Enhanced Rates of Transition-Metal-Ion-Catalyzed Oxidation of S(IV) in Aqueous Aerosols: Insights into Sulfate Aerosol Formation in the Atmosphere.

The oxidation of S(IV) is a critical step in the fate of sulfur dioxide emissions that determines the amount of sulfate aerosol in the atmosphere. Herein, we measured accelerated S(IV) oxidation rates in micron-sized aqueous aerosols compared to bulk solutions. We have investigated both buffered and unbuffered systems across a range of pH values in the presence of atmospherically relevant transition-metal ions and salts and consistently found the oxidation rate to be accelerated by ca. 1-2 orders of magnitude in the aerosol. This enhancement is greater than can be explained by the enrichment of species in the aerosol compared to the bulk and indicates that surface effects and potentially aerosol pH gradients play important roles in the S(IV) oxidation process in the aqueous aerosol. In addition, our experiments were performed with dissolved S(IV) ions (SO32-/HSO3-), allowing us to demonstrate that acceleration occurs in the condensed phase showing that enhanced sulfate formation is not exclusively due to gas-aerosol partitioning or interfacial SO2 oxidation. Our findings are an important step forward in understanding larger than expected sulfate concentrations observed in the atmosphere and show that inorganic oxidation processes can be accelerated in micron-sized aqueous droplets compared to the bulk solution.

American Society of Regional Anesthesia and Pain Medicine Local Anesthetic Systemic Toxicity checklist: 2020 version.

The American Society of Regional Anesthesia and Pain Medicine (ASRA) periodically updates its practice advisories and associated cognitive aids. The 2020 version of the ASRA Local Anesthetic Systemic Toxicity checklist was created in response to user feedback, simulation studies and advances in medical knowledge. This report presents the 2020 version and discusses the rationale for its update.

Vanderbilt Health Affiliated Network Statin Outreach Service.

Quality Improvement Success Stories are published by the American Diabetes Association in collaboration with the American College of Physicians and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of Clinical Diabetes. The following article describes the design and implementation of a pharmacist-led program to improve rates of statin use among appropriate patients in high-risk populations.

The Role of Computerized Clinical Decision Support in Reducing Inappropriate Medication Administration During Epidural Therapy.

Background: The use of epidural anesthesia has been shown to improve outcomes in the postoperative setting. To minimize risk of complications, avoiding certain medications with epidural anesthesia is advised. Objective: This study sought to determine the role of a computerized clinical decision support module implemented into the computerized physician order entry (CPOE) system on the incidence of administration of medications known to increase complications with epidural anesthesia. Methods: This study was a retrospective cohort chart review in adult patients receiving epidural anesthesia for at least 1 day. Patients were identified retrospectively and divided into 2 cohorts, those receiving an epidural 3 months prior to initiation of the module and those receiving an epidural 3 months following implementation. The primary end point was incidence of inappropriate medication administration before and after implementation. Complications of therapy were collected as secondary end points. Results: There was a reduction in the incidence of inappropriate medication administration in the postimplementation group versus the preimplementation group (6.3% vs 12.8%) although statistical significance was not achieved. In addition, the incidence of enoxaparin administration was significantly lower postimplementation than the preimplementation (0% vs 3.9%). There were no significant differences in other complications of therapy. Conclusions: This study demonstrated that application of decision support for this high-risk procedural population was able to eliminate the incidence of the most common inappropriate medication for epidural analgesia, enoxaparin. A reduction in incidence of other inappropriate medications was also observed; however, statistical significance was not reached. The use of computerized clinical decision support can be a powerful tool in reducing or ameliorating medication errors, and further study will be required to determine the most appropriate and effective implementation strategies.

ePrescribing: Reducing Costs through In-Class Therapeutic Interchange.

INTRODUCTION: Spending on pharmaceuticals in the US reached $373.9 billion in 2014. Therapeutic interchange offers potential medication cost savings by replacing a prescribed drug for an equally efficacious therapeutic alternative. METHODS: Hard-stop therapeutic interchange recommendation alerts were developed for four medication classes (HMG-CoA reductase inhibitors, serotonin receptor agonists, intranasal steroid sprays, and proton-pump inhibitors) in an electronic prescription-writing tool for outpatient prescriptions. Using prescription data from January 2012 to June 2015, the Compliance Ratio (CR) was calculated by dividing the number of prescriptions with recommended therapeutic interchange medications by the number of prescriptions with non-recommended medications to measure effectiveness. To explore potential cost savings, prescription data and medication costs were analyzed for the 45,000 Vanderbilt Employee Health Plan members. RESULTS: For all medication classes, significant improvements were demonstrated - the CR improved (proton-pump inhibitors 2.8 to 5.32, nasal steroids 2.44 to 8.16, statins 2.06 to 5.51, and serotonin receptor agonists 0.8 to 1.52). Quarterly savings through the four therapeutic interchange interventions combined exceeded $200,000 with an estimated annual savings for the health plan of $800,000, or more than $17 per member. CONCLUSION: A therapeutic interchange clinical decision support tool at the point of prescribing resulted in increased compliance with recommendations for outpatient prescriptions while producing substantial cost savings to the Vanderbilt Employee Health Plan - $17.77 per member per year. Therapeutic interchange rules require rational targeting, appropriate governance, and vigilant content updates.

Partial Decay of Thiamine Signal Transduction Pathway Alters Growth Properties of Candida glabrata.

The phosphorylated form of thiamine (Vitamin B1), thiamine pyrophosphate (TPP) is essential for the metabolism of amino acids and carbohydrates in all organisms. Plants and microorganisms, such as yeast, synthesize thiamine de novo whereas animals do not. The thiamine signal transduction (THI) pathway in Saccharomyces cerevisiae is well characterized. The ~10 genes required for thiamine biosynthesis and uptake are transcriptionally upregulated during thiamine starvation by THI2, THI3, and PDC2. Candida glabrata, a human commensal and opportunistic pathogen, is closely related to S. cerevisiae but is missing half of the biosynthetic pathway, which limits its ability to make thiamine. We investigated the changes to the THI pathway in C. glabrata, confirming orthologous functions. We found that C. glabrata is unable to synthesize the pyrimidine subunit of thiamine as well as the thiamine precursor vitamin B6. In addition, THI2 (the gene encoding a transcription factor) is not present in C. glabrata, indicating a difference in the transcriptional regulation of the pathway. Although the pathway is upregulated by thiamine starvation in both species, C. glabrata appears to upregulate genes involved in thiamine uptake to a greater extent than S. cerevisiae. However, the altered regulation of the THI pathway does not alter the concentration of thiamine and its vitamers in the two species as measured by HPLC. Finally, we demonstrate potential consequences to having a partial decay of the THI biosynthetic and regulatory pathway. When the two species are co-cultured, the presence of thiamine allows C. glabrata to rapidly outcompete S. cerevisiae, while absence of thiamine allows S. cerevisiae to outcompete C. glabrata. This simplification of the THI pathway in C. glabrata suggests its environment provides thiamine and/or its precursors to cells, whereas S. cerevisiae is not as reliant on environmental sources of thiamine.

Effect of Pharmacist Counseling Intervention on Health Care Utilization Following Hospital Discharge: A Randomized Control Trial.

BACKGROUND: Reduction in 30-day readmission rates following hospitalization for acute coronary syndrome (ACS) and acute decompensated heart failure (ADHF) is a national goal. OBJECTIVE: The aim of this study was to determine the effect of a tailored, pharmacist-delivered, health literacy intervention on unplanned health care utilization, including hospital readmission or emergency room (ER) visit, following discharge. DESIGN: Randomized, controlled trial with concealed allocation and blinded outcome assessors SETTING: Two tertiary care academic medical centers PARTICIPANTS: Adults hospitalized with a diagnosis of ACS and/or ADHF. INTERVENTION: Pharmacist-assisted medication reconciliation, inpatient pharmacist counseling, low-literacy adherence aids, and individualized telephone follow-up after discharge MAIN MEASURES: The primary outcome was time to first unplanned health care event, defined as hospital readmission or an ER visit within 30 days of discharge. Pre-specified analyses were conducted to evaluate the effects of the intervention by academic site, health literacy status (inadequate versus adequate), and cognition (impaired versus not impaired). Adjusted hazard ratios (aHR) and 95% confidence intervals (CI) are reported. KEY RESULTS: A total of 851 participants enrolled in the study at Vanderbilt University Hospital (VUH) and Brigham and Women's Hospital (BWH). The primary analysis showed no statistically significant effect on time to first unplanned hospital readmission or ER visit among patients who received interventions compared to controls (aHR = 1.04, 95% CI 0.78-1.39). There was an interaction of treatment effect by site (p = 0.04 for interaction); VUH aHR = 0.77, 95% CI 0.51-1.15; BWH aHR = 1.44 (95% CI 0.95-2.12). The intervention reduced early unplanned health care utilization among patients with inadequate health literacy (aHR 0.41, 95% CI 0.17-1.00). There was no difference in treatment effect by patient cognition. CONCLUSION: A tailored, pharmacist-delivered health literacy-sensitive intervention did not reduce post-discharge unplanned health care utilization overall. The intervention was effective among patients with inadequate health literacy, suggesting that targeted practice of pharmacist intervention in this population may be advantageous.

Comorbidity in Drivers with Parkinson's Disease.

OBJECTIVES: To determine the effect of comorbidity on fitness-to-drive recommendations that physicians and on-road driving assessors make and to investigate the agreement in fitness-to-drive recommendations between physicians and on-road driving assessors. DESIGN: Retrospective. SETTING: Data on comorbidities associated with Parkinson's disease (PD) and fitness-to-drive recommendations were investigated. PARTICIPANTS: Individuals with PD who underwent an official on-road test in Belgium (N = 72). MEASUREMENTS: Correlations between comorbidity and fitness-to-drive recommendations were calculated. Stepwise logistic regression models were used to investigate whether comorbidity was an independent predictor of fitness-to-drive recommendations (pass/fail) that the physicians or the on-road assessors made. The percentage of agreement and the prevalence and bias-adjusted kappa (PABAK) were used to investigate agreement between the physicians and the on-road assessors. RESULTS: Moderate correlations were found between comorbidity and fitness-to-drive recommendations that the physicians (ρ = 0.34, P = .004) and the on-road assessors (ρ = 0.30, P = .01) made. Comorbidity was the most important determinant (coefficient of determination = 0.16, P = .005) of the physicians fitness-to-drive recommendations. No significant effect of comorbidity on the on-road recommendations was found. The physicians and the on-road assessors agreed in 46 (64%) of the cases (PABAK = 0.46, P < .001). CONCLUSION: Comorbidity plays a role in physicians' recommendations of fitness to drive that may explain, in part, inconsistencies between physicians and on-road assessors' fitness-to-drive recommendations. This study indicates the need for an interdisciplinary dialogue between physicians and on-road assessors to reach a comprehensive fitness-to-drive decision.

Medication Discrepancies and Associated Risk Factors Identified in Home Health patients.

Medication discrepancies can place patients at increased risk for adverse drug events. We sought to determine the frequency, type, and reason for medication discrepancies in patients receiving home healthcare following hospital discharge. We conducted a retrospective, observational study of adults discharged from an academic medical center who received home healthcare following hospital discharge from one affiliated home healthcare agency. Medication discrepancies were identified by comparing the hospital discharge medication list to what the patient was taking at the first home healthcare visit. Almost all patients (66/70, 94%) had at least one medication discrepancy. The median number of discrepancies per patient was 5. Nearly half of the discrepancies were omissions (46%), in which the patient was not taking a medication on the discharge medication list. Increased age was significantly associated with fewer medication discrepancies overall (IRR = 0.99, p < 0.05). Higher health literacy was associated with more omissions (IRR = 1.85, p < 0.05).

Agreement Between Physician's Recommendation and Fitness-to-Drive Decision in Multiple Sclerosis.

OBJECTIVE: To investigate the agreement of fitness-to-drive decisions made by the referring physicians and by the on-road assessors in individuals with multiple sclerosis (MS). DESIGN: Retrospective analysis. SETTING: Driving institute. PARTICIPANTS: A sample of individuals with MS (N=218) who completed the medical and driving questionnaire and performed an official on-road test. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Fitness-to-drive decision made by the on-road assessor. RESULTS: The referring physician and on-road assessor agreed on fitness to drive in 191 (88%) of the cases (prevalence-adjusted and bias-adjusted κ=.81, P<.0001). When compared with the on-road assessor's judgment, the physician's recommendation of fitness to drive was overestimated in 16 individuals with MS and underestimated in 11 individuals with MS. Patients with poor binocular acuity were more likely to be inaccurately classified by the physician (P=.001). CONCLUSIONS: This study showed a high level of agreement between the fitness-to-drive decisions made by the physicians and the on-road assessors in individuals with MS. Visual functions should be assessed in the doctor's office for more accurate referrals.

Improving medication safety during hospital-based transitions of care.

Medication errors are common during transitions of care such as hospital admission and discharge. Problems range from minor discrepancies to actual patient harm. A systematic routine for medication reconciliation can minimize errors, thereby preventing adverse drug events and improving patient safety.

Care transitions: a leverage point for safe and effective medication use in older adults--a mini-review.

Older adults often face challenges as they transition out of the acute care hospital, especially with regard to adhering to their medications. In this narrative review, we discuss medication adherence in older adults across the continuum of care, describing reasons for nonadherence, methods to assess adherence and tools to improve adherence, with particular focus on emerging techniques and technologies. Taking steps at care transitions to assess medications and foster adherence to the medication regimen can increase the safety of older adults following hospitalization.

Inappropriate medication prescriptions in elderly adults surviving an intensive care unit hospitalization.

OBJECTIVES: To determine types of potentially (PIMs) and actually inappropriate medications (AIMs), which PIMs are most likely to be considered AIMs, and risk factors for PIMs and AIMs at hospital discharge in elderly intensive care unit (ICU) survivors. DESIGN: Prospective cohort study. SETTING: Tertiary care, academic medical center. PARTICIPANTS: One hundred twenty individuals aged 60 and older who survived an ICU hospitalization. MEASUREMENTS: Potentially inappropriate medications were defined according to published criteria; a multidisciplinary panel adjudicated AIMs. Medications from before admission, ward admission, ICU admission, ICU discharge, and hospital discharge were abstracted. Poisson regression was used to examine independent risk factors for hospital discharge PIMs and AIMs. RESULTS: Of 250 PIMs prescribed at discharge, the most common were opioids (28%), anticholinergics (24%), antidepressants (12%), and drugs causing orthostasis (8%). The three most common AIMs were anticholinergics (37%), nonbenzodiazepine hypnotics (14%), and opioids (12%). Overall, 36% of discharge PIMs were classified as AIMs, but the percentage varied according to drug type. Whereas only 16% of opioids, 23% of antidepressants, and 10% of drugs causing orthostasis were classified as AIMs, 55% of anticholinergics, 71% of atypical antipyschotics, 67% of nonbenzodiazepine hypnotics and benzodiazepines, and 100% of muscle relaxants were deemed AIMs. The majority of PIMs and AIMs were first prescribed in the ICU. Preadmission PIMs, discharge to somewhere other than home, and discharge from a surgical service predicted number of discharge PIMs, but none of the factors predicted AIMs at discharge. CONCLUSION: Certain types of PIMs, which are commonly initiated in the ICU, are more frequently considered inappropriate upon clinical review. Efforts to reduce AIMs in elderly ICU survivors should target these specific classes of medications.

Adverse drug events during AKI and its recovery.

BACKGROUND AND OBJECTIVES: The impact of AKI on adverse drug events and therapeutic failures and the medication errors leading to these events have not been well described. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A single-center observational study of 396 hospitalized patients with a minimum 0.5 mg/dl change in serum creatinine who were prescribed a nephrotoxic or renally eliminated medication was conducted. The population was stratified into two groups by the direction of their initial serum creatinine change: AKI and AKI recovery. Adverse drug events, potential adverse drug events, therapeutic failures, and potential therapeutic failures for 148 drugs and 46 outcomes were retrospectively measured. Events were classified for preventability and severity by expert adjudication. Multivariable analysis identified medication classes predisposing AKI patients to adverse drug events. RESULTS: Forty-three percent of patients experienced a potential adverse drug event, adverse drug event, therapeutic failure, or potential therapeutic failure; 66% of study events were preventable. Failure to adjust for kidney function (63%) and use of nephrotoxic medications during AKI (28%) were the most common potential adverse drug events. Worsening AKI and hypotension were the most common preventable adverse drug events. Most adverse drug events were considered serious (63%) or life-threatening (31%), with one fatal adverse drug event. Among AKI patients, administration of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, antibiotics, and antithrombotics was most strongly associated with the development of an adverse drug event or potential adverse drug event. CONCLUSIONS: Adverse drug events and potential therapeutic failures are common and frequently severe in patients with AKI exposed to nephrotoxic or renally eliminated medications.

Real-time pharmacy surveillance and clinical decision support to reduce adverse drug events in acute kidney injury: a randomized, controlled trial.

OBJECTIVES: Clinical decision support (CDS), such as computerized alerts, improves prescribing in the setting of acute kidney injury (AKI), but considerable opportunity remains to improve patient safety. The authors sought to determine whether pharmacy surveillance of AKI patients could detect and prevent medication errors that are not corrected by automated interventions. METHODS: The authors conducted a randomized clinical trial among 396 patients admitted to an academic, tertiary care hospital between June 1, 2010 and August 31, 2010 with an acute 0.5 mg/dl change in serum creatinine over 48 hours and a nephrotoxic or renally cleared medication order. Patients randomly assigned to the intervention group received surveillance from a clinical pharmacist using a web-based surveillance tool to monitor drug prescribing and kidney function trends. CDS alerting and standard pharmacy services were active in both study arms. Outcome measures included blinded adjudication of potential adverse drug events (pADEs), adverse drug events (ADEs) and time to provider modification or discontinuation of targeted nephrotoxic or renally cleared medications. RESULTS: Potential ADEs or ADEs occurred for 104 (8.0%) of control and 99 (7.1%) of intervention patient-medication pairs (p=0.4). Additionally, the time to provider modification or discontinuation of targeted nephrotoxic or renally cleared medications did not differ between control and intervention patients (33.4 hrs vs. 30.3 hrs, p=0.3). CONCLUSIONS: Pharmacy surveillance had no incremental benefit over previously implemented CDS alerts.

Effect of patient- and medication-related factors on inpatient medication reconciliation errors.

BACKGROUND: Little research has examined the incidence, clinical relevance, and predictors of medication reconciliation errors at hospital admission and discharge. OBJECTIVE: To identify patient- and medication-related factors that contribute to pre-admission medication list (PAML) errors and admission order errors, and to test whether such errors persist in the discharge medication list. DESIGN, PARTICIPANTS: We conducted a cross-sectional analysis of 423 adults with acute coronary syndromes or acute decompensated heart failure admitted to two academic hospitals who received pharmacist-assisted medication reconciliation during the Pharmacist Intervention for Low Literacy in Cardiovascular Disease (PILL-CVD) Study. MAIN MEASURES: Pharmacists assessed the number of total and clinically relevant errors in the PAML and admission and discharge medication orders. We used negative binomial regression and report incidence rate ratios (IRR) of predictors of reconciliation errors. KEY RESULTS: On admission, 174 of 413 patients (42%) had ≥1 PAML error, and 73 (18%) had ≥1 clinically relevant PAML error. At discharge, 158 of 405 patients (39%) had ≥1 discharge medication error, and 126 (31%) had ≥1 clinically relevant discharge medication error. Clinically relevant PAML errors were associated with older age (IRR = 1.46; 95% CI, 1.00- 2.12) and number of pre-admission medications (IRR = 1.17; 95% CI, 1.10-1.25), and were less likely when a recent medication list was present in the electronic medical record (EMR) (IRR = 0.54; 95% CI, 0.30-0.96). Clinically relevant admission order errors were also associated with older age and number of pre-admission medications. Clinically relevant discharge medication errors were more likely for every PAML error (IRR = 1.31; 95% CI, 1.19-1.45) and number of medications changed prior to discharge (IRR = 1.06; 95% CI, 1.01-1.11). CONCLUSIONS: Medication reconciliation errors are common at hospital admission and discharge. Errors in preadmission medication histories are associated with older age and number of medications and lead to more discharge reconciliation errors. A recent medication list in the EMR is protective against medication reconciliation errors.

Simultaneous measurement of intracellular triphosphate metabolites of zidovudine, lamivudine and abacavir (carbovir) in human peripheral blood mononuclear cells by combined anion exchange solid phase extraction and LC-MS/MS.

All nucleoside reverse transcriptase inhibitors (NRTI) must first be metabolized to their triphosphate forms in order to be active against HIV. Zidovudine (ZDV), abacavir (ABC) and lamivudine (3TC) have proven to be an efficacious combination. In order simultaneously to measure intracellular levels of the triphosphates (-TP) of ZDV, ABC (carbovir, CBV) and 3TC, either together or individually, we have developed a cartridge-LC-MS/MS method. The quantitation range was 2.5-250 pg/microl for 3TC-TP, 0.1-10.0 pg/microl for ZDV-TP and 0.05-5.00 pg/microl for CBV-TP. This corresponds to 0.1-11.0 pmol 3TC-TP per million cells, 4-375 fmol ZDV-TP per million cells and 2-200 fmol CBV-TP per million cells, extracted from 10 million cells. Patient samples demonstrated measured levels in the middle regions of our standard curves both at pre-dose and 4h post-dose times.

Rapid Ped-2E9 cell-based cytotoxicity analysis and genotyping of Bacillus species.

Bacillus species causing food-borne disease produce multiple toxins eliciting gastroenteritis. Toxin assays with mammalian cell cultures are reliable but may take 24 to 72 h to complete and also lack sensitivity. Here, a sensitive and rapid assay was developed using a murine hybridoma Ped-2E9 cell model. Bacillus culture supernatants containing toxins were added to a Ped-2E9 cell line and analyzed for cytotoxicity with an alkaline phosphatase release assay. Most Bacillus cereus strains produced positive cytotoxicity results within 1 h, and data were comparable to those obtained with the standard Chinese hamster ovary (CHO)-based cytotoxicity assay, which took about 72 h to complete. Moreover, the Ped-2E9 cell assay had 25- to 58-fold-higher sensitivity than the CHO assay. Enterotoxin-producing Bacillus thuringiensis also gave positive results with Ped-2E9 cells, while several other Bacillus species were negative. Eight isolates from food suspected of Bacillus contamination were also tested, and only one strain, which was later confirmed as B. cereus, gave a positive result. In comparison with two commercial diarrheal toxin assay kits (BDE-VIA and BCET-RPLA), the Ped-2E9 assay performed more reliably. Toxin fractions of >30 kDa showed the highest degree of cytotoxicity effects, and heat treatment significantly reduced the toxin activity, indicating the involvement of a heat-labile high-molecular-weight component in Ped-2E9 cytotoxicity. PCR results, in most cases, were in agreement with the cytotoxic potential of each strain. Ribotyping was used to identify cultures and indicated differences for several previously reported isolates. This Ped-2E9 cell assay could be used as a rapid (approximately 1-h) alternative to current methods for sensitive detection of enterotoxins from Bacillus species.