Comparison of Narrow-Versus Broad-Spectrum Antibiotics in Elderly Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

BACKGROUND: Little evidence is available regarding the choice of empiric antibiotic therapy in elderly patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The primary objective of this study is to compare the outcomes of elderly patients receiving broad- versus narrow-spectrum antibiotics during hospitalization for AECOPD. DESIGN: A multicenter, retrospective, cohort analysis was performed. Inpatients 65 years and older with a primary discharge diagnosis of AECOPD who received ≥48 hours of antibiotic therapy were included in the study population. Patients were compared based on the spectrum of their antibiotic therapy. Narrow-spectrum antibiotics included: azithromycin, doxycycline, sulfamethoxazole/trimethoprim, or aminopenicillin. The primary outcome was a composite of mechanical ventilation 48 hours after admission, transfer to the intensive care unit 48 hours after admission, 30-day chronic obstructive pulmonary disease (COPD) readmission, and oxygen saturation less than 90% on room air or increased oxygen requirements from baseline 48 hours after admission. RESULTS: Two hundred fifty-three patients were included in this analysis; 127 patients were included in the narrow-spectrum group, and 126 patients were included in the broad-spectrum group. Patient demographics and comorbid conditions were similarly distributed in each group. The incidence of the primary composite outcome occurred in 50 (39.3%) and 60 (47.6%) of patients in the narrow- and broad-spectrum groups, respectively (P = .19). CONCLUSIONS AND RELEVANCE: No difference was found in the primary outcome in inpatients aged ≥65 years with AECOPD who received empiric broad-spectrum or narrow-spectrum antibiotics.

Whole genome sequencing and de novo assembly of Staphylococcus pseudintermedius: a pangenome approach to unravelling pathogenesis of canine pyoderma.

BACKGROUND: Staphylococcus pseudintermedius is the main aetiological agent of canine pyoderma. Whole genome sequencing is the most comprehensive way of obtaining relevant genomic information about micro-organisms. HYPOTHESIS/OBJECTIVES: Oxford Nanopore technology enables quality sequencing and de novo assembly of the whole genome of S. pseudintermedius. Whole genome analysis of S. pseudintermedius may help to better understand the pathogenesis of canine pyodermas. METHODS AND MATERIALS: Twenty-two strains of S. pseudintermedius isolated from the skin of five healthy dogs and 33 strains isolated from skin of 33 dogs with pyoderma were analysed. DNA was extracted and sequenced using Oxford Nanopore MinION, a new technology that delivers longer reads in a hand-held device. The pangenome was analysed and visualised with Anvi'o 6.1. RESULTS: Nanopore technology allowed the sequencing and de novo assembly of the genomes of 55 S. pseudintermedius strains isolated from healthy dogs and from dogs with pyoderma. The average genome size of S. pseudintermedius was 2.62 Mbp, with 48% being core genome. Pyoderma isolates contained a higher number of antimicrobial resistance genes, yet the total number of virulence factors genes did not change between isolates from healthy dogs and from dogs with pyoderma. Genomes of meticillin-resistant S. pseudintermedius (MRSP) strains were larger than those of meticillin-susceptible (MSSP) strains (2.80 Mbp versus 2.59 Mbp), as a consequence of a greater presence of antimicrobial resistance genes, phages and prophages. CONCLUSIONS AND CLINICAL IMPORTANCE: This technique allows much more precise and easier characterisation of canine S. pseudintermedius populations and may lead to a better understanding of the pathogenesis of canine pyodermas.

National Trends in Statin Medication Prescribing in Patients With a History of Stroke or Transient Ischemic Attack.

BACKGROUND: Guidelines support statin therapy post-stroke or transient ischemic attack (TIA); however, previously reported utilization rates are suboptimal. OBJECTIVE: This study investigates the incidence of statin usage in patients with a documented stroke or TIA while identifying predictors of statin use. METHODS: A retrospective, cross-sectional study utilizing data from the National Ambulatory Medical Care Survey. RESULTS: A total of 2963 unweighted visits were included in the analysis, representing a total of 52 645 000 office visits when weighted. Statin therapy was initiated or continued in 35.7% (95% confidence interval [CI]: 32.4-39.0%) of office visits. Upon multivariate analysis, positive predictors of statin therapy included a diagnosis of hyperlipidemia (odds ratio [OR]: 3.60; 95% CI: 2.40-5.41), angiotensin-converting enzyme inhibitor (ACE-I) therapy (OR: 2.52; 95% CI: 1.69-3.76), aspirin therapy (OR: 2.02; 95% CI: 1.40-2.93), and clopidogrel therapy (OR: 2.60; 95% CI: 1.69-4.02). Negative predictors of statin therapy included office visits with neurologists when compared to visits with primary care practitioners (OR: 0.55; 95% CI: 0.33-0.90) and office visits in rural areas when compared to office visits in urban areas (OR: 0.64; 95% CI: 0.41-0.99). CONCLUSION: Various factors impact statin therapy use with overall utilization being suboptimal, highlighting an opportunity for medication optimization.

Pharmacologic interaction between oxfendazole and triclabendazole: In vitro biotransformation and systemic exposure in sheep.

The aim of the current work was to evaluate a potential pharmacokinetic interaction between the flukicide triclabendazole (TCBZ) and the broad-spectrum benzimidazole (BZD) anthelmintic oxfendazole (OFZ) in sheep. To this end, both an in vitro assay in microsomal fractions and an in vivo trial in lambs parasitized with Haemonchus contortus resistant to OFZ and its reduced derivative fenbendazole (FBZ) were carried out. Sheep microsomal fractions were incubated together with OFZ, FBZ, TCBZ, or a combination of either FBZ and TCBZ or OFZ and TCBZ. OFZ production was significantly diminished upon coincubation of FBZ and TCBZ, whereas neither FBZ nor OFZ affected the S-oxidation of TCBZ towards its sulfoxide and sulfone metabolites. For the in vivo trial, lambs were treated with OFZ (Vermox® oral drench at a single dose of 5 mg/kg PO), TCBZ (Fasinex® oral drench at a single dose of 12 mg/kg PO) or both compounds at a single dose of 5 (Vermox®) and 12 mg/kg (Fasinex®) PO. Blood samples were taken to quantify drug and metabolite concentrations, and pharmacokinetic parameters were calculated by means of non-compartmental analysis. Results showed that the pharmacokinetic parameters of active molecules and metabolites were not significantly altered upon coadministration. The sole exception was the increase in the mean residence time (MRT) of OFZ and FBZ sulfone upon coadministration, with no significant changes in the remaining pharmacokinetic parameters. This research is a further contribution to the study of metabolic drug-drug interactions that may affect anthelmintic efficacies in ruminants.

Efficacy of Tramadol for Pain Management in Patients Receiving Strong Cytochrome P450 2D6 Inhibitors.

STUDY OBJECTIVE: Tramadol is metabolized by cytochrome P450 (CYP) 2D6 to form an active metabolite that exhibits its analgesic effect. Medications that inhibit this enzyme are used often in practice, yet the clinical impact of this interaction on the analgesic effects of tramadol has yet to be fully described. The objective was to determine whether a clinically relevant decrease in pain control is observed in patients taking scheduled tramadol concomitantly with a strong CYP2D6 inhibitor. DESIGN: Retrospective cohort study. SETTING: Large health care system. PATIENTS: One hundred fifty-two adult inpatients who received scheduled tramadol for at least 24 hours with (76 patients) or without (76 patients) a strong CYP2D6 inhibitor between January 1, 2012, and February 28, 2017, were included in the analysis. Patients hospitalized for opioid use disorder or those receiving substandard dosing of tramadol were excluded. MEASUREMENTS AND MAIN RESULTS: The primary outcome was mean breakthrough opiate consumption in the presence and absence of CYP2D6 inhibitors. Secondary outcomes included mean pain scores, length of hospital stay, tramadol discontinuation rates, and prespecified subgroup analyses based on patient sex, race, and specific CYP2D6 inhibitor administered. Patients receiving concurrent CYP2D6 inhibitors required significantly more breakthrough morphine milligram equivalents per day compared with patients receiving scheduled tramadol without CYP2D6 inhibitors (geometric mean ± SD 18.2 ± 6.3 vs 5.7 ± 6.7 mg morphine milligram equivalents, p<0.001). No significant differences existed between cohorts for mean pain score, length of hospital stay, or tramadol discontinuation rate. CONCLUSION: This study demonstrated a clinically relevant decrease in the efficacy of tramadol when used for pain control in patients receiving a strong CYP2D6 inhibitor. These results should encourage clinicians to review medication lists for this interaction and adjust regimens accordingly to ensure adequate pain control.

Prevalence and Predictors of Benzodiazepine Monotherapy in Patients With Depression: A National Cross-Sectional Study.

OBJECTIVE: Depression guidelines discourage benzodiazepine monotherapy and limit use to short-term adjunctive therapy with antidepressants; however, patients with depression continue to receive benzodiazepine monotherapy. The prevalence and predictors of this prescribing pattern have not been described previously and are warranted to assist clinicians in identifying patients at highest risk of receiving benzodiazepine monotherapy. METHODS: A national, cross-sectional analysis of the National Ambulatory Medical Care Survey from 2012 to 2015 was performed for adults treated for depression. Depression was identified using a survey item specifically assessing the presence of depression. Office visits involving patients with bipolar disorder, schizoaffective disorder, or pregnancy were identified by ICD-9 code or specific survey item and were excluded. The primary endpoint was benzodiazepine monotherapy prescribing rate defined as initiation or continuation of a benzodiazepine in the absence of any antidepressant agent. A multivariate logistic regression model was created to identify variables associated with benzodiazepine monotherapy. RESULTS: In total, 9,426 unweighted visits were eligible for inclusion. Benzodiazepine monotherapy was identified in 9.3% of patients treated for depression (95% CI, 8.2%-10.6%). Predictors of benzodiazepine monotherapy included age of 45-64 years (OR = 1.39; 95% CI, 1.01-1.91), epilepsy-related office visit (OR = 5.34; 95% CI, 1.39-20.44), anxiety-related office visit (OR = 1.67; 95% CI, 1.23-2.27), underlying pulmonary disease (OR = 1.43; 95% CI, 1.09-1.87), and concomitant opiate prescribing (OR = 2.86; 95% CI, 2.01-4.06). Psychiatrists were less likely to prescribe benzodiazepine monotherapy than were other providers (OR = 0.42; 95% CI, 0.29-0.61). CONCLUSIONS: Benzodiazepine monotherapy is utilized in nearly 1 in 10 patients treated for depression. Adults aged 45 to 65 years, patients prescribed opioids, patients seen by primary care providers, and those with underlying anxiety, epilepsy, or pulmonary disorders are at highest risk.

Assessment of the pharmacological interactions between the nematodicidal fenbendazole and the flukicidal triclabendazole: In vitro studies with bovine liver microsomes and slices.

Parasitic diseases have a significant impact on livestock production. Nematodicidal drugs, such as fenbendazole (FBZ) or its oxidized metabolite oxfendazole (OFZ), can be used along with the trematodicidal triclabendazole (TCBZ), to broaden the spectrum of anthelmintic activity. However, co-exposure to these compounds could lead to drug-drug (D-D) interactions and eventually alter the clinical profile of each active principle. The aim of this study was to assess the presence of such interactions by means of two in vitro models, namely bovine liver microsomal fractions and bovine precision-cut liver slices (PCLSs). To this end, an in vitro assessment involving incubation of FBZ and TCBZ or a combination of FBZ and TCBZ was carried out. Results with microsomal fractions showed a 78.4% reduction (p = .002) in the rate of OFZ production upon co-incubation, whereas the sulfoxide metabolite of TCBZ (TCBZSO) exhibited a decreasing tendency. With PCLS, OFZ accumulation in the incubation medium increased 1.8-fold upon co-incubation, whereas TCBZSO accumulation decreased by 28%. The accumulation of FBZ and OFZ in the liver tissue increased upon 2-hr co-incubation, from 2.1 ± 1.5 to 18.2 ± 6.1 (p = .0009) and from 0.4 ± 0.1 to 1.3 ± 0.3 nmol (p = .0005), respectively. These results confirm the presence of D-D interactions between FBZ and TCBZ. Further studies are needed to determine the extent of involvement of drug-metabolizing enzymes and membrane transporters in interactions between compounds largely used in livestock production systems.

Species differences in hepatic biotransformation of the anthelmintic drug flubendazole.

Flubendazole (FLBZ) is a broad-spectrum benzimidazole anthelmintic used in pigs, poultry, and humans. It has been proposed as a candidate for development for use in elimination programmes for lymphatic filariasis and onchocerciasis in humans. Moreover, FLBZ has shown promise in cancer chemotherapy, particularly for neuroblastoma. This work investigated the hepatic carbonyl-reducing pathway of FLBZ in different species, including humans. Microsomal and cytosolic fractions were obtained from sheep, cattle, pig, hen, rat, and human liver. Both subcellular fractions of each species converted FLBZ into a reduced metabolite (red-FLBZ). The rate of microsomal red-FLBZ production was highest in sheep (1.92 ± 0.13 nmol/min.mg) and lowest in pigs (0.04 ± 0.02 nmol/min.mg); cytosolic red-FLBZ production ranged from 0.02 ± 0.01 (pig) to 1.86 ± 0.61 nmol/min.mg (sheep). Only subcellular fractions from sheep liver oxidized red-FLBZ to FLBZ in a NADP+ -dependent oxidative reaction. Liver microsomes from both pigs and humans transformed FLBZ to red-FLBZ and a hydrolyzed metabolite. Very significant differences in the pattern of FLBZ metabolism were observed among the tested species and humans. These results reinforce the need for caution in extrapolating data on metabolism, efficacy, and safety of drugs derived from studies performed in different species.

Impact of Tranexamic Acid in Total Knee and Total Hip Replacement.

OBJECTIVE: To evaluate the net clinical benefit of tranexamic acid use in patients undergoing total knee or total hip replacement. METHODS: This is a retrospective study of patients undergoing total knee or total hip replacement. The primary outcome was the net clinical benefit of tranexamic acid use. Secondary outcomes included length of stay, incidence of venous thromboembolism, change in hemoglobin, and number of units of blood transfused. RESULTS: Four hundred and six patients were screened for inclusion and 327 patients met inclusion criteria; 174 patients received tranexamic acid versus 153 patients who received usual care. Tranexamic acid demonstrated a positive net clinical benefit versus usual care (40.8% vs 13.7%, P < .01) but did not affect length of stay (3.39 vs 3.37 days, respectively, P = .76). Venous thromboembolism was comparable between groups (2.3% vs 0.7%, P = .38). Average change in hemoglobin and need for transfusion were lower in the treatment group versus the usual care group, respectively (3.46 vs 4.26 mg/dL, P < .01). CONCLUSION: Tranexamic acid demonstrated a significant benefit in decreasing change in hemoglobin as well as the need for blood transfusion with no increase in the risk of venous thromboembolism in patients undergoing total knee or total hip replacement.

Accuracy in Rietveld quantitative phase analysis: a comparative study of strictly monochromatic Mo and Cu radiations.

This study reports 78 Rietveld quantitative phase analyses using Cu Kα1, Mo Kα1 and synchrotron radiations. Synchrotron powder diffraction has been used to validate the most challenging analyses. From the results for three series with increasing contents of an analyte (an inorganic crystalline phase, an organic crystalline phase and a glass), it is inferred that Rietveld analyses from high-energy Mo Kα1 radiation have slightly better accuracies than those obtained from Cu Kα1 radiation. This behaviour has been established from the results of the calibration graphics obtained through the spiking method and also from Kullback-Leibler distance statistic studies. This outcome is explained, in spite of the lower diffraction power for Mo radiation when compared to Cu radiation, as arising because of the larger volume tested with Mo and also because higher energy allows one to record patterns with fewer systematic errors. The limit of detection (LoD) and limit of quantification (LoQ) have also been established for the studied series. For similar recording times, the LoDs in Cu patterns, ∼0.2 wt%, are slightly lower than those derived from Mo patterns, ∼0.3 wt%. The LoQ for a well crystallized inorganic phase using laboratory powder diffraction was established to be close to 0.10 wt% in stable fits with good precision. However, the accuracy of these analyses was poor with relative errors near to 100%. Only contents higher than 1.0 wt% yielded analyses with relative errors lower than 20%.

Prevalence and Predictors of Metformin Prescribing in Adults with Type 2 Diabetes Mellitus: A National Cross-Sectional Study.

OBJECTIVE: Metformin is the first-line oral type 2 diabetes treatment. Despite an abundance of evidence, metformin is routinely underused. This study evaluated the rates of metformin use in an appropriate outpatient type 2 diabetes population and identified predictors of metformin use. METHODS: A national cross-sectional study was conducted using data from the National Ambulatory Medical Care Survey. Office visits involving patients aged 18-79 years with a diagnosis of type 2 diabetes were included, and visits involving patients with a diagnosis of chronic renal failure or heart failure were excluded. The primary outcome was metformin-prescribing rate. Multivariate logistic regression identified variables associated with metformin prescribing. RESULTS: A total of 2348 patient visits were eligible for inclusion, representing 88,671,714 office visits nationally. Metformin was continued or initiated in 40.6% of these visits. The strongest independent predictors of metformin prescribing were insulin use (odds ratio [OR] 0.32; 95% confidence interval [CI] 0.21-0.47), presence of four or more chronic conditions (OR 0.58; 95% CI 0.34-0.98), patients with Medicare insurance (OR 0.57; 95% CI 0.39-0.83), visit with a surgical specialist (OR 0.39; 95% CI 0.25-0.61) or a medical specialist (OR 0.59; 95% CI 0.38-0.92), and Hispanic ethnicity (OR 2.03; 95% CI 1.28-3.22). CONCLUSION: Metformin-prescribing rates are low, particularly in patients receiving insulin, with Medicare insurance, seen by medical or surgical specialists, or with four or more chronic conditions. The observed low rates of metformin use represent an important opportunity to improve the quality of care for patients with type 2 diabetes.

Economic and patient satisfaction outcomes of a layered learning model in a small community hospital.

PURPOSE: Results of a study of economic and patient satisfaction outcomes of implementing a "layered learning model" (LLM) in a community hospital are presented. METHODS: An LLM consisting of a clinical pharmacist, two postgraduate year 1 pharmacy residents, and pharmacy students participating in rounds and providing patient education was implemented at a small community hospital. The primary endpoint was the difference in mean total drug cost per discharge in cases managed by physicians who rounded with pharmacy representatives (the intervention group) and cases managed by physicians who rounded with no pharmacist present (the control group). Secondary outcomes were drug expenditures associated with eight common diagnoses and patient satisfaction scores in medication education domains of the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey. Statistical analysis was performed using Student's t test and chi-square tests. RESULTS: The intervention-group data comprised 2737 hospital discharges, as compared with 3983 discharges for the control group. The geometric mean total drug cost per discharge was $161.52 for the intervention group, as compared with $210.15 for the control group (difference, $48.63; p < 0.001); drug costs for pneumonia and urinary tract infection were significantly lower for the intervention group. Patient satisfaction scores were significantly improved in the intervention group relative to baseline scores (8th percentile versus 39th percentile, p < 0.001). CONCLUSION: Implementation of the LLM in a small community hospital reduced medication costs and improved HCAHPS patient satisfaction scores.

Effect of Intravenous Versus Subcutaneous Phytonadione on Length of Stay for Patients in Need of Urgent Warfarin Reversal.

This institutional review board-approved retrospective cohort study evaluated the impact of intravenous versus subcutaneous phytonadione on length of stay in hospitalized patients requiring urgent warfarin reversal. All patients were 18 years or older, on warfarin therapy with an international normalized ratio (INR) between 3.1 and 10.0, and had warfarin therapy restarted at discharge. Patients who received intramuscular or oral phytonadione, phytonadione by more than 1 route, fresh frozen plasma, or any other blood products containing clotting factors, patients with active or severe liver disease, and patients who received other forms of anticoagulation were excluded. A total of 4425 patients receiving phytonadione were evaluated and 79 patients were included. Baseline characteristics were similar between the intravenous and subcutaneous groups, including mean age, gender, warfarin indication, Charlson comorbidity index, and indication for phytonadione. Geometric mean length of stay in the intravenous group was 211.7 hours compared with 191.0 hours in the subcutaneous group (P = 0.47). Though intravenous phytonadione administration resulted in significantly lower INRs at all time points <36 hours, geometric mean time to restart of warfarin therapy was not impacted (66.3 hours vs. 64.1 hours, P = 0.72). Despite demonstrating significantly greater INR reductions, hospital length of stay and time to restart of warfarin therapy were not improved with the administration of intravenous over subcutaneous phytonadione.

Coaching for Success: A Residency Search Primer and Update for Preceptors and Faculty.

Pharmacy residency programs have become increasingly competitive in recent years, and changes to the residency search and application process have altered the process for matching with a residency. In this article, major residency topics, from the benefits of residency training to searching for and ranking programs, are summarized. A discussion of tips and tricks for applying for residencies and interviewing for positions is included along with specific suggestions developed with data following the implementation of the Pharmacy Online Residency Centralized Application Service (PhORCAS). The article is organized in a question and answer format to help facilitate understanding of key concepts and common questions that may arise from applicants. Many changes have taken place in the residency search and application process in recent years, and the process of obtaining a residency is complex. Residency applicants and those advising applicants may find value in the answers to commonly asked residency application questions to help ensure the greatest chance of a successful residency match.

Cytochrome P450 3A expression and function in liver and intestinal mucosa from dexamethasone-treated sheep.

The effects of repeated administrations of dexamethasone (DEX) (3 mg/kg/day by i.m. route for 7 days) on the gene expression profile of a cytochrome P450 (CYP) 3A28-like isoenzyme, on the expression of a CYP3A-immunoreactive protein and on CYP3A-dependent metabolic activities in sheep liver and small intestinal mucosa were evaluated in the current work. CYP 3A-dependent metabolic activities (erythromycin and triacetyl-oleandomycin N-demethylations) were assessed in microsomal fractions. The mRNA expression of CYP3A28-like, glucocorticoid receptor, constitutive androstane receptor, pregnane X receptor and retinoic X receptor alpha (RXRα) was determined by quantitative real-time PCR. The expression of a CYP3A-immunoreactive protein was measured by Western blot analyses. In the liver, DEX treatment increased CYP3A28-like mRNA levels (2.67-fold, P<0.01) and CYP3A apoprotein expression (1.34-fold, P<0.05) and stimulated CYP3A-dependent metabolism. High and significant correlation coefficients between CYP3A-dependent activities and CYP3A28-like gene (r=0.835-0.856, P<0.01) or protein (r=0.728-0.855, P<0.05) expression profiles were observed. Among the transcriptional factors, DEX only stimulated (2.1-fold, P<0.01) the mRNA expression of RXRα. In sheep small intestine, DEX caused a slight increment (34.6%, P<0.05) in erythromycin N-demethylase activity in the jejunal mucosa and a significant enhancement (P<0.05) of CYP3A apoprotein level in the duodenal mucosa.

South American camelid illegal traffic detection by means of molecular markers.

South American camelids comprise the wild species guanaco and vicuña and their respective domestic relatives llama and alpaca. The aim of the present study was to determine by DNA analysis to which of these species belong a herd of camelids confiscated from a llama breeder but alleged to be alpacas by the prosecution, and to evaluate the usefulness of mitochondrial and autosomal DNA markers to solve judicial cases involving camelid taxa. Cytochrome b and cytochrome oxidase I mitochondrial genes and 7 STR were analyzed in 25 confiscated samples. Mitochondrial results were inconclusive because 18 of the sequestered samples presented haplotypes that corresponded to the guanaco haplogroup and the remaining seven belonged to a vicuña linage. Microsatellite data of casework samples and llama reference samples revealed different genetic profiles by the presence of private alleles at two microsatellites suggesting that the confiscated animals could be alpaca, or at least alpaca hybrids instead of pure llama.