UW Neurological Surgery Recent PubMed Publications

A Consensus-Based Management Protocol For The Treatment Of Severe Traumatic Brain Injury Based On Imaging And Clinical Examination For Use When Intracranial Pressure Monitoring Is Not Employed.

J Neurotrauma. 2020 Feb 04;:

Authors: Chesnut R, Temkin N, Videtta W, Petroni G, Lujan S, Pridgeon J, Dikmen S, Chaddock K, Barber J, Machamer J, Guadagnoli N, Hendrickson P, Aguilera S, Alanis V, Bello Quezada ME, Bautista Coronel E, Bustamante LA, Cacciatroi A, Carricondo CJ, Carvajal F, Davila R, Dominguez M, Figueroa JA, Fillipi MM, Godoy D, Gomez DC, Lacerda Gallardo AJ, Guerra Garcia JA, Zerain GF, Lavendez Cuientas LA, Lequipe C, Grajales Yuca GV, Jibaja Vega M, Kessler ME, Lopez Delgado HJ, Sandi Lora F, Mazzola AM, Maldonado RM, Mezquia de Pedro N, Martinez Zubieta JR, Mijangos Mendez JC, Mora J, Ochoa Parra JM, Pahnke PB, Paranhos J, Pinero G, Rivadeneira Pilacuán FA, Mendez Rivera MN, Romero Figueroa RL, Rubiano A, Saraguro Orozco AM, Silesky Jiménez JI, Silva Naranjo LV, Soler Morejon C, Urbina Z

Abstract
Globally, intracranial pressure (ICP) monitoring use in severe traumatic brain injury (sTBI) is inconsistent and susceptible to resource limitations and clinical philosophies. For situations without monitoring, there is no published comprehensive management algorithm specific to identifying and treating suspected intracranial hypertension (SICH) outside of the one ad hoc protocol in the BEST TRIP trial. As part of an ongoing NIH-supported project, a consensus conference involving 43 experienced Latin American Intensivists and Neurosurgeons who routinely care for sTBI patients without ICP monitoring, refined, revised, and augmented the original BEST TRIP algorithm. Based on BEST TRIP trial data and pre-meeting polling, 11 issues were target for development. We used Delphi-based methodology to codify individual statements and the final algorithm, using a group agreement threshold of 80%. The resulting algorithm defines SICH and addresses both general management and specific treatment. SICH treatment modalities are organized into tiers to guide treatment escalation and tapering. Treatment schedules were developed to facilitate targeted management of disease severity. A decision-support model, based on the group's combined practices, is provided to guide this process. This algorithm provides the first comprehensive management algorithm for treating sTBI patients when ICP monitoring is not available. It is intended to provide a framework to guide clinical care and direct future research toward sTBI management. Due to the dearth of relevant literature, it is explicitly consensus based, and is provided solely as a resource (a "consensus-based curbside consult") to assist in treating sTBI in general intensive care units in resource-limited environments.

PMID: 32013721 [PubMed - as supplied by publisher]

Adoption of coronary artery disease - Reporting and Data System (CAD-RADS™) and observed impact on medical therapy and systolic blood pressure control.

J Cardiovasc Comput Tomogr. 2020 Sep - Oct;14(5):421-427

Authors: Hull RA, Berger JM, Boster JM, Williams MU, Sharp AJ, Fentanes E, Maroules CD, Cury RC, Thomas DM

Abstract
BACKGROUND: CAD-RADS was developed to standardize communication of per-patient maximal stenosis on coronary CT angiography (CCTA) and provide treatment recommendations and may impact primary prevention care and resource utilization. The authors sought to evaluate CAD-RADS adoption on preventive medical therapy and risk factor control amongst a mixed provider population.
METHODS: Statins, aspirin (ASA), systolic blood pressure and, when available, lipid panel changes were abstracted for 1796 total patients undergoing CCTA in the 12 months before (non-standard reporting, NSR, cohort) and after adoption of the CAD-RADS reporting template. Only initiation of a medication in a treatment naïve patient, escalation from baseline dose, or transition to a higher potency was considered an escalation/initiation in lipid therapy.
RESULTS: The CAD-RADS reporting template was utilized in 83.7% (751/897) of CCTAs after the CAD-RADS adoption period. After adjusting for any coronary artery disease (CAD) on CCTA, statin initiation/escalation was more commonly observed in the CAD-RADS cohort (aOR 1.46; 95%CI 1.12-1.90, p = 0.005), driven by higher rates of new statin initiation (aOR 1.79; 95%CI 1.23-2.58, p = 0.002). This resulted in a higher observed rates of total cholesterol improvement in the CAD-RADS cohort (58% vs 49%, p = 0.016). New ASA initiation was similar between reporting templates after adjustment for CAD on CCTA (aOR 1.40; 95%CI 0.97-2.02, p = 0.069). The ordering provider's specialty (cardiology vs non-cardiology) did not significantly impact the observed differences in initiation/escalation of statins and ASA (pinteraction = NS).
CONCLUSIONS: Adoption of CAD-RADS reporting was associated with increased utilization of preventive medications, regardless of ordering provider specialty.

PMID: 32005447 [PubMed - indexed for MEDLINE]

Clinical Perspectives on Headache after Traumatic Brain Injury.

PM R. 2020 Jan 31;:

Authors: Hoffman JM, Lucas S, Dikmen S, Temkin N

Abstract
INTRODUCTION: Headache after traumatic brain injury (TBI) is frequent and persistent over the first year after injury. Providers may need to focus on different symptoms presentations depending on their patient's TBI severity.
OBJECTIVE: We evaluated headache symptoms in those with moderate-to-severe TBI compared to those with mild TBI and examined our data from two perspectives: 1) from providers who treat individuals after TBI and manage multiple post-injury symptoms including headache, and 2) from headache specialists who see individuals after TBI to manage headache.
DESIGN: Prospective enrollment of individuals after TBI with telephone follow up at one-year post-injury.
SETTING: Enrollment from hospital then community follow up.
PARTICIPANTS: 346 individuals with moderate-to-severe TBI were enrolled during acute inpatient rehabilitation across seven TBI Model System Centers. 189 individuals with mild TBI were enrolled within one week of injury at a single center.
INTERVENTION: None.
MAIN OUTCOME MEASURE: Headache frequency, headache type, pain intensity, headache impact test-6 item (HIT-6), and depressive symptoms measured one year after injury.
RESULTS: Headache prevalence is high in both TBI groups. TBI Providers are more likely to evaluate and treat headache from individuals sustaining a mild TBI vs moderate-to-severe TBI. Those with mild TBI are most likely to report tension-type headache followed by migraine-type headache. The migraine-type headache has higher impact (HIT-6) and greater pain intensity. Headache specialists may encounter those with moderate-to-severe TBI who report more frequent headache and higher average pain scores compared to those with mild TBI. The severity of TBI was unrelated to depressive symptoms one year after injury, but those with headache were significantly more likely to have higher scores.
CONCLUSIONS: TBI Providers vs headache specialists should be aware of differences in patient symptom presentation to their respective clinics. Ongoing assessment of headache and depression over time is important following TBI of any severity. This article is protected by copyright. All rights reserved.

PMID: 32003524 [PubMed - as supplied by publisher]

cIMPACT-NOW update 5: recommended grading criteria and terminologies for IDH-mutant astrocytomas.

Acta Neuropathol. 2020 Jan 29;:

Authors: Brat DJ, Aldape K, Colman H, Figrarella-Branger D, Fuller GN, Giannini C, Holland EC, Jenkins RB, Kleinschmidt-DeMasters B, Komori T, Kros JM, Louis DN, McLean C, Perry A, Reifenberger G, Sarkar C, Stupp R, van den Bent MJ, von Deimling A, Weller M

PMID: 31996992 [PubMed - as supplied by publisher]

Stereotactic body radiotherapy for benign spinal tumors: Meningiomas, schwannomas, and neurofibromas.

J Radiosurg SBRT. 2019;6(3):167-177

Authors: Hwang L, Okoye CC, Patel RB, Sahgal A, Foote M, Redmond KJ, Hofstetter C, Saigal R, Mossa-Basha M, Yuh W, Mayr NA, Chao ST, Chang EL, Lo SS

Abstract
Stereotactic body radiation therapy (SBRT) is a relatively new technology, and its use among patients with benign spinal tumors has limited prospective data. Similar to intracranial benign tumors treated successfully with SBRT, benign spinal tumors of the same histology can also develop, and SBRT may be an effective treatment alternative in inoperable or recurrent cases. Outcomes in patients with neurofibromatosis type 1, neurofibromatosis type 2, or schwannomatosis treated with SBRT have also been reported. Single institution reports have shown local control rates over 90% and improvement in clinical symptoms. The optimum dose and fractionation to maximize local control and minimize toxicity is unknown, with few incidences of radiation treatment-related toxicities. Given the location and benign nature of these tumors, careful management of dose to critical organs is essential. With continued follow-up, the optimum use of SBRT in patients with benign spinal tumors can be better defined.

PMID: 31998537 [PubMed]

Benign harbinger of portal venous gas and pneumatosis intestinalis.

ANZ J Surg. 2020 Jan 28;:

Authors: Wheatley L, Williams M, Swinson B, Crawley-Smith T

PMID: 31994306 [PubMed - as supplied by publisher]

Identification of a human skin commensal bacterium that selectively kills Cutibacterium acnes.

J Invest Dermatol. 2020 Jan 22;:

Authors: O'Neill AM, Nakatsuji T, Hayachi A, Williams MR, Mills RH, Gonzalez DJ, Gallo RL

Abstract
The microbiome represents a vast resource for drug discovery as its members engage in constant conflict to outcompete one another by deploying diverse strategies for survival. Cutibacterium acnes (C. acnes) is one of the most common bacterial species on human skin and can promote the common disease acne vulgaris. By employing a combined strategy of functional screening, genetics and proteomics we discovered a strain of Staphylococcus capitis (S. capitis E12) that selectively inhibited growth of C. acnes with potency greater than antibiotics commonly used in the treatment of acne. Antimicrobial peptides secreted from S. capitis E12 were identified as four distinct phenol soluble modulins acting synergistically. These peptides were not toxic to human keratinocytes and the S. capitis extract did not kill other commensal skin bacteria but was effective against C. acnes on pig skin and on mice. Overall, these data show how a member of the human skin microbiome can be useful as a biotherapy for acne vulgaris.

PMID: 31981578 [PubMed - as supplied by publisher]

Routine Assessment of Symptoms of Substance Use Disorders in Primary Care: Prevalence and Severity of Reported Symptoms.

J Gen Intern Med. 2020 Jan 23;:

Authors: Sayre M, Lapham GT, Lee AK, Oliver M, Bobb JF, Caldeiro RM, Bradley KA

Abstract
BACKGROUND: Most patients with substance use disorders (SUDs) never receive treatment and SUDs are under-recognized in primary care (PC) where patients can be treated or linked to treatment. Asking PC patients to directly report SUD symptoms on questionnaires might help identify SUDs but to our knowledge, this approach is previously untested.
OBJECTIVE: To describe the prevalence and severity of DSM-5 SUD symptoms reported by PC patients as part of routine care.
DESIGN: Cross-sectional study using secondary data.
PARTICIPANTS: A total of 241,265 adult patients who visited one of 25 PC sites in an integrated health system in Washington state and had alcohol, cannabis, or other drug use screening documented in their EHRs (March 2015-July 2018) were included in main analyses if they had a positive screen for high-risk substance use defined as AUDIT-C score 7-12 points, or report of past-year daily cannabis use or any other drug use.
MAIN MEASURES: The main outcome was number of SUD symptoms based on Diagnostic and Statistical Manual, 5th edition (DSM-5), reported on Symptom Checklists (0-11) for alcohol or other drugs: 2-3 mild; 4-5 moderate; 6-11 severe.
RESULTS: Of screened patients, 16,776 (5.7%) reported high-risk use of alcohol (2.4%), cannabis (3.9%), and/or other drugs (1.7%), and 65.0-69.9% of those completed Symptom Checklists. Of those with high-risk alcohol use, 52.5% (95% CI 50.9-54.0%) reported ≥ 2 symptoms consistent with mild-severe alcohol use disorders. Of those reporting daily cannabis use, 29.8% (28.6-30.9%) reported ≥ 2 symptoms consistent with mild-severe SUDs. Of those reporting any other drug use, 37.5% (35.7-39.3%) reported ≥ 2 symptoms consistent with mild-severe SUDs.
CONCLUSIONS AND RELEVANCE: Many PC patients who screened positive for high-risk substance use reported symptoms consistent with DSM-5 SUDs on self-report Symptom Checklists. Use of SUD Symptom Checklists could support PC providers in making SUD diagnoses and initiating discussions of substance use.

PMID: 31974903 [PubMed - as supplied by publisher]

Sex Differences in Misperceptions of Sexual Interest Can Be Explained by Sociosexual Orientation and Men Projecting Their Own Interest Onto Women.

Psychol Sci. 2020 02;31(2):184-192

Authors: Lee AJ, Sidari MJ, Murphy SC, Sherlock JM, Zietsch BP

Abstract
Sex differences in misperceptions of sexual interest have been well documented; however, it is unclear whether this cognitive bias could be explained by other factors. In the current study, 1,226 participants (586 men, 640 women) participated in a speed-dating task in which they rated their sexual interest in each other as well as the sexual interest they perceived from their partners. Consistent with previous findings, results showed that men tended to overperceive sexual interest from their partners, whereas women tended to underperceive sexual interest. However, this sex difference became negligible when we considered potential mediators, such as the raters' sociosexual orientation and raters' tendency to project their own levels of sexual interest onto their partners. These findings challenge the popular notion that sex differences in misperceptions of sexual interest have evolved as a specialized adaptation to different selection pressures in men and women.

PMID: 31971873 [PubMed - indexed for MEDLINE]

Transcutaneous contrast-enhanced ultrasound imaging of the posttraumatic spinal cord.

Spinal Cord. 2020 Jan 21;:

Authors: Khaing ZZ, Cates LN, Hyde JE, Hammond R, Bruce M, Hofstetter CP

Abstract
STUDY DESIGN: Experimental animal study.
OBJECTIVE: The current study aims to test whether the blood flow within the contused spinal cord can be assessed in a rodent model via the acoustic window of the laminectomy utilizing transcutaneous ultrasound.
SETTING: Department of Neurological Surgery, University of Washington, Seattle WA.
METHODS: Long-Evans rats (n = 12) were subjected to a traumatic thoracic spinal cord injury (SCI). Three days and 10 weeks after injury, animals underwent imaging of the contused spinal cord using ultrafast contrast-enhanced ultrasound with a Vantage ultrasound research system in combination with a 15 MHz transducer. Lesion size and signal-to-noise ratios were estimated via transcutaneous, subcutaneous, or epidural ultrasound acquisition through the acoustic window created by the original laminectomy.
RESULTS: Following laminectomy, transcutaneous and subcutaneous contrast-enhanced ultrasound imaging allowed for assessment of perfusion and vascular flow in the contused rodent spinal cord. An average loss of 7.2 dB from transcutaneous to subcutaneous and the loss of 5.1 dB from subcutaneous to epidural imaging in signal-to-noise ratio (SNR) was observed. The hypoperfused injury center was measured transcutaneously, subcutaneously and epidurally (5.78 ± 0.86, 5.91 ± 0.53, 5.65 ± 1.07 mm2) at 3 days post injury. The same animals were reimaged again at 10 weeks following SCI, and the area of hypoperfusion had decreased significantly compared with the 3-day measurements detected via transcutaneous, subcutaneous, and epidural imaging respectively (0.69 ± 0.05, 1.09 ± 0.11, 0.95 ± 0.11 mm2, p < 0.001).
CONCLUSIONS: Transcutaneous ultrasound allows for measurements and longitudinal monitoring of local hemodynamic changes in a rodent SCI model.

PMID: 31965060 [PubMed - as supplied by publisher]

A management algorithm for adult patients with both brain oxygen and intracranial pressure monitoring: the Seattle International Severe Traumatic Brain Injury Consensus Conference (SIBICC).

Intensive Care Med. 2020 Jan 21;:

Authors: Chesnut R, Aguilera S, Buki A, Bulger E, Citerio G, Cooper DJ, Arrastia RD, Diringer M, Figaji A, Gao G, Geocadin R, Ghajar J, Harris O, Hoffer A, Hutchinson P, Joseph M, Kitagawa R, Manley G, Mayer S, Menon DK, Meyfroidt G, Michael DB, Oddo M, Okonkwo D, Patel M, Robertson C, Rosenfeld JV, Rubiano AM, Sahuquillo J, Servadei F, Shutter L, Stein D, Stocchetti N, Taccone FS, Timmons S, Tsai E, Ullman JS, Vespa P, Videtta W, Wright DW, Zammit C, Hawryluk GWJ

Abstract
BACKGROUND: Current guidelines for the treatment of adult severe traumatic brain injury (sTBI) consist of high-quality evidence reports, but they are no longer accompanied by management protocols, as these require expert opinion to bridge the gap between published evidence and patient care. We aimed to establish a modern sTBI protocol for adult patients with both intracranial pressure (ICP) and brain oxygen monitors in place.
METHODS: Our consensus working group consisted of 42 experienced and actively practicing sTBI opinion leaders from six continents. Having previously established a protocol for the treatment of patients with ICP monitoring alone, we addressed patients who have a brain oxygen monitor in addition to an ICP monitor. The management protocols were developed through a Delphi-method-based consensus approach and were finalized at an in-person meeting.
RESULTS: We established three distinct treatment protocols, each with three tiers whereby higher tiers involve therapies with higher risk. One protocol addresses the management of ICP elevation when brain oxygenation is normal. A second addresses management of brain hypoxia with normal ICP. The third protocol addresses the situation when both intracranial hypertension and brain hypoxia are present. The panel considered issues pertaining to blood transfusion and ventilator management when designing the different algorithms.
CONCLUSIONS: These protocols are intended to assist clinicians in the management of patients with both ICP and brain oxygen monitors but they do not reflect either a standard-of-care or a substitute for thoughtful individualized management. These protocols should be used in conjunction with recommendations for basic care, management of critical neuroworsening and weaning treatment recently published in conjunction with the Seattle International Brain Injury Consensus Conference.

PMID: 31965267 [PubMed - as supplied by publisher]

Crowdsourcing in health and medical research: a systematic review.

Infect Dis Poverty. 2020 Jan 20;9(1):8

Authors: Wang C, Han L, Stein G, Day S, Bien-Gund C, Mathews A, Ong JJ, Zhao PZ, Wei SF, Walker J, Chou R, Lee A, Chen A, Bayus B, Tucker JD

Abstract
BACKGROUND: Crowdsourcing is used increasingly in health and medical research. Crowdsourcing is the process of aggregating crowd wisdom to solve a problem. The purpose of this systematic review is to summarize quantitative evidence on crowdsourcing to improve health.
METHODS: We followed Cochrane systematic review guidance and systematically searched seven databases up to September 4th 2019. Studies were included if they reported on crowdsourcing and related to health or medicine. Studies were excluded if recruitment was the only use of crowdsourcing. We determined the level of evidence associated with review findings using the GRADE approach.
RESULTS: We screened 3508 citations, accessed 362 articles, and included 188 studies. Ninety-six studies examined effectiveness, 127 examined feasibility, and 37 examined cost. The most common purposes were to evaluate surgical skills (17 studies), to create sexual health messages (seven studies), and to provide layperson cardio-pulmonary resuscitation (CPR) out-of-hospital (six studies). Seventeen observational studies used crowdsourcing to evaluate surgical skills, finding that crowdsourcing evaluation was as effective as expert evaluation (low quality). Four studies used a challenge contest to solicit human immunodeficiency virus (HIV) testing promotion materials and increase HIV testing rates (moderate quality), and two of the four studies found this approach saved money. Three studies suggested that an interactive technology system increased rates of layperson initiated CPR out-of-hospital (moderate quality). However, studies analyzing crowdsourcing to evaluate surgical skills and layperson-initiated CPR were only from high-income countries. Five studies examined crowdsourcing to inform artificial intelligence projects, most often related to annotation of medical data. Crowdsourcing was evaluated using different outcomes, limiting the extent to which studies could be pooled.
CONCLUSIONS: Crowdsourcing has been used to improve health in many settings. Although crowdsourcing is effective at improving behavioral outcomes, more research is needed to understand effects on clinical outcomes and costs. More research is needed on crowdsourcing as a tool to develop artificial intelligence systems in medicine.
TRIAL REGISTRATION: PROSPERO: CRD42017052835. December 27, 2016.

PMID: 31959234 [PubMed - indexed for MEDLINE]

Frailty in Elderly Patients Undergoing Cardiac Surgery Increases Hospital Stay and 12-Month Readmission Rate.

Heart Lung Circ. 2019 Dec 05;:

Authors: Lal S, Gray A, Kim E, Bunton RW, Davis P, Galvin IF, Williams MJA

Abstract
BACKGROUND: Cardiac surgery risk scoring systems predict operative mortality but not outcomes related to preoperative frailty. The aim of this study was to assess frailty in a cohort of older cardiac surgery patients as a predictor of postoperative outcomes.
METHODS: Prospective data was collected on patients 65 years of age and older undergoing cardiac surgery between September 2015 and October 2016 at Dunedin Hospital. Frailty was assessed with the Edmonton frail scale and five-metre gait speed. The primary endpoint was length of hospital stay. Secondary outcomes included postoperative complications, major adverse events, death and 12-month readmission rate.
RESULTS: Among the 96 patients, median age was 74 (interquartile range 10.5) and 65 (68%) were males. Of the sample 64 (67%) were scored as not frail, 22 (23%) as vulnerable, and 10 (10%) as frail. The median (interquartile range) postoperative days' stay were: not frail 6 (2), vulnerable 9.5 (8), and frail 15 (13). Survival analysis adjusting for EuroSCORE II, age, sex and surgery type showed that greater Edmonton frail scale scores were independently predictive of longer post-surgery hospital stay with a hazard ratio for discharge of 0.83 (95% confidence interval 0.76-0.91, p<0.001) per point. The Edmonton frail scale score was associated with the 12-month post discharge number of readmissions (adjusted incidence rate ratio 1.24 (95% confidence interval 1.13-1.37, p<0.001) per point.
CONCLUSIONS: The Edmonton frail scale score predicts length of hospital stay post cardiac surgery and 12-month readmission rate in patients older than 65 years of age.

PMID: 31959552 [PubMed - as supplied by publisher]

IMPACT and CRASH prognostic models for traumatic brain injury: external validation in a South-American cohort.

Inj Prev. 2020 Jan 20;:

Authors: Wongchareon K, Thompson HJ, Mitchell PH, Barber J, Temkin N

Abstract
OBJECTIVE: To develop a robust prognostic model, the more diverse the settings in which the system is tested and found to be accurate, the more likely it will be generalisable to untested settings. This study aimed to externally validate the International Mission for Prognosis and Clinical Trials in Traumatic Brain Injury (IMPACT) and Corticosteroid Randomization after Significant Head Injury (CRASH) models for low-income and middle-income countries using a dataset of patients with severe traumatic brain injury (TBI) from the Benchmark Evidence from South American Trials: Treatment of Intracranial Pressure study and a simultaneously conducted observational study.
METHOD: A total of 550 patients with severe TBI were enrolled in the study, and 466 of those were included in the analysis. Patient admission characteristics were extracted to predict unfavourable outcome (Glasgow Outcome Scale: GOS<3) and mortality (GOS 1) at 14 days or 6 months.
RESULTS: There were 48% of the participants who had unfavourable outcome at 6 months and these included 38% who had died. The area under the receiver operating characteristic curve (AUC) values were 0.683-0.775 and 0.640-0.731 for the IMPACT and CRASH models respectively. The IMPACT CT model had the highest AUC for predicting unfavourable outcomes, and the IMPACT Lab model had the best discrimination for predicting 6-month mortality. The discrimination for both the IMPACT and CRASH models improved with increasing complexity of the models. Calibration revealed that there were disagreement between observed and predicted outcomes in the IMPACT and CRASH models.
CONCLUSION: The overall performance of all IMPACT and CRASH models was adequate when used to predict outcomes in the dataset. However, some disagreement in calibration suggests the necessity for updating prognostic models to maintain currency and generalisability.

PMID: 31959626 [PubMed - as supplied by publisher]

Development of a System for Postmarketing Population Pharmacokinetic and Pharmacodynamic Studies Using Real-World Data From Electronic Health Records.

Clin Pharmacol Ther. 2020 04;107(4):934-943

Authors: Choi L, Beck C, McNeer E, Weeks HL, Williams ML, James NT, Niu X, Abou-Khalil BW, Birdwell KA, Roden DM, Stein CM, Bejan CA, Denny JC, Van Driest SL

Abstract
Postmarketing population pharmacokinetic (PK) and pharmacodynamic (PD) studies can be useful to capture patient characteristics affecting PK or PD in real-world settings. These studies require longitudinally measured dose, outcomes, and covariates in large numbers of patients; however, prospective data collection is cost-prohibitive. Electronic health records (EHRs) can be an excellent source for such data, but there are challenges, including accurate ascertainment of drug dose. We developed a standardized system to prepare datasets from EHRs for population PK/PD studies. Our system handles a variety of tasks involving data extraction from clinical text using a natural language processing algorithm, data processing, and data building. Applying this system, we performed a fentanyl population PK analysis, resulting in comparable parameter estimates to a prior study. This new system makes the EHR data extraction and preparation process more efficient and accurate and provides a powerful tool to facilitate postmarketing population PK/PD studies using information available in EHRs.

PMID: 31957870 [PubMed - indexed for MEDLINE]

A Risk Score Including Carotid Plaque Inflammation and Stenosis Severity Improves Identification of Recurrent Stroke.

Stroke. 2020 03;51(3):838-845

Authors: Kelly PJ, Camps-Renom P, Giannotti N, Martí-Fàbregas J, McNulty JP, Baron JC, Barry M, Coutts SB, Cronin S, Delgado-Mederos R, Dolan E, Fernández-León A, Foley S, Harbison J, Horgan G, Kavanagh E, Marnane M, McCabe J, McDonnell C, Sharma VK, Williams DJ, O'Connell M, Murphy S

Abstract
Background and Purpose- In randomized trials of symptomatic carotid endarterectomy, only modest benefit occurred in patients with moderate stenosis and important subgroups experienced no benefit. Carotid plaque 18F-fluorodeoxyglucose uptake on positron emission tomography, reflecting inflammation, independently predicts recurrent stroke. We investigated if a risk score combining stenosis and plaque 18F-fluorodeoxyglucose would improve the identification of early recurrent stroke. Methods- We derived the score in a prospective cohort study of recent (<30 days) non-severe (modified Rankin Scale score ≤3) stroke/transient ischemic attack. We derived the SCAIL (symptomatic carotid atheroma inflammation lumen-stenosis) score (range, 0-5) including 18F-fluorodeoxyglucose standardized uptake values (SUVmax <2 g/mL, 0 points; SUVmax 2-2.99 g/mL, 1 point; SUVmax 3-3.99 g/mL, 2 points; SUVmax ≥4 g/mL, 3 points) and stenosis (<50%, 0 points; 50%-69%, 1 point; ≥70%, 2 points). We validated the score in an independent pooled cohort of 2 studies. In the pooled cohorts, we investigated the SCAIL score to discriminate recurrent stroke after the index stroke/transient ischemic attack, after positron emission tomography-imaging, and in mild or moderate stenosis. Results- In the derivation cohort (109 patients), recurrent stroke risk increased with increasing SCAIL score (P=0.002, C statistic 0.71 [95% CI, 0.56-0.86]). The adjusted (age, sex, smoking, hypertension, diabetes mellitus, antiplatelets, and statins) hazard ratio per 1-point SCAIL increase was 2.4 (95% CI, 1.2-4.5, P=0.01). Findings were confirmed in the validation cohort (87 patients, adjusted hazard ratio, 2.9 [95% CI, 1.9-5], P<0.001; C statistic 0.77 [95% CI, 0.67-0.87]). The SCAIL score independently predicted recurrent stroke after positron emission tomography-imaging (adjusted hazard ratio, 4.52 [95% CI, 1.58-12.93], P=0.005). Compared with stenosis severity (C statistic, 0.63 [95% CI, 0.46-0.80]), prediction of post-positron emission tomography stroke recurrence was improved with the SCAIL score (C statistic, 0.82 [95% CI, 0.66-0.97], P=0.04). Findings were confirmed in mild or moderate stenosis (adjusted hazard ratio, 2.74 [95% CI, 1.39-5.39], P=0.004). Conclusions- The SCAIL score improved the identification of early recurrent stroke. Randomized trials are needed to test if a combined stenosis-inflammation strategy improves selection for carotid revascularization where benefit is currently uncertain.

PMID: 31948355 [PubMed - indexed for MEDLINE]

medExtractR: A targeted, customizable approach to medication extraction from electronic health records.

J Am Med Inform Assoc. 2020 03 01;27(3):407-418

Authors: Weeks HL, Beck C, McNeer E, Williams ML, Bejan CA, Denny JC, Choi L

Abstract
OBJECTIVE: We developed medExtractR, a natural language processing system to extract medication information from clinical notes. Using a targeted approach, medExtractR focuses on individual drugs to facilitate creation of medication-specific research datasets from electronic health records.
MATERIALS AND METHODS: Written using the R programming language, medExtractR combines lexicon dictionaries and regular expressions to identify relevant medication entities (eg, drug name, strength, frequency). MedExtractR was developed on notes from Vanderbilt University Medical Center, using medications prescribed with varying complexity. We evaluated medExtractR and compared it with 3 existing systems: MedEx, MedXN, and CLAMP (Clinical Language Annotation, Modeling, and Processing). We also demonstrated how medExtractR can be easily tuned for better performance on an outside dataset using the MIMIC-III (Medical Information Mart for Intensive Care III) database.
RESULTS: On 50 test notes per development drug and 110 test notes for an additional drug, medExtractR achieved high overall performance (F-measures >0.95), exceeding performance of the 3 existing systems across all drugs. MedExtractR achieved the highest F-measure for each individual entity, except drug name and dose amount for allopurinol. With tuning and customization, medExtractR achieved F-measures >0.90 in the MIMIC-III dataset.
DISCUSSION: The medExtractR system successfully extracted entities for medications of interest. High performance in entity-level extraction provides a strong foundation for developing robust research datasets for pharmacological research. When working with new datasets, medExtractR should be tuned on a small sample of notes before being broadly applied.
CONCLUSIONS: The medExtractR system achieved high performance extracting specific medications from clinical text, leading to higher-quality research datasets for drug-related studies than some existing general-purpose medication extraction tools.

PMID: 31943012 [PubMed - indexed for MEDLINE]

Use of Amitriptyline in the Treatment of Headache After Traumatic Brain Injury: Lessons Learned From a Clinical Trial.

Headache. 2020 Jan 13;:

Authors: Hurwitz M, Lucas S, Bell KR, Temkin N, Dikmen S, Hoffman J

Abstract
OBJECTIVES: The primary outcome of this study was to assess the efficacy and safety of preventive treatment with amitriptyline on headache frequency and severity after mild traumatic brain injury (mTBI).
BACKGROUND: Despite the fact that headache is the most common and persistent physical symptom after TBI, there has been little research on the longitudinal course or pharmacologic treatment of this disorder. Of those who have headache after injury, about 60% continue to complain of headache at 3 months post injury, with higher levels of disability than those without headache. There have been no prospective, randomized, controlled trials of a pharmacologic agent for headache after TBI. Additionally, a brain-injured population may be more susceptible to side effects of medication.
DESIGN: This is a single-center phase II trial of amitriptyline to prevent persistent headache after an mTBI. Medication dose was gradually increased from 10 to 50 mg daily.
RESULTS: Fifty participants were enrolled and 33 who completed the 90-day assessment were included in the final analysis. In order to detect a possible cognitive impact of the study drug, 24 participants were randomly assigned to start amitriptyline immediately after study enrollment and 26 were assigned to start 30 days after enrollment. Forty-nine percent (18/37) of those assigned to take medication took none throughout the study period, with less compliance in younger participants with mean ages of 32.7 in those who did not take any medication, 33.4 who were less than 80% compliant, and 42.3 who were compliant (P = .013). Compliance in keeping a daily headache diary was low, with 29/50 participants (58%) meeting daily entry completion, and only 10 participants maintaining 100% diary completion. No differences were found between those who started medication immediately vs at day 30 in headache frequency or severity.
CONCLUSIONS: While headache is the most common symptom following mTBI, current evidence does not support a specific treatment. No differences were noted in headache frequency compared to our prior study. However, the current sample had significantly lower headache severity (15% vs 36% with pain rating of 6 or above, P = .015) compared to our prior study. Our current study was not able to determine whether there is any benefit for the use of amitriptyline as a headache preventive because of difficulty with study recruitment and compliance. The challenges with recruitment and retention in the mTBI population were instructive, and future research in this area will need to identify strategies to improve recruitment, diary compliance, and medication adherence in this population.

PMID: 31943197 [PubMed - as supplied by publisher]

Editorial: Misclassification of Type 2 Myocardial Infarction: Implications for Value-Based Programs and Quality Metrics.

Cardiovasc Revasc Med. 2020 02;21(2):180-181

Authors: Wasfy JH, Murphy SP

PMID: 31932169 [PubMed - indexed for MEDLINE]

Senescent mesenchymal stem cells remodel extracellular matrix driving breast cancer cells to more invasive phenotype.

J Cell Sci. 2020 Jan 13;:

Authors: Ghosh D, Mejia-Pena C, Quach N, Xuan B, Lee AH, Dawson MR

Abstract
Mesenchymal stem cells accumulated in tissue specific sites are essential for the regenerative process; however, biological aging and environmental stress can induce senescence - an irreversible state of growth arrest - that not only affects the behavior of cells but also disrupts their ability to restore tissue integrity. While abnormal tissue properties including increased extracellular matrix stiffness are linked with the risk of developing breast cancer, the role and contribution of senescent MSCs to the disease progression to malignancy are not well understood. Here, we investigated senescence associated biophysical changes in MSCs and how they influence cancer cell behavior in a 3D matrix interface model. Although senescent MSCs were far less motile than pre-senescent MSCs, they induced an invasive breast cancer phenotype, characterized by increased spheroid growth and cell invasion in collagen gels. Further analysis of collagen gels using second harmonic generation showed increased collagen density when senescent MSCs were present, suggesting that senescent MSCs actively remodel the surrounding matrix. This study provides direct evidence of the pro-malignant effects of senescent MSCs in tumors.

PMID: 31932504 [PubMed - as supplied by publisher]