UW Neurological Surgery Recent PubMed Publications

Costs of using evidence-based implementation strategies for behavioral health integration in a large primary care system.

Health Serv Res. 2020 Dec;55(6):913-923

Authors: Yeung K, Richards J, Goemer E, Lozano P, Lapham G, Williams E, Glass J, Lee A, Achtmeyer C, Caldeiro R, Parrish R, Bradley K

Abstract
OBJECTIVE: To describe the cost of using evidence-based implementation strategies for sustained behavioral health integration (BHI) involving population-based screening, assessment, and identification at 25 primary care sites of Kaiser Permanente Washington (2015-2018).
DATA SOURCES/STUDY SETTING: Project records, surveys, Bureau of Labor Statistics compensation data.
STUDY DESIGN: Labor and nonlabor costs incurred by three implementation strategies: practice coaching, electronic health records clinical decision support, and performance feedback.
DATA COLLECTION/EXTRACTION METHODS: Personnel time spent on these strategies was estimated for five broad roles: (a) project leaders and administrative support, (b) practice coaches, (c) clinical decision support programmers, (d) performance metric programmers, and (e) primary care local implementation team members.
PRINCIPAL FINDING: Implementation involved 286 persons, 18 131 person-hours, costing $1 587 139 or $5 per primary care visit with screening or $38 per primary care visit identifying depression, suicidal thoughts and/or alcohol or substance use disorders, in a single year. The majority of person-hours was devoted to project leadership (35%) and practice coaches (34%), and 36% of costs were for the first three sites.
CONCLUSIONS: When spread across patients screened in a single year, BHI implementation costs were well within the range for commonly used diagnostic assessments in primary care (eg, laboratory tests). This suggests that implementation costs alone should not be a substantial barrier to population-based BHI.

PMID: 33258127 [PubMed - in process]

Developments in Heart Failure With Reduced Ejection Fraction-Reply.

JAMA. 2020 12 01;324(21):2215-2216

Authors: Murphy SP, Ibhrahim NE, Januzzi JL

PMID: 33258887 [PubMed - indexed for MEDLINE]

A Pilot Study on Data-Driven Adaptive Deep Brain Stimulation in Chronically Implanted Essential Tremor Patients.

Front Hum Neurosci. 2020;14:541625

Authors: Castaño-Candamil S, Ferleger BI, Haddock A, Cooper SS, Herron J, Ko A, Chizeck HJ, Tangermann M

Abstract
Deep brain stimulation (DBS) is an established therapy for Parkinson's disease (PD) and essential-tremor (ET). In adaptive DBS (aDBS) systems, online tuning of stimulation parameters as a function of neural signals may improve treatment efficacy and reduce side-effects. State-of-the-art aDBS systems use symptom surrogates derived from neural signals-so-called neural markers (NMs)-defined on the patient-group level, and control strategies assuming stationarity of symptoms and NMs. We aim at improving these aDBS systems with (1) a data-driven approach for identifying patient- and session-specific NMs and (2) a control strategy coping with short-term non-stationary dynamics. The two building blocks are implemented as follows: (1) The data-driven NMs are based on a machine learning model estimating tremor intensity from electrocorticographic signals. (2) The control strategy accounts for local variability of tremor statistics. Our study with three chronically implanted ET patients amounted to five online sessions. Tremor quantified from accelerometer data shows that symptom suppression is at least equivalent to that of a continuous DBS strategy in 3 out-of 4 online tests, while considerably reducing net stimulation (at least 24%). In the remaining online test, symptom suppression was not significantly different from either the continuous strategy or the no treatment condition. We introduce a novel aDBS system for ET. It is the first aDBS system based on (1) a machine learning model to identify session-specific NMs, and (2) a control strategy coping with short-term non-stationary dynamics. We show the suitability of our aDBS approach for ET, which opens the door to its further study in a larger patient population.

PMID: 33250727 [PubMed]

Systems Biology Methods Applied to Blood and Tissue for a Comprehensive Analysis of Immune Response to Hepatitis B Vaccine in Adults.

Front Immunol. 2020;11:580373

Authors: Ben-Othman R, Cai B, Liu AC, Varankovich N, He D, Blimkie TM, Lee AH, Gill EE, Novotny M, Aevermann B, Drissler S, Shannon CP, McCann S, Marty K, Bjornson G, Edgar RD, Lin DTS, Gladish N, Maclsaac J, Amenyogbe N, Chan Q, Llibre A, Collin J, Landais E, Le K, Reiss SM, Koff WC, Havenar-Daughton C, Heran M, Sangha B, Walt D, Krajden M, Crotty S, Sok D, Briney B, Burton DR, Duffy D, Foster LJ, Mohn WW, Kobor MS, Tebbutt SJ, Brinkman RR, Scheuermann RH, Hancock REW, Kollmann TR, Sadarangani M

Abstract
Conventional vaccine design has been based on trial-and-error approaches, which have been generally successful. However, there have been some major failures in vaccine development and we still do not have highly effective licensed vaccines for tuberculosis, HIV, respiratory syncytial virus, and other major infections of global significance. Approaches at rational vaccine design have been limited by our understanding of the immune response to vaccination at the molecular level. Tools now exist to undertake in-depth analysis using systems biology approaches, but to be fully realized, studies are required in humans with intensive blood and tissue sampling. Methods that support this intensive sampling need to be developed and validated as feasible. To this end, we describe here a detailed approach that was applied in a study of 15 healthy adults, who were immunized with hepatitis B vaccine. Sampling included ~350 mL of blood, 12 microbiome samples, and lymph node fine needle aspirates obtained over a ~7-month period, enabling comprehensive analysis of the immune response at the molecular level, including single cell and tissue sample analysis. Samples were collected for analysis of immune phenotyping, whole blood and single cell gene expression, proteomics, lipidomics, epigenetics, whole blood response to key immune stimuli, cytokine responses, in vitro T cell responses, antibody repertoire analysis and the microbiome. Data integration was undertaken using different approaches-NetworkAnalyst and DIABLO. Our results demonstrate that such intensive sampling studies are feasible in healthy adults, and data integration tools exist to analyze the vast amount of data generated from a multi-omics systems biology approach. This will provide the basis for a better understanding of vaccine-induced immunity and accelerate future rational vaccine design.

PMID: 33250895 [PubMed - in process]

Circadian variation in sudden unexpected infant death in the United States.

Acta Paediatr. 2020 Nov 29;:

Authors: Anderson TM, Allen K, Ramirez JM, Mitchell EA

Abstract
AIM: To determine which factors are associated with sudden unexpected infant death (SUID) by time of day.
METHODS: Data were analyzed from the National Fatality Review Case Reporting System (2006-2015). Out of 20,005 SUID deaths in 37 states, 12,191 (60.9%) deaths had a recorded nearest hour of discovery of the infant. We compared distribution patterns between time of death and 118 variables to determine which were significantly correlated with SUID time of death using advanced statistical modelling techniques.
RESULTS: The 12-hour time periods which were most different were 10:00 to 21:00 (daytime) and 22:00 to 09:00 (nighttime). The main features that were associated with nighttime SUID were bed sharing, younger infants, non-white infants, placed supine to sleep, found supine, and caregiver was the parent. Daytime SUID was associated with older infants, daycare, white infants, sleeping in an adult bed, and prone sleep position. Factors not associated with time of death were sex of the infant, smoking, and breastfeeding.
CONCLUSION: SUID deaths that occur at night are associated with a separate set of risk factors compared to deaths that occur during the day. However, to minimize risk, it is important to practice safe sleep guidelines during both nighttime and daytime sleep.

PMID: 33251652 [PubMed - as supplied by publisher]

Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial.

Lancet Oncol. 2021 01;22(1):107-117

Authors: Boorjian SA, Alemozaffar M, Konety BR, Shore ND, Gomella LG, Kamat AM, Bivalacqua TJ, Montgomery JS, Lerner SP, Busby JE, Poch M, Crispen PL, Steinberg GD, Schuckman AK, Downs TM, Svatek RS, Mashni J, Lane BR, Guzzo TJ, Bratslavsky G, Karsh LI, Woods ME, Brown G, Canter D, Luchey A, Lotan Y, Krupski T, Inman BA, Williams MB, Cookson MS, Keegan KA, Andriole GL, Sankin AI, Boyd A, O'Donnell MA, Sawutz D, Philipson R, Coll R, Narayan VM, Treasure FP, Yla-Herttuala S, Parker NR, Dinney CPN

Abstract
BACKGROUND: BCG is the most effective therapy for high-risk non-muscle-invasive bladder cancer. Nadofaragene firadenovec (also known as rAd-IFNa/Syn3) is a replication-deficient recombinant adenovirus that delivers human interferon alfa-2b cDNA into the bladder epithelium, and a novel intravesical therapy for BCG-unresponsive non-muscle-invasive bladder cancer. We aimed to evaluate its efficacy in patients with BCG-unresponsive non-muscle-invasive bladder cancer.
METHODS: In this phase 3, multicentre, open-label, repeat-dose study done in 33 centres (hospitals and clinics) in the USA, we recruited patients aged 18 years or older, with BCG-unresponsive non-muscle-invasive bladder cancer and an Eastern Cooperative Oncology Group status of 2 or less. Patients were excluded if they had upper urinary tract disease, urothelial carcinoma within the prostatic urethra, lymphovascular invasion, micropapillary disease, or hydronephrosis. Eligible patients received a single intravesical 75 mL dose of nadofaragene firadenovec (3 × 1011 viral particles per mL). Repeat dosing at months 3, 6, and 9 was done in the absence of high-grade recurrence. The primary endpoint was complete response at any time in patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour). The null hypothesis specified a complete response rate of less than 27% in this cohort. Efficacy analyses were done on the per-protocol population, to include only patients strictly meeting the BCG-unresponsive definition. Safety analyses were done in all patients who received at least one dose of treatment. The study is ongoing, with a planned 4-year treatment and monitoring phase. This study is registered with ClinicalTrials.gov, NCT02773849.
FINDINGS: Between Sept 19, 2016, and May 24, 2019, 198 patients were assessed for eligibility. 41 patients were excluded, and 157 were enrolled and received at least one dose of the study drug. Six patients did not meet the definition of BCG-unresponsive non-muscle-invasive bladder cancer and were therefore excluded from efficacy analyses; the remaining 151 patients were included in the per-protocol efficacy analyses. 55 (53·4%) of 103 patients with carcinoma in situ (with or without a high-grade Ta or T1 tumour) had a complete response within 3 months of the first dose and this response was maintained in 25 (45·5%) of 55 patients at 12 months. Micturition urgency was the most common grade 3-4 study drug-related adverse event (two [1%] of 157 patients, both grade 3), and there were no treatment-related deaths.
INTERPRETATION: Intravesical nadofaragene firadenovec was efficacious, with a favourable benefit:risk ratio, in patients with BCG-unresponsive non-muscle-invasive bladder cancer. This represents a novel treatment option in a therapeutically challenging disease state.
FUNDING: FKD Therapies Oy.

PMID: 33253641 [PubMed - indexed for MEDLINE]

Strategies for writing a successful National Institutes of Health grant proposal for the early-career neurointerventionalist.

J Neurointerv Surg. 2020 Nov 25;:

Authors: Kan P, Mokin M, Mack WJ, Starke RM, Sheth KN, Albuquerque FC, Levitt MR

Abstract
OBJECTIVE: The goal of this article is to provide a succinct review of the key components of a NIH grant application and the NIH reviewprocess for the early career neurointerventionalist.
METHODS: The authors reviewed NIH rules and regulations and also reflected on their own collective experiencein writing NIH grant proposals in the area of cerebrovascular disease andneurointerventional surgery.
RESULTS: Key components of theresearch strategy include specific aims, significance, innovation and approach.The specific aims page is the most important page of the application and should be written first. The NIH review isbased on these key components along with an assessment of the appropriatenessof the investigators and environment for the research.
CONCLUSION: Detailed knowledge ofthe key components of the research grant is critical to a successful application.The information in the article may aid in the grant writing for early careerneurointerventionalists.

PMID: 33239307 [PubMed - as supplied by publisher]

National Institutes of Health grant opportunities for the neurointerventionalist: preparation and choosing the right mechanism.

J Neurointerv Surg. 2020 Nov 25;:

Authors: Kan P, Levitt MR, Mack WJ, Starke RM, Sheth KN, Albuquerque FC, Mokin M

Abstract
OBJECTIVE: The goal of this article is to provide recommendations for the early career neurointerventionalist in writing a successful grant application to the National Institutes of Health (NIH) and similar funding agencies.
METHODS: The authors reviewed NIH rules and regulations and also reflected on their own collective experience in writing NIH grant proposals in the area of cerebrovascular disease and neurointerventional surgery.
RESULTS: A strong proposal should address an important scientific problem where there is a gap in knowledge. The solution offered needs to be innovative but at the same time based on a strong scientific premise. The proposed research must be feasible to implement and investigate in the researcher's environment.
CONCLUSION: Successful grant writing is critical in funding and enhancing research. The information in the article may aid in the preparation stage of grant writing for early career neurointerventionalists.

PMID: 33239308 [PubMed - as supplied by publisher]

Rodent and fly models in behavioral neuroscience: an evaluation of methodological advances, comparative research, and future perspectives.

Neurosci Biobehav Rev. 2020 Nov 23;:

Authors: Moulin TC, Covill LE, Itskov PM, Williams MJ, Schiöth HB

Abstract
The assessment of behavioral outcomes is a central component of neuroscientific research, which has required continuous technological innovations to produce more detailed and reliable findings. In this article, we provide an in-depth review on the progress and future implications for three model organisms (mouse, rat, and Drosophila) essential to our current understanding of behavior. By compiling a comprehensive catalog of popular assays, we are able to compare the diversity of tasks and usage of these animal models in behavioral research. This compilation also allows for the evaluation of existing state-of-the-art methods and experimental applications, including optogenetics, machine learning, and high-throughput behavioral assays. We go on to discuss novel apparatuses and inter-species analyses for centrophobism, feeding behavior, aggression and mating paradigms, with the goal of providing a unique view on comparative behavioral research. The challenges and recent advances are evaluated in terms of their translational value, ethical procedures, and trustworthiness for behavioral research.

PMID: 33242563 [PubMed - as supplied by publisher]

Reply to Wenzel and Kubiak: Neuroticism is best defined by mean levels of negative emotion, not emotional variability.

Proc Natl Acad Sci U S A. 2020 12 29;117(52):32859-32860

Authors: Kalokerinos EK, Murphy SC, Koval P, Mestdagh M, Bastian B, Kuppens P

PMID: 33234570 [PubMed - indexed for MEDLINE]

Phenotypic characterization with somatic genome editing and gene transfer reveals the diverse oncogenicity of ependymoma fusion genes.

Acta Neuropathol Commun. 2020 Nov 23;8(1):203

Authors: Takadera M, Satomi K, Szulzewsky F, Cimino PJ, Holland EC, Yamamoto T, Ichimura K, Ozawa T

Abstract
Recurrent RELA and YAP1 fusions are intimately associated with tumorigenesis in supratentorial ependymomas. Chromothripsis and focal copy number alterations involving 11q are hallmarks of these tumors. However, it is unknown whether the chromosomal alterations are a direct causal event resulting in fusion transcripts. In addition, the biological significance of the RELA fusion variants and YAP1 fusions is not yet fully characterized. In this study, we generated gene rearrangements on 11q with the CRISPR/Cas9 system and investigated the formation of oncogenic ependymoma fusion genes. Further, we examined the oncogenic potential of RELA fusion variants and YAP1 fusions in a lentiviral gene transfer model. We observed that endogenous RELA fusion events were successfully induced by CRISPR/Cas9-mediated genome rearrangement in cultured cells. In vivo genome editing in mouse brain resulted in the development of ependymoma-like brain tumors that harbored the Rela fusion gene. All RELA fusion variants tested, except a variant lacking the Rel homology domain, were able to induce tumor formation, albeit with different efficacy. Furthermore, expression of YAP1-FAM118B and YAP1-MAMLD1 fusions induced the formation of spindle-cell-like tumors at varying efficacy. Our results indicate that chromosomal rearrangements involving the Rela locus are the causal event for the formation of Rela fusion-driven ependymomas in mice. Furthermore, the type of RELA. fusion might affect the aggressiveness of tumors and that the Rel homology domain is essential for the oncogenic functions of RELA. fusions. The YAP1 fusion genes are also oncogenic when expressed in mice.

PMID: 33228790 [PubMed - in process]

The only difference between a jail and a psychiatric hospital is a pillow.

Schizophr Res. 2020 Nov 19;:

Authors: Williams MJ

Abstract
This is an article looking at the problems I have noticed in psychiatric hospitals as a patient with schizophrenia.

PMID: 33223348 [PubMed - as supplied by publisher]

Development of a robust crystallization platform for immune receptor TREM2 using a crystallization chaperone strategy.

Protein Expr Purif. 2020 Nov 19;:105796

Authors: Byrne NJ, Lee AC, Kostas J, Reid JC, Partridge AT, So SS, Cowan JE, Abeywickrema P, Huang H, Zebisch M, Barker JJ, Soisson SM, Brooun A, Su HP

Abstract
TREM2 has been identified by genomic analysis as a potential and novel target for the treatment of Alzheimer's disease. To enable structure-based screening of potential small molecule therapeutics, we sought to develop a robust crystallization platform for the TREM2 Ig-like domain. A systematic set of constructs containing the structural chaperone, maltose binding protein (MBP), fused to the Ig domain of TREM2, were evaluated in parallel expression and purification, followed by crystallization studies. Using protein crystallization and high-resolution diffraction as a readout, a MBP-TREM2 Ig fusion construct was identified that generates reproducible protein crystals diffracting at 2.0Å, which makes it suitable for soaking of potential ligands. Importantly, analysis of crystal packing interfaces indicates that most of the surface of the TREM2 Ig domain is available for small molecule binding. A proof of concept co-crystallization study with a small library of fragments validated potential utility of this system for the discovery of new TREM2 therapeutics.

PMID: 33221505 [PubMed - as supplied by publisher]

Anthracycline Cardiotoxicity in a Patient with Diffuse Large B-Cell Lymphoma: A Case Report.

Cureus. 2020 Oct 19;12(10):e11038

Authors: Teixeira da Silva F, Morais Passos R, Esteves A, Carvalho J, Ferreira M

Abstract
Cardiotoxicity is a relevant side effect of cancer therapy that leads to increased patient morbidity and mortality. It is fundamental to understand and remember it as a cause of disease since accurate and timely diagnosis is crucial. We present the case of a patient who developed chemotherapy-associated cardiac dysfunction after receiving treatment for a diffuse large B-cell lymphoma. Clinical history, echocardiography, and differential diagnosis led us to attribute her condition to heart failure (HF) due to early doxorubicin-induced cardiomyopathy. The patient outcome was favorable. We discuss the pathogenesis and incidence of anthracycline-induced cardiotoxicity as well as strategies for its detection, prevention, and treatment.

PMID: 33214965 [PubMed]

Geoffrey Burnstock - An accidental pharmacologist.

Biochem Pharmacol. 2020 Oct 23;:114300

Authors: Di Virgilio F, Jacobson KA, Williams M

Abstract
Geoffrey Burnstock, the founder of the field of purinergic signaling research passed away in Melbourne, Australia on June 3rd, 2020, at the age of 91. With his death, the world of biomedical research lost one of its most passionate, creative and unconventional thought leaders. He was an inspiration to the many researchers he interacted with for more than 50 years and a frequent irritation to those in the administrative establishment. Geoff never considered himself a pharmacologist having being trained as a zoologist and becoming an autonomic neurophysiologist based on his evolving interests in systems and disease-related research. By the end of his life he had: published some 1550 papers; been cited more than 125,000 times; had an h-index of 156 and had supervised over 100 Ph.D. students. His indelible legacy, based on a holistic, data-based, multidisciplinary, unconventional "outside the box" approach to research was reflected in two of the seminal findings in late 20th century biomedical research: the purinergic neurotransmitter hypothesis and the concept of co-neurotransmission, both of which were initially received by his peers with considerable skepticism that at times verged on disdain. Nonetheless, while raising hackles and threatening the status quo, Geoff persevered and prevailed, becoming a mentor for several generations of biomedical researchers. In this review we provide a joint perspective on Geoff Burnstock's legacy in research.

PMID: 33203518 [PubMed - as supplied by publisher]

Transcirculation approach for stent-assisted coiling of intracranial aneurysms: a multicenter study.

J Neurointerv Surg. 2020 Nov 17;:

Authors: Mascitelli JR, Levitt MR, Griessenauer CJ, Kim LJ, Gross B, Abla A, Winkler E, Jankowitz B, Grandhi R, Goren O, Schirmer CM

Abstract
BACKGROUND: The transcirculation approach (TCA) for stent-assisted coiling (SAC) of intracranial aneurysms may be useful for certain wide-neck bifurcation aneurysms as well as those with acute-angle efferent branches.
OBJECTIVE: To describe a multicenter experience using the TCA for SAC.
METHODS: A multicenter, retrospective study (2016-2020) of aneurysm treatment using SAC via the TCA. Angiographic outcome was scored using the Raymond Scale (adequate occlusion 1 and 2), and clinical outcome was scored using a modified Rankin Scale (good outcome 0-2) RESULTS: Twenty-nine patients with 29 aneurysms were included (62.1% female; average age 61; 89.7% unruptured; 13.8% previously treated; average dome size 6.4 mm; average neck 4.4 mm). Aneurysm locations included internal carotid artery-fetal posterior cerebral artery (n=4), internal carotid artery terminus (n=4), anterior communicating artery (n=8), vertebral artery-posterior inferior cerebellar artery (n=2), and basilar tip (n=11). The TCA used communicating arteries (93.1%; average 1.6 mm), intermediate catheters (51.7%), jailing technique (62.1%), and staged procedures (10.3%). The most common stent was the Neuroform Atlas (Stryker; 69%). Immediate adequate occlusion was obtained in 75.9%, and five patients with inadequate occlusion progressed to adequate occlusion at follow-up. One (3.4%) procedural complication occurred: a watershed stroke in the setting of baseline four-vessel extracranial disease. Two patients had a poor outcome unrelated to the TCA. The majority of patients (86.4%) had a good clinical outcome. One case of in-stent stenosis due to non-compliance with medication was seen, which resolved with medication resumption.
CONCLUSIONS: The TCA for SAC can be performed for a variety of aneurysms with a low complication rate and good clinical outcomes.

PMID: 33203763 [PubMed - as supplied by publisher]

Author Correction: Multicellular 3D Neurovascular Unit Model for Assessing Hypoxia and Neuroinflammation Induced Blood-Brain Barrier Dysfunction.

Sci Rep. 2020 Nov 18;10(1):20384

Authors: Nzou G, Wicks RT, VanOstrand NR, Mekky GA, Seale SA, El-Taibany A, Wicks EE, Nechtman CM, Marrotte EJ, Makani VS, Murphy SV, Seeds MC, Jackson JD, Atala AJ

Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.

PMID: 33204010 [PubMed]

Variability in multimodality treatment influences survival in non-metastatic gastric cancer patients.

J Gastrointest Oncol. 2020 Oct;11(5):952-963

Authors: Hoang T, Dayyani F, Alfaro A, Huynh J, Ji J, Ko AH, Cho M, Hiyama D

Abstract
Background: While gastric cancer is a leading cause of cancer-related mortality in Eastern Europe and Asia, it is less common in the USA. Recommendations regarding optimal treatment of non-metastatic gastric cancer (nmGC) with regard to type and extent of surgery, choice and sequence of chemotherapeutic agents, and use of radiation therapy vary across geographic locations. To determine how variability in treatment practices affects patient outcomes, we conducted a retrospective study to evaluate clinical outcomes in nmGC patients treated at four high-volume academic institutions.
Methods: California Cancer Registry data were collected for nmGC patients who underwent gastrectomy with curative intent from 2010 to 2018. We conducted chart reviews of the patients' electronic health records to validate clinical factors and outcomes. We performed multivariable Cox regressions to determine prognostic factors for outcomes.
Results: Demographics of study cohort (n=326): mean age 66 years; 64% male; 44% Caucasian, 35% Asian, 16% Latino. Tumor stage: 48% loco-regional (pT4 or pN1+) vs. 52% localized (pT1-3, pN0). Histology: 47% intestinal, 30% diffuse, 8% mixed, 15% unknown. Surgery: 34% open gastrectomy, 48% laparoscopic, 18% unknown; number of recovered lymph nodes varied from 0 to 60 in any tumor stage. Chemotherapy: 20% neoadjuvant alone, 25% adjuvant alone, 16% perioperative, 39% none. Multimodality therapy: 44% surgery only, 31% chemotherapy, 25% chemotherapy and radiation. With a median post-surgical follow-up of 6 years, 24% of patients developed recurrence and 40% had died. Compared to open surgery, laparoscopic surgeries were associated with fewer recovered lymph nodes (mean =18 vs. 25, P=0.0042). Fewer recovered lymph nodes were associated with a significant decrease in 5-year overall survival [hazard ratio (HR) =1.9, 95% confidence interval (CI): 1.3-2.8]. Timing of chemotherapy and addition of radiation therapy to chemotherapy did not confer further improvements in survival; in contrast, greater lymph node recovery plus chemotherapy were associated with a significant increase in survival (HR =0.3, 95% CI: 0.1-0.6).
Conclusions: This study highlights major practice differences in the management of nmGC patients across providers and institutions. Further efforts should be made to standardize the use of chemotherapy and adequate recovery and assessment of lymph nodes in this patient population.

PMID: 33209490 [PubMed]

Ultrasonographic cystometry for neurogenic bladder using elastography.

Neurourol Urodyn. 2020 Nov 16;:

Authors: Do MT, Kim K, Kim L, Im YJ, Choi YH, Park K

Abstract
AIM: Ultrasound shear wave elastography (SWE) has been used to measure elasticity (Young's modulus: YM) in solid organs. It was reported to show a better correlation with intravesical pressure (Pves) than with compliance, supporting its potential use in noninvasive cystometry. Contrariwise, conceptually, YM should be more correlated with compliance than with Pves. To optimize the potential use of YM as a noninvasive urodynamic study, the relationship between YM, Pves, and compliance was reassessed in this study.
METHOD: YM was serially measured using SWE along with bladder filling. To overcome problems inherent to current compliance measurements, modified dynamic compliance was developed from cystometry by a locally weighted scatter plot smoothing algorithm. Then it was matched with YM from SWE. YM was also correlated with Pves. Furthermore, to understand the nature of YM, which was measured by ultrasound, the bladder wall's modulus, which was the mathematical assessment of YM derived from cystometric data, was also calculated and compared.
RESULTS: Thirty-two neurogenic bladder patients were included in this study. YM correlated with Pves (r = .72, p < .0001) better than with modified dynamic compliance (r = -0.43, p < .0001). The correlation of YM with Pves was even higher than that with the calculated bladder wall's modulus (r = .52, p < .0001).
CONCLUSION: YM measured by SWE associates with Pves better than with compliance, confirming the results of previous studies. SWE reflects the integration of both the holding capability of the bladder wall and urine rather than either of one, implying its potential utilization in noninvasive cystometry.

PMID: 33197068 [PubMed - as supplied by publisher]

The cost of opioid use disorder and the value of aversion.

Drug Alcohol Depend. 2020 Oct 26;:108382

Authors: Murphy SM

Abstract
BACKGROUND: The objective of this study was twofold. First, to update and estimate the economic burden of opioid use disorder (OUD) to the U.S. from the perspectives of the healthcare sector, taxpayer, and society, overall and by age. Second, to estimate the mean present value of averting an OUD, overall and by age, for use in economic evaluations of prevention-focused interventions.
METHODS: This was a retrospective secondary analysis using 2018 data from the National Survey on Drug Use and Health, and the CDC WONDER Database on all U.S. persons, at least 12 years old, with an OUD, or who died of opioid overdose. Total OUD-related costs were estimated according to age and stakeholder perspective. Mean costs weighted by insurance type and the probability of mortality were estimated for each age, then used to estimate the mean present value of OUD aversion according to age and stakeholder perspective.
RESULTS: The total annual OUD-related costs to the U.S. in 2018 were $786.8 billion to society, $93 billion to taxpayers, and $89.1 billion to the healthcare sector. The mean present value of averting an OUD, across all ages, was $2.2 million, $325,125, and $244,030 from the societal, taxpayer, and healthcare sector perspectives, respectively.
CONCLUSIONS AND RELEVANCE: The age-specific values of averting an OUD allow for more robust and targeted economic evaluations of competing interventions to reduce the burden of opioids on multiple stakeholders. The rise in the annual OUD-related cost largely reflects the increase in overdose deaths attributable to synthetic opioids (e.g., fentanyl).

PMID: 33183909 [PubMed - as supplied by publisher]