Utilization of Colistin Versus ß-Lactam and ß-Lactamase Inhibitor Agents in Relation to Acute Kidney Injury in Patients with Severe Gram-Negative Infections.

INTRODUCTION: Colistin is used to treat severe antibiotic-resistant Gram-negative infections (GNIs). With the rise of antibiotic resistance, colistin has been used increasingly as a 'last-line' therapy for multidrug-resistant GNIs. We evaluated the incidence of acute kidney injury (AKI) and mortality among patients receiving colistin or one of the new ß-lactam/ß-lactamase inhibitors (ßL + ßLI) (ceftazidime/avibactam, ceftolozane/tazobactam, or meropenem/vaborbactam). METHODS: This retrospective cohort study used data from the Premier Healthcare Database. The cohort included propensity score-matched adults with an inpatient stay between January 2016 and December 2018. Patients given both colistin and BL + BLI as treatment for ≥ 72 h were excluded. AKI was defined as acute renal failure or dialysis during hospitalization with antibiotic administration. Propensity score matching was used to control for selection bias and confounding. Logistic regression evaluated associations between treatment, AKI, and in-hospital mortality. RESULTS: The total number of patients in the matched cohorts were 256 in each. Overall, 23.8% and 13.3% of patients receiving colistin or new ßL + ßLI agents, respectively, experienced AKI during hospitalization (p = 0.002); odds of AKI for colistin were 3.0 (95% CI 1.71, 5.21). Following propensity score-matching, patients without baseline renal disease experienced AKI during hospitalization to a higher degree in the colistin group compared to the ßL + ßLI group (17.1% vs. 6.8%); colistin use was associated with 3.7 times higher odds (95% CI 1.84, 7.42) of AKI compared to ßL + ßLI agents. The odds of mortality in patients on colistin developing AKI were more than three times that of patients receiving a BL + BLI agent who developed AKI. Among patients receiving colistin, incident AKI was associated with 6.1 times higher odds (95% CI 2.53, 14.71) of mortality. CONCLUSIONS: Patients receiving colistin for GNIs had significantly higher odds of AKI and mortality than those receiving ßL + ßLI.

Real-world Experience of Bezlotoxumab for Prevention of Clostridioides difficile Infection: A Retrospective Multicenter Cohort Study.

BACKGROUND: Bezlotoxumab is approved for prevention of recurrence of Clostridioides difficile infection (CDI) in adults receiving standard of care (SoC) therapy based on findings from MODIFY clinical trials. However, utilization practices and validation of trial results in the real world are limited. METHODS: Records of patients receiving bezlotoxumab between April 2017 and December 2018 across 34 infusion centers in the United States were retrospectively reviewed. Recurrent CDI (rCDI), defined as diarrhea lasting ≥2 days resulting in treatment, was assessed 90 days postbezlotoxumab. RESULTS: The study cohort included 200 patients (median age, 70 years; 66% female; median Charlson comorbidity index, 5), of whom 86% (n = 173) had prior CDI episodes and 79% (n = 158) had ≥2 risk factors for rCDI. SoC antibiotics included vancomycin (n = 137, 68%), fidaxomicin (n = 60, 30%), and metronidazole (n = 3, 2%). Median time from C. difficile stool test to bezlotoxumab and initiation of SoC to bezlotoxumab were 15 days and 11 days, respectively. Within 90 days, 31 of 195 patients (15.9%) experienced rCDI, which corresponds to a success rate of 84.1%. Patients with ≥2 CDI recurrences prebezlotoxumab had a higher risk of subsequent rCDI compared with those with 1 recurrence or primary CDI (hazard ratio, 2.77; 95% confidence interval, 1.14-6.76; P = .025). CONCLUSIONS: This real-world multicenter study demonstrated successful prevention of rCDI with bezlotoxumab comparable to clinical trial results regardless of type of SoC and timing of infusion. Multiple prior CDI recurrences were associated with a higher risk of subsequent rCDI, supporting the use of bezlotoxumab earlier in the disease course.

Incidence of and risk factors for recurrent Clostridioidesdifficile infection in Japan using a claims database: A retrospective cohort study.

This retrospective cohort study aimed to determine the incidence rates of and risk factors for recurrent Clostridioides difficile infection (rCDI) in Japan using a claims database. Inpatients of any age with ≥1 record of C. difficile infection (CDI) during the study period (January 2012-September 2016) were analyzed. We estimated the incidence rate of health care onset, health care facility associated (HO-HCFA) primary CDI and HO-HCFA rCDI for each of the first to fifth recurrences. Risk factors for the first recurrence were investigated using a univariate, and subsequently, a multivariable Cox regression model. The incidence rates (95% confidence interval [CI]) of CDI and HO-HCFA CDI were 2.43 (2.40-2.46) and 1.26 (1.24-1.28) cases per 10,000 inpatient-days, respectively. Among the 11,287 inpatients with ≥1 HO-HCFA CDI, 1424 patients had ≥1 recurrent episode (12.6% [95% CI 12.0-13.2]). The rCDI incidence rates consistently increased, with the number of recurrences ranging from 29.2 to 181.8 cases per 10,000 inpatient-days. The multivariable analysis revealed five risk factors (hazard ratio [95% CI]): age ≥65 years (vs. <65 years; 65-74 years, 1.275 [1.048-1.551]; 75-79 years, 1.612 [1.315-1.975]; ≥80 years, 2.110 [1.776-2.507]); cephalosporin use both before (vs. without cephalosporin; 1.241 [1.098-1.402]) and during the primary CDI (vs. without cephalosporin; 1.137 [1.011-1.279]); higher number of comorbidities (vs. ≤10 comorbidities; 11-14 comorbidities: 1.336 [1.131-1.580]; 15-20 comorbidities: 1.433 [1.219-1.685]; ≥21 comorbidities: 1.310 [1.099-1.561]); and gastrointestinal surgery (vs. without surgery; 0.823 [0.701-0.965]). In conclusion, CDI recurred in some Japanese patients, and the incidence rates increased with the number of recurrences. Special care is needed in patients aged ≥65 years, those with a higher number (>10) of comorbidities, and those who have received cephalosporin before or during the primary CDI.

Attributable Healthcare Resource Utilization and Costs for Patients With Primary and Recurrent Clostridium difficile Infection in the United States.

Background: The economic burden of Clostridium difficile infection (CDI), the leading cause of nosocomial infectious diarrhea, is not well understood. The objective of this study was to estimate the healthcare resource utilization (HCRU) and costs attributable to primary CDI and recurrent CDI (rCDI). Methods: This is a database (MarketScan) study. Patients without CDI were matched 1:1 by propensity score to those with primary CDI but no recurrences to obtain HCRU and costs attributable to primary CDI. Patients with primary CDI but no recurrences were matched 1:1 by propensity score to those with primary CDI plus 1 recurrence in order to obtain HCRU and costs attributable to rCDI. Adjusted estimates for incremental cumulative hospitalized days and healthcare costs over a 6-month follow-up period were obtained by generalized linear models with a Poisson or gamma distribution and a log link. Bootstrapping was used to obtain 95% confidence intervals (CIs). Results: A total of 55504 eligible CDI patients were identified. Approximately 25% of these CDI patients had rCDI. The cumulative hospitalized days attributable to primary CDI and rCDI over the 6-month follow-up period were 5.20 days (95% CI, 5.01-5.39) and 1.95 days (95% CI, 1.48-2.43), respectively. The healthcare costs attributable to primary CDI and rCDI over the 6-month follow-up period were $24205 (95% CI, $23436-$25013) and $10580 (95% CI, $8849-$12446), respectively. Conclusions: The HCRU and costs attributable to primary CDI and rCDI are quite substantial. It is necessary to reduce the burden of CDI, especially rCDI.

Impact of recurrent Clostridium difficile infection: hospitalization and patient quality of life.

Objectives: Data quantifying outcomes of recurrent Clostridium difficile infection (rCDI) are lacking. We sought to determine the UK hospital resource use and health-related quality of life (HRQoL) associated with rCDI hospitalizations. Patients and methods: A non-interventional study in six UK acute hospitals collected retrospective clinical and resource use data from medical records of 64 adults hospitalized for rCDI and 64 matched inpatient controls with a first episode only (f)CDI. Patients were observed from the index event (date rCDI/fCDI confirmed) for 28 days (or death, if sooner); UK-specific reference costs were applied. HRQoL was assessed prospectively in a separate cohort of 30 patients hospitalized with CDI, who completed the EQ-5D-3L questionnaire during their illness. Results: The median total management cost (post-index) was £7539 and £6294 for rCDI and fCDI, respectively (cost difference, P = 0.075); median length of stay was 21 days and 15.5 days, respectively (P = 0.269). The median cost difference between matched rCDI and fCDI cases was £689 (IQR=£1873-£3954). Subgroup analysis demonstrated the highest median costs (£8542/patient) in severe rCDI cases. CDI management costs were driven primarily by hospital length of stay, which accounted for >85% of costs in both groups. Mean EQ-5D index values were 46% lower in CDI patients compared with UK population values (0.42 and 0.78, respectively); EQ visual analogue scale scores were 38% lower (47.82 and 77.3, respectively). Conclusions: CDI has considerable impact on patients and healthcare resources. This multicentre study provides a contemporaneous estimate of the real-world UK costs associated with rCDI management, which are substantial and comparable to fCDI costs.

Posaconazole vs fluconazole or itraconazole for prevention of invasive fungal diseases in patients with acute myeloid leukemia or myelodysplastic syndrome: a cost-effectiveness analysis in an Asian teaching hospital.

BACKGROUND: Posaconazole is superior to fluconazole/itraconazole in preventing invasive fungal diseases (IFDs) in neutropenic patients. Whether the higher cost of posaconazole is offset by decreases in IFDs in a given institute requires cost-effective analysis encompassing the spectrum of IFDs and socioeconomic factors specific to that geographic area. METHODS: This study performed a cost-effective analysis of posaconazole prophylaxis for IFDs in an Asian teaching hospital, employing decision modeling and data of IFDs and medication costs specific to the institute, in neutropenic patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). RESULTS: In the cost-effectiveness analysis, the higher cost of posaconazole was partially offset by a reduction in the cost of treating IFDs that were prevented, resulting in an incremental cost of 125,954 Hong Kong dollars/16,148 USD per IFD avoided. Over a lifetime horizon, assuming same case fatality rate of IFDs in both groups, use of posaconazole results in 0.07 discounted life years saved. This corresponds to an incremental cost of 116,023 HKD/14,875 USD per life year saved. This incremental cost per life year saved in posaconazole prophylaxis fulfilled the World Health Organization defined threshold for cost-effectiveness. CONCLUSION: Posaconazole prophylaxis was cost-effective in Hong Kong.

Differences in open versus laparoscopic gastric bypass mortality risk using the Obesity Surgery Mortality Risk Score (OS-MRS).

BACKGROUND: The Obesity Surgery Mortality Risk Score (OS-MRS) was developed to ascertain preoperative mortality risk of patients having bariatric surgery. To date there has not been a comparison between open and laparoscopic operations using the OS-MRS. OBJECTIVE: To determine whether there are differences in mortality risk between open and laparoscopic Roux-en-Y Gastric Bypass (RYGB) using the OS-MRS. SETTING: Three university-affiliated hospitals. METHODS: The 90-day mortality of 2467 consecutive patients who had primary open (1574) or laparoscopic (893) RYGB performed by one surgeon was determined. Univariate and multivariate analysis using 5 OS-MRS risk factors including body mass index (BMI) gender, age>45, presence of hypertension and preoperative deep vein thrombosis (DVT) risk was performed in each group. Each patient was placed in 1 of 3 OS-MRS risk classes based on the number of risks: A (0-1), B (2-3), and C (4-5). RESULTS: Preoperative BMI and DVT risk factors were significantly greater in the open group (OG). Preoperative age was significantly greater in the laparoscopic group (LG). There were significantly more class B and C patients in LG. Ninety-day mortality rates for OG and LG patients were 1.0% and .9%, respectively. Pulmonary embolism was the most common cause of death. All deaths in LG occurred during first 4 years of that experience. Mortality rate by class was A = .1%; B = 1.5%; C = 2.3%. The difference in mortality between class B and C patients was not significant. Univariate analysis in the OG indicated that BMI, age, gender, and DVT risk were significant predictors of mortality. In the LG only BMI and DVT were significant predictors of death. Presence of hypertension was not a significant predictor in either group. Multivariate analysis excluding hypertension found that age was predictive of mortality in the OG while BMI (P = .057) and gender (P = .065) approached statistical significance. Conversely, only BMI was predictive of mortality in the LG with age approaching significance (P = .058). In multivariate analysis DVT risk was not predictive of mortality in either group. CONCLUSIONS: There are significant differences in the predictive value of the OS-MRS between open and laparoscopic RYGB. Although laparoscopic patients were significantly older versus the open patients, age was not predictive of mortality after laparoscopic RYGB. BMI trended toward increased mortality risk in both groups. Changes in technique and protocol likely contributed toward no mortality during the last 6 years of our laparoscopic experience.

An update to the cost-effectiveness of posaconazole vs fluconazole or itraconazole in the prevention of invasive fungal disease among neutropenic patients in the United States.

OBJECTIVES: Posaconazole has shown superior clinical efficacy in the prevention of invasive fungal disease (IFD) among neutropenic patients as well as cost-effectiveness in the US healthcare setting vs fluconazole or itraconazole (FLU/ITRA) based on oral suspension formulations of each therapy. This study aims to provide an update on the cost-effectiveness of posaconazole in the current US healthcare setting to reflect bioequivalent tablet formulations of posaconazole and fluconazole, as well as changes in healthcare and drug costs. METHODS: An existing model was used to assess the cost-effectiveness of posaconazole vs FLU/ITRA in the prevention of IFD among patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) and chemotherapy-induced neutropenia. Drug efficacy, mortality related to IFD, and death from other causes were estimated for tablet formulations using data from a randomized clinical trial of oral suspensions based on bioequivalence. IFD treatment costs were updated using the average inflation rate over 8 years (2006-2014) and drug costs were based on 2014 Analysource data. RESULTS: Trial data show a lower IFD probability over 100 days of follow-up with posaconazole compared to standard azole therapy (0.05 vs 0.11). The treatment duration on posaconazole is 29 days compared to 24 days for FLU and 29 days for ITRA. The average cost of prophylaxis is higher in the posaconazole group compared to FLU/ITRA ($4673 vs $353); however, the costs associated with treating the IFD are lower in the posaconazole group compared to FLU/ITRA ($2205 vs $5303). The incremental cost effectiveness ratio of IFD avoided for posaconazole is $18,898 vs FLU/ITRA. CONCLUSIONS: In the current healthcare cost environment where both drug costs and overall IFD treatment costs have increased since 2007, posaconazole tablets are a cost-effective alternative to fluconazole or itraconazole in the prevention of IFD among neutropenic patients with AML and MDS in the US.

Personal protective equipment use among students with special health care needs reporting injuries in school-sponsored vocational, career, and technical education programs in New Jersey.

Students with special health care needs (SHCNs) and individualized education plans (IEPs) may be injured more often in vocational, career, and technical education (CTE) programs. No research to date considers personal protective equipment (PPE) use among students with SHCNs in school-based programs reporting injuries to agencies. Data from 1999 to 2011 on PPE use among injured students in CTE programs in public schools and private secondary schools for the disabled were analyzed; students with SHCNs were distinguished by IEP status within New Jersey Safe Schools surveilance data. Among students with IEPs using PPE, 36% of injuries occurred to body parts PPE was meant to protect. Likely injury types were cuts-lacerations and burns for students with IEPs using PPE and cuts-lacerations and sprains for students with IEPs not using PPE. Females with IEPs using PPE were injured less often than males across ages. Results suggested students with SHCNs with IEPs need further job-related training with increased emphasis on properly selecting and fitting PPE.

Effects of maternal exposure to phthalates and bisphenol A during pregnancy on gestational age.

OBJECTIVE: Phthalates and bisphenol A (BPA) are ubiquitous environmental toxicants, present in high concentrations in numerous consumer products. We hypothesized that maternal exposure to phthalates and BPA in pregnancy is associated with shortened gestation. METHODS: Urinary phthalate and BPA metabolites from 72 pregnant women were measured at the last obstetric clinic visit prior to delivery. Using linear regression models, we estimated the change in gestational age associated with each interquartile range (IQR) increase in phthalate and BPA metabolite concentration. RESULTS: IQR increases in urinary mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and BPA concentrations were associated with 4.2 and 1.1 d decreases in gestation, respectively. When stratified by gender, these alterations were found only in male infants. CONCLUSIONS: We conclude that MEHHP and BPA (free + glucuronide) are associated with reductions in gestation, with effects observed only in males. Our findings are consistent with the idea that these agents induce gender-specific alterations in signaling via PPAR-γ transcription factor, androgen precursors and/or inflammatory mediators during the initiation of labor.

Statin use and fatal prostate cancer: a matched case-control study.

BACKGROUND: Statins are some of the most commonly prescribed medications in medical practice, and prostate cancer is the most common malignancy among men. Although there has been no consistent evidence that statins affect cancer incidence, including prostate cancer, several reports suggest they may decrease the rate of advanced prostate cancer. However, no study to date has specifically examined statin use and prostate cancer mortality. The authors conducted this population-based case-control investigation to examine this association. METHODS: This was a matched case-control study. Cases were residents of New Jersey ages 55 to 79 years who died from prostate cancer between 1997 and 2000. The cases were matched individually to population-based controls by 5-year age group and race. Medication data were obtained identically for cases and controls from blinded medical chart review. Conditional logistic regression was used to adjust for confounders. RESULTS: In total, 718 cases were identified, and cooperation was obtained from 77% of their spouses (N = 553). After a review of medical records, 387 men were eligible, and 380 were matched to a control. The unadjusted odds ratio was 0.49 (95% confidence interval, 0.34-0.70) and decreased to 0.37 (P < .0001) after adjusting for education, waist size, body mass index, comorbidities, and antihypertensive medication. There was little difference between lipophilic and hydrophilic statins, but more risk reduction was noted for high-potency statins (73%; P < .0001) compared with low-potency statins (31%; P = .32). CONCLUSIONS: Statin use was associated with substantial protection against prostate cancer death, adding to the epidemiologic evidence for an inhibitory effect on prostate cancer.

Prostate-specific antigen screening and mortality from prostate cancer.

BACKGROUND: There is no available evidence from randomized trials that early detection of prostate cancer improves health outcomes, but the prostate-specific antigen (PSA) test is commonly used to screen men for prostate cancer. OBJECTIVE: The objective of the study is to see if screening with PSA decreases mortality from prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: This is a case-control study using one-to-one matching on race, age, and time of availability of exposure to PSA screening. Decedents, 380, from New Jersey Vital Statistics 1997 to 2000 inclusive, 55-79 years of age at diagnosis were matched to living controls without metastatic prostate cancer. Medical records were obtained from all providers, and we abstracted information about PSA tests from 1989 to the time of diagnosis in each index case. MEASUREMENTS: Measurements consist of a comparison of screening (yes, no) between cases and controls. Measure of association was the odds ratio. RESULTS: Eligible cases were diagnosed each year from 1989 to 1999 with the median year being 1993. PSA screening was evident in 23.2-29.2% of cases and 21.8-26.1% of controls depending on the screening criteria. The unadjusted, matched odds ratio for dying of prostate cancer if ever screened was 1.09 (95% CI 0.76 to 1.60) for the most restrictive criteria and 1.19 (95% CI, 0.85 to 1.66) for the least restrictive. Adjustment for comorbidity and education level made no significant differences in these values. There were no significant interactions by age or race. CONCLUSIONS: PSA screening using an ever/never tabulation for tests from 1989 until 2000 did not protect New Jersey men from prostate cancer mortality.

Weekend versus weekday admission and mortality from myocardial infarction.

BACKGROUND: Management of acute myocardial infarction requires urgent diagnostic and therapeutic procedures, which may not be uniformly available throughout the week. METHODS: We examined differences in mortality between patients admitted on weekends and those admitted on weekdays for a first acute myocardial infarction, using the Myocardial Infarction Data Acquisition System. All such admissions in New Jersey from 1987 to 2002 (231,164) were included and grouped in 4-year intervals. RESULTS: There were no significant differences in demographic characteristics, coexisting conditions, or infarction site between patients admitted on weekends and those admitted on weekdays. However, patients admitted on weekends were less likely to undergo invasive cardiac procedures, especially on the first and second days of hospitalization (P<0.001). In the interval from 1999 to 2002 (59,786 admissions), mortality at 30 days was significantly higher for patients admitted on weekends (12.9% vs. 12.0%, P=0.006). The difference became significant the day after admission (3.3% vs. 2.7%, P<0.001) and persisted at 1 year (1% absolute difference in mortality). The difference in mortality at 30 days remained significant after adjustment for demographic characteristics, coexisting conditions, and site of infarction (hazard ratio, 1.048; 95% confidence interval [CI], 1.022 to 1.076; P<0.001), but it became nonsignificant after additional adjustment for invasive cardiac procedures (hazard ratio, 1.023; 95% CI, 0.997 to 1.049; P=0.09). CONCLUSIONS: For patients with myocardial infarction, admission on weekends is associated with higher mortality and lower use of invasive cardiac procedures. Our findings suggest that the higher mortality on weekends is mediated in part by the lower rate of invasive procedures, and we speculate that better access to care on weekends could improve the outcome for patients with acute myocardial infarction.

Pregnancy interruption after second trimester diagnosis of fetal structural anomalies: the New Jersey Fetal Abnormalities Registry.

OBJECTIVE: The purpose of this study was to identify factors that predict a decision to interrupt a pregnancy in which there are fetal anomalies in the second trimester. STUDY DESIGN: The New Jersey Fetal Abnormalities Registry prospectively recruits and collects information on pregnancies (> or = 15 weeks of gestation) from New Jersey residents in whom a fetal structural anomaly has been suspected by maternal-fetal medicine specialists. Enrolled pregnancies that have major fetal structural abnormalities identified from 15 to 23 weeks of gestation were included. Outcomes were classified as either elective interruption or a natural pregnancy course, which might include a spontaneous fetal death or live birth. Predictors of elective interruption of pregnancy were examined with univariable and multivariable logistic regression analyses. RESULTS: Of the 97 cases, 33% of the women (n = 32) interrupted the pregnancy. Significant variables in the regression model that were associated with a decision to interrupt a pregnancy were earlier identification of fetal anomalies (19.0 +/- 2 weeks of gestation vs 20.5 +/- 2 weeks of gestation; P = .003), the presence of multiple anomalies (78% [25/32] vs 52% [33/63]; P = .01], and a presumption of lethality (56% [18/32] vs 14% [9/65]; P = .0001). These variables corresponded to an odds ratio for pregnancy interruption of 4.2 (95% CI, 1.0, 17.0) for multiple anomalies, 0.8 (95% CI, 0.7, 1.0) for each week of advancing gestational age, and 36.1 (95% CI, 2.9, 450.7) for presumed lethal abnormalities. CONCLUSION: Early diagnosis, the identification of multiple abnormalities, and an assessment of likely lethality of fetal anomalies are important factors for the optimization of parental autonomy in deciding pregnancy management.