenotypic and genotypic characteristics. Clinical and research aspects are accordingly varied, ranging from epidemiological to molecular, spanning clinical trials and outcomes, gene and drug discovery, imaging, electroencephalography, pathology, epilepsy surgery, digital technologies, and numerous others. Epilepsy data are collected in the terabytes and petabytes, pushing the limits of current capabilities. Modern computing firepower and advances in machine and deep learning, pioneered in other diseases, open up exciting possibilities for epilepsy too. However, without carefully designed approaches to acquiring, standardizing, curating, and making available such data, there is a risk of failure. Thus, careful construction of relevant ontologies, with intimate stakeholder inputs, provides the requisite scaffolding for more ambitious big data undertakings, such as an epilepsy data commons. In this review, we assess the clinical and research epilepsy landscapes in the big data arena, current challenges, and future directions, and make the case for a systematic approach to epilepsy big data.

OBJECTIVE The object of this study was to ascertain outcomes of cochlear implantation (CI) following stereotactic radiosurgery (SRS) for vestibular schwannoma (VS). METHODS The authors conducted a retrospective chart review of adult patients with VS treated with SRS who underwent CI between 1990 and 2019 at a single tertiary care referral center. Patient demographics, tumor features, treatment parameters, and pre- and postimplantation audiometric and clinical outcomes are presented. RESULTS Seventeen patients (18 ears) underwent SRS and ipsilateral CI during the study period. Thirteen patients (76%) had neurofibromatosis type 2 (NF2). Median age at SRS and CI were 44 and 48 years, respectively. Median time from SRS to CI was 60 days, but notably, 4 patients underwent SRS and CI within 1 day and 5 patients underwent CI more than 7 years after SRS. Median marginal dose was 13 Gy. Median treatment volume at the time of SRS was 1400 mm 3 (range 84–6080 mm 3 , n = 15 patients). Median post-CI PTA was 28 dB HL, improved from 101 dB HL preoperatively (p < 0.001). Overall, 11 patients (12 ears) exhibited open-set speech understanding. Sentence testing was performed at a median of 10 months (range 1–143 months) post-CI. The median AzBio sentence score for patients with open-set speech understanding was 76% (range 19%–95%, n = 10 ears). Two ears exhibited Hearing in Noise Test (HINT) sentence scores of 49% and 95%, respectively. Four patients achieved environmental sound awareness without open-set speech recognition. Two had no detectable auditory percepts. CONCLUSIONS Most patients who underwent CI following SRS for VS enjoyed access to sound at near-normal levels, with the majority achieving good open-set speech understanding. Implantation can be performed immediately following SRS or in a delayed fashion, depending on hearing status as well as other factors. This strategy may be applied to cases of sporadic or NF2-associated VS.

Abstract Structural grey matter covariance networks provide an individual quantification of morphological patterns in the brain. The network integrity is disrupted in sporadic Alzheimer’s disease, and network properties show associations with the level of amyloid pathology and cognitive decline. Therefore, these network properties might be disease progression markers. However, it remains unclear when and how grey matter network integrity changes with disease progression. We investigated these questions in autosomal dominant Alzheimer’s disease mutation carriers, whose conserved age at dementia onset allows individual staging based upon their estimated years to symptom onset. From the Dominantly Inherited Alzheimer Network observational cohort, we selected T1-weighted MRI scans from 269 mutation carriers and 170 non-carriers (mean age 38 ± 15 years, mean estimated years to symptom onset −9 ± 11), of whom 237 had longitudinal scans with a mean follow-up of 3.0 years. Single-subject grey matter networks were extracted, and we calculated for each individual the network properties which describe the network topology, including the size, clustering, path length and small worldness. We determined at which time point mutation carriers and non-carriers diverged for global and regional grey matter network metrics, both cross-sectionally and for rate of change over time. Based on cross-sectional data, the earliest difference was observed in normalized path length, which was decreased for mutation carriers in the precuneus area at 13 years and on a global level 12 years before estimated symptom onset. Based on longitudinal data, we found the earliest difference between groups on a global level 6 years before symptom onset, with a greater rate of decline of network size for mutation carriers. We further compared grey matter network small worldness with established biomarkers for Alzheimer disease (i.e. amyloid accumulation, cortical thickness, brain metabolism and cognitive function). We found that greater amyloid accumulation at baseline was associated with faster decline of small worldness over time, and decline in grey matter network measures over time was accompanied by decline in brain metabolism, cortical thinning and cognitive decline. In summary, network measures decline in autosomal dominant Alzheimer’s disease, which is alike sporadic Alzheimer’s disease, and the properties show decline over time prior to estimated symptom onset. These data suggest that single-subject networks properties obtained from structural MRI scans form an additional non-invasive tool for understanding the substrate of cognitive decline and measuring progression from preclinical to severe clinical stages of Alzheimer’s disease.

Several antiepileptic drugs (AEDs) have US Food and Drug Administration (FDA) approval for use as mood stabilizers in bipolar disorder (BD), but not all BD patients respond to these AED mood stabilizers (AED‐MSs). To identify genetic polymorphisms that contribute to the variability in AED‐MS response, we performed a discovery genome‐wide association study (GWAS) of 199 BD patients from the Mayo Clinic Bipolar Disorder Biobank. Most of these patients had been treated with the AED‐MS valproate/divalproex and/or lamotrigine. AED‐MS response was assessed using the Alda scale, which quantifies clinical improvement while accounting for potential confounding factors. We identified two genome‐wide significant single‐nucleotide polymorphism (SNP) signals that mapped to the THSD7A (rs78835388, P = 7.1E‐09) and SLC35F3 (rs114872993, P = 3.2E‐08) genes. We also identified two genes with statistically significant gene‐level associations: ABCC1 (P = 6.7E‐07; top SNP rs875740, P = 2.0E‐6), and DISP1 (P = 8.9E‐07; top SNP rs34701716, P = 8.9E‐07). THSD7A SNPs were previously found to be associated with risk for several psychiatric disorders, including BD. Both THSD7A and SLC35F3 are expressed in excitatory/glutamatergic and inhibitory/γ‐aminobutyric acidergic (GABAergic) neurons, which are targets of AED‐MSs. ABCC1 is involved in the transport of valproate and lamotrigine metabolites, and the SNPs in ABCC1 and DISP1 with the strongest evidence of association in our GWAS are strong splicing quantitative trait loci in the human gut, suggesting a possible influence on drug absorption. In conclusion, our pharmacogenomic study identified novel genetic loci that appear to contribute to AED‐MS treatment response, and may facilitate precision medicine in BD.

Objective: Definitive treatment of sporadic vestibular schwannoma (VS) following documented growth is common practice at most centers in the United States. However, as a natural extension of this paradigm, very little evidence exists surrounding the natural history of growing tumors. The primary objective of the current work was to describe the natural history of sporadic VS following documentation of initial tumor growth. Study Design: Retrospective cohort study. Setting: Tertiary referral center. Patients: Patients diagnosed with sporadic VS between January 1, 2001 and December 31, 2015 who elected continued observation despite having volumetric growth ≥20% of original tumor volume on interval magnetic resonance imaging (MRI). Main Outcome Measure: Survival free of subsequent volumetric growth. Results: Of 361 patients undergoing observation with serial imaging during the study period, 85 patients met inclusion criteria at a median age of 66 years (interquartile ranges [IQR] 55–71). Within this cohort, 40 patients demonstrated subsequent volumetric growth at a median of 1.7 years (IQR 1.0–2.6) from the date of initial MRI that documented growth. The median volumetric growth was 43% (IQR 28–57), and the median growth rate was 0.026 cm3 per year (IQR 0.009–0.107). Survival free of subsequent volumetric growth rates (95% CI; number still at risk) at 1, 2, 3, 4, and 5 years were 93% (87–99; 75), 67% (58–79; 45), 54% (43–67; 29), 44% (33–59; 19), and 41% (30–56; 12), respectively. Conclusions: In a cohort exclusively comprised of sporadic VS with documented growth, over 40% of tumors demonstrated no subsequent volumetric growth after 5 years of continued MRI surveillance. These data challenge the supposition that once growth occurs, all tumors will exhibit sustained growth. Continued observation after documented growth of sporadic VS is a reasonable consideration in appropriately selected cases.