Adherence to stewardship recommendations for antibiotic discontinuation reduces antibiotic-associated adverse drug events.

Inappropriate antibiotic use may lead to increased adverse drug events (ADEs). This study assessed whether an antimicrobial stewardship recommendation to discontinue antibiotics in patients with low likelihood for bacterial infection reduced antibiotic duration and antibiotic-associated ADEs. At a 4-hospital system, hospitalized adult patients receiving empiric antibiotics for suspected infection were identified between May 2, 2016 and June 30, 2018. For those patients who were deemed unlikely to have a bacterial infection, a note was left by an infectious diseases physician recommending antibiotic discontinuation. Patient cases were considered "adherent" to recommendations if antibiotics were discontinued within 48 hours of the note and "non-adherent" to recommendations if antibiotics were continued beyond this. Duration of antibiotics and potential antibiotic-associated ADEs were collected retrospectively. Attribution of the adverse event to the antibiotic was decided upon by the investigators. The incidence of ADEs and duration of antibiotics between the adherent and non-adherent groups were compared. Of 253 patients deemed unlikely to have a bacterial infection, 114 (45%) treatment teams stopped antibiotics within 48 hours of the recommendation, and 139 (55%) continued antibiotics. The total number of ADEs was significantly higher in the non-adherent group compared to the adherent group (34 ADEs vs 9 ADEs, P = .001). The median number of total prescribed antibiotic days was higher in the non-adherent group than in the adherent group (5 days vs 1 day, P < .001). This study demonstrates that stewardship programs may prevent ADEs by recommending antibiotic discontinuation in patients with low suspicion for bacterial infection.

Accuracy of frameless image-guided implantation of depth electrodes for intracranial epilepsy monitoring.

OBJECTIVE: Various techniques are available for stereotactic implantation of depth electrodes for intracranial epilepsy monitoring. The goal of this study was to evaluate the accuracy and effectiveness of frameless MRI-guided depth electrode implantation. METHODS: Using a frameless MRI-guided stereotactic approach (Stealth), depth electrodes were implanted in patients via burr holes or craniotomy, mostly into the medial temporal lobe. In all cases in which it was possible, postoperative MR images were coregistered to planning MR images containing the marked targets for quantitative analysis of intended versus actual location of each electrode tip. In the subset of MR images done with sufficient resolution, qualitative assessment of anatomical accuracy was performed. Finally, the effectiveness of implanted electrodes for identifying seizure onset was retrospectively examined. RESULTS: Sixty-eight patients underwent frameless implantation of 413 depth electrodes (96% to mesial temporal structures) via burr holes by one surgeon at 2 institutions. In 36 patients (203 electrodes) planning and postoperative MR images were available for quantitative analysis; an additional 8 procedures with 19 electrodes implanted via craniotomy for grid were also available for quantitative analysis. The median distance between intended target and actual tip location was 5.19 mm (mean 6.19 ± 4.13 mm, range < 2 mm-29.4 mm). Inaccuracy for transtemporal depths was greater along the electrode (i.e., deep), and posterior, whereas electrodes inserted via an occipital entry deviated radially. Failure to localize seizure onset did not result from implantation inaccuracy, although 2 of 62 patients (3.2%)-both with electrodes inserted occipitally-required reoperation. Complications were mostly transient, but resulted in long-term deficit in 2 of 68 patients (3%). CONCLUSIONS: Despite modest accuracy, frameless depth electrode implantation was sufficient for seizure localization in the medial temporal lobe when using the orthogonal approach, but may not be adequate for occipital trajectories.

Neurological and functional outcomes of subdural hematoma evacuation in patients over 70 years of age.

BACKGROUND: Subdural hematoma (SDH) is a common disease entity treated by neurosurgical intervention. Although the incidence increases in the elderly population, there is a paucity of studies examining their surgical outcomes. OBJECTIVES: To determine the neurological and functional outcomes of patients over 70 years of age undergoing surgical decompression for subdural hematoma. MATERIALS AND METHODS: We retrospectively reviewed data on 45 patients above 70 years who underwent craniotomy or burr holes for acute, chronic or mixed subdural hematomas. We analyzed both neurological and functional status before and after surgery. RESULTS: Forty-five patients 70 years of age or older were treated in our department during the study period. There was a significant improvement in the neurological status of patients from admission to follow up as assessed using the Markwalder grading scale (1.98 vs. 1.39; P =0.005), yet no improvement in functional outcome was observed as assessed by Glasgow Outcome Score. Forty-one patients were admitted from home, however only 20 patients (44%) were discharged home, 16 (36%) discharged to nursing home or rehab, 6 (13%) to hospice and 3 (7%) died in the postoperative period. Neurological function improved in patients who were older, had a worse pre-operative neurological status, were on anticoagulation and had chronic or mixed acute and chronic hematoma. However, no improvement in functional status was observed. CONCLUSION: Surgical management of SDH in patients over 70 years of age provides significant improvement in neurological status, but does not change functional status.

Randomized study of basal-bolus insulin therapy in the inpatient management of patients with type 2 diabetes undergoing general surgery (RABBIT 2 surgery).

OBJECTIVE: The optimal treatment of hyperglycemia in general surgical patients with type 2 diabetes mellitus is not known. RESEARCH DESIGN AND METHODS: This randomized multicenter trial compared the safety and efficacy of a basal-bolus insulin regimen with glargine once daily and glulisine before meals (n = 104) to sliding scale regular insulin (SSI) four times daily (n = 107) in patients with type 2 diabetes mellitus undergoing general surgery. Outcomes included differences in daily blood glucose (BG) and a composite of postoperative complications including wound infection, pneumonia, bacteremia, and respiratory and acute renal failure. RESULTS: The mean daily glucose concentration after the 1st day of basal-bolus insulin and SSI was 145 ± 32 mg/dL and 172 ± 47 mg/dL, respectively (P < 0.01). Glucose readings <140 mg/dL were recorded in 55% of patients in basal-bolus and 31% in the SSI group (P < 0.001). There were reductions with basal-bolus as compared with SSI in the composite outcome [24.3 and 8.6%; odds ratio 3.39 (95% CI 1.50-7.65); P = 0.003]. Glucose <70 mg/dL was reported in 23.1% of patients in the basal-bolus group and 4.7% in the SSI group (P < 0.001), but there were no significant differences in the frequency of BG <40 mg/dL between groups (P = 0.057). CONCLUSIONS: Basal-bolus treatment with glargine once daily plus glulisine before meals improved glycemic control and reduced hospital complications compared with SSI in general surgery patients. Our study indicates that a basal-bolus insulin regimen is preferred over SSI in the hospital management of general surgery patients with type 2 diabetes.

A comparison study of continuous insulin infusion protocols in the medical intensive care unit: computer-guided vs. standard column-based algorithms.

PURPOSE: To compare the safety and efficacy of continuous insulin infusion (CII) via a computer-guided and a standard paper form protocol in a medical intensive care unit (ICU). METHODS: Multicenter randomized trial of 153 ICU patients randomized to CII using the Glucommander (n = 77) or a standard paper protocol (n = 76). Both protocols used glulisine insulin and targeted blood glucose (BG) between 80 mg/dL and 120 mg/dL. RESULTS: The Glucommander resulted in a lower mean BG value (103 ± 8.8 mg/dL vs. 117 ± 16.5 mg/dL, P < 0.001) and in a shorter time to reach BG target (4.8 ± 2.8 vs.7.8 hours ± 9.1 hours, P < 0.01), and once at target resulted in a higher percentage of BG readings within target (71.0 ± 17.0% vs. 51.3 ± 19.7%, P < 0.001) than the standard protocol. Mean insulin infusion rate in the Glucommander was similar to the standard protocol (P = 0.12). The percentages of patients with ≥1 episode of BG <40 mg/dL and <60 mg/dL were 3.9% and 42.9% in the Glucommander and 5.6% and 31.9% in the standard, respectively [P = not significant (NS)]. Repeated measures analyses show that the probabilities of BG reading <40 mg/dL or <60 mg/dL were not significantly different between groups (P = 0.969, P = 0.084) after accounting for within-patient correlations with or without adjusting for time effect. There were no differences between groups in the length of hospital stay (P = 0.704), ICU stay (P = 0.145), or inhospital mortality (P = 0.561). CONCLUSION: Both treatment algorithms resulted in significant improvement in glycemic control in critically ill patients in the medical ICU. The computer-based algorithm resulted in tighter glycemic control without an increased risk of hypoglycemic events compared to the standard paper protocol.

Safety and efficacy of continuous insulin infusion in noncritical care settings.

BACKGROUND: Continuous insulin infusion (CII) to manage hyperglycemia is the accepted standard of care in the intensive care unit (ICU); however, the safety and efficacy of CII in the non-ICU setting has not been determined. RESEARCH DESIGN AND METHODS: This is a retrospective analysis of 200 consecutive patients receiving CII while admitted to general medical-surgical units at Emory University Hospital. We evaluated clinical outcomes and rates of hyperglycemia (blood glucose [BG] >200 mg/dL) and hypoglycemia (BG <60 mg/dL) events during CII. RESULTS: A total of 200 patients (age 52 +/- 16 years; male/female [M/F] 108/92) were admitted to general medicine (45%) or surgery (55%) services, 88.5% with history of diabetes and 41% treated with corticosteroids. The mean BG prior to and during the CII was 323 mg/dL and 170 mg/dL, respectively. Blood glucose of

Insulin analogs versus human insulin in the treatment of patients with diabetic ketoacidosis: a randomized controlled trial.

OBJECTIVE: To compare the safety and efficacy of insulin analogs and human insulins both during acute intravenous treatment and during the transition to subcutaneous insulin in patients with diabetic ketoacidosis (DKA). RESEARCH DESIGN AND METHODS: In a controlled multicenter and open-label trial, we randomly assigned patients with DKA to receive intravenous treatment with regular or glulisine insulin until resolution of DKA. After resolution of ketoacidosis, patients treated with intravenous regular insulin were transitioned to subcutaneous NPH and regular insulin twice daily (n = 34). Patients treated with intravenous glulisine insulin were transitioned to subcutaneous glargine once daily and glulisine before meals (n = 34). RESULTS: There were no differences in the mean duration of treatment or in the amount of insulin infusion until resolution of DKA between intravenous treatment with regular and glulisine insulin. After transition to subcutaneous insulin, there were no differences in mean daily blood glucose levels, but patients treated with NPH and regular insulin had a higher rate of hypoglycemia (blood glucose <70 mg/dl). Fourteen patients (41%) treated with NPH and regular insulin had 26 episodes of hypoglycemia and 5 patients (15%) in the glargine and glulisine group had 8 episodes of hypoglycemia (P = 0.03). CONCLUSIONS: Regular and glulisine insulin are equally effective during the acute treatment of DKA. A transition to subcutaneous glargine and glulisine after resolution of DKA resulted in similar glycemic control but in a lower rate of hypoglycemia than with NPH and regular insulin. Thus, a basal bolus regimen with glargine and glulisine is safer and should be preferred over NPH and regular insulin after the resolution of DKA.

TRAIL agonists on clinical trials for cancer therapy: the promises and the challenges.

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is normally expressed in the human immune system and plays a critical role in antitumor immunity. TRAIL interacts with the death receptors, DR4 and DR5, and activates intracellular apoptotic pathway in cancer cells. This discovery has resulted in a rapid development of cancer therapeutic agents that can activate this apoptotic pathway. These therapeutic agents include recombinant human TRAIL (rhTRAIL) and its agonistic monoclonal antibody (MAb) against DR4 and DR5. Phase I trials have established the safety and tolerability of these TRAIL agonists in patients. Phase II trials are currently evaluating the therapeutic efficacy of TRAIL agonists as single agents or in combination with established cancer therapeutics. This review outlines the advances and the challenges in the development of these TRAIL agonists as effective clinical cancer therapeutics.