What is the relative risk of urologic malignancy in microscopic hematuria patients after negative evaluation? A long-term population-based retrospective analysis of 8465 patients.

OBJECTIVE: To evaluate whether microscopic hematuria (MH) patients with a negative initial evaluation have an elevated risk for urinary carcinoma. METHODS: This is a population-based retrospective study with a matched control identified 8465 adults with an MH ICD code, an initial negative urinary malignancy work-up of cystoscopy and CT urography, and at least 35 months of clinical care. 8465 hematuria naïve controls were age, gender, and smoking status matched. Subsequent coding of non-prostatic urinary cancer, or any following hematuria codes: additional microscopic unspecified or unspecified hematuria, and gross hematuria was obtained. Χ2 tests were performed. RESULTS: There was no statistically significant difference in urinary malignancy rates (p > 0.05). Any urinary cancer: cases 0.74% (63/8465; 95% CI 0.58-0.95%)/controls 0.83% (71/8465; 95% CI 0.66-1.04%%) (p = 0.54); bladder: 0.45%/0.47% (p = 0.82); renal: 0.31%/0.38% (p = 0.43); ureteral: 0.01%/0.02% (p = 0.56). Subsequent gross hematuria in both males and females increased the odds of cancer: males 2.35 (p = 0.001; CI 1.42-3.91); females 4.25 (p < 0.001; CI 1.94-9.34). Males without additional hematuria had decreased odds ratio: 0.32 (p = 0.001; CI 0.16-0.64). Females without additional hematuria 0.58 (p = 0.19; CI 0.26-1.30) and both genders with additional unspecified hematuria/microscopic hematuria males 1.02 (p = 0.97; CI 0.50-2.08) and females 1.00 (p = 0.99; CI 0.38-2.66) did not have increased odds ratios (p > 0.05). CONCLUSION: MH patients with initial negative evaluation have a subsequent urologic malignancy rate of less than 1% and likely do not need further urinary evaluation unless they develop gross hematuria.

Evaluation of an Opioid Overdose Composite Risk Score Cutoff in Active Duty Military Service Members.

OBJECTIVE: To evaluate the current cutoff score and a recalibrated adaptation of the Veterans Health Administration (VHA) Risk Index for Serious Prescription Opioid-Induced Respiratory Depression or Overdose (RIOSORD) in active duty service members. DESIGN: Retrospective case-control. SETTING: Military Health System. SUBJECTS: Active duty service members dispensed ≥ 1 opioid prescription between January 1, 2018, and December 31, 2019. METHODS: Service members with a documented opioid overdose were matched 1:10 to controls. An active duty-specific (AD) RIOSORD was constructed using the VHA RIOSORD components. Analyses examined the risk stratification and predictive characteristics of two RIOSORD versions (VHA and AD). RESULTS: Cases (n = 95) were matched with 950 controls. Only 6 of the original 17 elements were retained in the AD RIOSORD. Long-acting or extended-release opioid prescriptions, antidepressant prescriptions, hospitalization, and emergency department visits were associated with overdose events. The VHA RIOSORD had fair performance (C-statistic 0.77, 95% CI 0.75, 0.79), while the AD RIOSORD did not demonstrate statistically significant performance improvement (C-statistic 0.78, 95% CI, 0.77, 0.80). The DoD selected cut point (VHA RIOSORD > 32) only identified 22 of 95 ORD outcomes (Sensitivity 0.23), while an AD-specific cut point (AD RIOSORD > 16) correctly identified 53 of 95 adverse events (Sensitivity 0.56). CONCLUSIONS: Results highlight the need to continually recalibrate predictive models and to consider multiple measures of performance. Although both models had similar overall performance with respect to the C-statistic, an AD-specific index threshold improves sensitivity. The calibrated AD RIOSORD does not represent an end-state, but a bridge to a future model developed on a wider range of patient variables, taking into consideration features that capture both care received, and care that was not received.

Development, implementation, and evaluation of a clinical decision support tool to improve naloxone coprescription within Military Health System pharmacies.

PURPOSE: To describe the development, implementation, and evaluation of a pharmacy clinical decision support tool designed to increase naloxone coprescription among people at risk for opioid overdose in a large healthcare system. SUMMARY: The Military Health System Opioid Registry and underlying presentation layer were used to develop a clinical decision support capability to improve naloxone coprescription at the pharmacy point of care. Pharmacy personnel use a patient identification card barcode scanner or manually enter a patient's identification number to quickly visualize information on a patient's risk for opioid overdose and medical history related to pain and, when appropriate, receive a recommendation to coprescribe naloxone. The tool was made available to military treatment facility pharmacy locations. An interactive dashboard was developed to support monitoring, utilization, and impact on naloxone coprescription to patients at risk for opioid overdose. CONCLUSION: Initial implementation of the naloxone tool was slow from a lack of end-user awareness. Efforts to increase utilization were, in part, successful owing to a number of enterprise-wide educational initiatives. In early 2020, the naloxone tool was used in 15% of all opioid prescriptions dispensed at a military pharmacy. Data indicate that the frequency of naloxone coprescription to patients at risk for opioid overdose was significantly higher when the naloxone tool was used than when the tool was not used.

THE IMPACT OF GLP-1 RECEPTOR AGONISTS ON PATIENTS WITH DIABETES ON INSULIN THERAPY.

Objective: The clinical benefit of adding a glucagon-like peptide-1 receptor agonist (GLP-1RA) to basal-bolus or very high dose insulin regimens is unclear. This study investigated the impact of adding a GLP-1RA to a spectrum of insulin regimens (basal, basal-bolus, and U-500) to determine the impact on hemoglobin A1c (HbA1c), weight loss, and total daily insulin dose (TDD) over the course of 12 months. Methods: A retrospective chart review was conducted on 113 participants with type 2 diabetes mellitus using insulin therapy. Each participant's HbA1c, body weight, and TDD were recorded prior to initiation of GLP-1RA therapy and at the 3, 6, and 12-month time points while on combination therapy. Results: Across all participants, the HbA1c values decreased significantly from a baseline of 8.9 (74 mmol/mol) ± 0.14% to 8.2 (66 mmol/mol) ± 0.14% (P<.01) in the first 3 months, 8.0 (64 mmol/mol) ± 0.12% (P<.01) at 6 months, to 8.3 (67 mmol/mol) ± 0.14% (P<.01) at 12 months. There was no significant decrease in weight or TDD with the addition of a GLP-1RA overall or in different insulin groups. However, there was a clinically significant decrease in weight over the study duration. Conclusion: The results of this study suggest that adding a GLP-1RA to various insulin regimens may help to achieve glycemic goals while avoiding the less desirable side effects of weight gain and increasing insulin regimens. However, the expected weight loss and decrease in TDD may not be as sizable in the clinical setting. Abbreviations: DCOE = Diabetes Center of Excellence; DM = diabetes mellitus; GLP-1RA = glucagon-like peptide-1 receptor agonist; HbA1c = hemoglobin A1c; RCT = randomized controlled trial; TDD = total daily dose.

Effect of Military Deployment on Diabetes Mellitus in Air Force Personnel.

Introduction: Military deployments relocate service members to austere locations with limited medical capabilities, raising uncertainties whether members with diabetes can participate safely. Military regulations require a medical clearance for service members with diabetes prior to deployment, but there is a dearth of data that can guide the provider in this decision. To alleviate the lack of evidence in this area, we analyzed the change in glycated hemoglobin (HbA1c) and body mass index (BMI) before and after a deployment among active duty U.S. Air Force personnel who deployed with diabetes. Materials and Methods: A retrospective analysis was conducted using HbA1c and BMI values obtained within 3 mo before and within 3 mo after repatriation from a deployment of at least 90 d between January 1, 2004 through December 31, 2014. The study population consisted of 103 and 195 subjects who had an available pre- and post-deployment HbA1c and BMI values, respectively. Paired t-tests were conducted to determine significant differences in HbA1C and BMI values. Results: The majority (73.8%) of members had a HbA1c <7.0% (53 mmol/mol) prior to deployment. For the overall population, HbA1c before and after deployment decreased from 6.7% (50 mmol/mol) to 6.5% (40 mmol/mol) (p = 0.03). Subgroup analysis demonstrated a significant decline in HbA1c among males, those aged 31-40 yr, and those with a pre-deployment HbA1c of >7%. BMI declined for the overall population (28.3 kg/m2 vs. 27.7 kg/m2, p < 0.0001) and for most of the subgroups. Conclusion: Air Force service members who deployed with diabetes, including those with a HbA1c > 7%, experienced a statistically significant improvement in HbA1c and BMI upon repatriation. A prospective study design in the future can better reconcile the effect of a military deployment on a more comprehensive array of diabetes parameters.

Dopamine D(2) receptor function is compromised in the brain of the methionine sulfoxide reductase A knockout mouse.

Previous research suggests that brain oxidative stress and altered rodent locomotor behavior are linked. We observed bio-behavioral changes in methionine sulfoxide reductase A knockout mice associated with abnormal dopamine signaling. Compromised ability of these knockout mice to reduce methionine sulfoxide enhances accumulation of sulfoxides in proteins. We examined the dopamine D(2)-receptor function and expression, which has an atypical arrangement and quantity of methionine residues. Indeed, protein expression levels of dopamine D(2)-receptor were higher in knockout mice compared with wild-type. However, the binding of dopamine D(2)-receptor agonist was compromised in the same fractions of knockout mice. Coupling efficiency of dopamine D(2)-receptors to G-proteins was also significantly reduced in knockout mice, supporting the compromised agonist binding. Furthermore, pre-synaptic dopamine release in knockout striatal sections was less responsive than control sections to dopamine D(2)-receptor ligands. Behaviorally, the locomotor activity of knockout mice was less responsive to the inhibitory effect of quinpirole than wild-type mice. Involvement of specific methionine residue oxidation in the dopamine D(2)-receptor third intracellular loop is suggested by in vitro studies. We conclude that ablation of methionine sulfoxide reductase can affect dopamine signaling through altering dopamine D(2)-receptor physiology and may be related to symptoms associated with neurological disorders and diseases.