Publications by authors named "M S Cox"

2,399 Publications

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An informatics consult approach for generating clinical evidence for treatment decisions.

BMC Med Inform Decis Mak 2021 Oct 12;21(1):281. Epub 2021 Oct 12.

Institute of Health Informatics, University College London, London, UK.

Background: An Informatics Consult has been proposed in which clinicians request novel evidence from large scale health data resources, tailored to the treatment of a specific patient. However, the availability of such consultations is lacking. We seek to provide an Informatics Consult for a situation where a treatment indication and contraindication coexist in the same patient, i.e., anti-coagulation use for stroke prevention in a patient with both atrial fibrillation (AF) and liver cirrhosis.

Methods: We examined four sources of evidence for the effect of warfarin on stroke risk or all-cause mortality from: (1) randomised controlled trials (RCTs), (2) meta-analysis of prior observational studies, (3) trial emulation (using population electronic health records (N = 3,854,710) and (4) genetic evidence (Mendelian randomisation). We developed prototype forms to request an Informatics Consult and return of results in electronic health record systems.

Results: We found 0 RCT reports and 0 trials recruiting for patients with AF and cirrhosis. We found broad concordance across the three new sources of evidence we generated. Meta-analysis of prior observational studies showed that warfarin use was associated with lower stroke risk (hazard ratio [HR] = 0.71, CI 0.39-1.29). In a target trial emulation, warfarin was associated with lower all-cause mortality (HR = 0.61, CI 0.49-0.76) and ischaemic stroke (HR = 0.27, CI 0.08-0.91). Mendelian randomisation served as a drug target validation where we found that lower levels of vitamin K1 (warfarin is a vitamin K1 antagonist) are associated with lower stroke risk. A pilot survey with an independent sample of 34 clinicians revealed that 85% of clinicians found information on prognosis useful and that 79% thought that they should have access to the Informatics Consult as a service within their healthcare systems. We identified candidate steps for automation to scale evidence generation and to accelerate the return of results.

Conclusion: We performed a proof-of-concept Informatics Consult for evidence generation, which may inform treatment decisions in situations where there is dearth of randomised trials. Patients are surprised to know that their clinicians are currently not able to learn in clinic from data on 'patients like me'. We identify the key challenges in offering such an Informatics Consult as a service.
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http://dx.doi.org/10.1186/s12911-021-01638-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8506488PMC
October 2021

Literal text analysis of poly-class and polydrug overdose deaths in North Carolina, 2015-2019.

Drug Alcohol Depend 2021 Sep 20;228:109048. Epub 2021 Sep 20.

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, 2101 McGavran-Greenberg Hall, CB #7435, Chapel Hill, NC 27599-7435, United States; Injury Prevention Research Center, University of North Carolina at Chapel Hill, 725 Martin Luther King Jr. Blvd, Chapel Hill, NC 27514, United States.

Background: The literal text on death certificates was leveraged to enhance the examination of trends in the specific drugs and drug combinations involved in North Carolina (NC) overdose deaths from 2015 to 2019.

Methods: Using NC death certificate data, overdose deaths included those with a drug poisoning as the underlying ICD-10 cause-of-death code (n = 10,117). The literal text from three death certificate fields were searched for drug mentions by integrating a tool developed by the Council of State and Territorial Epidemiologists Overdose Subcommittee with search terms originating from a National Center for Health Statistics/Food and Drug Administration collaboration. Descriptive statistics were calculated to evaluate substance classes, specific drugs, and drug combinations most frequently involved in these deaths over time.

Results: From 2015-2019, polydrug involvement in NC overdose deaths increased (71% in 2015 to 75% in 2019). During the study period, opioid involvement shifted from heroin and/or oxycodone in 2015 to predominantly fentanyl in 2019, with fentanyl involvement increasing from 15% to 58%. Psychostimulant involvement increased for both cocaine (2015: 21%, 2019: 35%) and methamphetamine (2015: 3%, 2019: 13%). Benzodiazepine involvement, including alprazolam and clonazepam, declined during the study period, while the involvement of alcohol and antiepileptics/sedative-hypnotics, specifically gabapentin, remained stable. The top polydrug combinations in 2019 were fentanyl + cocaine (15% of all overdose deaths), fentanyl + heroin (10%), fentanyl + cocaine + heroin (6%), and fentanyl + methamphetamine (4%).

Conclusions: Incorporation of literal text methodology into ongoing overdose surveillance can facilitate the identification of specific, emerging drugs and combinations and inform targeted overdose prevention approaches.
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http://dx.doi.org/10.1016/j.drugalcdep.2021.109048DOI Listing
September 2021

Arterial spin labeling as an ancillary assessment to postoperative conventional angiogram in pediatric moyamoya disease.

J Neurosurg Pediatr 2021 Oct 1:1-8. Epub 2021 Oct 1.

8Department of Anesthesiology and Critical Care Medicine, Children's Hospital of Philadelphia, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania.

Objective: Digital subtraction angiography (DSA) is commonly performed after pial synangiosis surgery for pediatric moyamoya disease to assess the degree of neovascularization. However, angiography is invasive, and the risk of ionizing radiation is a concern in children. In this study, the authors aimed to identify whether arterial spin labeling (ASL) can predict postoperative angiogram grading. In addition, they sought to determine whether patients who underwent ASL imaging without DSA had similar postoperative outcomes when compared with patients who received ASL imaging and postoperative DSA.

Methods: The medical records of pediatric patients who underwent pial synangiosis for moyamoya disease at a quaternary children's hospital were reviewed during a 10-year period. ASL-only and ASL+DSA cohorts were analyzed. The frequency of preoperative and postoperative symptoms was analyzed within each cohort. Three neuroradiologists assigned a visual ASL grade for each patient indicating the change from the preoperative to postoperative ASL perfusion sequences. A postoperative neovascularization grade was also assigned for patients who underwent DSA.

Results: Overall, 21 hemispheres of 14 patients with ASL only and 14 hemispheres of 8 patients with ASL+DSA were analyzed. The groups had similar rates of MRI evidence of acute or chronic stroke preoperatively (61.9% in the ASL-only group and 64.3% in the ASL+DSA group). In the entire cohort, transient ischemic attack (TIA) (p = 0.027), TIA composite (TIA or unexplained neurological symptoms; p = 0.0006), chronic headaches (p = 0.035), aphasia (p = 0.019), and weakness (p = 0.001) all had decreased frequency after intervention. The authors found a positive association between revascularization observed on DSA and the visual ASL grading (p = 0.048). The visual ASL grades in patients with an angiogram indicating robust neovascularization demonstrated improved perfusion when compared with the ASL grades of patients with a poor neovascularization.

Conclusions: Noninvasive ASL perfusion imaging had an association with postoperative DSA neoangiogenesis following pial synangiosis surgery in children. There were no significant postoperative stroke differences between the ASL-only and ASL+DSA cohorts. Both cohorts demonstrated significant improvement in preoperative symptoms after surgery. Further study in larger cohorts is necessary to determine whether the results of this study are validated in order to circumvent the invasive catheter angiogram.
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http://dx.doi.org/10.3171/2021.7.PEDS21302DOI Listing
October 2021

Inhibition of Scavenger Receptor Class B Type 1 (SR-B1) Expression and Activity as a Potential Novel Target to Disrupt Cholesterol Availability in Castration-Resistant Prostate Cancer.

Pharmaceutics 2021 Sep 18;13(9). Epub 2021 Sep 18.

Department of Urological Sciences, Faculty of Medicine, University of British Columbia, Vancouver Prostate Centre, Vancouver, BC V6T 1Z3, Canada.

There have been several studies that have linked elevated scavenger receptor class b type 1 (SR-B1) expression and activity to the development and progression of castration-resistant prostate cancer (CRPC). SR-B1 facilitates the influx of cholesterol to the cell from lipoproteins in systemic circulation. This influx of cholesterol may be important for many cellular functions, including the synthesis of androgens. Castration-resistant prostate cancer tumors can synthesize androgens de novo to supplement the loss of exogenous sources often induced by androgen deprivation therapy. Silencing of SR-B1 may impact the ability of prostate cancer cells, particularly those of the castration-resistant state, to maintain the intracellular supply of androgens by removing a supply of cholesterol. SR-B1 expression is elevated in CRPC models and has been linked to poor survival of patients. The overarching belief has been that cholesterol modulation, through either synthesis or uptake inhibition, will impact essential signaling processes, impeding the proliferation of prostate cancer. The reduction in cellular cholesterol availability can impede prostate cancer proliferation through both decreased steroid synthesis and steroid-independent mechanisms, providing a potential therapeutic target for the treatment of prostate cancer. In this article, we discuss and highlight the work on SR-B1 as a potential novel drug target for CRPC management.
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http://dx.doi.org/10.3390/pharmaceutics13091509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467449PMC
September 2021

Intrasinus tPA for Successful Treatment of Extensive Dural Sinus Thrombosis in a Young Patient With COVID-19: Rationale and Protocol.

Neurohospitalist 2021 Oct 21;11(4):382-384. Epub 2021 Apr 21.

Division of Interventional Neuroradiology, Baylor University Medical Center, Dallas, TX, USA.

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http://dx.doi.org/10.1177/19418744211000955DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442149PMC
October 2021
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