Quality-of-life outcomes of the ROBOtic-assisted versus Conventional Open Partial nephrectomy (ROBOCOP) II trial.

OBJECTIVES: To comprehensively compare quality-of-life (QoL) outcomes between open partial nephrectomy (OPN) and robot-assisted PN (RAPN) from the randomised ROBOtic-assisted versus Conventional Open Partial nephrectomy (ROBOCOP) II trial, as QoL data comparing OPN and RAPN are virtually non-existent, especially not from randomised controlled trials (RCTs). PATIENTS AND METHODS: The ROBOCOP II was a single-centre, open-label RCT between OPN and RAPN. The pre-planned analyses of QoL outcomes are presented. Data were analysed descriptively in a modified intention-to-treat population. RESULTS: A total of 50 patients underwent surgery. At postoperative Day 90 (POD90), there was no significant difference for the Kidney Disease Quality of Life-Short Form questionnaire score (mean [sd] OPN 72 [20] vs RAPN 76 [15], P = 0.850), while there were advantages for RAPN in the subdomains of 'Pain' (P = 0.006) and 'Physical functioning' (P = 0.011) immediately after surgery. For the European Organisation for Research and Treatment of Cancer quality of life questionnaire 30-item core there were overall advantages directly after surgery (mean [sd] score OPN 63 [20] vs RAPN 75 [17], P = 0.031), as well as for the subdomains 'Fatigue' (P = 0.026), 'Pain' (P = 0.002) and 'Constipation' (P = 0.045) but no differences at POD90. There were no differences for the EuroQoL five Dimensions five Levels questionnaire at POD90 (mean [sd] score OPN 70 [22] vs RAPN 72 [17], P = 1.0) or at any other time point. Finally, no significant differences were found for the overall Convalescence and Recovery Evaluation questionnaire score at POD90 (mean [sd] OPN 84 [13] vs RAPN 86 [10], P = 0.818) but less pain in the RAPN group (P = 0.017) directly after surgery. CONCLUSIONS: Pain and physical functioning as subdomains of QoL are improved after RAPN compared to OPN in the early postoperative course, while there are no differences anymore after 3 months.

Comparing the effects of decreasing prescription opioid shipments and the release of an abuse deterrent OxyContin formulation on opioid overdose fatalities in WV: an interrupted time series study.

INTRODUCTION: The 2010 release of an abuse deterrent formulation (ADF) of OxyContin, a brand name prescription opioid, has been cited as a major driver for the reduction in prescription drug misuse and the associated increasing illicit opioid use and overdose rates. However, studies of this topic often do not account for changes in supplies of other prescription opioids that were widely prescribed before and after the ADF OxyContin release, including generic oxycodone formulations and hydrocodone. We therefore sought to compare the impact of the ADF OxyContin release to that of decreasing prescription opioid supplies in West Virginia (WV). METHODS: Opioid tablet shipment and overdose data were extracted from The Washington Post ARCOS (2006-2014) and the WV Forensic Drug Database (2005-2020), respectively. Locally estimated scatterplot smoothing (LOESS) was used to estimate the point when shipments of prescription opioids to WV began decreasing, measured via dosage units and morphine milligram equivalents (MMEs). Interrupted time series analysis (ITSA) was used to compare the impact LOESS-identified prescription supply changes and the ADF OxyContin release had on prescription (oxycodone and hydrocodone) and illicit (heroin, fentanyl, and fentanyl analogues) opioid overdose deaths in WV. Model fit was compared using Akaike Information Criteria (AIC). RESULTS: The majority of opioid tablets shipped to WV from 2006 to 2014 were generic oxycodone or hydrocodone, not OxyContin. After accounting for a 6-month lag from ITSA models using the LOESS-identified change in prescription opioid shipments measured via dosage units (2011 Q3) resulted in the lowest AIC for both prescription (AIC = -188.6) and illicit opioid-involved overdoses (AIC = -189.4), indicating this intervention start date resulted in the preferred model. The second lowest AIC was for models using the ADF OxyContin release as an intervention start date. DISCUSSION: We found that illicit opioid overdoses in WV began increasing closer to when prescription opioid shipments to the state began decreasing, not when the ADF OxyContin release occurred. Similarly, the majority of opioid tablets shipped to the state for 2006-2014 were generic oxycodone or hydrocodone. This may indicate that diminishing prescription supplies had a larger impact on opioid overdose patterns than the ADF OxyContin release in WV.

Randomized Controlled Feasibility Trial of Robot-assisted Versus Conventional Open Partial Nephrectomy: The ROBOCOP II Study.

BACKGROUND: There is no evidence from randomized controlled trials (RCTs) comparing robot-assisted partial nephrectomy (RAPN) and open partial nephrectomy (OPN). OBJECTIVE: To assess the feasibility of trial recruitment and to compare surgical outcomes between RAPN and OPN. DESIGN, SETTING, AND PARTICIPANTS: ROBOCOP II was designed as single-center, open-label, feasibility RCT. Patients with suspected localized renal cell carcinoma referred for PN were randomized at a 1:1 ratio to either RAPN or OPN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the feasibility of recruitment, assessed as the accrual rate. Secondary outcomes included perioperative and postoperative data. Data were analyzed descriptively in a modified intention-to-treat population consisting of randomized patients who underwent surgery. RESULTS AND LIMITATIONS: A total of 50 patients underwent RAPN or OPN (accrual rate 65%). In comparison to OPN, RAPN had lower blood loss (OPN 361 ml, standard deviation [SD] 238; RAPN 149 ml, SD 122; difference 212 ml, 95% confidence interval [CI] 105-320; p < 0.001), less need for opioids (OPN 46%; RAPN 16%; difference 30%, 95% CI 5-54; p = 0.024), and fewer complications according to the mean Comprehensive Complication Index (OPN 14, SD 16; RAPN 5, SD 15; difference 9, 95% CI 0-18; p = 0.008). OPN has a shorter operative time (OPN 112 min, SD 29; RAPN 130 min, SD 32; difference -18 min, 95% CI -35 to -1; p = 0.046) and warm ischemia time (OPN 8.7 min, SD 7.1; RAPN 15.4 min, SD 7.0; difference 6.7 min, 95% CI -10.7 to -2.7; p = 0.001). There were no differences between RAPN and OPN regarding postoperative kidney function. CONCLUSIONS: This first RCT comparing OPN and RAPN met the primary outcome of the feasibility of recruitment; however, the window for future RCTs is closing. Each approach has advantages over the other, and both remain safe and effective options. PATIENT SUMMARY: For patients with a kidney tumor, open surgery and robot-assisted keyhole surgery are both feasible and safe approaches for partial removal of the affected kidney. Each approach has known advantages. Long-term follow-up will explore differences in quality of life and cancer control outcomes.

Quantifying a potential protective effect of buprenorphine on fatality risk during acute fentanyl exposures.

INTRODUCTION: Buprenorphine is an important therapy for opioid use disorder and may also reduce the risk of fatal overdoses in fentanyl exposures. However, the role of buprenorphine in reducing this risk has not been quantified. This cross-sectional study examined the association between buprenorphine presence, decedent characteristics, and other factors with the predicted fentanyl concentrations in overdose deaths. METHODS: The study identified unintentional fentanyl overdose decedents (n = 3036) from the West Virginia Forensic Drug Database, 2011 through mid-2020. The main outcome was fentanyl concentrations in overdose deaths in the presence and absence of buprenorphine. A multiple linear regression model examined the association of fentanyl concentrations with buprenorphine presence based on the concentrations of the parent drug buprenorphine (B) and its metabolite norbuprenorphine (N), adjusting for demographics, toxicological characteristics (presence of multiple opioids, benzodiazepines, stimulants, marijuana, and alcohol), and comorbidities. We used a B/N concentration ratio < 1 as an indirect indicator of longer-term buprenorphine exposure prior to drug overdose death. RESULTS: The median fentanyl concentration was 65 % higher when buprenorphine was present (N = 168) vs. absent (N = 2868) (0.028 vs. 0.017 µg/mL, p < 0.001). In the multivariable model, statistically significant associations occurred between buprenorphine presence and increased fentanyl concentrations (+28.7 %) with a B/N ratio < 1. Obesity, male sex, alcohol presence, and comorbid cardiovascular diseases were statistically significantly associated with lower (-11.3 % to -20.7 %) fentanyl concentrations, whereas marijuana presence and a history of substance use disorder were associated with statistically significant higher fentanyl concentrations (+8.8 % to +31.3 %). CONCLUSIONS: These findings suggest that sustained or longer-term buprenorphine intake might exert some protective effect on fatalities resulting from fentanyl exposure as documented by the association of higher fentanyl blood concentrations with buprenorphine presence among fatal drug overdoses. As fentanyl availability and overdose rates increase nationally, buprenorphine is a vital tool for effective opioid use disorder treatment that might also reduce the risk of fatality in an acute fentanyl exposure.

Framework for a living systematic review and meta-analysis for the surgical treatment of bladder cancer: introducing EVIglance to urology.

Background: Knowledge of current and ongoing studies is critical for identifying research gaps and enabling evidence-based decisions for individualized treatment. However, the increasing number of scientific publications poses challenges for healthcare providers and patients in all medical fields to stay updated with the latest evidence. To overcome these barriers, we aim to develop a living systematic review and open-access online evidence map of surgical therapy for bladder cancer (BC), including meta-analyses. Methods: Following the guidelines provided in the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement, a systematic literature search on uro-oncological therapy in BC will be performed across various literature databases. Within the scope of a meta-analysis and living systematic review, relevant randomized controlled trials will be identified. Data extraction and quantitative analysis will be conducted, along with a critical appraisal of the quality and risk of bias of each study. The available research evidence will be entered into an open-access framework (www.evidencemap.surgery) and will also be accessible via the EVIglance app. Regular semi-automatic updates will enable the implementation of a real-living review concept and facilitate resource-efficient screening. Discussion: A regularly updated evidence map provides professionals and patients with an open-access knowledge base on the current state of research, allowing for decision-making based on recent evidence. It will help identify an oversupply of evidence, thus avoiding redundant work. Furthermore, by identifying research gaps, new hypotheses can be formulated more precisely, enabling planning, determination of sample size, and definition of endpoints for future trials.

Characterization of Unintentional Deaths Among Buprenorphine Users.

OBJECTIVE: Medications used to treat opioid use disorder (OUD) reduce drug overdose risk. Buprenorphine is often the preferred treatment for OUD because of its high safety profile. Given expanding buprenorphine use, this study sought to examine buprenorphine-involved deaths (BIDs) and compare them with other drug-related deaths. METHOD: West Virginia drug-related deaths from 2005 to early 2020 were identified. Study data included decedent demographics, toxicology, autopsy findings, and medical and prescription histories. Characteristics of BIDs compared with other drug-related deaths were statistically analyzed. RESULTS: Among 11,764 drug-related deaths, only 564 (4.8%) involved buprenorphine. Buprenorphine alone was present in 32 deaths, of which 20 were considered the direct cause of death (0.2% of all drug-related deaths). Significantly more BIDs involved five or more drugs (23%) compared with other opioid deaths (14.9%). Co-intoxicants found most frequently in BIDs were benzodiazepines (47.3%), methamphetamine (27.1%), and fentanyl (22.9%). Cardiovascular and pulmonary comorbidities were identified in 43% and 21% of BIDs, respectively. Of the 564 BIDs, a current buprenorphine prescription was present in 132 deaths (23.4%). CONCLUSIONS: Despite increasing buprenorphine use, BIDs comprised less than 5% of overall West Virginia drug-related deaths. Seldom was it the only drug found, and most decedents did not have current prescriptions for buprenorphine. Although buprenorphine is effective, with a wide safety margin, clinicians and patients should be aware that buprenorphine can be involved in overdose deaths, especially when buprenorphine is taken in combination with drugs such as benzodiazepines, methamphetamine, or fentanyl, and in persons with underlying cardiovascular or pulmonary comorbidities.

Characteristics of xylazine-related deaths in West Virginia-Xylazine-related deaths.

BACKGROUND AND OBJECTIVES: The involvement of xylazine, a veterinary drug, in West Virginia (WV) human drug-related deaths was examined. METHODS: WV drug deaths from 2019 (when xylazine was first identified) to mid-2021. Characteristics including toxicology findings were compared between xylazine and nonxylazine deaths. RESULTS: Of 3292 drug deaths, 117 involved xylazine, and the proportions of deaths with it have increased (1% [2019] to 5% [mid-2021)]. Xylazine decedents had more cointoxicants, with fentanyl (98%) predominant followed by methamphetamine. Xylazine decedents had a significantly greater history of drug or alcohol misuse and hepatic disease. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: In one of the largest analyses of xylazine-involved deaths in a predominantly rural state, identification of xylazine was increasing with multiple cointoxicants (especially fentanyl), and was present in a few deaths with only one other substance involved. Health professionals should be aware of possible enhanced toxicity from xylazine ingestion especially since naloxone does not reverse xylazine's adverse effects.

Artificial intelligence for renal cancer: From imaging to histology and beyond.

Artificial intelligence (AI) has made considerable progress within the last decade and is the subject of contemporary literature. This trend is driven by improved computational abilities and increasing amounts of complex data that allow for new approaches in analysis and interpretation. Renal cell carcinoma (RCC) has a rising incidence since most tumors are now detected at an earlier stage due to improved imaging. This creates considerable challenges as approximately 10%-17% of kidney tumors are designated as benign in histopathological evaluation; however, certain co-morbid populations (the obese and elderly) have an increased peri-interventional risk. AI offers an alternative solution by helping to optimize precision and guidance for diagnostic and therapeutic decisions. The narrative review introduced basic principles and provide a comprehensive overview of current AI techniques for RCC. Currently, AI applications can be found in any aspect of RCC management including diagnostics, perioperative care, pathology, and follow-up. Most commonly applied models include neural networks, random forest, support vector machines, and regression. However, for implementation in daily practice, health care providers need to develop a basic understanding and establish interdisciplinary collaborations in order to standardize datasets, define meaningful endpoints, and unify interpretation.

Fentanyl and other opioid involvement in methamphetamine-related deaths.

Background: Methamphetamine-related deaths have been rising along with those involving synthetic opioids, mostly fentanyl and fentanyl analogs (FAs). However, the extent to which methamphetamine involvement in deaths differs from those changes occurring in synthetic opioid involvement is unknown.Objectives: To determine the patterns and temporal changes in methamphetamine-related deaths with and without other drug involvement.Methods: Data from all methamphetamine-related deaths in West Virginia from 2013 to 2018 were analyzed. Quasi-Poisson regression analyses over time were conducted to compare the rates of change in death counts among methamphetamine and fentanyl//FA subgroups.Results: A total of 815 methamphetamine-related deaths were analyzed; 572 (70.2%) were male and 527 (64.7%) involved an opioid. The proportion of methamphetamine only deaths stayed relatively flat over time although the actual numbers of deaths increased. Combined fentanyl/FAs and methamphetamine were involved in 337 deaths (41.3%) and constituted the largest increase from 2013 to 2018. The modeling of monthly death counts in 2017-2018 found that the average number of deaths involving fentanyl without methamphetamine significantly declined (rate of change -0.025, p < .001), while concomitant fentanyl with methamphetamine and methamphetamine only death counts increased significantly (rate of change 0.056 and 0.057, respectively, p < .001).Conclusions: Fentanyl and FAs played an increasingly significant role in methamphetamine-related deaths. The accelerating number of deaths involving fentanyl/FAs and methamphetamine indicates the importance of stimulants and opioids in unintentional deaths. Comprehensive surveillance efforts should continue to track substance use patterns to ensure that appropriate prevention programs are undertaken.

ROBOCOP II (ROBOtic assisted versus conventional open partial nephrectomy) randomised, controlled feasibility trial: clinical trial protocol.

INTRODUCTION: Randomised controlled trials comparing robotic-assisted partial nephrectomy (RAPN) and open PN (OPN) are lacking. Therefore, we aim to report the study protocol and a trial update for a randomised controlled feasibility trial comparing RAPN versus OPN for renal neoplasms. METHODS AND ANALYSIS: The ROBOtic assisted versus conventional Open Partial nephrectomy II trial is designed as a single-centre, randomised, open-label, feasibility trial. Participation will be offered to patients with renal neoplasms and deemed feasible for both, OPN and RAPN. We aim to enrol 50 patients within 15 months using a 1:1 allocation ratio. The primary endpoint of the trial is feasibility of recruitment and will be successful if one third of eligible patients agree to participate. Secondary endpoints include perioperative results, health-related quality of life, inflammatory response as well as surgical ergonomics of the operating team. If the primary outcome, feasibility of recruitment, is successful, the secondary results of the trial will be used for planning a confirmative phase III trial. ETHICS AND DISSEMINATION: Ethical approval was obtained from the local institutional review board (Ethik-Kommission II at Heidelberg University: 2020-542N). Results will be made publicly available in peer-reviewed scientific journals and presented at appropriate congresses and social media. TRIAL REGISTRATION NUMBER: NCT04534998.

Robotic-Assisted Versus Conventional Open Partial Nephrectomy (Robocop): A Propensity Score-Matched Analysis of 249 Patients.

OBJECTIVES: The objective of this study was to compare open partial nephrectomy (OPN) and robotic-assisted PN (RAPN) based on a propensity score-matched sample and to test the Comprehensive Complication Index (CCI) as an end point for complications. METHODS: Patients undergoing PN from 2010 to 2018 at a university care center were included. OPN and RAPN cases were matched in a 2:1 ratio using propensity score-matching with age, gender, BMI, RENAL score, and tumor size as confounders. The primary end point was complications measured with the CCI as continuous score (0-100, 100 indicating death). RESULTS: Data of 570 patients were available. After matching, both cohorts (OPN = 166; RAPN = 83) showed no baseline differences. For the primary end point, CCI, RAPN was superior (RAPN 2.6 ± 7.9 vs. OPN 8.7 ± 13.9; p < 0.001). Additionally, RAPN was superior for length of stay (RAPN 6.5 ± 4.0 vs. OPN 7.4 ± 3.5 days; p < 0.001), hemoglobin drop (RAPN 2.8 ± 1.4 vs. OPN 3.8 ± 1.6 g/dL; p < 0.001), and drop of glomerular filtration rate (RAPN 11.4 ± 14.2 vs. OPN 19.5 ± 14.3 mL/min; p < 0.001). OPN had shorter operating times (RAPN 157 ± 43 vs. OPN 143 ± 45 min; p = 0.014) and less ischemia (RAPN 13% vs. OPN 28%; p = 0.016). CONCLUSIONS: RAPN provides superior short-term results regarding overall complications without compromising renal function for small and less complex tumors. However, OPN remains an important option for more complex and larger tumors.

Recommendations for integration of foundational and clinical sciences throughout the pharmacy curriculum.

INTRODUCTION: Pharmacy faculty have the often difficult task of translating and incorporating existing concepts and advances from the foundational sciences into the clinical sciences and practice. This commentary focuses on content integration as a curricular and educational strategy, outcomes data from integration, and recommendations for programs employing or considering curricular integration. COMMENTARY: Integration of foundational and clinical sciences across the curriculum has been emphasized in accreditation standards but met with mixed reactions by faculty across different disciplines in the academy. Many pharmacy programs have already incorporated some level of integration in didactic courses. However, most report coordination of curricular delivery rather than higher levels of integration in which different disciplines work together to design and deliver instructional materials across the entire curriculum. IMPLICATIONS: Curricular integration models should be optimized to minimize or eliminate the risks of marginalization of foundational sciences in pharmacy curricula. A significant problem in implementing curricular integration is determining the appropriate balance between foundational and clinical sciences. Well-designed curricular integration with ongoing reinforcement that builds in complexity over time could enhance knowledge retention, critical thinking abilities, and clinical decision making. Further research is needed into the outcomes achieved from various integrated curricular approaches in pharmacy education.

Quantifying enhanced risk from alcohol and other factors in polysubstance-related deaths.

BACKGROUND: To quantify how alcohol, polysubstance use and other factors influence opioid concentrations in drug-related deaths in West Virginia (WV), United States. METHODS: Multiple linear regression models were employed to identify relationships among alcohol, other factors, and the concentrations of four commonly identified opioids (fentanyl, hydrocodone, oxycodone, methadone), accounting for demographic, toxicological and comorbid characteristics in WV drug-related deaths from 2005 to 2018. RESULTS: Alcohol concentrations of 0.08% or above were associated with significant reductions in blood concentrations of fentanyl (27.5%), hydrocodone (30.5%) and methadone (32.4%). Significantly lower predicted concentrations of all opioids studied were associated with multiple opioid vs. single opioid presence, with predicted concentration reductions ranging from 13.7% for fentanyl to 65-66% for hydrocodone and oxycodone. Benzodiazepine presence was associated with small, non-statistically significant changes in opioid concentrations, while stimulant presence was associated with statistically significant reductions in hydrocodone and oxycodone concentrations. CONCLUSIONS: Co-ingestion of alcohol, multiple opioids or stimulants were associated with significantly decreased predicted concentrations of commonly identified opioids in drug deaths. Further evidence is provided for enhanced risks from polysubstance use with opioids, which has important public health implications.

Fentanyl and fentanyl-analog involvement in drug-related deaths.

BACKGROUND: To describe and analyze the involvement of fentanyl and fentanyl analogs (FAs) in drug-related deaths in West Virginia (WV), United States. METHODS: Retrospective analyses of all WV drug-related deaths from 2005 to 2017 were performed, including comparisons of demographic and toxicological characteristics among total deaths, deaths in which fentanyl/FAs were present, deaths in which they were absent, heroin-related deaths, and prescription opioid-related deaths. RESULTS: Most of the 8813 drug-related deaths were overdoses, with about 11% resulting from transportation/other injuries in which drugs were contributors. Prescription opioid presence (without fentanyl) decreased by 75% from 2005-14 to 2015-17 (3545 deaths to 859 deaths, respectively), while fentanyl involvement in the deaths increased by 122% between these periods (487 to 1082 deaths). Ten FAs were identified (427 instances) after 2015. Alprazolam and ethanol were among the top five most frequently identified substances across years. Fentanyl, heroin and cocaine replaced oxycodone, diazepam and hydrocodone in the top five beginning in 2015. Few decedents had a prescription for fentanyl after 2015, with fewer prescriptions also present for other controlled substances identified. CONCLUSIONS: Fentanyl, rapidly emerging FAs, and other illicit drugs in recent years pose a serious health threat even though prescription opioid-related deaths decreased over the same time period.

Characterization of drug and alcohol use among senior drivers fatally injured in U.S. motor vehicle collisions, 2008-2012.

OBJECTIVE: Adults 65 years of age and older comprise the fastest growing demographic in the United States. As substance use is projected to increase in this population, there is concern that more seniors will drive under the influence of impairing drugs. The purpose of this analysis was to characterize the drug and alcohol usage among senior drivers fatally injured (FI) in traffic collisions. METHODS: Data from the Fatality Analysis Reporting System were analyzed from 2008 to 2012. Commonly used classes and specific drugs were explored. Rates of drug use, multiple drugs, concomitant drug and alcohol use, and alcohol use alone were generated using Poisson regression with robust error variance estimation. Rates were compared to a reference population of FI middle-aged drivers (30 to 50 years old) using rate ratios. RESULTS: Drug use among FI senior drivers occurred in 20.0% of those tested. Among drug-positive FI senior drivers, narcotics and depressants were frequent. The prevalence of testing positive for any drug, multiple drugs, combined drug and alcohol, and alcohol use alone among FI seniors were 47% less (relative risk [RR] = 0.53, 95% confidence interval [CI], 0.47, 0.62), 59% less (RR = 0.41, 95% CI, 0.34, 0.51), 87% less (RR = 0.13, 95% CI, 0.09, 0.19), and 77% less (RR = 0.23, 95% CI, 0.19, 0.28), respectively, compared to FI middle-aged drivers. CONCLUSIONS: Though overall drug use is less common among FI senior drivers relative to FI middle-aged drivers, driving under the influence of drugs may be a relevant traffic safety concern in a portion of this population.

Medication use and the risk of motor vehicle collision in West Virginia drivers 65 years of age and older: a case-crossover study.

BACKGROUND: The current generation of older adults reports a higher lifetime prevalence of prescription, over-the-counter, and recreational drug use. The purpose of this analysis is to characterize the drug usage and determine the risk of motor vehicle collision associated with individual medications in a population of drivers ≥ 65 years. METHODS: A case-crossover study was conducted at West Virginia University Healthcare's facilities using data obtained from the electronic health records (n = 611) of drivers ≥ 65 years admitted for medical treatment following a motor vehicle collision which occurred between Jan. 1, 2009 and June 30, 2014. Patients' medication usage 14 days before collision were matched and compared to their medication usage during four control periods prior to collision. Odds ratios were then calculated for the most prevalent individual medications and pharmaceutical sub-classes using conditional logistic regression. RESULTS: Analgesic, cardiovascular and gastrointestinal medicines were common. Few drivers tested positive for either licit or illicit drugs. Of those testing positive for drugs, benzodiazepines and opiates were prevalent. Drivers consuming Tramadol (adjusted OR 11.41; 95% CI 1.27, 102.15) were at a significantly increased risk of motor vehicle collision. CONCLUSIONS: Older adult drivers who have a prescription for this medication may need to be aware of the potential risk. Further research is necessary in a larger, more nationally representative population.

Additive Effects of Cointoxicants in Single-Opioid Induced Deaths.

A forensic drug database (FDD) was used to capture comprehensive data from all drug-related deaths in West Virginia, with deaths also included from the northern New England states of Maine, Vermont, and New Hampshire. All four states serve predominantly rural populations under two million and all have similar state medical examiner systems that employ statewide uniform death certification policies and practices. This study focused on 1482 single opioid deaths (fentanyl, hydrocodone, methadone, and oxycodone) in the FDD from 2007-2011. We modeled relationships between the opioid concentrations and the presence or absence of the following commonly occurring non-opioid cointoxicants: benzodiazepines (alprazolam and diazepam), alcohol, tricyclic antidepressants, selective serotonin reuptake inhibitors, and diphenhydramine. Additional covariates of state, age, body mass index, and sex were included. Results showed that the presence of alcohol, benzodiazepines, and antidepressants were each associated with statistically significant lower concentrations of some but not all of the opioids studied, which may obscure the interpretation of postmortem toxicology results alone. Fentanyl concentrations appeared to be the least associated with the presence or absence of the variables studied, and cointoxicant alcohol appeared to be associated with lower concentrations in opioid concentrations than were most of the other factors in the model studied. These findings underscore the importance of documenting all potential cointoxicants in opioid-related deaths.

Parent and Metabolite Opioid Drug Concentrations in Unintentional Deaths Involving Opioid and Benzodiazepine Combinations.

Effects of benzodiazepines on postmortem opioid parent and parent/metabolite blood concentration ratios were determined for fentanyl-, hydrocodone-, methadone-, or oxycodone-related accidental deaths. These opioids are partially metabolized by the CYP3A4 enzyme system, which is also affected by diazepam and alprazolam. Opioid/metabolite combinations examined were as follows: fentanyl/norfentanyl, hydrocodone/dihydrocodeine, methadone/EDDP, and oxycodone/oxymorphone. Parent opioid concentrations were analyzed for 877 deaths. Parent/metabolite concentration ratios were analyzed for 349 deaths, excluding cases with co-intoxicants present known to interfere with opioid elimination. Alprazolam in combination with diazepam significantly decreased median hydrocodone concentrations by 48% (p = 0.01) compared to hydrocodone alone. The methadone parent/metabolite concentration ratio was reduced by 35% in the presence of diazepam compared to methadone alone (p = 0.03). Benzodiazepines did not statistically significantly affect fentanyl or oxycodone concentrations. Possible factors affecting opioid concentrations and possible toxicity development, including any differential effects on specific opioids, should continue to be explored.

Introduction of a continuing professional development tool for preceptors: lessons learned.

Accreditation Council for Pharmacy Education (ACPE) guidelines state that preceptors should "have a systematic, self-directed approach to their own continuing professional development (CPD)." The objective of this study was to encourage preceptors to take advantage of the ACPE CPD resources and implement the concept of CPD (reflect, plan, act, evaluate, record) as a framework for guiding individual preceptor's continuing development as educators and to determine their opinion regarding the usefulness, effectiveness, and obstacles to implementation of this approach. A total of 3713 preceptors from the participating schools were encouraged to undergo CPD training and invited to respond to a series of questions. Of the initial respondents, 48% represented health system/hospital preceptors, followed by community/independent pharmacists (64 of 236, 28%). Preceptor respondents often train students from multiple schools/colleges (average = 1.9 schools/colleges per preceptor) and 90% agreed or strongly agreed with the statement, "the CPD model, as learned in the webcasts, is beneficial for ongoing preceptor development." The general consensus was that the preceptor portfolio provided motivation to reflect, plan, and set more defined and realistic goals for students, residents, and themselves as educators and could be a valuable starting point for promoting preceptors' reflection, planning, and action related to rotation management, professional teaching, and student learning goals.

Trends in drug use among drivers killed in U.S. traffic crashes, 1999-2010.

OBJECTIVE: Driving under the influence of drugs is a global traffic safety and public health concern. This trend analysis examines the changes in general drug usage other than alcohol, broad categories, and typical prescription and illegal drugs among drivers fatally injured in motor vehicle crashes from 1999 to 2010 in the U.S. METHODS: Data from the Fatality Analysis Reporting System were analyzed from 1999 to 2010. Drug prevalence rates and prevalence ratios (PR) were determined comparing rates in 2009-2010 to 1999-2000 using a random effects model. Changes in general drug usage, broad categories, and representative prescription and illegal drugs including, methadone, oxycodone, hydrocodone, barbiturates, benzodiazepines, and cocaine, were explored. RESULTS: Comparing 2009-2010 to 1999-2000, prevalence of drug usage increased 49% (PR=1.49; 95% confidence interval [CI] 1.42, 1.55). The largest increases in broad drug categories were narcotics (PR=2.73; 95% CI 2.41, 3.08), depressants (PR=2.01; 95% CI 1.80, 2.25), and cannabinoids (PR=1.99; 95% CI 1.84, 2.16). The PR were 6.37 (95% CI 5.07, 8.02) for hydrocodone/oxycodone, 4.29 (95% CI 2.88, 6.37) for methadone, and 2.27 (95% CI 2.00, 2.58) for benzodiazepines. Barbiturates declined in rate over the 12-year period (PR=0.53; 95% CI 0.37, 0.75). Cocaine use increased until 2005 then progressively declined, though the rate remained relatively unchanged (PR=0.94; 95% CI 0.84, 1.06). CONCLUSIONS: While more drivers are being tested and found drug-positive, there is evidence that a shift from illegal to prescription drugs may be occurring among fatally injured drivers in the U.S. Driving under the influence of prescription drugs is a growing traffic concern.