Cefepime extended infusion versus intermittent infusion: Clinical and cost evaluation.

Background: Extended infusion cefepime (1 gram every 6 hours administered over 3 hours) achieves pharmacodynamic efficacy against bacteria with a MIC of ≤8 mg/L in Monte Carlo simulations. This regimen has not been evaluated in clinical practice. Objective: Compare clinical and economic outcomes for cefepime by intermittent infusion and by extended infusion in the acute-care setting. Design: Single-center, retrospective cohort study. Setting: Tertiary-care academic medical center. Patients: Hospitalized adults who received cefepime between August 2016 and July 2018 with a diagnosis of sepsis or pneumonia. Methods: Clinical and economic outcomes were compared for patients who received empiric cefepime via intermittent infusion (30-minute infusion of 2 g every 8 hours) or extended infusion (3-hour infusion of 1 g every 6 hours). Clinical outcomes analyses were carried out using appropriate statistical methods. Results: Overall, 111 patients received intermittent infusion and 93 patients received extended infusion. Approximately half of the included patients had a positive culture for a bacterial pathogen (intermittent infusion 45.9% vs extended infusion 47.3%). Median hospital length of stay (intermittent infusion 6 days vs extended infusion 6 days; P = .67) and 90-day readmission rates (intermittent infusion 61.3% vs extended infusion 67.7%; P = .34) did not differ between the groups. Mortality was infrequent in both groups (intermittent infusion 2.9% vs extended infusion 1.5%; P = .45). Cefepime cost per patient was lower with cefepime by extended infusion: average total daily cost $86.06 for intermittent infusion versus $43.39 for extended infusion. Conclusions: Cefepime via extended infusion (4 grams/day) did not differ in clinical outcomes compared to intermittent infusion (6 grams/day) but reduced drug expenditure. Prospective, multicenter, high-quality studies should be conducted to evaluate a mortality difference between these regimens.

The effects of sex and neuter status on trauma survival in dogs: A Veterinary Committee on Trauma registry study.

OBJECTIVE: To determine the effect of sex and neuter status on trauma survival in dogs. DESIGN: Multi-institutional prospective case series, September 2013 to March 2019, retrospectively analyzed. SETTING: Level I and II Veterinary Trauma Centers. ANIMALS: Consecutive sample of 2649 dogs in the American College of Veterinary Emergency and Critical Care Veterinary Committee on Trauma patient registry meeting inclusion criteria. For inclusion, dogs had to have complete data entries, be postpubertal (≥7 months age in females and ≥10 months age in males), and have sustained moderate to severe trauma (animal trauma triage [ATT] score ≥5/18). Dogs that were dead upon arrival, euthanized for financial or unknown reasons alone, or that were presented by a Good Samaritan but subsequently humanely euthanized were excluded. MEASUREMENTS AND MAIN RESULTS: Data collected included age, sex, neuter status (intact, neutered), trauma type (blunt, penetrating, both), outcome (survived to hospital discharge, died, euthanized), and reason for euthanasia (grave prognosis, financial reasons, or both). Of 2649 eligible dogs, 56% survived to hospital discharge (n = 1469). Neutered females had a significantly higher survival rate (58.3% vs 51.3%; P = 0.03) compared to intact females, and neutered males had a significantly higher survival rate (56.6% vs 50.7%; P = 0.04) compared to intact males. There was no significant difference in survival between intact females and intact males (P = 0.87) or between neutered females and neutered males (P = 0.46). Mean cumulative ATT score was higher in intact groups and was found to be a significant predictor of survival (P < 0.01). Based on logistic models, overall odds of survival were 20.7% greater in neutered dogs. CONCLUSIONS: Gonadectomy is associated with lower ATT scores and improved survival after moderate to severe trauma in both female and male dogs.

Evaluation of matrix metalloproteinases and tissue inhibitors of metalloproteinases in aqueous humor of dogs with versus without naturally occurring primary angle-closure glaucoma.

OBJECTIVE: To compare concentrations of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in aqueous humor from ophthalmologically normal dogs and dogs with naturally occurring primary angle-closure glaucoma (cPACG). SAMPLE: Aqueous humor samples from 12 eyes with cPACG and 18 ophthalmologically normal eyes of dogs. PROCEDURES: A multiplex fluorescence-based ELISA was used to measure concentrations of MMP-1, MMP-2, MMP-3, MMP-8, MMP-9, MMP-10, MMP-13, TIMP-1, TIMP-2, and TIMP-4. Results for eyes with versus without cPACG were compared. RESULTS: Significantly higher mean concentrations of MMP-1 (45% higher), MMP-2 (55% higher), MMP-3 (39% higher), MMP-8 (79% higher), MMP-9 (29% higher), MMP-10 (60% higher), TIMP-1 (63% higher), and TIMP-2 (136% higher) were detected in aqueous humor from eyes with cPACG, compared with ophthalmologically normal eyes. CLINICAL RELEVANCE: MMPs and TIMPs have pivotal roles in extracellular matrix turnover and homeostasis in the outflow pathways of the eye. Results of the present study documented higher concentrations of MMPs and TIMPs in aqueous humor samples from dog eyes with late-stage cPACG. Although, to our knowledge, TIMPs have not previously been evaluated in the context of cPACG, the markedly higher concentration of TIMPs in eyes with cPACG suggested that inhibition of proteolysis and extracellular matrix turnover might be a factor in the development of glaucoma in susceptible individuals. However, because the present study used samples from dogs with late-stage cPACG, further work is required to characterize the temporal relationship between MMP and TIMP concentration changes and onset or progression of disease.

COVID-19 Pandemic and Pediatric Type 1 Diabetes: No Significant Change in Glycemic Control During The Pandemic Lockdown of 2020.

Importance: There is no consensus on the impact of the 2020 COVID-19 pandemic lockdown on glycemic control in children and adolescents with type 1 diabetes (T1D) in the US. Aim: To determine the impact of the pandemic lockdown of March 15th through July 6th, 2020 on glycemic control after controlling for confounders. Subjects and Methods: An observational study of 110 subjects of mean age 14.8 ± 4.9 years(y), [male 15.4 ± 4.0y, (n=57); female 14.1 ± 3.8y, (n=53), p=0.07] with T1D of 6.31 ± 4.3y (95% CI 1.0-19.7y). Data were collected at 1-4 months before the lockdown and 1-4 months following the lifting of the lockdown at their first post-lockdown clinic visit. Results: There was no significant change in A1c between the pre- and post-pandemic lockdown periods, 0.18 ± 1.2%, (95% CI -0.05 to 0.41), p=0.13. There were equally no significant differences in A1c between the male and female subjects, -0.16 ± 1.2 vs -0.19 ± 1.2%, p=0.8; insulin pump users and non-pump users, -0.25 ± 1.0 vs -0.12 ± 1.4%, p=0.5; and pubertal vs prepubertal subjects, 0.18 ± 1.3 vs -0.11 ± 0.3%, p=0.6. The significant predictors of decrease in A1c were pre-lockdown A1c (p<0.0001) and the use of CGM (p=0.019). The CGM users had significant reductions in point-of-care A1c (0.4 ± 0.6%, p=0.0012), the CGM-estimated A1c (p=0.0076), mean glucose concentration (p=0.022), a significant increase in sensor usage (p=0.012), with no change in total daily dose of insulin (TDDI). The non-CGM users had significantly increased TDDI (p<0.0001) but no change in HbA1c, 0.06 ± 1.8%, p=0.86. Conclusions: There was no change in glycemic control during the pandemic lockdown of 2020 in US children.

Mechanisms and early patterns of dyslipidemia in pediatric type 1 and type 2 diabetes.

Objectives The is no consensus on the early patterns of lipid-based cardiovascular disease (CVD) risk in youth with either type 1 diabetes (T1D) or type 2 diabetes (T2D). The aim was todetermine the differences in CVD risk, using lipid profiles, in children and adolescents with either T1D or T2D at the time of their first lipid assessment, after stratifying the T1D cohort into remitters and non-remitters based on their honeymoon history. Methods A cross-sectional study of 249 subjects consisting of 73 controls, 53 T2D subjects, and 123 T1D subjects stratified into remitters (n=44), and non-remitters (n=79). Partial clinical remission (PCR) was defined as insulin-dose adjusted HbA1c of ≤9. Pubertal status was determined by Tanner staging. Results After adjusting for age, sex, BMI, race, and pubertal status, T2D patients had significantly higher LDL-C compared to the controls (p=0.022), the remitters (p=0.029), but not the non-remitters (103.1 ± 5.9 mg/dL vs. 91.4 ± 4.2 mg/dL, p=0.49). Similarly, T2D patients had significantly higher non-HDL-C compared to the controls (p=0.006), the remitters (p=0.0002), but not the non-remitters (137.6 ± 7.1 mg/dL vs. 111.71 ± 5.0 mg/dL, p=0.053). Total cholesterol was also significantly higher in T2D patients compared to the controls (p=0.0005), the remitters (p=0.006) but not the non-remitters (183.5 ± 6.6 mg/dL vs. 166.2 ± 4.8 mg/dL, p=0.27). Conclusions Lack of the honeymoon phase in children and adolescents with T1D confers early and significantly increased lipid-based cardiovascular risk to these patients that is similar to the elevated cardiovascular risk seen in T2D.

Continuous glucose monitoring reduces pubertal hyperglycemia of type 1 diabetes.

Background Physiologic hyperglycemia of puberty is a major contributor to poor glycemic control in youth with type 1 diabetes (T1D). This study's aim was to determine the effectiveness of continuous glucose monitoring (CGM) to improve glycemic control in pubertal youth with T1D compared to a non-CGM cohort after controlling for age, sex, BMI, duration, and insulin delivery methodology. The hypothesis is that consistent CGM use in puberty improves compliance with diabetes management, leading to increased percentage (%) time in range (TIR70-180 mg/dL) of glycemia, and lowering of HbA1c. Methods A longitudinal, retrospective, case-controlled study of 105 subjects consisting of 51 T1D controls (60.8% male) age 11.5 ± 3.8 y; and 54 T1D subjects (48.1% male) age 11.1 ± 5.0 y with confirmed CGM use for 12 months. Pubertal status was determined by Tanner staging. Results were adjusted for baseline HbA1c and diabetes duration. Results HbA1c was similar between the controls and the CGM group at baseline: 8.2 ± 1.1% vs 8.3 ± 1.2%, p=0.48 respectively; but was significantly lower in the CGM group 12 months later, 8.2 ± 1.1% vs. 8.7 ± 1.4%, p=0.035. Longitudinal change in HbA1c was similar in the prepubertal cohort between the control- and CGM groups: -0.17 ± 0.98% vs. 0.38 ± 1.5%, p=0.17. In contrast, HbA1c increased with advancing age and pubertal status in the pubertal controls but not in the pubertal CGM group: 0.55 ± 1.4 vs -0.22 ± 1.1%, p=0.020. Percent TIR was inversely related to HbA1c in the CGM group, r=-0.6, p=0.0004, for both prepubertal and pubertal subjects. Conclusions CGM use significantly improved glycemic control in pubertal youth with T1D compared to non-CGM users.

Pubertal Lipid Levels Are Significantly Lower in Youth With Type 1 Diabetes Who Experienced Partial Clinical Remission.

IMPORTANCE: The physiologic changes in lipids during puberty in type 1 diabetes (T1D) are unclear because subjects in previous studies were not stratified by partial clinical remission status. AIM: To determine the effect of partial clinical remission on lipid changes during puberty in youth with T1D. SUBJECTS AND METHODS: A retrospective cross-sectional study of 194 subjects consisting of 71 control subjects of age 12.9 ± 1.3 years and 123 subjects with T1D stratified into remitters (n = 44; age, 13.0 ± 0.8 years) and nonremitters (n = 79; age, 11.2 ± 0.6 years). Partial clinical remission was defined as insulin-dose adjusted HbA1c of ≤9. Pubertal status was determined by Tanner staging. RESULTS: Among the pubertal cohort, low-density lipoprotein cholesterol concentration was significantly higher in the nonremitters compared with remitters (91.1 ± 25.6 vs 77.2 ± 25.8 mg/dL, P = 0.018) and with normal-weight control subjects (91.1 ± 25.6 vs 70.4 ± 22.9 mg/dL, P = 0.009) but was similar between overweight/obese control subjects and nonremitters (89.7 ± 28.9 vs 91.1± 25.6 mg/dL, P = 0.81) and between normal-weight control subjects and remitters (70.4 ± 22.9 vs 77.2 ± 25.8 mg/dL, P = 0.39). Total cholesterol was also significantly higher in nonremitters compared with remitters (167.8 ± 30.5 vs 149.8 ± 32.1 mg/dL, P = 0.012) and with normal-weight control subjects (167.8 ± 30.5 vs 143.2 ± 30.1 mg/dL, P = 0.011) but was similar between nonremitters and overweight/obese control subjects (P = 0.098) and between remitters and normal-weight control subjects (P = 0.51). Non-high-density lipoprotein cholesterol was equally significantly higher in nonremitters compared with remitters (111.3 ± 30.1 vs 95.9 ± 29.1 mg/dL, P = 0.028) and normal-weight control subjects (111.3 ± 30.1 vs 86.2 ± 32.2 mg/dL, P = 0.028) but was similar between nonremitters and overweight/obese control subjects (P = 0.48) and between remitters vs normal-weight control subjects (P = 0.39). CONCLUSIONS: Puberty-related reductions in low-density lipoprotein, total cholesterol, and non-high-density lipoprotein occur in remitters and normal-weight control subjects but not in nonremitters and overweight/obese control subjects.