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Safety and Effectiveness of a Standardized Intravenous Insulin Infusion Order Set for Managing Uncontrolled Hyperglycemia Outside the Intensive Care Unit

Background: Few studies have evaluated the administration of intravenous (IV) insulin infusions for uncontrolled hyperglycemia in non-intensive care unit (ICU) patients, and there is inadequate data to guide how to appropriately administer IV insulin infusions to this patient population. Objective: Determine the effectiveness and safety of our institution’s non-critical care IV insulin infusion order set. Methods: This retrospective study was conducted at 2 institutions within a health care system. The primary outcome was the number of individuals who achieved a glucose level ≤180 mg/dL. For those meeting this endpoint, the time to achieving this outcome and the percentage of glucose checks within the goal range were determined. The primary safety endpoint was the number of individuals who experienced hypoglycemia (glucose level <70 mg/dL). Patients were included if they were ≥18 years of age and received the non-critical care IV insulin infusion order set outside of the ICU. Results: Twenty-one (84%) patients achieved a glucose level ≤180 mg/dL. The median (inter-quartile range [IQR]) time to achieving the primary outcome was 5.7 h (3.9-8.3). In patients who achieved the primary outcome, 41.8% of the glucose readings obtained after achieving this outcome were within goal range. Two (8%) patients experienced hypoglycemia. Both of these events occurred within 8 hours of therapy initiation and neither patient received prior doses of subcutaneous insulin. Of the 4 patients who did not achieve a glucose level ≤180 mg/dL, 2 received high-dose corticosteroids, and 3 achieved a glucose level between 181 and 200 mg/dL. Conclusion and Relevance: Our findings support the safe administration of IV insulin infusions to non-ICU patients when targeting a glucose range of 140 to 180 mg/dL and limiting the infusion duration.

Latency Antibiotics in Preterm Prelabor Rupture of Membranes: A Comparison of Azithromycin Regimens

Background: Treatment with antibiotics at the time of preterm prelabor rupture of membranes (PPROM) has been shown to prolong pregnancy. Due to the recurrent shortage of erythromycin, azithromycin has been substituted in the traditional regimen; however, there are little data on optimal dosing. Objective: The objective of this study was to determine whether there is a difference in latency from onset of PPROM to delivery in patients who received a single dose of azithromycin compared with a 5-day course. Methods: This was a single-center, multisite, retrospective, IRB approved analysis of patients admitted with a diagnosis of PPROM. Patients were included if rupture occurred between 22 0/7 and 33 6/7 weeks of gestation and received either a single dose or a 5-day course of azithromycin along with a beta lactam. Results: A total of 376 patients were reviewed with 296 patients included in the final analysis. There was no statistical difference in the primary outcome of latency days in patients who received the 5-day versus the single-dose course (4 vs 5 days, P = 0.641). There was a significantly higher rate of histologic chorioamnionitis in the single-dose course of azithromycin (46.4% vs 62.6%, P = 0.006). Conclusions and Relevance: There was no difference in latency for patients who received a 5-day course of azithromycin versus a single dose for the treatment of PPROM. A higher rate of histologic chorioamnionitis was observed in those who received the single-day course. Prospective follow-up studies are needed to confirm these findings.

Cidofovir for Viral Infections in Immunocompromised Children: Guidance on Dosing, Safety, Efficacy, and a Review of the Literature

To describe the use of cidofovir (CDV) for viral infections in immunocompromised children (IC) and provide guidance on dosing and supportive care. A PubMed search was conducted for literature published between 1997 and January 2022 using the following terms: cidofovir, plus children or pediatrics. Limits were set to include human subjects less than 24 years of age receiving intravenous (IV) or intrabladder CDV for treatment of infections due to adenovirus, polyomavirus-BK (BKV), herpesviruses, or cytomegalovirus. Data were heterogeneous, with largely uncontrolled studies. Conventional dosing (CDV 5 mg/kg/dose weekly) was commonly used in 60% (31/52) of studies and modified dosing (CDV 1 mg/kg/dose 3 times/week) was used in 17% (9/52) of studies, despite being off-label. Nephrotoxicity reported across studies totaled 16% (65/403 patients), which was higher for conventional dosing 29 of 196 patients (15%) than modified dosing 1 of 27 patients (4%). Saline hyperhydration and concomitant probenecid remain the cornerstones of supportive care, while some regimens omitting probenecid are emerging to target BKV. To our knowledge, this is the first comprehensive review of CDV use (indications, dosing, supportive care, response, and nephrotoxicity) in pediatric IC. Effective utilization of CDV in IC remains challenging. Further prospective studies are needed to determine the optimal CDV dosing; however, less aggressive dosing regimens such as modified thrice weekly dosing or low dosing once weekly omitting probenecid to enhance urinary penetration may be reasonable alternatives to conventional dosing in some IC.

Candidemia in Adult Patients in the ICU: A Reappraisal of Susceptibility Testing and Antifungal Therapy

To provide updates on the epidemiology and recommendations for management of candidemia in patients with critical illness. A literature search using the PubMed database (inception to March 2023) was conducted using the search terms "invasive candidiasis," "candidemia," "critically ill," "azoles," "echinocandin," "antifungal agents," "rapid diagnostics," "antifungal susceptibility testing," "therapeutic drug monitoring," "antifungal dosing," "persistent candidemia," and "Candida biofilm." Clinical data were limited to those published in the English language. Ongoing trials were identified through ClinicalTrials.gov. A total of 109 articles were reviewed including 25 pharmacokinetic/pharmacodynamic studies and 30 studies including patient data, 13 of which were randomized controlled clinical trials. The remaining 54 articles included fungal surveillance data, in vitro studies, review articles, and survey data. The current 2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Management of Candidiasis provides recommendations for selecting empiric and definitive antifungal therapies for candidemia, but data are limited regarding optimized dosing strategies in critically ill patients with dynamic pharmacokinetic changes or persistent candidemia complicated. Outcomes due to candidemia remain poor despite improved diagnostic platforms, antifungal susceptibility testing, and antifungal therapy selection for candidemia in critically ill patients. Earlier detection and identification of the species causing candidemia combined with recognition of patient-specific factors leading to dosing discrepancies are crucial to improving outcomes in critically ill patients with candidemia. Treatment of candidemia in critically ill patients must account for the incidence of non-albicans Candida species and trends in antifungal resistance as well as overcome the complex pathophysiologic changes to avoid suboptimal antifungal exposure.

Hepatorenal Syndrome With Acute Kidney Injury: Diagnosis and Medical Management

To review the current definitions and diagnostic criteria for acute kidney injury (AKI) and type 1 hepatorenal syndrome (HRS) now termed HRS-AKI and discuss the challenges in deciding the most appropriate medication regimens to treat patients with HRS-AKI. PubMed (inception to April 2023) with bibliographies of retrieved articles searched for additional articles; organizational websites for clinical practice guidelines (CPGs). Randomized controlled trials (RCTs) evaluating albumin and vasoconstrictors for HRS-AKI. A major change in the most recent revision of definitions and diagnostic criteria for HRS-AKI is the elimination of the set cutoff serum creatinine values for AKI. This change should be considered when comparing studies of HRS-AKI over time. Albumin has been administered to both vasoconstrictor treatment and placebo groups in all recent RCTs; however, there has never been a large RCT evaluating a no-albumin group. Most prospective trials comparing a midodrine/octreotide combination or norepinephrine to placebo or terlipressin have enrolled less than 100 patients limiting any conclusions regarding clinically important outcomes. Terlipressin with albumin has shown mixed results for complete HRS-AKI reversal with no reductions in crude mortality but adverse effect concerns involving ischemic and pulmonary events. Type 1 hepatorenal syndrome with acute kidney injury is a potentially life-threatening syndrome with diagnostic and treatment challenges. Albumin plus a vasoconstrictor has become the routine HRS-AKI treatment even though there has not been a large RCT evaluating a no-albumin group. Terlipressin is the vasoconstrictor of choice for HRS-AKI in current CPGs, but it has adverse effect concerns and, until recently, was not available in the United States. In conjunction with changes in the definitions and diagnostic criteria for HRS-AKI, debate continues regarding the optimal therapy for HRS-AKI, particularly considering recent trials demonstrating ischemic and pulmonary adverse events with terlipressin used in combination with albumin.

Sodium Phenylbutyrate and Taurursodiol: A New Therapeutic Option for the Treatment of Amyotrophic Lateral Sclerosis

To review the safety and efficacy of sodium phenylbutyrate and taurursodiol (SP + T) in slowing progression of amyotrophic lateral sclerosis (ALS) compared with pre-existing therapies. A PubMed (from January 1, 2009, to April 13, 2023) and ClinicalTrials.gov search conducted using sodium phenylbutyrate, taurursodiol, AMX0035, riluzole, and edaravone. Additional articles were identified by hand from references. This included English-language articles evaluating SP + T efficacy or safety in humans for decreasing neuronal death and slowing the progression of ALS. In one phase II clinical trial that encompassed an open-label extension phase, disease severity, assessed by the rate of decline in overall score on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised with higher scores indicating more functional ability, was -1.24 points per month with active drug and -1.66 points per month with placebo (difference, 0.42 points per month; 95% CI, 0.03-0.81; P = 0.03). Post hoc analysis found survival benefit of median 4.8 months with active medication compared with placebo. SP + T is a new US Food and Drug Administration-approved oral suspension for the treatment of ALS. Patients who received active medication through the phase II trial showed decreased rates of disease progression. Overall, SP + T could be considered a potential agent for the treatment of ALS which has a high unmet need. SP + T is an option for the treatment of ALS; however, additional data regarding efficacy in phase III trials with long-term safety profile considerations, as well as trials to compare current therapy with SP + T, are needed.