A Baker's Dozen of Top Antimicrobial Stewardship Intervention Publications in 2022.

Keeping abreast of the antimicrobial stewardship-related articles published each year is challenging. The Southeastern Research Group Endeavor identified antimicrobial stewardship-related, peer-reviewed literature that detailed an actionable intervention during 2022. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight actionable interventions used by antimicrobial stewardship programs to capture potentially effective strategies for local implementation.

Clinical assessment of a point-of-care assay to determine protective vaccinal antibody titers to canine viral diseases.

Guidelines recommend that dogs are vaccinated for canine distemper virus (CDV), canine parvovirus (CPV), and canine adenovirus (CAV) every 3 years. Alternatively, their antibody titers are measured and vaccines given when titers fall below a protective threshold. In this study, a point-of-care (POC) assay was compared to hemagglutination inhibition (for CPV) and virus neutralization (for CAV and CDV) assays to predict the need for revaccination Ninety-two dogs presented for vaccination were enrolled. The POC assay indicated protective titers against CDV in 79/80, CPV in 89/90, and CAV in 91/91 dogs with reference standard antibody measurements that were over a protective threshold. The sensitivity of the POC assay for to detect protective concentrations of CDV antibodies was 99% (95% confidence interval [CI 95%], 93.3-99.9%). Ten dogs were falsely considered protected against CDV by the POC assay with a specificity of 17% (CI 95%, 3.0-44.8%). The sensitivity of the POC assay for protective concentrations of CPV titers was 99% (CI 95%, 93.9-99.9%). The sensitivity of the POC assay to detect protective concentrations of CAV antibodies was 100% (CI 95%, 95.9-100%). Only classifying high-positive CDV and CPV titers on the POC assay as protective improved assay specificity to 100%, but sensitivity decreased to 51% and 76% respectively. This POC assay had a high sensitivity for the detection of protective antibody titers; however, some dogs were falsely categorized as protected, especially for CDV.

Re-evaluation of the low-dose dexamethasone suppression test in dogs.

OBJECTIVES: This study aims to re-evaluate the low-dose dexamethasone suppression test 8-hour cortisol cut-point for the diagnosis of hypercortisolism in dogs using a solid-phase, competitive chemiluminescent enzyme immunoassay. MATERIALS AND METHODS: Twenty-seven client-owned dogs with naturally occurring hypercortisolism and 30 healthy control dogs were prospectively recruited. Performance of the low-dose dexamethasone suppression test was assessed using sensitivity, specificity and a receiver operating characteristic curve compared to a clinical diagnosis of hypercortisolism including response to treatment. RESULTS: Twenty-four dogs were diagnosed with pituitary-dependent hypercortisolism and three with adrenal-dependent hypercortisolism. In 30 healthy control dogs, 8-hour post-dexamethasone cortisol concentrations ranged from 5.5 to 39 nmol/L. A receiver operating characteristic curve curve constructed from the 8-hour post-dexamethasone cortisol concentrations of hypercortisolism and control dogs demonstrated that the most discriminatory cut-point was more than 39 nmol/L with sensitivity of 85.2% (95% confidence interval, 67.5% to 94.1%) and specificity of 100% (95% confidence interval, 88.7% to 100.0%) and an area under the curve of 0.963. CLINICAL SIGNIFICANCE: The optimal cut-point of more than 36 nmol/L proposed by this study is similar to the currently accepted 8-hour cortisol concentration cut-point for diagnosing hypercortisolism when using a solid-phase, competitive chemiluminescent enzyme immunoassay.

Impact of Clinical Pharmacy Expansion within a Rural Federally Qualified Health Center through Implementation of Pharmacist-Led Medicare Annual Wellness Visits.

Medicare Annual Wellness Visits (AWVs) are annual appointments with the primary care team to prepare personalized prevention plans and focus on gaps in care. Although beneficial, AWVs are often difficult for providers to schedule and complete due to the increased time commitments compared to other visits. The purpose of this study was to assess the clinical, economic and patient-level value of newly implemented pharmacist-led AWVs within a rural Federally Qualified Health Center (FQHC). This retrospective, cohort study included patients who completed an AWV between 1 October 2021, and 14 February 2022. The primary objective was to compare the per clinician rate of completed AWVs between pharmacists and providers. The secondary objectives were to compare revenue generated, interventions made, and patient satisfaction between pharmacist- and provider-led AWVs. During the study period, nine providers completed 139 AWVs (15.4/provider) and two pharmacists completed 116 AWVs (58/pharmacist). Proportions of interventions ordered among those due in eligible patients were similar between pharmacists and providers (47.6% vs. 44.5%; p = 0.356). Patient satisfaction was overall positive with no difference between groups. Pharmacist-led AWVs increased completion of AWVs by 83% over a 20-week period, including significantly more initial, compared to subsequent, AWVs than providers. Sustainability of pharmacist-led AWVs at this FQHC is supported by study outcomes.

Effect of an oral probiotic nutraceutical containing Aspergillus-derived ingredients on a serum and urine galactomannan antigen assay in dogs.

A commercial Aspergillus galactomannan antigen (GMA) enzyme linked immunosorbent assay (ELISA) is used to support a diagnosis of systemic aspergillosis in dogs. In human patients, false positive results have been associated with administration of medications derived from molds. We sought to determine the effect of administration of a commercially available oral probiotic nutraceutical that contained Aspergillus-derived ingredients on serum and urine Aspergillus GMA levels in dogs by conducting a prospective, cross-over study. Galactomannan index (GMI) was measured on the solubilized probiotic nutraceutical and was positive (GMI ≥ 0.5) with a mean of 7.91. Serum and urine galactomannan indices were measured in 10 healthy dogs before (day 0) and after 1 week (day 7) of probiotic nutraceutical administration, then again 2 weeks after the probiotic nutraceutical was discontinued (day 21). Median (range) serum GMI were 0.19 (0.08-0.62), 0.22 (0.07-1.15) and 0.17 (0.14-0.63) at day 0, 7 and 21, respectively. Two of 10 dogs developed positive GMI (≥0.5) results after probiotic nutraceutical administration; however, no significant changes were noted over the study period. Median (range) urine GMI results were 0.06 (0.04-0.22), 0.07 (0.05-0.41) and 0.06 (0.03-0.16) at day 0, 7 and 21, respectively. A trend towards an increase urine GMI was noted between day 0 and 7 (P = 0.18), and decrease was noted between day 7 and 21 (P = 0.09). Administration of probiotics containing Aspergillus-derived ingredients to dogs did not reliably result in elevated Aspergillus GMA levels.

Machine learning algorithm as a diagnostic tool for hypoadrenocorticism in dogs.

Canine hypoadrenocorticism (CHA) is a life-threatening condition that affects approximately 3 of 1,000 dogs. It has a wide array of clinical signs and is known to mimic other disease processes, including kidney and gastrointestinal diseases, creating a diagnostic challenge. Because CHA can be fatal if not appropriately treated, there is risk to the patient if the condition is not diagnosed. However, the prognosis is excellent with appropriate therapy. A major hurdle to diagnosing CHA is the lack of awareness and low index of suspicion. Once suspected, the application and interpretation of conclusive diagnostic tests is relatively straight forward. In this study, machine learning methods were employed to aid in the diagnosis of CHA using routinely collected screening diagnostics (complete blood count and serum chemistry panel). These data were collected for 908 control dogs (suspected to have CHA, but disease ruled out) and 133 dogs with confirmed CHA. A boosted tree algorithm (AdaBoost) was trained with 80% of the collected data, and 20% was then utilized as test data to assess performance. Algorithm learning was demonstrated as the training set was increased from 0 to 600 dogs. The developed algorithm model has a sensitivity of 96.3% (95% CI, 81.7%-99.8%), specificity of 97.2% (95% CI, 93.7%-98.8%), and an area under the receiver operator characteristic curve of 0.994 (95% CI, 0.984-0.999), and it outperforms other screening methods including logistic regression analysis. An easy-to-use graphical interface allows the practitioner to easily implement this technology to screen for CHA leading to improved outcomes for patients and owners.

Concurrent administration of an intranasal vaccine containing feline herpesvirus-1 (FHV-1) with a parenteral vaccine containing FHV-1 is superior to parenteral vaccination alone in an acute FHV-1 challenge model.

The administration of intranasal (IN) or subcutaneous (SC) vaccines containing modified live feline herpesvirus 1 (FHV-1) offers some level of protection against FHV-1 challenge, but relative efficacy is <100%. In this study, clinical signs and viral shedding in kittens were compared among three groups: (1) kittens vaccinated concurrently with IN and SC vaccines containing FHV-1 (Group 1, n = 8); (2) kittens vaccinated with a SC FHV-1 vaccine alone (Group 2, n = 8), and (3) unvaccinated control kittens (Group 3, n = 8). All kittens were FHV-1 naïve at enrolment, and challenge with a virulent strain of FHV-1 was performed 1 week after vaccination. Daily clinical signs and pharyngeal FHV-1 shedding were recorded over a 21-day infection period. Overall, kittens in Group 1 had significantly less severe clinical illness than those in Group 2 (P < 0.05). Additionally, significantly less FHV-1 DNA was detected on pharyngeal swabs from kittens in Group 1 compared to those in Group 2 (P < 0.001). Concomitant administration of IN and SC FHV-1 vaccines was superior to administration of the SC FHV-1 vaccine alone in this challenge model of FHV-1 naïve kittens.

Use of the glycophorin A somatic mutation assay for rapid, unambiguous identification of Fanconi anemia homozygotes regardless of GPA genotype.

A 7-year-old girl was hospitalized with pancytopenia requiring blood transfusion. She and an older brother with suspicious symptoms were referred for laboratory testing to confirm a clinical diagnosis of Fanconi anemia (FA). Blood samples from these two children and one parent were examined with the GPA somatic mutation assay. The patient's total GPA somatic mutation frequency of 1.4 x 10(-4) was determined despite the confounding effects of her recent transfusion, and was greater than 10-fold higher than that of a population of pediatric controls, consistent with the known FA phenotype. Her brother was not informative for the standard GPA assay, which requires heterozygosity for the MN blood group, but was analyzed with a modified assay that measured only allele loss mutation. His mutation frequency, 6.8 x 10(-4) was also supportive of a diagnosis of FA. Both analyses also showed evidence of ongoing mutation through terminal erythroblast differentiation, a characteristic of patients with DNA repair syndromes which further confirmed the diagnoses. These conclusions were confirmed with traditional DEB-induced chromosome breakage studies. The quantitative and qualitative aspects of the GPA assay relevant for applying this test for FA diagnosis, and perhaps for carrier detection, are discussed.

Provocative use test of nickel coins in nickel-sensitized subjects and controls.

BACKGROUND: Consensus exists on levels of nickel release that are well tolerated in exposure to nickel-containing items in direct and continuous contact with skin (e.g. watches). The clinical relevance of nickel-containing coins eliciting nickel dermatitis associated with extensive occupational exposure (e.g. coins handled by cashiers) has not been determined. OBJECTIVES: To examine whether nickel-containing coins might be an elicitor of allergic contact dermatitis (ACD) in occupational settings with extensive exposure to coins (i.e. cashiers). METHODS: Eighteen subjects (10 nickel sensitized and eight non-nickel sensitized) completed this study after screening of history, physical examination and diagnostic patch testing (5% nickel sulphate). Each volunteer handled 10 coins (nickel-containing coins or non-nickel-containing coins) in a cross-over design at 5-min intervals (5 min handling followed by 5 min rest) for 8 h per day, for a total of 12 days excluding the weekend. One hand was gloved while the other was not during coin handling. Visual scoring and bioengineering measurements were recorded at each of four predetermined sites at baseline (day 1), end of day 5 and day 12 (last day of exposure). RESULTS: There were no statistical differences for either visual or bioengineering data comparing: (i) nickel-sensitized vs. non-nickel-sensitized subjects handling nickel-containing coins at day 1, day 5 and day 12; (ii) day 12 vs. day 1 (baseline) for nickel-sensitized subjects handling nickel-containing coins; (iii) handling of nickel-containing coins vs. non-nickel-containing coins by nickel-sensitized subjects at day 5 and day 12; (iv) gloved hand vs. ungloved hand of nickel-sensitized subjects handling nickel-containing coins at day 12. Limitations of the method and clinical extrapolation are detailed. CONCLUSIONS: Individuals handling these nickel-containing coins daily did not develop ACD, as judged by visual signs or bioengineering parameters.

Humeral retroversion and its relationship to glenohumeral rotation in the shoulder of college baseball players.

BACKGROUND: Previous studies have documented changes in musculature, bony anatomy, and glenohumeral rotation in the dominant shoulder of baseball players. HYPOTHESIS: In a group of asymptomatic college baseball players the total range of motion in the dominant and nondominant shoulders will be similar. Any measured increase in external rotation and decrease in internal rotation occurring between the two sides will be consistent and directly correlate with an increased angle of humeral retroversion in the dominant extremity. STUDY DESIGN: Descriptive anatomic study. METHODS: Fifty-four asymptomatic college baseball players were examined. Standard measurements of glenohumeral range of motion were made and humeral retroversion was determined radiologically. RESULTS: Total rotational motion, measured at 90 degrees of glenohumeral abduction, was 159.5 degrees for the dominant shoulders and 157.8 degrees for the nondominant shoulders. Mean differences in external and internal rotation in the dominant versus nondominant extremities were 9.7 degrees and 8.2 degrees, respectively. Humeral retroversion measured 36.6 degrees +/- 9.8 degrees in the dominant and 26 degrees +/- 9.4 degrees in the nondominant extremity. The mean difference in retroversion correlated significantly by Pearson's product moment with the difference in external (P = 0.001) and internal (P = 0.003) rotation measurements. CONCLUSIONS: There is a pattern of increased external rotation and decreased internal rotation in the dominant extremity that significantly correlates with an increase in humeral retroversion. The loss of internal rotation and gains in external rotation may be more strongly related to adaptive changes in proximal humeral anatomy than to changes in the soft tissues.

Neurotoxicity of ethyl methacrylate in rats.

Ethyl methacrylate (ethyl 2-methyl-2-propenoate, EMA) has been implicated in the development of neurologic impairment following occupational exposure. The potential of EMA to produce neurotoxicity was investigated in adult male Sprague-Dawley rats in two experiments. In the first experiment, animals were administered 100, 200, 400, or 800 mg/kg by daily intraperitoneal (i.p.) injections for 60 d. Control rats received daily i.p. injections of 1 ml saline/kg. Clinical observations, spontaneous motor activity, and performance in the Morris water maze were assessed. Alterations in clinical parameters in the higher dose groups included lethargy, impaired breathing, decreased weight gain, and increased mortality. Alterations in motor activity were observed at 100 mg/kg, a dose that did not cause alterations in clinical parameters, body weight gain, or mortality. There was also a dose-dependent impairment in performance in the Morris water maze. In the second experiment, animals were administered EMA in drinking water at concentrations of 0.1, 0.2, or 0.5% for 60 d. Control rats were administered tap water. Animals were perfused at the termination of exposure and samples of brain, spinal cord, and sciatic nerve were prepared for histological examination. Spongiform alterations were observed in fiber tracts of the forebrain, brainstem, and spinal cord. Clusters of axonal swellings were scattered throughout the dorsal, ventral, and lateral columns of the spinal cord, and typically involved internodal segments of two or three neighboring axons. Shrunken axons with separated myelin lamellae and large axons with thinner than normal myelin sheaths were apparent in the sciatic nerve. The patterns of alterations in the white matter of the spinal cord and the sciatic nerve are consistent with myelinopathy, but additional experiments are necessary to confirm whether oligodendroglia and Schwann cells are the primary sites of injury. In addition to the alterations associated with myelin, there was a decrease in the density of neurons in the ventral horn of the spinal cord. While the observed effects of EMA on the nervous system of rats are consistent with neurologic symptoms of workers exposed to EMA, additional experiments are necessary to determine if the level and route of exposures associated with occupational use produce these impairments in experimental animals.

Hepatitis C virus serology in parenteral drug users with chronic liver disease.

Chronic liver disease is a common complication of parenteral drug use, and liver cirrhosis is frequently seen in users of both parenteral drugs and alcohol. In 1978-83, we studied 88 parenteral drug users with sufficient evidence of chronic liver disease to warrant liver biopsy. Current alcohol abuse was noted in 63 (72%), and six (7%) were former alcohol abusers. Cirrhosis was found in 33 (38%). Hepatitis C antibody (anti-HCV) was detected in 86 (98%). Also, 40 of the anti-HCV positive sera were tested with recombinant immunoblot assay and all of these were reactive. All but one of the 31 patients with anti-HCV and cirrhosis were alcohol abusers. We conclude that parenteral drug users with chronic liver disease almost always have evidence of HCV infection.

In vitro calcium and calmodulin-dependent kinase-mediated phosphorylation of rat brain and spinal cord neurofilament proteins is increased by glycidamide administration.

This study was carried out to determine the action of glycidamide (2,3-epoxy-1-propanamide), a neurotoxic metabolite of acrylamide, on Ca2+/calmodulin (CaM)-dependent protein kinase phosphorylation of cytoskeletal proteins. Acrylamide has been shown to increase Ca2+/CaM-dependent phosphorylation of neurofilament (NF) triplet proteins and autophosphorylation of Ca2+/CaM-dependent protein kinase II (CaM kinase II; EC 2.7.1.37). A daily intraperitoneal dose of 0.7 mmol/kg b.wt. of glycidamide or deionized water was administered to male Sprague-Dawley rats. Animals were sacrificed when signs of severe neurotoxicity became apparent at 13-16 days of treatment. Axonal floatation was used to isolate neurofilaments (NFs) and endogenous kinases from brains and spinal cords of treated and control animals. Samples isolated from brain and spinal cord of glycidamide-treated animals showed increased in vitro Ca2+/CaM-dependent phosphorylation of endogenous and exogenous NF proteins and increased autophosphorylation of CaM kinase II when compared with controls. CaM binding to the alpha, beta, and beta' subunits of CaM kinase II and antibody binding to the alpha-subunit of CaM kinase II in brain supernatant isolates was increased as a result of glycidamide treatment. These results suggest that increased Ca2+/CaM-dependent phosphorylation of cytoskeletal proteins may be involved in the pathogenesis of glycidamide-induced neurotoxicity.

Acrylamide increases in vitro calcium and calmodulin-dependent kinase-mediated phosphorylation of rat brain and spinal cord neurofilament proteins.

Male Sprague-Dawley rats were administered a daily i.p. dose of 0.70 mmol/kg body weight of acrylamide, propionamide (a non-neurotoxic structural analog of acrylamide) or deionized water. Animals were sacrificed when signs of severe neurotoxicity were apparent. Neurofilaments (NFs) and endogenous kinase were isolated from the brain and spinal cord by axonal floatation. Increased in vitro Ca2+/calmodulin-dependent phosphorylation of endogenous and exogenous NF proteins and autophosphorylation of Ca2+/calmodulin protein kinase II (CaM kinase II, EC 2-7-1-37) were observed in samples from both brain and spinal cord of acrylamide-treated animals compared with controls. There was no significant difference between samples isolated from propionamide-treated animals and controls. Increased calmodulin binding to brain supernatant CaM kinase II was also observed as a result of acrylamide treatment. There was no significant difference observed in the amount of antibody binding to the alpha-subunit of brain supernatant CaM kinase II between treated or control animals. These results suggest that increased CaM kinase II-dependent phosphorylation of cytoskeletal proteins may be involved in the mechanisms of acrylamide-induced neurotoxicity.

Introduction to coronary arteriography.

Coronary arteriography is the most reliable means of investigating and quantitating the severity of coronary artery occlusive disease. Although the procedure is no longer performed exclusively by radiologists, their input into its interpretation is valued. Furthermore, current and future advances in nonangiographic means of demonstrating coronary artery morphology, including magnetic resonance angiography, reinforce the need for radiologists to remain familiar with techniques for the performance of coronary arteriography, the basic anatomy of the coronary artery tree, and patterns of congenital and acquired coronary artery disease.

Angiocardiography in the diagnosis of congenital heart disease.

Despite tremendous advances in cardiac imaging technology, there still exists an important role for the performance of angiocardiography in children with congenital heart disease. This article contains an outline describing the facilities in which the examinations are performed, how the examination is performed, and, most importantly, the basic tenets of interpretation.

Estimation of pulmonary artery pressure in patients with primary pulmonary hypertension by quantitative analysis of magnetic resonance images.

The use of magnetic resonance (MR) images for estimating mean pulmonary artery pressure (PAP) was tested by comparing main pulmonary artery (MPA) and middescending thoracic aorta (AO) caliber in 12 patients with primary pulmonary hypertension (PPH) with measurements made in eight other patients who were observed for diseases other than heart disease (controls). The ratio MPA/AO and the ratios of vessel caliber normalized to body surface area (MPAI and AOI, respectively) were computed. The PAP was obtained in all PPH patients and compared with caliber measurements. The PPH MPA (3.6 +/- 0.8 cm) was significantly larger than the control MPA (2.9 +/- 0.3 cm, p = 0.02); the PPH MPAI (2.8 +/- 0.7 cm/M2) was significantly greater than the control MPA (1.7 +/- 0.2 cm/M2, p < 0.0001). Control AO (2.2 +/- 0.3 cm) was significantly greater than PPH AO (1.6 +/- 0.4 cm, p < 0.0001); there was no significant difference between control AOI (1.3 +/- 0.2 cm/M2) and PPH AOI (1.2 +/- 0.2 cm/M2, p = 0.25). The PPH MPA/AO (2.3 +/- 0.6) was significantly greater than the control MPA/AO (1.3 +/- 0.1, p < 0.0001); overlap between MPA in the two groups was eliminated by indexing values to AO caliber (MPA/AO). Among PPH patients there was strong correlation between PAP and MPA/AO (PAP = 24 x MPA/AO + 3.7, r = 0.7, p < 0.01). Increased MPA/AO denotes the presence of pulmonary hypertension and may be used to estimate PAP.

Normal plain film examination of the heart and great arteries in the adult.

A plain film chest examination is nearly always obtained in the management of patients suspected of cardiac disease. The wealth of diagnostic information obtained from posteroanterior and lateral thoracic images is often essential data needed to direct the evaluation and treatment of these patients. Appreciation of the normal cardiac, pulmonary, and great vessel anatomy provides a basis for the identification and characterization of the abnormal. Furthermore, the chest radiograph provides an important means to appreciate the pathophysiologic mechanisms underlying the morphologic changes in patients with congenital heart disease.