Publications by authors named "Joshua D Brown"

92 Publications

Physiologically-based pharmacokinetics modeling to investigate formulation factors influencing the generic substitution of dabigatran etexilate.

CPT Pharmacometrics Syst Pharmacol 2021 Jan 15. Epub 2021 Jan 15.

Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, Florida, USA.

The exposure-response relationship of direct acting oral anti-coagulants (DOACs) for bleeding risk is steep relative to ischemic stroke reduction. As a result, small changes in exposure may lead to bleeding events. The overall goal of this project was to determine the effect of critical formulation parameters on the pharmacokinetics (PKs) and thus safety and efficacy of generic DOACs. In this first installment of our overall finding, we developed and verified a physiologically-based PK (PBPK) model for dabigatran etexilate (DABE) and its metabolites. The model was developed following a middle out approach leveraging available in vitro and in vivo data. External validity of the model was confirmed by overlapping predicted and observed PK profiles for DABE as well as free and total dabigatran for a dataset not used during model development. The verified model was applied to interrogate the impact of modulating the microenvironment pH on DABE systemic exposure. The PBPK exploratory analyses highlighted the high sensitivity of DABE exposure to supersaturation ratio and precipitation kinetics.
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http://dx.doi.org/10.1002/psp4.12589DOI Listing
January 2021

Association between a Deficit Accumulation Frailty Index and Mobility Outcomes in Older Adults: Secondary Analysis of the Lifestyle Interventions and Independence for Elders (LIFE) Study.

J Clin Med 2020 Nov 22;9(11). Epub 2020 Nov 22.

Institute on Aging, University of Florida College of Pharmacy, Gainesville, FL 32610, USA.

Frailty is a geriatric syndrome represented by susceptibility to precipitating health events and reduced functional reserve. Frailty can be difficult to measure in clinical practice and research. One approach to approximate frailty is based on a deficit accumulation approach, which assesses a larger number of less specific measures such as the presence of comorbidities, physical or cognitive assessments, and lab tests, and summarizes these as a frailty index. The objective of this study was to develop such an index using the Lifestyle Interventions and Independence for Elders (LIFE) Study and evaluate the validity of the frailty measure derived based on baseline information via its association with the primary outcomes of the trial, namely major mobility disability (MMD) and persistent MMD (pMMD). Further, this study aimed to evaluate the effectiveness of the physical activity intervention among participants based on their baseline frailty score. Subjects in the LIFE Study were evaluated at baseline for demographics, clinical history, and a battery of physical and cognitive functioning assessments. In total, 75 possible deficits were scored either as present (yes/no) or based on each score's quintiles for score-based assessments. The frailty index was measured as the total sum of deficits divided by the total number of possible deficits on a continuous scale between 0 and 100 (i.e., percent of deficits present). The frailty index was further divided into quintiles for comparison. A proportional hazards model was estimated for the MMD outcome controlling for other baseline information. A data driven approach was also used to determine relevant cut-offs in the frailty index where the trial intervention appeared to be modified. Among 1635 trial participants, the mean frailty index was 30.4 ± 6.6 and normally distributed. Over 2.5 years of average follow-up, 14.6%, 16.5%, 18.6%, 22.6%, and 27.6% of participants experienced MMD in quintiles 1-5, respectively. Each 1-unit increase in the frailty index increased the hazard of MMD by 4% (2-5%), and there was a nearly 2-fold increase in MMD between the highest and lowest frailty quintiles. Using log-rank criteria, a cut-point at the median was identified. Further, iterations tested for a frailty cut-off and indicated a subgroup beyond the 85th percentile wherein the physical activity intervention appeared to be no longer be effective. This internally derived deficit accumulation frailty index was uniquely able to identify individuals at higher risk of MMD and pMMD and showed that along the spectrum of frailty, the physical activity intervention remained effective for the majority of participants.
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http://dx.doi.org/10.3390/jcm9113757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7700674PMC
November 2020

Survey-reported medication changes among older adults during the SARS-CoV-2 (COVID-19) pandemic.

Res Social Adm Pharm 2020 Nov 12. Epub 2020 Nov 12.

Institute on Aging, Division of Epidemiology and Data Science in Gerontology, Department of Aging and Geriatric Research, University of Florida College of Medicine, Gainesville, FL, USA. Electronic address:

Background: Speculation on benefits and harms of prescription, over-the-counter and complementary medications has been widespread during the SARS-CoV-2 (or COVID-19) pandemic. This community-based survey assessed self-reported changes in medications including those stopped, started, or if access had been impacted.

Methods: A survey was collected via Research Electronic Data Capture (REDCap). The survey was advertised in the community through social media, email lists, websites, and post-cards. Survey responses were collected between 5/21/2020 and 6/24/2020. Variables included demographic characteristics such as age, sex, race, marital status, education, employment, income, and community type. Questions related to medication changes included: "Have you started any medication due to COVID-19?", "Have you stopped any medication due to COVID-19?" and "Have you had issues getting your prescription medications?". Respondents aged 50 years or older were included.

Results: There were N = 1397 responses of which 1169 were older adults ≥50 years-old. Of these, 1141 responded to the medication changes survey questions and 28 had missing responses and were excluded from the survey sample for this analysis. Among these, 31 (2.7%) reported a medication change included 5 (0.4%) reported stopping a medication, 18 (1.6%) reported starting a medication, and 8 (0.7%) reported trouble obtaining medications. Medications started included mostly vitamins or other supplements including zinc (n = 9), vitamin C (6), and other supplements (3). Among prescription medications, antidepressants and anti-anxiety medications (4) were reported as well as aspirin (1), losartan (1), and low dose naltrexone (1). One respondent reported unidentified homeopathy. There were no significant differences between those with medication changes and those with none.

Conclusions: In this community-based survey sample of over one thousand older adults, only a small percentage (2.7%; n = 31) reported any changes to medications during the pandemic. As essential workers during this crisis, pharmacists have played a critical role in providing medication information and continued access.
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http://dx.doi.org/10.1016/j.sapharm.2020.11.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659512PMC
November 2020

A Pharmacoepidemiologic Approach to Evaluate Real-world Effectiveness of Hormonal Contraceptives in the Presence of Drug-drug Interactions.

Epidemiology 2021 Mar;32(2):268-276

From the Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, FL.

Background: Accurate estimation of conception is critical in the assessment of the effects of drugs used during pregnancy or to prevent pregnancy. In a novel application, we studied the effectiveness of oral contraceptives (OCs), where misclassification of conception relative to OC exposure may obscure effect estimates.

Methods: We studied OC failure, in a large claims database, among women who used antiepileptic drugs with metabolizing enzyme-inducing properties (carbamazepine or oxcarbazepine), which reduce OC's effectiveness or enzyme-neutral properties (lamotrigine or levetiracetam), with no expected impact on OC effectiveness. We compared conception rates in women 12-48 years of age concomitantly using OCs and enzyme-inducing drugs with rates in concomitant users of OCs and enzyme-neutral drugs. We measured conception with a validated algorithm that estimates gestational age based on pregnancy endpoints. We estimated relative and attributable risk using generalized estimating equation models after standardized mortality ratio weighting.

Results: We identified 89,777 concomitant use episodes with adjusted contraceptive failure rates of 1.6 (95% confidence interval (CI) = 1.4, 1.8) per 100 person-years among users of enzyme-neutral drugs and 18,964 episodes with a rate of 2.3 (1.9, 2.8) among users of enzyme-inducing drugs. The relative risk of conception for enzyme-inducing group was 1.4 (1.1, 1.8), and the rate difference was 0.7 (0.2, 1.2).

Conclusions: OCs in combination with antiepileptic drugs that interact with metabolic enzymes were associated with increased contraceptive failure rates. Measurement of conception in claims data had adequate accuracy to uncover a strong drug-drug interaction, offering promise for broader application in comparative effectiveness studies on hormonal contraceptives to inform clinical and regulatory decisionmaking.
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http://dx.doi.org/10.1097/EDE.0000000000001302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850590PMC
March 2021

What Do You Meme, Professor? An Experiment Using "Memes" in Pharmacy Education.

Authors:
Joshua D Brown

Pharmacy (Basel) 2020 Oct 29;8(4). Epub 2020 Oct 29.

Department of Pharmaceutical Outcomes and Policy, Center for Drug Evaluation and Safety, University of Florida College of Pharmacy, Gainesville, FL 32610, USA.

Memes are social or cultural constructs and ideas dispersed from person to person. The modern definition of memes applies to images, photographs, or videos shared on digital platforms juxtaposed with text that utilizes the emotion, meaning, or joke behind the original "meme" to communicate the author's message. Younger generations of learners are more prone to utilize digital and social media to distribute and consume information and use of these platforms has increased in modern classrooms. However, there are few examples of using memes for educational purposes, including student-generated content, and no known examples in pharmacy education. This commentary introduces the concept of a meme and describes an attempt to incorporate a student-generated meme assignment in a pharmacy course. Experiences and lessons learned are discussed as words of caution in incorporating and evaluating memes or other informal communication tools for educational purposes.
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http://dx.doi.org/10.3390/pharmacy8040202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712418PMC
October 2020

Quantitative Benefit-Risk Assessment of P-gp-Mediated Drug-Drug Interactions of Dabigatran Coadministered With Pharmacokinetic Enhancers in Patients With Renal Impairment.

Clin Pharmacol Ther 2021 Jan 10;109(1):193-200. Epub 2020 Dec 10.

Department of Pharmaceutics, Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, University of Florida, Orlando, Florida, USA.

Drug-drug interactions (DDIs) between dabigatran and ritonavir/cobicistat are of major concern in people living with HIV, particularly in those with impaired renal function, because they can result in increased dabigatran exposure and thus an increased risk of major bleeding events. However, the extent of this interaction and subsequent need for dose adjustment in subjects with varying degrees of renal function is currently not yet fully understood. To close this knowledge gap, we conducted an integrated population physiologically-based pharmacokinetic/pharmacodynamic analysis linking changes in dabigatran exposure due to DDIs and varying degrees of renal function to the probability of experiencing an ischemic stroke or major bleeding event within 1 year. The results of our analysis suggest that coadministration of dabigatran etexilate (dabigatran prodrug) and ritonavir/cobicistat should be avoided in subjects with severe renal impairment. A 2-hour dose separation or dabigatran etexilate dose reduction to 110 mg b.i.d. (twice daily) should be considered in subjects with moderate renal impairment when coadministered with ritonavir, while the dabigatran etexilate dose should be further reduced to 75 mg b.i.d. when coadministered with cobicistat. No dabigatran etexilate dose adjustment is needed in subjects with normal renal function receiving ritonavir, but dabigatran etexilate dose reduction to 110 mg b.i.d. should be considered when coadministered with cobicistat.
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http://dx.doi.org/10.1002/cpt.2087DOI Listing
January 2021

NMR Studies of Retroviral Genome Packaging.

Viruses 2020 09 30;12(10). Epub 2020 Sep 30.

Howard Hughes Medical Institute and Department of Chemistry and Biochemistry, University of Maryland Baltimore County, Baltimore, MD 21250, USA.

Nearly all retroviruses selectively package two copies of their unspliced RNA genomes from a cellular milieu that contains a substantial excess of non-viral and spliced viral RNAs. Over the past four decades, combinations of genetic experiments, phylogenetic analyses, nucleotide accessibility mapping, in silico RNA structure predictions, and biophysical experiments were employed to understand how retroviral genomes are selected for packaging. Genetic studies provided early clues regarding the protein and RNA elements required for packaging, and nucleotide accessibility mapping experiments provided insights into the secondary structures of functionally important elements in the genome. Three-dimensional structural determinants of packaging were primarily derived by nuclear magnetic resonance (NMR) spectroscopy. A key advantage of NMR, relative to other methods for determining biomolecular structure (such as X-ray crystallography), is that it is well suited for studies of conformationally dynamic and heterogeneous systems-a hallmark of the retrovirus packaging machinery. Here, we review advances in understanding of the structures, dynamics, and interactions of the proteins and RNA elements involved in retroviral genome selection and packaging that are facilitated by NMR.
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http://dx.doi.org/10.3390/v12101115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599994PMC
September 2020

Impact of Anticholinergic Medication Burden on Mobility and Falls in the Lifestyle Interventions for Elders (LIFE) Study.

J Clin Med 2020 Sep 16;9(9). Epub 2020 Sep 16.

Department of Pharmaceutical Outcomes & Policy, University of Florida College of Pharmacy, Gainesville, FL 32611, USA.

Anticholinergic cognitive burden (ACB) may be associated with detrimental effects on mobility and physical independence in older adults. We evaluated the incidence of major mobility disability (MMD), persistent major mobility disability (PMMD), and injurious falls among participants within the Lifestyle Interventions for Elders (LIFE) trial according to varied anticholinergic burden levels. Participants aged 70-89 years were randomized to a physical activity (PA) or successful aging (SA) intervention and evaluated by ACB medication use as a summed score of a previously developed ACB scale. Confounders included demographic characteristics, physical function, cognitive function, and fall history. Average participant follow-up was 2.6 years and included outcome assessment for MMD, PMMD, and injurious falls every six months. Adjusted proportional hazards models evaluated the independent effects of ACB scores as well as interaction effects with the intervention. Of the 1635 participants, 986 (60%) used ≥1 anticholinergic medication. Compared to those with no burden, participants with an ACB score of 1 demonstrated increased MMD (HR = 1.42 [1.13-1.78]), PMMD (HR = 1.53 [1.12-2.09]), and injurious falls (HR = 1.60 [1.10-2.32]). Results similar in magnitude were observed for all other ACB levels versus the no burden group. Stepwise dose-response comparisons between ACB groupings did not demonstrate significant differences in outcomes. Stratification by PA or SA interventions demonstrated few differences from the combined overall trial results. Compared to those not taking anticholinergic medications, participants taking anticholinergic medications generally demonstrated increased risk of MMD, PMMD, and injurious falls. Total anticholinergic burden was not associated with a stepwise dose-response relationship in mobility disability and may lack sensitivity to capture varied responses.
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http://dx.doi.org/10.3390/jcm9092989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564216PMC
September 2020

Updating the Cost Effectiveness of Oral Anticoagulants for Patients with Atrial Fibrillation Based on Varying Stroke and Bleed Risk Profiles.

Pharmacoeconomics 2020 12 14;38(12):1333-1343. Epub 2020 Sep 14.

Center for Drug Evaluation and Safety, Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, 1225 Center Drive, Gainesville, FL, 32610, USA.

Background: Previous investigations into the cost effectiveness of direct oral anticoagulants only considered individual stroke risk but not bleed risk even though bleeding is an important and potentially fatal side effect for anticoagulated patients.

Objective: This study aimed to evaluate the cost effectiveness of dabigatran, rivaroxaban, apixaban, and edoxaban vs warfarin in patients with atrial fibrillation with varying stroke/bleed risk profiles over a lifetime horizon.

Methods: A Markov micro-simulation was adapted to examine the lifetime costs and quality-adjusted survival of five anticoagulants from a US private payer's perspective. The study hypothetical cohort consisted of 10,000 patients with atrial fibrillation with age, CHADS-VASc, and HAS-BLED scores similar to a commercially insured patient with atrial fibrillation cohort. Model input parameters including the efficacy and safety of each strategy, utilities, and cost were estimated from public sources, published literature, and analysis conducted in the IBM MarketScan database. Lifetime cost, quality-adjusted life-years, and incremental cost-effectiveness ratios were assessed for each treatment strategy. Subgroup analyses stratified by age, stroke risk score alone, bleed risk score alone and both were performed. Uncertainty was assessed by a deterministic sensitivity analysis and a probabilistic sensitivity analysis.

Results: The base-case analysis suggested dabigatran was the optimal treatment with an incremental cost-effectiveness ratio of $35,055 per quality-adjusted life-year relative to warfarin. Subgroup analyses stratified by age, stroke risk score, and bleed risk score alone were largely consistent with the base-case analysis. Subgroup analyses stratified by both stroke and bleed risk score showed edoxaban was the preferred treatment in patients with a low stroke and a low or medium bleed risk, and patients with a high stroke and low bleed risk. Apixaban was the preferred treatment in patients with a medium stroke and high bleed risk. Results of the deterministic sensitivity analysis indicate the model results were most sensitive to the drug cost and hazard ratio for stroke and bleeding event. Results of the probability sensitivity analysis showed dabigatran is cost effective vs. other treatments in 32.8% and 42.4% of iterations at a willingness to pay of $50,000/quality-adjusted life-year and a willingness to pay of $100,000/quality-adjusted life year, respectively.

Conclusions: From a US private payer's perspective, dabigatran appears cost effective compared with other anticoagulants. This study indicated risk stratification especially considering both stroke and bleed risk simultaneously is important not only in clinical practice but also in health technology assessment exercises among patients with atrial fibrillation.
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http://dx.doi.org/10.1007/s40273-020-00960-0DOI Listing
December 2020

A Call to Action to Track Generic Drug Quality Using Real-World Data and the FDA's Sentinel Initiative.

Authors:
Joshua D Brown

J Manag Care Spec Pharm 2020 Aug;26(8):1050

Center for Drug Evaluation and Safety, Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville.

Disclosures: The author reports funding from the U.S. Food and Drug Administration to study real-world data approaches to detect generic drug quality issues. There are no further conflicts or disclosures.
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http://dx.doi.org/10.18553/jmcp.2020.26.8.1050DOI Listing
August 2020

Trajectories of Short Physical Performance Battery Are Strongly Associated with Future Major Mobility Disability: Results from the LIFE Study.

J Clin Med 2020 Jul 22;9(8). Epub 2020 Jul 22.

Institute on Aging, Department of Aging and Geriatric Research, University of Florida College of Medicine, Gainesville, FL 32610, USA.

Short Physical Performance Battery (SPPB) assessment is a widely used measure of lower extremity function, strength, and balance. In the Lifestyles Interventions and Independence for Elders (LIFE) Study, baseline SPPB and changes throughout the trial were strongly associated with major mobility disability (MMD). This study further investigated this association by identifying trajectories of SPPB and evaluating the predictive validity of SPPB trajectories for future MMD. Participants ( = 1635) aged 70-89 years were randomized to a physical activity or health education intervention and assessed every 6 months for MMD. We used group-based trajectory models (GBTMs) to identify trajectories of a binary outcome for a decrease from baseline SPPB of ≥1. Multinomial logistic regression explored baseline factors associated with group membership. Survival analyses evaluated the association between trajectories with MMD. The GBTM identified a 3-group model which included a "No Decline" group (46.0%), "Late Decline" group (27.7%), and an "Early Decline" group (26.3%). Adjusting for all other baseline characteristics, group assignment during the previous follow-up visit was strongly associated with MMD at the subsequent period. Comparisons between groups showed a 2-to-3-fold increase in MMD comparing the "Late" to "No" decline group and a 4-to-5-fold increase in MMD comparing the "Early" to "No" decline group. Group membership and impact on MMD was not different between intervention arms. Group-based trajectories of SPPB scores identified distinct subgroups in LIFE Study participants. Using these group assignments in outcome models were highly associated with MMD. GBTMs have potential to identify and improve prediction of aging-related decline to better design and identify patients for interventions.
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http://dx.doi.org/10.3390/jcm9082332DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465072PMC
July 2020

Association of Oral Anticoagulants and Verapamil or Diltiazem With Adverse Bleeding Events in Patients With Nonvalvular Atrial Fibrillation and Normal Kidney Function.

JAMA Netw Open 2020 04 1;3(4):e203593. Epub 2020 Apr 1.

Department of Pharmaceutical Outcomes & Policy, University of Florida College of Pharmacy, Gainesville.

Importance: Direct oral anticoagulants (DOACs) are purported to have fewer drug-drug interactions than warfarin. However, potential interactions with coprescribed medications are still a safety concern. Verapamil hydrochloride and diltiazem hydrochloride are combined P-glycoprotein (P-gp) and CYP3A4 inhibitors and may be associated with increases in the risk of bleeding with DOACs.

Objective: To evaluate the risk of bleeding with DOACs and verapamil or diltiazem using an active comparator design.

Design, Setting, And Participants: A comparative effectiveness active comparator cohort study was conducted using US population-based data (2010-2015) analyzed between January 1 and July 15, 2019. Data were obtained on 48 442 patients with nonvalvular atrial fibrillation who had received an index prescription of dabigatran, rivaroxaban, or apixaban between October 19, 2010, through June 30, 2015, with final follow-up on October 1, 2015. Analysis was restricted to individuals with no history of kidney disease who were receiving standard doses of the DOACs.

Exposures: Patients with initial prescriptions of DOACs who were receiving verapamil or diltiazem were compared with those receiving amlodipine or metoprolol.

Main Outcomes And Measures: Overall and gastrointestinal major, moderate, and minor bleeding using primary or secondary diagnoses. Hazard ratios and 95% CIs were estimated using inverse probability of treatment weights in Cox proportional hazards regression models.

Results: Of the 48 442 patients reviewed, analysis was conducted on 1764 patients receiving DOACs with verapamil or diltiazem compared with 3105 receiving amlodipine and 1793 patients receiving DOACs with verapamil or diltiazem compared with 3224 receiving metoprolol. Depending on the comparison, approximately 60% of the cohort were younger than 65 years and male, which differed by treatment group. Rivaroxaban and apixaban were not associated with increased rates of bleeding for patients receiving verapamil or diltiazem compared with those receiving amlodipine or metoprolol. Among patients receiving dabigatran etexilate, the overall bleeding rate was 52% higher (hazard ratio, 1.52; 95% CI, 1.05-2.20) with verapamil or diltiazem vs amlodipine and 43% higher (hazard ratio, 1.43; 95% CI, 1.02-2.00) vs metoprolol. Bleeding rates for dabigatran with verapamil or diltiazem were higher overall for other bleeding types (244.9 vs 158.4 per 1000 person-years; adjusted hazard ratios of overall GI bleeding: 2.16; 95% CI, 1.30-3.60; minor bleeding: 1.56; 95% CI, 1.07-2.27; and minor GI bleeding: 2.16; 95% CI, 1.29-3.63). Sensitivity analyses showed consistent results for dabigatran when used with verapamil and diltiazem, with magnitudes ranging from 50% to 100% increased hazard rates and no significant results for apixaban or rivaroxaban.

Conclusions And Relevance: Current US prescribing information only recommends prescribing changes with dabigatran and P-gp inhibitors with lower kidney function. This study found increased bleeding risk associated with dabigatran when used concomitantly with the P-gp inhibitors verapamil and diltiazem in individuals with normal kidney function. Clinicians and patients may need to consider these drug-drug interactions when choosing oral anticoagulation.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.3593DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7182798PMC
April 2020

Structural basis for transcriptional start site control of HIV-1 RNA fate.

Science 2020 04;368(6489):413-417

Howard Hughes Medical Institute and Department of Chemistry and Biochemistry, University of Maryland Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA.

Heterogeneous transcriptional start site usage by HIV-1 produces 5'-capped RNAs beginning with one, two, or three 5'-guanosines (1G, 2G, or 3G, respectively) that are either selected for packaging as genomes (1G) or retained in cells as translatable messenger RNAs (mRNAs) (2G and 3G). To understand how 5'-guanosine number influences fate, we probed the structures of capped HIV-1 leader RNAs by deuterium-edited nuclear magnetic resonance. The 1G transcript adopts a dimeric multihairpin structure that sequesters the cap, inhibits interactions with eukaryotic translation initiation factor 4E, and resists decapping. The 2G and 3G transcripts adopt an alternate structure with an elongated central helix, exposed splice donor residues, and an accessible cap. Extensive remodeling, achieved at the energetic cost of a G-C base pair, explains how a single 5'-guanosine modifies the function of a ~9-kilobase HIV-1 transcript.
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http://dx.doi.org/10.1126/science.aaz7959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351118PMC
April 2020

Safety signals for QT prolongation or Torsades de Pointes associated with azithromycin with or without chloroquine or hydroxychloroquine.

Res Social Adm Pharm 2021 02 19;17(2):483-486. Epub 2020 Apr 19.

Center for Drug Evaluation and Safety, Department of Pharmaceutical Outcomes & Policy, University of Florida College of Pharmacy, Gainesville, FL, USA. Electronic address:

Background: Combinations of hydroxychloroquine (HCQ) and azithromycin have been promoted as treatments for COVID-19 based on small, uncontrolled clinical trials that have not assessed potential risks. Risks of treatment include QT segment prolongation, Torsades de Pointes (TdP), and death. This comparative pharmacovigilance analysis evaluated the risk of these events.

Methods: Data from the U.S. Food and Drug Administration's Adverse Event Reporting System (FAERS) (>13 million total reports) were used. Queries extracted reports based on exposures of HCQ/chloroquine (CQ) alone, azithromycin alone, HCQ/CQ + azithromycin, amoxicillin alone, HCQ/CQ + amoxicillin alone. Amoxicillin served as a control. Events of interest included death and TdP/QT prolongation as well as accidents/injuries and depression as control events. Proportional Reporting Ratios (PRR) and 95% confidence intervals (CI) were calculated where a lower limit of the of 95% CI (Lower95CI) value of ≥2.0 is interpreted as a potential safety signal.

Results: Lower95CIs for HCQ/CQ alone showed no potential safety signals for TdP/QT prolongation, death, or any of the control events included. The PRRs and 95% CIs for TdP/QT prolongation was 1.43 (1.29-2.59) with HCQ/CQ use alone and 4.10 (3.80-4.42) for azithromycin alone. For the combined HCQ/CQ + azithromycin group, the PRR and 95% CI was 3.77 (1.80-7.87). For the control of amoxicillin, there were no safety signals when used alone or in combination with HCQ/CQ.

Conclusions: HCQ/CQ use was not associated with a safety signal in this analysis of FAERS data. However, azithromycin used alone was associated with TdP/QT prolongation events and should be used with caution.
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http://dx.doi.org/10.1016/j.sapharm.2020.04.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166303PMC
February 2021

Characteristics of Older Adults Who Were Early Adopters of Medical Cannabis in the Florida Medical Marijuana Use Registry.

J Clin Med 2020 Apr 18;9(4). Epub 2020 Apr 18.

Center for Drug Evaluation & Safety, Department of Pharmaceutical Outcomes & Policy, University of Florida College of Pharmacy, Gainesville, FL 32610, USA.

Use of medical marijuana is increasing in the United States and older adults are the fastest growing user group. There is little information about the characteristics and outcomes related to medical marijuana use. This study is a descriptive analysis of older adults (aged ≥50 years old) who were early adopters of a medical marijuana program in the U.S. state of Florida. Per state legislation, initial and follow-up treatment plans were submitted to the University of Florida College of Pharmacy. Data collection included demographics, clinical history, medical conditions, substance use history, prescription history, and health status. Follow-up treatment plans noted changes in the chief complaint and actions taken since the initial visit. Of the state's 7548 registered users between August 2016 and July 2017, = 4447 (58.9%) were older adults. Patients utilized cannabidiol (CBD)-only preparations (45%), preparations that had both tetrahydrocannabinol (THC) and CBD (33.3%) or were recorded to use both CBD-only and THC + CBD products (21.7%). The chief complaints indicating medical cannabis treatment were musculoskeletal disorders and spasms (48.4%) and chronic pain (45.4%). Among other prescription medications, patients utilized antidepressants (23.8%), anxiolytics and benzodiazepines (23.5%), opioids (28.6%), and cardiovascular agents (27.9%). Among all drug classes with potential sedating effects, 44.8% of the cohort were exposed to at least one. Patients with follow-up visits (27.5%) exhibited marked improvement as assessed by the authorizing physicians. However, the patient registry lacked detailed records and linkable information to other data resources to achieve complete follow up in order to assess safety or efficacy. Future improvements to registries are needed to more adequately capture patient information to fill knowledge gaps related to the safety and effectiveness of medical marijuana, particularly in the older adult population.
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http://dx.doi.org/10.3390/jcm9041166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230351PMC
April 2020

Cannabidiol as prophylaxis for SARS-CoV-2 and COVID-19? Unfounded claims versus potential risks of medications during the pandemic.

Authors:
Joshua D Brown

Res Social Adm Pharm 2021 01 31;17(1):2053. Epub 2020 Mar 31.

Center for Drug Evaluation & Safety, Department of Pharmaceutical Outcomes & Policy, University of Florida College of Pharmacy, USA. Electronic address:

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http://dx.doi.org/10.1016/j.sapharm.2020.03.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7269703PMC
January 2021

Three-Year, Postintervention, Follow-up Comparison of Health Care Resource Utilization and Costs in the Lifestyle Interventions and Independence for Elders (LIFE) Study.

J Gerontol A Biol Sci Med Sci 2021 Jan;76(2):272-276

Department of Aging & Geriatric Research, University of Florida College of Medicine, Gainesville.

Background: The Lifestyle Interventions and Independence for Elders (LIFE) Study physical activity (PA) intervention was found to be cost-effective compared to health education (HE). However, long-term effects postintervention are unknown.

Method: This was a secondary analysis of LIFE Study data linked to Medicare claims data (2014-2016). Participants were linked via Social Security Numbers to Medicare claims data. Utilization and cost variables were analyzed using generalized linear models with negative binomial and Tweedie distributions. Unadjusted means and 95% confidence intervals were compared by year and overall stratified. Each model compared PA versus HE and adjusted for other baseline characteristics and stratified by study site. Additional models were stratified by baseline physical functioning assessment scores.

Results: Of the 1,635 LIFE Study participants, 804 (53.5%) were linked to Medicare claims with an average of 33 months of follow-up time during the 3-year data linkage period. Mean outpatient (6.6 vs 6.8), inpatient (0.40 vs 0.40), and other utilization metrics were similar between PA and HE groups. Costs were also similar for each group and each type of service, for example, outpatient: $2,070 versus $2,093 and inpatient: $4,704 versus $4,792. Regression results indicated no statistically significant differences between PA and HE groups.

Conclusions: While the LIFE Study demonstrated that PA reduced mobility disability in older adults and was cost-effective, it did not appear to affect long-term health care utilization costs posttrial. These findings suggest that it remains challenging to affect long-term health care costs using PA interventions effects.
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http://dx.doi.org/10.1093/gerona/glaa088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812479PMC
January 2021

OB/GYN perceptions of prescription drug monitoring programs as a primary prevention tool for neonatal abstinence syndrome.

Res Social Adm Pharm 2020 Dec 31;16(12):1789-1791. Epub 2020 Mar 31.

Center for Drug Evaluation & Safety, Department of Pharmaceutical Outcomes & Policy, University of Florida College of Pharmacy, Gainesville, FL, USA.

Background: The U.S. Centers for Disease Control and Prevention recommend clinicians use Prescription Drug Monitoring Program (PDMPs) as a risk assessment tool for opioid-related harms. This survey assessed perceptions of PDMPs for the purpose of Neonatal Abstinence Syndrome (NAS) prevention among a national sample of obstetricians-gynecologists (OB/GYNs) who are the primary care providers for most pregnancies.

Methods: A survey was emailed to a random sample of active American College of Obstetricians and Gynecologists (ACOG) members. Proxy data for the intensity of the opioid epidemic and state policies related to NAS were added to respondents survey answers. Chi-squared analyses were used to compare response frequencies.

Results: Among 397 submitted responses, nearly 70% identified PDMPs having a role in preventing diversion and opioid use disorders but only 25.1% identified PDMPs as a tool to prevent NAS. States with stricter NAS policies (e.g. child abuse, mandatory testing) generally had higher positive responses for PDMPs' role in preventing NAS. States with voluntary PDMP use versus mandatory reported higher positive responses for PDMPs with NAS but differences were not statistically significant (30.6% vs. 23.8%, p = 0.374). State-specific measures of the overall intensity of the opioid epidemic were not associated with perceptions of PDMP.

Conclusions: OB/GYNs do not associate PDMPs as a primary prevention tool against NAS despite endorsements. Tailored educational interventions to this practice environment are needed. Pharmacist engagement with pregnant patients and as champions of PDMP usage may help fill these gaps.
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http://dx.doi.org/10.1016/j.sapharm.2020.03.010DOI Listing
December 2020

Potential Adverse Drug Events with Tetrahydrocannabinol (THC) Due to Drug-Drug Interactions.

Authors:
Joshua D Brown

J Clin Med 2020 Mar 27;9(4). Epub 2020 Mar 27.

Center for Drug Evaluation & Safety, Consortium for Medical Marijuana Clinical Outcomes Research, Department of Pharmaceutical Outcomes & Policy, University of Florida College of Pharmacy, Gainesville, FL 32610, USA.

Tetrahydrocannabinol (THC) is the primary psychoactive ingredient in cannabis. While the safety of THC and cannabis has been extrapolated from millennia of recreational use, medical marijuana programs have increased exposure among medically complex individuals with comorbid conditions and many co-prescribed medications. Thus, THC should be recognized as a pharmacologically complex compound with potential for drug-drug interactions and adverse drug events. This review summarizes potential adverse drug events related to THC when combined with other medications. Metabolic drug-drug interactions are primarily due to THC conversion by CYP3A4 and CYP2C9, which can be impacted by several common medications. Further, CYP2C9 polymorphisms are highly prevalent in certain racial groups (up to 35% in Caucasians) and increase the bioavailability of THC. THC also has broad interactions with drug-metabolizing enzymes and can enhance adverse effects of other medications. Pharmacodynamic interactions include neurological effects, impact on the cardiovascular system, and risk of infection. General clinical recommendations for THC use include starting with low doses and titrating to desired effects. However, many interactions may be unavoidable, dose-limiting, or a barrier to THC-based therapy. Future work and research must establish sufficient data resources to capture medical marijuana use for such studies. Meanwhile, clinicians should balance the potential risks of THC and cannabis and the lack of strong evidence of efficacy in many conditions with patient desires for alternative therapy.
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http://dx.doi.org/10.3390/jcm9040919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231229PMC
March 2020

Antihypertensive drugs and risk of COVID-19?

Authors:
Joshua D Brown

Lancet Respir Med 2020 05 26;8(5):e28. Epub 2020 Mar 26.

Center for Drug Evaluation & Safety, Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, FL 32606, USA. Electronic address:

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http://dx.doi.org/10.1016/S2213-2600(20)30158-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7194728PMC
May 2020

Atopic Disease and Anemia in Korean Patients: Cross-Sectional Study with Propensity Score Analysis.

Int J Environ Res Public Health 2020 03 18;17(6). Epub 2020 Mar 18.

College of Pharmacy, Seoul National University, Seoul 08826, Korea.

Atopic disease is associated with chronic inflammation, and anemia has been reported in patients with inflammatory disorders such as rheumatoid arthritis, chronic obstructive pulmonary disease, and irritable bowel disease. The objective of this study was to determine whether atopic disease is associated with an increased risk of anemia. A cross-sectional study with propensity score weighting was conducted using a health insurance review agency claims dataset comprised of randomized patients who used the Korean national health system at least once in 2016. The association between atopic disease (asthma, atopic dermatitis, allergic rhinitis) and anemia (iron deficiency anemia (IDA) and/or anemia of inflammation (AI)) was examined. A total of 1,468,033 patients were included in this study. The IDA/AI prevalence was 3.1% (45,681 patients). After propensity score weighting, there were 46,958 and 45,681 patients in the non-anemic and anemic groups, respectively. The prevalence of IDA/AI in patients with atopic dermatitis, allergic rhinitis, or asthma had an odds ratio (OR) of 1.40 (95% confidence interval (CI), 1.33-1.48; < 0.001), 1.17 (95% CI, 1.14-1.21; < 0.001), and 1.32 (95% CI, 1.28-1.36; < 0.001), respectively. In addition, the prevalence of IDA increased with higher numbers of atopic diseases. In conclusion, the prevalence of IDA/AI was higher in patients with atopic disease, even after adjusting for demographic characteristics and other risk factors. Further study is needed to distinguish between IDA and AI and to enhance understanding of the etiology of anemia in patients with inflammatory conditions.
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http://dx.doi.org/10.3390/ijerph17061978DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7142528PMC
March 2020

Reliability and Validity of the Short-Form 12 Item Version 2 (SF-12v2) Health-Related Quality of Life Survey and Disutilities Associated with Relevant Conditions in the U.S. Older Adult Population.

J Clin Med 2020 Feb 29;9(3). Epub 2020 Feb 29.

Center for Drug Evaluation and Safety, Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, FL 32610, USA.

This study aimed to validate the Short-Form 12-Item Survey-version 2 (SF-12v2) in an older (≥65 years old) US population as well as estimate disutilities associated with relevant conditions, using data from the Medical Expenditure Panel Survey longitudinal panel (2014-2015). The physical component summary (PCS) and mental component summary (MCS) scores were examined for reliability (internal consistency, test-retest), construct validity (convergent and discriminant, structural), and criterion validity (concurrent and predictive). The study sample consisted of 1040 older adults with a mean age of 74.09 years (standard deviation: 6.19) PCS and MCS demonstrated high internal consistency (Cronbach's alpha-PCS: 0.87, MCS: 0.86) and good and moderate test-retest validity, respectively (intraclass correlation coefficient: PCS:0.79, MCS:0.59)). The questionnaire demonstrated sufficient convergent and discriminant ability. Confirmatory factor analysis showed adequate fit with the theoretical model and structural validity (goodness of fit = 0.9588). Concurrent criterion validity and predictive criterion validity were demonstrated. Activity limitations, functional limitations, arthritis, coronary heart disease, diabetes, myocardial infarction, stroke, angina, and high blood pressure were associated with disutilities of 0.18, 0.15, 0.06, 0.07, 0.07, 0.06, 0.09, 0.06, and 0.08, respectively, and demonstrated the responsiveness of the instrument to these conditions. The SF-12v2 is a valid and reliable instrument in an older US population.
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http://dx.doi.org/10.3390/jcm9030661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7141358PMC
February 2020

Application of a Graphical Depiction of Longitudinal Study Designs to Managed Care Pharmacy Research.

J Manag Care Spec Pharm 2020 Mar;26(3):268-274

Division of Pharmacoepidemiology, Brigham and Womens Hospital and Harvard Medical School, Boston, Massachusetts.

Managed care pharmacists apply real-world evidence (RWE) to support activities such as pipeline forecasting, clinical policy development, and contracting for pharmaceutical products. Managed care pharmacy researchers strive to produce studies that can be applied in practice. While asking the right research question is necessary, it is not sufficient. As with all studies, consumers of RWE look for internal and external validity, as well as sources of bias, to determine how the study findings can be applied in their work. To date, however, some of the safeguards that exist for clinical trials-such as public registration of study protocols-are lacking for RWE. Several leading professional organizations have initiatives dedicated to improving the credibility and reliability of such research. One component common to these initiatives is enhanced transparency and completeness of methodologic reporting. Graphical representations of study designs can improve the reporting and design of research conducted in health care databases, specifically by enhancing the transparency and clarity of often complex studies. As such, Schneeweiss et al. (2019) proposed a graphical framework for longitudinal study designs in health care databases. Herein, we apply this framework to 2 studies published in the that represent common research designs and report how application of the framework revealed deficiencies in reporting. We advocate for adoption of this framework in the effort to increase the usability of RWE studies using health care databases by managed care pharmacy. DISCLOSURES: No funding was provided for this work. Gatwood has received research funding from Merck & Co., AstraZeneca, and GlaxoSmithKline, unrelated to this work. Schneeweiss is a consultant to Aetion, of which he also owns equity. He is the principal investigator of investigator-initiated grants to the Brigham and Women's Hospital from Bayer, Genentech, Boehringer Ingelheim, and Vertex. Wang reports support from investigator-initiated grants from Novartis, Boehringer Ingelheim, and Johnson & Johnson to Brigham and Women's Hospital, unrelated to this work. Happe and Brown have nothing to disclose.
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http://dx.doi.org/10.18553/jmcp.2020.26.3.268DOI Listing
March 2020

Risk of Opioid Overdose Associated With Concomitant Use of Opioids and Skeletal Muscle Relaxants: A Population-Based Cohort Study.

Clin Pharmacol Ther 2020 07 17;108(1):81-89. Epub 2020 Mar 17.

Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, Florida, USA.

The recent opioid prescribing guideline cautions about the concomitant prescribing of opioids and skeletal muscle relaxants (SMRs) given the additive central nervous system depressant effect. However, the clinical relevance remains unclear. In this retrospective cohort study, we compared the risk of opioid overdose associated with concomitant use of opioids and SMRs vs. opioid use alone. Adjusted hazard ratios were 1.09 (95% confidence interval (CI), 0.74-1.62) and 1.26 (95% CI, 1.00-1.58) in the incident and prevalent opioid user cohorts, respectively, generating a combined estimate of 1.21 (95% CI, 1.00-1.48). This risk seemed to increase with treatment duration (≤ 14 days: 0.91 and 95% CI, 0.67-1.22; 15-60 days: 1.37 and 95% CI, 0.81-2.37; >60 days: 1.80 and 95% CI, 1.30-2.48) and for baclofen (1.83 and 95% CI, 1.11-3.04) and carisoprodol (1.84 and 95% CI, 1.34-2.54). Concomitant users with daily opioid dose ≥50 mg (1.50 and 95% CI, 1.18-1.92) and benzodiazepine use (1.39 and 95% CI, 1.08-1.79) also had elevated risk. Clinicians should be cautious about these potentially unsafe practices to optimize pain care and improve patient safety.
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http://dx.doi.org/10.1002/cpt.1807DOI Listing
July 2020

Association of Adverse Drug Events with Hospitalization Outcomes and Costs in Older Adults in the USA using the Nationwide Readmissions Database.

Pharmaceut Med 2019 08;33(4):321-329

Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, FL, USA.

Background: Adverse drug events (ADEs) are a primary cause of significant morbidity, mortality, and healthcare utilization in older adults.

Objective: The objective of this study was to evaluate the clinical outcomes and cost of ADEs during hospitalization in older adults.

Methods: Discharges for patients aged 65 years or older were identified in the 2014 Nationwide Readmissions Database. ADEs were selected based on a previously developed algorithm of 442 unique diagnoses and external causes of injury codes. Patients were categorized into ADE or non-ADE groups. Regression models were used for a multivariable analysis for each outcome metric, which included all-cause readmission, in-hospital mortality, length of stay, and costs.

Results: The study included 3,832,322 patients. Among these patients, 203,432 (5.3%) had at least one ADE during hospitalization. The majority of ADEs were related to broad categories of "medications affecting blood constituents" (22%) and "adverse effects of biological and medicinal substances in therapeutic use" (23%). In adjusted models, older adults with ADEs during hospitalization had a 25% (p < 0.0001) and 9% (p < 0.0001) higher odds of readmission and in-hospital mortality, respectively, as compared with those without ADEs. A 17% (p < 0.0001) increase in the length of stay was estimated in the ADE group and 1% point estimate (p > 0.05) rise in cost was observed in the ADE group when compared with the non-ADE group.

Conclusions: ADEs have a substantial burden on in-patient care of older adults both clinically (increased readmission, in-hospital mortality, and length of stay) and financially. Targeted interventions can help to prevent ADEs and, consequently, the associated clinical and economic burden.
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http://dx.doi.org/10.1007/s40290-019-00286-zDOI Listing
August 2019

Trends, Patient and Prescriber Characteristics in Gabapentinoid Use in a Sample of United States Ambulatory Care Visits from 2003 to 2016.

J Clin Med 2019 Dec 29;9(1). Epub 2019 Dec 29.

Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.

Increasing gabapentinoid use has raised concerns of misuse and abuse in the United States (US). Little is known about the characteristics of gabapentinoid use in general clinical practice over time. This cross-sectional study used data from the National Ambulatory Medical Care Survey. We examined the trends of patient and prescriber characteristics and the diagnoses associated with US ambulatory care visits involving gabapentinoids for adult visits from 2003 to 2016. Using multivariable logistic regression, we estimated the adjusted proportion of gabapentinoid-involved visits among all visits and tested for trend significance. Among the weighted estimate of 260.1 million gabapentinoid-involved visits (aged 18-64 years: 61.8%; female: 61.9%; white: 85.5%), the adjusted annual proportion of gabapentinoid-involved visits nearly quadrupled from 2003 to 2016 (9.1 to 34.9 per 1000 visits; < 0.0001), driven mainly by gabapentin. Nearly half had concurrent use with opioids (32.9%) or benzodiazepines (15.3%). Primary care physicians (45.8%), neurologists (8.2%), surgeons (6.2%), and psychiatrists (4.8%) prescribed two-thirds of the gabapentinoids. Most (96.6%) of the gabapentinoid visits did not have an approved indication for gabapentinoids among the first three diagnoses. Among US ambulatory care visits from 2003 to 2016, gabapentinoid use increased substantially, commonly prescribed by primary care physicians.
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http://dx.doi.org/10.3390/jcm9010083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019734PMC
December 2019

Machine Learning in Drug Discovery and Development Part 1: A Primer.

CPT Pharmacometrics Syst Pharmacol 2020 03 11;9(3):129-142. Epub 2020 Mar 11.

e-Quantify LLC, La Jolla, California, USA.

Artificial intelligence, in particular machine learning (ML), has emerged as a key promising pillar to overcome the high failure rate in drug development. Here, we present a primer on the ML algorithms most commonly used in drug discovery and development. We also list possible data sources, describe good practices for ML model development and validation, and share a reproducible example. A companion article will summarize applications of ML in drug discovery, drug development, and postapproval phase.
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http://dx.doi.org/10.1002/psp4.12491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7080529PMC
March 2020

Patients' reasons for weight loss and their relations to clinical weight loss outcomes in a comprehensive lifestyle intervention.

Obes Sci Pract 2019 Dec 24;5(6):548-554. Epub 2019 Nov 24.

Weight Management Center, Department of Psychiatry and Behavioral Sciences Medical University of South Carolina Charleston South Carolina USA.

Objective: Research suggests that individuals seeking weight loss treatment do so for a variety of reasons. Limited work has explored relations of reasons for weight loss to patient characteristics or to weight loss outcomes. The current study examined these relations.

Methods: The sample consisted of 588 patients in a 15-week fee-for-service weight loss programme. Prior to the intervention, patients completed questionnaires including items on reasons for weight loss, demographic characteristics, and a variety of weight-based characteristics. Patients' weight change outcomes were expressed as percent weight loss and also categorized into one of three previously described weight loss trajectories.

Results: The results of chi-squared and -test analyses suggested that endorsement of health concerns, mobility concerns, or another person's recommendation was associated with higher body mass index (BMI) and older age. These reasons were more likely to be endorsed by White patients than Black patients and by male patients than female patients. Endorsement of doctor recommendation was more likely to be seen among Black patients than White patients. There was no significant relation of any weight loss reason with weight loss outcome.

Conclusions: While certain reasons for weight loss were more often cited by certain patient groups, no specific reason predicted a better or worse outcome.
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http://dx.doi.org/10.1002/osp4.372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934423PMC
December 2019

Healthcare Utilization and Physical Functioning in Older Adults in the United States.

J Am Geriatr Soc 2020 02 22;68(2):266-271. Epub 2019 Nov 22.

Department of Pharmaceutical Outcomes & Policy, University of Florida College of Pharmacy, Gainesville, Florida.

Objectives: Decline in physical function is associated with older age. Healthcare utilization and expenditures related to physical functioning declines will likely increase as the proportion of the population of older adults rises. This study evaluated resource utilization associated with differences in physical functioning in a nationally representative sample of older adults.

Design: A retrospective panel study nationally representative for 26 809 552 older adults in the United States.

Setting: Medical Expenditure Panel Survey (MEPS) data from 2013 to 2014.

Participants: Adults aged 70 years or older who completed both rounds of the Self-Administered Questionnaire in MEPS.

Measurements: Physical Component Score (PCS) from the Short-Form Health Survey as a measure of physical functioning was stratified into quartiles. Healthcare utilization (count of medical visits by setting) and total expenditures were assessed during and after the PCS measurements. Generalized linear mixed models, adjusted for demographic and clinical covariates, estimated the relationship between healthcare utilization and physical functioning.

Results: The lowest functional status (Q1) was associated with significantly increased healthcare utilization of emergency department, inpatient, home health, outpatient, and total medical visits compared with the three higher quartiles groups (P < .001, all). When compared with the lowest functioning group (Q1), the percentage savings for direct healthcare expenditures were 26.7% (95% confidence interval [CI] = 7.8-41.7) in Q2, 50.1% (95% CI = 35.6-61.4) in Q3, and 65.2% (95% CI = 54.7-73.2) in Q4. Similarly, there were 10.4% (95% CI = 9.2-11.7), 11.9% (95% CI = 10.5-13.6), and 14.0% (95% CI = 2.2%-15.9%) reductions in total medical visits, respectively.

Conclusion: Lower physical functioning was associated with higher healthcare utilization and expenditures. These estimates are conservative because they do not capture long-term care utilization due to the nature of MEPS. These results can be used to benchmark other healthcare resource benefits of interventions to maintain or improve physical functioning in older adults in noninstitutionalized settings. J Am Geriatr Soc 68:266-271, 2020.
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http://dx.doi.org/10.1111/jgs.16260DOI Listing
February 2020

Impact of Schedule IV controlled substance classification on carisoprodol utilization in the United States: An interrupted time series analysis.

Drug Alcohol Depend 2019 09 19;202:172-177. Epub 2019 Jul 19.

Department of Pharmaceutical Outcomes and Policy, College of Pharmacy, University of Florida, FL, USA; Department of Epidemiology, College of Public Health and Health Professions and College of Medicine, University of Florida, FL, USA.

Background: In January 2012, the Drug Enforcement Agency (DEA) classified carisoprodol as a Schedule IV controlled substance at the US federal level. We aimed to examine the effect of this policy on the use of carisoprodol in a commercially-insured population.

Methods: This interrupted time series study included individuals with musculoskeletal disorders in the IBM MarketScan Commercial Database between December 2009 and February 2014. We used comparative segmented linear regression to assess changes in the proportions of patients who filled/newly filled carisoprodol each month.

Results: A total of 13.3 million patients were included. 29 states with no scheduling prior to the DEA classification had lower baseline prevalence of carisoprodol use compared to 17 states that had scheduled carisoprodol individually before 2010 (11.0 vs. 21.1 patients with fills per 1000 patients). The federal scheduling was associated with an immediate decline (-1.12 per 1000 patients, p < 0.01) and decreasing trend in prevalence (-0.07 per 1000 patients per month, p = 0.02). This effect was not modified by existing state-level scheduling status. During the first, second, third, and fourth 6-month periods after federal scheduling, the relative difference between observed and predicted prevalence was 7.8%, 10.5%, 13.4%, and 19.8%. Similar patterns were observed for carisoprodol initiation. Overall, declining use was more pronounced among younger age groups and patients with injury.

Conclusions: Schedule IV controlled substance classification at the federal level was associated with a moderate reduction in the dispensing of carisoprodol regardless of whether scheduling was already present at the state level.
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http://dx.doi.org/10.1016/j.drugalcdep.2019.05.025DOI Listing
September 2019