Clinical Note: Use of Clonidine to Detoxify Opiate-Addicted Patients

This study investigated the utility of systematically administering clonidine to detoxify opiate-dependent inpatients. Fifteen patients received a 0.1 mg dose of clonidine orally at 8:00 am, 12:00 noon, 4:00 pm, and at bedtime. A 0.1 mg dose was also administered as needed if any withdrawal signs were evidenced, but this additional dose was rarely needed after the second day of treatment. Night sweats were the only significant complaint reported. All 15 patients were successfully detoxified after ten days of treatment

Colistin-associated Stevens-Johnson syndrome and toxic epidermal necrolysis reactions: a retrospective case-non-case pharmacovigilance study

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening skin reactions. Colistin is a last resort antibiotic with a historically poor safety profile. The association between colistin and SJS/TEN has not been previously quantified. Research design and methods: We identified colistin and SJS/TEN adverse event reports from the Food and Drug Administration Adverse Event Reporting System (FAERS) and calculated effect estimates using OpenEpi. Results: From January 2013 through March 2021, 964 adverse events were reported for colistin. Colistin was listed as a secondary suspect drug in 13 SJS/TEN adverse event reports (1.3%), with a reporting odds ratio of 29.6 (95% confidence interval [CI] 17.1–51.1), and proportional reporting ratio of 29.2 (95% CI 17.0–50.2). Limitations of any FAERS study include the voluntary nature of reporting, unclear causal relationship between drug and adverse reaction, underreporting, and wide confidence intervals for rare adverse events like SJS/TEN. Conclusions: Colistin was not the primary suspect drug in any SJS/TEN adverse event reports. We did identify a statistically significant safety signal for SJS/TEN with colistin as a secondary suspect drug. SJS/TEN is not currently included in the colistin product label. This association should be further explored in other pharmacoepidemiologic drug safety studies

470. Concomitant Antibiotic Use and Death Among a National Cohort of Veterans With Clostridium difficile Infection (CDI)

Background: Antibiotic use is a well-known risk factor for development of CDI, and there is preliminary evidence suggesting concomitant antibiotic use may result in poor outcomes, including death. This work investigated the effect of concomitant antibiotic exposure during CDI treatment on mortality among patients with CDI. Methods: We conducted a national retrospective study of Veterans with a first CDI between 2010 and 2014, defined as a positive C. difficile toxin(s) and no episode in the year prior. Those treated with guideline recommended CDI treatment were included (10–14 days of PO or IV metronidazole, PO or PR vancomycin, or fidaxomicin). The exposure of interest was any non-CDI antibiotic use during CDI treatment; and the outcome was all cause death within 30 days of the end of CDI treatment. Inverse probability of treatment weighted Cox proportional hazards models were used to estimate the effect of concomitant antibiotic use on time to mortality. Weights were derived from propensity score modeling of the probability of exposure to antibiotics during CDI treatment as a function of potential confounders. Sensitivity analyses by antibiotic class were conducted. Results: Of the 9,517 patients included in the study cohort, mean age was 65.3 years (±SD 14.6), 92.5% (n = 8,802) were male, and 75.03% (n = 7,141) were white. Half were exposed to non-CDI antibiotics during CDI treatment (51.8%, n = 4,925) and 8.9% (n = 849) died. In unadjusted and adjusted analyses, concomitant antibiotic use was associated with death (HR 5.74, 95% CI 4.75–6.93; aHR 2.39, 95% CI 2.07–2.75). Advanced generation cephalosporin (aHR 2.36, 95% CI 2.05–2.71), β-lactam/β-lactamase inhibitor combinations (aHR 1.45, 95% CI 1.16–1.82), and clindamycin (aHR 1.95, 95% CI 1.26–3.02) were associated with death, while fluoroquinolone use was not (aHR 0.97, 95% CI 0.84–1.12) Conclusion: Among our national cohort, concomitant antibiotic use was common during CDI treatment. Any concomitant antibiotic use increased the risk of death; however, results suggest risk might vary by antibiotic class. Results support continued efforts in the reduction of unnecessary antibiotic use during CDI treatment, and future studies into which antibiotics may have the least risk of death when treatment is necessary

What is the role for metronidazole in the treatment of Clostridium difficile infection? Results from a national cohort study of Veterans with initial mild disease

Background: Metronidazole may still be an appropriate therapeutic option for mild Clostridium difficile infection (CDI) in select patients, but data is limited to guide clinicians in identifying these patients. Methods: Our two-stage study included a national cohort of Veterans with a first episode of mild CDI (2010–2014). First, among those treated with metronidazole, we identified predictors of success, defined as absence of all-cause mortality or recurrence 30-days post-treatment, using multivariable unconditional logistic regression. Second, among a subgroup of patients with characteristic/s predictive of success identified in the first-stage, we compared clinical outcomes among those treated with metronidazole compared with vancomycin, using Cox proportional hazards models for time to 30-day all-cause mortality, CDI recurrence, and failure. Results: Among 3,656 patients treated with metronidazole, we identified 3,282 patients with success and 374 patients without success (failure). Younger age was the only independent predictor of success. Age ≤65 years was associated with an odds of success 1.63 times higher (95% confidence interval [CI] 1.29 – 2.06) than age \u3e65 years. Among 115 propensity-score matched pairs ≤65 years of age, no significant differences were observed between metronidazole and vancomycin (reference) for all-cause mortality (hazard ratio [HR] 0.29, 95% CI 0.06–1.38), CDI recurrence (HR 0.62, 95% CI 0.26–1.49), or failure (HR 0.50, 95% CI 0.23–1.07). Conclusion: Among patients ≤65 years of age with initial mild CDI, clinical outcomes were similar with metronidazole and vancomycin. These data suggest metronidazole may be considered for the treatment of initial mild CDI among patients 65 years of age or younger

Sea Level Rise and Storm Surge Projections for the National Park Service

Over one quarter of the units of the National Park System occur along ocean coastlines. Ongoing changes in relative sea levels and the potential for increasing storm surges due to anthropogenic climate change and other factors present challenges to national park managers. This report summarizes work done by the University of Colorado in partnership with the National Park Service (NPS) to provide sea level rise and storm surge projections to coastal area national parks using information from the United Nations Intergovernmental Panel on Climate Change (IPCC) and storm surge scenarios from National Oceanic and Atmospheric Administration (NOAA) models. This research is the first to analyze IPCC and NOAA projections of sea level and storm surge under climate change for U.S. national parks. Results illustrate potential future inundation and storm surge under four greenhouse gas emissions scenarios. In addition to including multiple scenarios, the analysis considers multiple time horizons (2030, 2050 and 2100). This analysis provides sea level rise projections for 118 park units and storm surge projections for 79 of those parks. Within the National Park Service, the National Capital Region is projected to experience the highest average rate of sea level change by 2100. The coastline adjacent to the Outer Banks Group of parks in the Southeast Region is projected to experience the highest sea level rise by 2100. The Southeast Region is projected to experience the highest storm surges based on historical data and NOAA storm surge models. These results are intended to inform park planning and adaptation strategies for resources managed by the National Park Service. Sea level change and storm surge pose considerable risks to infrastructure, archeological sites, lighthouses, forts, and other historic structures in coastal units of the national park system. Understanding projections for continued change can better guide protection of such resources for the benefit of long-term visitor enjoyment and safety

Risk Factors Associated with Mupirocin Resistance in Methicillin-Resistant Staphylococcus aureus

Implementation of meticillin-resistant Staphylococcus aureus (MRSA) decolonisation programmes has been increasing and the emergence of mupirocin resistance has been reported. However, the patient-level risk factors associated with mupirocin resistance are not clear. In this study, independent predictors of mupirocin resistance in MRSA among Providence Veterans Affairs Medical Center patients with MRSA-positive culture dates between 1 July 2004 and 30 June 2008 were identified using a frequency-matched case–control study. Forty cases (mupirocin-resistant) were matched on culture date quarter and year to 270 controls (mupirocin-susceptible). The adjusted conditional logistic regression model identified three significant independent predictors associated with mupirocin resistance in MRSA: (1) exposure to mupirocin in the year prior to the culture date [odds ratio (OR): 9.84; 95% confidence interval (CI): 2.93–33.09]; (2) Pseudomonas aeruginosa infection in the year before the culture-related admission (4.85; 1.20–19.61); and (3) cefepime use in the year prior to culture (2.80; 1.03–7.58). In sensitivity analyses, previous mupirocin exposure was associated with low-level [minimum inhibitory concentration (MIC) 8–128 mg/L; 23 cases, 202 controls; OR: 6.32; 95% CI: 1.58–25.33] and high-level (MIC ≥256 mg/L; 17 cases, 151 controls; OR: 11.18; 95% CI: 1.89–66.30) mupirocin resistance. To our knowledge, this is the first case–control study to reveal a strong association between previous mupirocin exposure and subsequent mupirocin resistance in MRSA, with demonstrated robustness in low- and high-level mupirocin resistance. Mupirocin susceptibility monitoring is critical for facilities instituting decolonisation with mupirocin as increased use may reduce effectiveness through resistance

Optimization of NTP System Truss to Reduce Radiation Shield Mass

The benefits of nuclear thermal propulsion are numerous and relevant to the current NASA mission goals involving but not limited to the crewed missions to mars and the moon. They do however also present new and unique challenges to the design and logistics of launching/operating spacecraft. One of these challenges, relevant to this discussion, is the significant mass of the shielding which is required to ensure an acceptable radiation environment for the spacecraft and crew. Efforts to reduce shielding mass are difficult to accomplish from material and geometric design points of the shield itself, however by increasing the distance between the nuclear engines and the main body of the spacecraft the required mass of the shielding is lessened considerably. The mass can be reduced significantly per unit length, though any additional mass added by the structure to create this distance serves to offset those savings, thus the design of a lightweight structure is ideal. The challenges of designing the truss are bounded by several limiting factors including; the loading conditions, the capabilities of the launch vehicle, and achieving the ideal truss length when factoring for the overall mass reduced. Determining the overall set of mass values for a truss of varying length is difficult since to maintain an optimally designed truss the geometry of the truss or its members must change. Thus the relation between truss mass and length for these loading scenarios is not linear, and instead has relation determined by the truss design. In order to establish a mass versus length trend for various truss designs to compare with the mass saved from the shield versus length, optimization software was used to find optimal geometric properties that still met the design requirements at established lengths. By solving for optimal designs at various lengths, mass trends could be determined. The initial design findings show a clear benefit to extending the engines as far from the main structure of the spacecraft as the launch vehicle's payload volume would allow when comparing mass savings verse the additional structure

Shielding Development for Nuclear Thermal Propulsion

Radiation shielding analysis and development for the Nuclear Cryogenic Propulsion Stage (NCPS) effort is currently in progress and preliminary results have enabled consideration for critical interfaces in the reactor and propulsion stage systems. Early analyses have highlighted a number of engineering constraints, challenges, and possible mitigating solutions. Performance constraints include permissible crew dose rates (shared with expected cosmic ray dose), radiation heating flux into cryogenic propellant, and material radiation damage in critical components. Design strategies in staging can serve to reduce radiation scatter and enhance the effectiveness of inherent shielding within the spacecraft while minimizing the required mass of shielding in the reactor system. Within the reactor system, shield design is further constrained by the need for active cooling with minimal radiation streaming through flow channels. Material selection and thermal design must maximize the reliability of the shield to survive the extreme environment through a long duration mission with multiple engine restarts. A discussion of these challenges and relevant design strategies are provided for the mitigation of radiation in nuclear thermal propulsion

Vancomycin Dosing Considerations in a Real-World Cohort of Obese and Extremely Obese Patients

Study Objective: To compare the effects of empiric vancomycin dosing regimens on attainment of optimal target trough concentrations in obese (body mass index [BMI] 30–40 kg/m2) and extremely obese (BMI ≥ 40 kg/m2) patients. Design: Retrospective cohort study. Data Source: National Veterans Affairs standardized databases. Patients: A total of 263 obese and 71 extremely obese (actual body weight range 72–244 kg in both groups) inpatients from all Veterans Affairs facilities nationally who had suspected methicillin-resistant Staphylococcus aureus pneumonia and were treated with vancomycin between 2002 and 2012. Measurements and Main Results: Patients with steady-state trough concentrations (measured ≤ 2 hours before the next vancomycin dose) and no evidence of acute kidney injury before vancomycin initiation were included. Logistic regression models were used to measure the effect of various vancomycin dosing regimens on attainment of optimal target trough concentrations (15–20 mg/L). The mean total daily vancomycin dose was lower in obese versus extremely obese patients (2005 ± 736 vs 2306 ± 934 mg, p Conclusion: In this real-world study, we offer additional consideration of vancomycin dosing in obese and extremely obese patients. Extremely obese patients may require a lower weight-based daily dose than obese patients to reach target vancomycin trough concentrations