Diverse Role of blaCTX-M and Porins in Mediating Ertapenem Resistance among Carbapenem-Resistant Enterobacterales.

Among carbapenem-resistant Enterobacterales (CRE) are diverse mechanisms, including those that are resistant to meropenem but susceptible to ertapenem, adding further complexity to the clinical landscape. This study investigates the emergence of ertapenem-resistant, meropenem-susceptible (ErMs) Escherichia coli and Klebsiella pneumoniae CRE across five hospitals in San Antonio, Texas, USA, from 2012 to 2018. The majority of the CRE isolates were non-carbapenemase producers (NCP; 54%; 41/76); 56% of all NCP isolates had an ErMs phenotype. Among ErMs strains, E. coli comprised the majority (72%). ErMs strains carrying blaCTX-M had, on average, 9-fold higher copies of blaCTX-M than CP-ErMs strains as well as approximately 4-fold more copies than blaCTX-M-positive but ertapenem- and meropenem-susceptible (EsMs) strains (3.7 vs. 0.9, p < 0.001). Notably, carbapenem hydrolysis was observed to be mediated by strains harboring blaCTX-M with and without a carbapenemase(s). ErMs also carried more mobile genetic elements, particularly IS26 composite transposons, than EsMs (37 vs. 0.2, p < 0.0001). MGE- ISVsa5 was uniquely more abundant in ErMs than either EsMs or ErMr strains, with over 30 more average ISVsa5 counts than both phenotype groups (p < 0.0001). Immunoblot analysis demonstrated the absence of OmpC expression in NCP-ErMs E. coli, with 92% of strains lacking full contig coverage of ompC. Overall, our findings characterize both collaborative and independent efforts between blaCTX-M and OmpC in ErMs strains, indicating the need to reappraise the term "non-carbapenemase (NCP)", particularly for strains highly expressing blaCTX-M. To improve outcomes for CRE-infected patients, future efforts should focus on mechanisms underlying the emerging ErMs subphenotype of CRE strains to develop technologies for its rapid detection and provide targeted therapeutic strategies.

Pilot study evaluating feasibility and utility of pharmacist-driven oral antineoplastic agent monitoring program.

INTRODUCTION: Oncologists are increasingly prescribing oral antineoplastic agents which have benefits and challenges impacting patient outcomes. Practice guidelines recommend monitoring symptoms and adherence without outlining any specific tools or methods for monitoring. Pharmacists are successful in monitoring patients on therapy and improving outcomes. We aimed to assess the feasibility and utility of a pharmacist-delivered and medical record-integrated adherence and symptom monitoring program for patients on oral antineoplastic agents. METHODS: This single-center, prospective, interventional study designed and implemented an adherence and monitoring program. A pharmacist contacted patients twice between clinic visits for three months. During telephone encounters, patients were verbally screened for medication adherence and assessed for new or changing symptoms using the Edmonton Symptom Assessment System as a signal of possible adverse events. We measured feasibility via patient enrollment, completed proportion of scheduled contacts, and pharmacist time. Utility was assessed through patient adherence, satisfaction surveys, healthcare resource utilization, and pharmacist interventions (i.e., patient education, adherence assistance, and symptom management). RESULTS: Fifty-one patients participated. Ninety-one percent of scheduled patient contacts were completed. Edmonton Symptom Assessment System was administered by pharmacy personnel 102 times. Patient-reported adherence was 100%. Overall satisfaction was 85% and 100%, for patients and physicians, respectively. Fifty-one (98%) pharmacist recommendations were accepted. There were 14 total utilizations of healthcare resources-5.2 per 1000 patient days. CONCLUSIONS: This study suggests a pharmacist monitoring program for patients taking oral antineoplastic agents is feasible and provides utility. Further research is needed to evaluate whether this program improves safety, adherence, and outcomes in patients using oral antineoplastic agents.

A Survey of Vaping Use, Perceptions, and Access in Adolescents from South-Central Texas Schools.

Despite efforts to dissuade major manufacturers and retailers from marketing and selling vape products to adolescents, the practice of vaping continues to increase in this population. Few studies have assessed adolescent perceptions of vaping, access to vaping, and use of vaping, and most rely, at least in part, on inferential conclusions drawn from data on smoking traditional combustible cigarettes. A novel electronic survey was created to assess the use of vapes, perceptions of vaping, and access to vaping among a convenience sample of adolescents (ages 12-20 years) in eleven schools in South-Central Texas from May to August 2021. The students' perceived threat of negative health outcomes due to vaping was calculated based on questions soliciting perceptions of severity (perceived danger) and susceptibility (perceived likelihood of illness). Trends were identified using descriptive and bivariate statistical tests. A total of 267 respondents were included; 26% had tried vaping. A majority (63%) did not believe vaping and smoking were synonymous. Most (70%) thought it was easy to obtain supplies and (76%) vape before and after (88%) or even during (64%) school. Respondents who vaped had a 34% lower perceived threat when compared to respondents who did not vape. In this sample of adolescents from South-Central Texas, one in four reported that they had tried vaping. Easy access to vapes and misperceptions regarding the safety of vaping might create a false sense of security with respect to vaping as an alternative to smoking, particularly among those who reported vaping, and is likely contributing to the increased use of vapes.

Health Equity in Patients Receiving Durvalumab for Unresectable Stage III Non-Small Cell Lung Cancer in the US Veterans Health Administration.

BACKGROUND: Real-world evidence is limited regarding the relationship between race and use of durvalumab, an immunotherapy approved for use in adults with unresectable stage III non-small cell lung cancer (NSCLC) post-chemoradiotherapy (CRT). This study aimed to evaluate if durvalumab treatment patterns differed by race in patients with unresectable stage III NSCLC in a Veterans Health Administration (VHA) population. MATERIALS AND METHODS: This was a retrospective analysis of White and Black adults with unresectable stage III NSCLC treated with durvalumab presenting to any VHA facility in the US from January 1, 2017, to June 30, 2020. Data captured included baseline characteristics and durvalumab treatment patterns, including treatment initiation delay (TID), interruption (TI), and discontinuation (TD); defined as CRT completion to durvalumab initiation greater than 42 days, greater than 28 days between durvalumab infusions, and more than 28 days from the last durvalumab dose with no new durvalumab restarts, respectively. The number of doses, duration of therapy, and adverse events were also collected. RESULTS: A total of 924 patients were included in this study (White = 726; Black = 198). Race was not a significant factor in a multivariate logistic regression model for TID (OR, 1.39; 95% CI, 0.81-2.37), TI (OR, 1.58; 95% CI, 0.90-2.76), or TD (OR, 0.84; 95% CI, 0.50-1.38). There were also no significant differences in median (interquartile range [IQR]) number of doses (White: 15 [7-24], Black: 18 [7-25]; P = .25) or median (IQR) duration of therapy (White: 8.7 months [2.9-11.8], Black: 9.8 months [3.6-12.0]; P = .08), although Black patients were less likely to experience an immune-related adverse event (28% vs. 36%, P = .03) and less likely to experience pneumonitis (7% vs. 14%, P < .01). CONCLUSION: Race was not found to be linked with TID, TI, or TD in this real-world study of patients with unresectable stage III NSCLC treated with durvalumab at the VHA.

Economic Evaluation of Three BRAF + MEK Inhibitors for the Treatment of Advanced Unresectable Melanoma With BRAF Mutation From a US Payer Perspective.

BACKGROUND: The combinations of BRAF + MEK inhibitors-encorafenib (ENC) + binimetinib (BIN), cobimetinib (COB) + vemurafenib (VEM), and dabrafenib (DAB) + trametinib (TRA)-are recommended for the treatment of BRAF-mutated advanced melanoma. OBJECTIVE: To assess the cost-effectiveness and cost-utility of ENC + BIN versus COB + VEM versus DAB + TRA from a US payer perspective. METHODS: A Markov model was constructed to simulate a hypothetical cohort over a time horizon of 10 years. The overall survival (OS) and progression-free survival (PFS) curves were independently digitized from a randomized controlled trial for ENC + BIN and fitted using R software. Published and indirectly estimated hazard ratios were used to fit OS and PFS curves for COB + VEM and DAB + TRA. Costs, life-year gains, and quality-adjusted life years (QALYs) associated with the 3 treatment combinations were estimated. A base case analysis and probabilistic sensitivity analysis (PSA) were conducted to estimate the incremental cost-utility ratio (ICUR). A discount rate of 3.5% was applied on cost and outcomes. RESULTS: The ENC + BIN versus COB + VEM comparison was associated with an ICUR of $656 233 per QALY gained. The ENC + BIN versus DAB + TRA comparison was associated with an ICUR of $3 135 269 per QALY gained. The DAB + TRA combination dominated COB + VEM. The base case analysis estimates were confirmed by the PSA estimates. ENC + BIN was the most cost-effective combination at a high willingness-to-pay (WTP) threshold of $573 000 per QALY and $1.5 million/QALY when compared to COB + VEM and DAB + TRA, respectively. CONCLUSION AND RELEVANCE: Given current prices and acceptable WTP thresholds, our study suggests that DAB + TRA is the optimum treatment. In this study, ENC + BIN was cost-effective only at a very high WTP per QALY threshold.

Clostridioides difficile Infection Treatment and Outcome Disparities in a National Sample of United States Hospitals.

Clostridioides difficile infection (CDI) disproportionately affects certain populations, but few studies have investigated health outcome disparities among patients with CDI. This study aimed to characterize CDI treatment and health outcomes among patients by age group, sex, race, and ethnicity. This was a nationally representative, retrospective cohort study of patients with laboratory-confirmed CDI within the Premier Healthcare Database from January 2018 to March 2021. CDI therapies received and health outcomes were compared between patients by age group, sex, race, and Hispanic ethnicity using bivariable and multivariable statistical analyses. A total of 45,331 CDI encounters were included for analysis: 38,764 index encounters and 6567 recurrent encounters. CDI treatment patterns, especially oral vancomycin use, varied predominantly by age group. Older adult (65+ years), male, Black, and Hispanic patients incurred the highest treatment-related costs and were at greatest risk for severe CDI. Male sex was an independent predictor of in-hospital mortality (aOR 1.17, 95% CI 1.05−1.31). Male sex (aOR 1.25, 95% CI 1.18−1.32) and Black race (aOR 1.29, 95% CI 1.19−1.41) were independent predictors of hospital length of stay >7 days in index encounters. In this nationally representative study, CDI treatment and outcome disparities were noted by age group, sex, and race.

Cost-effectiveness of palonosetron and dexamethasone-based triple and quadruple regimens in preventing highly emetogenic chemotherapy-induced nausea and vomiting.

OBJECTIVE: Cost-effectiveness analyses that consider all currently used antiemetics in the case of emetogenic chemotherapy-induced nausea and vomiting (CINV) have not been performed yet. We aim to compare the cost-effectiveness of olanzapine (OLA), or/and neurokinin-1 receptor antagonists (NK-1-RAs), in combination with palonosetron (PAL) and dexamethasone (DEX) in preventing highly emetogenic CINV. METHODS: Two decision analytic models were constructed. The first model was based on overall complete response (CR); the second model was based on rate of absence of nausea. Four antiemetic regimens PAL + DEX, NK-1-RAs + PAL + DEX, OLA + PAL + DEX, and PAL + NK-1-RA + DEX + OLA were compared in terms of cost, overall CR and rate of absence of nausea. Base case incremental cost-effectiveness ratio (ICER) estimates were calculated. The study was from the US payer perspective. RESULTS: In terms of CR, the PAL + NK-1-RA + DEX + OLA was associated with the highest gains in the percentage of CR among all treatment regimens at base case ICERs of $4220 versus PAL + DEX, $4656 versus NK-1-RA + PAL + DEX, $16,471 versus OLA + PAL + DEX. In term of rate of absence of nausea, the PAL + NK-1-RA + DEX + OLA was associated with the highest rate of absence of nausea among all the treatment regimens at base case ICERs of $2291 versus PAL + DEX, $1304 versus NK-1-RA + PAL + DEX, $2657 versus OLA + PAL + DEX. CONCLUSION: from an economic perspective, our study revealed that whether to use overall CR or/and rate of absence of nausea as determinants in the antiemetic decision for the CINV patients, the CR-based-, and rate of absence of nausea-based cost-effectiveness analyses, showed negotiable ICER estimates for the treatment PAL + NK-1-RA + DEX + OLA over the combinations PAL + DEX, NK-1-RA + PAL + DEX, and OLA + PAL + DEX regimens.

National Disparities in Antibiotic Prescribing by Race, Ethnicity, Age Group, and Sex in United States Ambulatory Care Visits, 2009 to 2016.

While efforts have been made in the United States (US) to optimize antimicrobial use, few studies have explored antibiotic prescribing disparities that may drive future interventions. The objective of this study was to evaluate disparities in antibiotic prescribing among US ambulatory care visits by patient subgroups. This was a retrospective, cross-sectional study utilizing the National Ambulatory Medical Care Survey from 2009 to 2016. Antibiotic use was described as antibiotic visits per 1000 total patient visits. The appropriateness of antibiotic prescribing was determined by ICD-9 or ICD-10 codes assigned during the visit. Subgroup analyses were conducted by patient race, ethnicity, age group, and sex. Over 7.0 billion patient visits were included; 11.3% included an antibiotic prescription. Overall and inappropriate antibiotic prescription rates were highest in Black (122.2 and 78.0 per 1000) and Hispanic patients (138.6 and 79.8 per 1000). Additionally, overall antibiotic prescription rates were highest in patients less than 18 years (169.6 per 1000) and female patients (114.1 per 1000), while inappropriate antibiotic prescription rates were highest in patients 18 to 64 years (66.0 per 1000) and in males (64.8 per 1000). In this nationally representative study, antibiotic prescribing disparities were found by patient race, ethnicity, age group, and sex.

Evaluating Six Commercially Available Closed-System Drug-Transfer Devices Against NIOSH's 2015 Draft Vapor Protocol.

Purpose: In 2015, the National Institute for Occupational Safety and Health (NIOSH) published a draft vapor containment protocol to quantitatively evaluate combined liquid, aerosol, and vapor containment performance of commercially available closed-system drug-transfer devices (CSTDs) that claim to be effective for gas/vapor containment within a controlled test environment. Until the release of this proposed protocol, no standard method for evaluating airtightness of CSTDs existed. The aim of this study was to evaluate six commercially available CSTDs utilizing NIOSH draft protocol methodology to evaluate vapor containment under a robust vapor challenge. Methods: In this study, six commercially available CSTDs were tested utilizing draft NIOSH vapor containment protocol methodology to simulate drug compounding and administration using 70% isopropyl alcohol (IPA) as the challenge agent. All device manipulations were carried out in an enclosed test chamber. A Miran sapphIRe gas analyzer was used to detect IPA vapor levels that escaped the device. Study test included the two tasks designated by the NIOSH protocol, with additional steps added to the evaluation. Tasks were repeated 10 times for each device. Results: Only three of the six tested CSTDs (Equashield®, HALO®, and PhaSealTM) had an average IPA vapor release below the quantifiable performance threshold (1.0 ppm) for all tasks performed. This value was selected by NIOSH to represent the performance threshold for successful containment. The remaining three CSTDs had vapor release above 1 ppm at various times during the IPA manipulation process. Conclusion: Equashield®, HALO®, and PhaSealTM devices tested met the 2015 NIOSH protocol quantifiable performance threshold, functioning as a truly closed system. Quantifiable effective data may be useful in product selection.

Comparing real-world evidence among patients with metastatic pancreatic ductal adenocarcinoma treated with liposomal irinotecan.

There are questions surrounding the real-world effectiveness of chemotherapeutic treatments for pancreatic ductal adenocarcinoma. This literature review compared the clinical characteristics and outcomes of available real-world evidence (RWE) for liposomal irinotecan in combination with 5-fluorouracil (5-FU) and leucovorin (LV), a treatment regimen indicated for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who previously progressed on gemcitabine-based therapy. A targeted literature search was conducted in the PubMed Central® and Embase® databases to identify available RWE regarding patients with mPDAC receiving liposomal irinotecan published within the last 5 years (January 2014-September 2019). Data were extracted for prior lines of therapy, performance status, overall survival (OS), progression-free survival (PFS), duration of exposure, and adverse events. Six studies met inclusion criteria. A comparison of baseline patient characteristics and results with the included evidence reveals a clinically fragile, real-world patient population in terms of age (range: 61-68), prior lines of therapy with 34-61% of patients receiving ⩾2 lines of lines of prior therapy and performance status [49.8-100% of patients with Eastern Cooperative Oncology Group (ECOG) 0-1]. Studies observed wide OS (range: 5.3-9.4 months) and similar PFS (range: 2.3-4.1 months), with two studies measuring duration of exposure (7.3 weeks, 3.1 months). Patients analyzed by RWE studies tended to be older with significant disease progression, poor performance status, and more heavily pretreated compared with the phase III registrational trial (NAPOLI-1). Despite this, patients treated with liposomal irinotecan + 5-FU/LV therapy had similar outcomes as those in NAPOLI-1.

Derivation and Validation of a Clostridium difficile Infection Recurrence Prediction Rule in a National Cohort of Veterans.

STUDY OBJECTIVE: Prior studies have identified risk factors for recurrent Clostridium difficile infection (CDI), but few studies have integrated these factors into a clinical prediction rule that can aid clinical decision-making. The objectives of this study were to derive and validate a CDI recurrence prediction rule to identify patients at risk for first recurrence in a national cohort of veterans. DESIGN: Retrospective cohort study. DATA SOURCE: Veterans Affairs Informatics and Computing Infrastructure. PATIENTS: A total of 22,615 adult Veterans Health Administration beneficiaries with first-episode CDI between October 1, 2002, and September 30, 2014; of these patients, 7538 were assigned to the derivation cohort and 15,077 to the validation cohort. MEASUREMENTS AND MAIN RESULTS: A 60-day CDI recurrence prediction rule was created in a derivation cohort using backward logistic regression. Those variables significant at p<0.01 were assigned an integer score proportional to the regression coefficient. The model was then validated in the derivation cohort and a separate validation cohort. Patients were then split into three risk categories, and rates of recurrence were described for each category. The CDI recurrence prediction rule included the following predictor variables with their respective point values: prior third- and fourth-generation cephalosporins (1 point), prior proton pump inhibitors (1 point), prior antidiarrheals (1 point), nonsevere CDI (2 points), and community-onset CDI (3 points). In the derivation cohort, the 60-day CDI recurrence risk for each score ranged from 7.5% (0 points) to 57.9% (8 points). The risk score was strongly correlated with recurrence (R2  = 0.94). Patients were split into low-risk (0-2 points), medium-risk (3-5 points), and high-risk (6-8 points) classes and had the following recurrence rates: 8.9%, 20.2%, and 35.0%, respectively. Findings were similar in the validation cohort. CONCLUSION: Several CDI and patient-specific factors were independently associated with 60-day CDI recurrence risk. When integrated into a clinical prediction rule, higher risk scores and risk classes were strongly correlated with CDI recurrence. This clinical prediction rule can be used by providers to identify patients at high risk for CDI recurrence and help guide preventive strategy decisions, while accounting for clinical judgment.

Shift to community-onset Clostridium difficile infection in the national Veterans Health Administration, 2003-2014.

BACKGROUND: Clostridium difficile infection (CDI) occurs frequently in inpatient settings; however, community-onset cases have been reported more frequently in recent years. This study evaluated hospital-onset and community-onset CDI in the national Veterans Health Administration (VHA) population over a 12-year period. METHODS: This was a retrospective cohort study of all adult VHA beneficiaries with CDI between October 1, 2002, and September 30, 2014. Data were obtained from the Veterans Affairs Informatics and Computing Infrastructure. CDI was categorized into community-associated CDI (CA-CDI); community-onset, health care facility-associated CDI; and health care facility-onset CDI (HCFO-CDI). Each type was described longitudinally and was assessed as an independent risk factor for health outcomes using multivariable logistic regression. RESULTS: Overall, 30,326 patients with a first CDI episode were included. HCFO-CDI was the predominant type (60.2%), followed by CO-HCFA-CDI (20.6%) and CA-CDI (19.2%). The proportion of patients with HCFO-CDI decreased from 73.5% during fiscal year 2003 to 53.2% during fiscal year 2014, whereas CA-CDI increased from 8.3% to 26.7%. HCFO-CDI was a positive predictor of severe CDI (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.59-1.84) and 30-day mortality (OR, 1.46; 95% CI, 1.32-1.61), but a negative predictor of 60-day recurrence (OR, 0.41; 95% CI, 0.37-0.46). CONCLUSIONS: HCFO-CDI was the predominant CDI type. The proportion of patients with CA-CDI increased and HCFO-CDI decreased in recent years. Patients with HCFO-CDI experienced higher rates of severe CDI and mortality.

National epidemiology of initial and recurrent Clostridium difficile infection in the Veterans Health Administration from 2003 to 2014.

INTRODUCTION: Prior studies demonstrated marked increases in Clostridium difficile infection (CDI) in the United States (U.S.) in recent years. The objective of this study was to describe the epidemiology of initial and recurrent CDI in a national Veterans Health Administration (VHA) cohort over a 12-year period. METHODS: This was a retrospective cohort study of all adult VHA beneficiaries with CDI (ICD-9-CM code 008.45) plus a positive CDI stool test between October 1, 2002 and September 30, 2014. Data were obtained from the VA Informatics and Computing Infrastructure. Recurrence was defined as a second ICD-9-CM code plus a new course of CDI therapy following a minimum three-day gap after the initial therapy was completed. CDI incidence and outcomes were presented descriptively and longitudinally. RESULTS: Overall, 30,326 patients met study inclusion criteria. CDI incidence increased from FY 2003 (1.6 per 10,000) to FY 2013 (5.1 per 10,000). Thereafter, CDI incidence decreased through FY 2014 (4.6 per 10,000). A total of 5,011 patients (17%) experienced a first recurrence and, of those, 1,713 (34%) experienced a second recurrence. Recurrence incidence increased 10-fold over the study period, from (0.1 per 10,000) in FY 2003, to (1.0 per 10,000) in FY 2014. Overall, 30-day mortality and median hospital length of stay (LOS) decreased among initial episodes over the study period. Mortality was higher for initial episodes (21%) compared to first recurrences (11%) and second recurrences (7%). Median hospital LOS was longer for first episodes (13 days) compared to first (9 days) and second recurrences (8 days). CONCLUSIONS: Initial and recurrent CDI episodes increased among veterans over a 12-year period. Outcomes, such as mortality and hospital LOS improved in recent years; both of these outcomes are worse for initial CDI episodes than recurrent episodes.

Evaluation of Long-Term Chronic Myeloid Leukemia Treatment Practices with Tyrosine Kinase Inhibitors in a National Cohort of Veterans.

STUDY OBJECTIVE: To evaluate nationwide chronic myeloid leukemia (CML) treatment practices over an extended period and across multiple lines of tyrosine kinase inhibitor (TKI) therapy with imatinib, dasatinib, and nilotinib. DESIGN: Retrospective cohort study. DATA SOURCE: Veterans Health Administration (VHA) national database. PATIENTS: A total of 2873 VHA beneficiaries aged 18-89 years who had at least one encounter at any of the ~150 VHA hospitals and 800 VHA clinics, had a diagnosis code for CML, and filled at least one prescription for imatinib, nilotinib, or dasatinib between October 1, 2001, and September 30, 2010. MEASUREMENT AND MAIN RESULTS: The VHA database was used for the time period of October 1, 2000, to September 30, 2012, allowing for a 1-year observation period to identify CML treatments prior to study enrollment and a minimum of a 2-year follow-up period to assess study end points. Primary study end points included change in TKI treatment, gaps in TKI treatment, TKI treatment persistence, and patient survival. Persistence for each distinct line of treatment was defined as the time of continuous therapy, quantified by the number of days covered by the drug from treatment initiation until a 60-day gap in treatment was identified or a switch in treatment occurred. A Kaplan-Meier model was used to evaluate persistence and survival. Of the 2873 patients receiving first-line TKI treatment, 586 (20.4%) switched to a different TKI, constituting second-line treatment. Overall, 245 patients (8.5%) were switched again to third-line treatment. Only 4.4% of patients receiving first-line treatment experienced a gap in therapy of 60 or more days. First-line treatment persistence rates were 75%, 65%, and 55% for the first, second, and third years of treatment, respectively. Five-year survival with first-line treatment was 62%. CONCLUSION: In this national cohort of VHA patients, 1-year persistence of first-line TKI treatment was similar to that in prior studies. Five-year survival was comparable with that in other observational studies but was lower than that in prospective clinical trials. Persistence rates declined after the introduction of the new TKIs.

Application of a methicillin-resistant Staphylococcus aureus risk score for community-onset pneumonia patients and outcomes with initial treatment.

BACKGROUND: Community-onset (CO) methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is an evolving problem, and there is a great need for a reliable method to assess MRSA risk at hospital admission. A new MRSA prediction score classifies CO-pneumonia patients into low, medium, and high-risk groups based on objective criteria available at baseline. Our objective was to assess the effect of initial MRSA therapy on mortality in these three risk groups. METHODS: We conducted a retrospective cohort study using data from the Veterans Health Administration (VHA). Patients were included if they were hospitalized with pneumonia and received antibiotics within the first 48 h of admission. They were stratified into MRSA therapy and no MRSA therapy treatment arms based on antibiotics received in the first 48 h. Multivariable logistic regression was used to adjust for potential confounders. RESULTS: A total of 80,330 patients met inclusion criteria, of which 36% received MRSA therapy and 64% did not receive MRSA therapy. The majority of patients were classified as either low (51%) or medium (47%) risk, with only 2% classified as high-risk. Multivariable logistic regression analysis demonstrated that initial MRSA therapy was associated with a lower 30-day mortality in the high-risk group (adjusted odds ratio 0.57; 95% confidence interval 0.42-0.77). Initial MRSA therapy was not beneficial in the low or medium-risk groups. CONCLUSIONS: This study demonstrated improved survival with initial MRSA therapy in high-risk CO-pneumonia patients. The MRSA risk score might help spare MRSA therapy for only those patients who are likely to benefit.

Comparative value of four measures of retention in expert care in predicting clinical outcomes and health care utilization in HIV patients.

This study compared the ability of four measures of patient retention in HIV expert care to predict clinical outcomes. This retrospective study examined Veterans Health Administration (VHA) beneficiaries with HIV (ICD-9-CM codes 042 or V08) receiving expert care (defined as HIV-1 RNA viral load and CD4 cell count tests occurring within one week of each other) at VHA facilities from October 1, 2006, to September 30, 2008. Patients were ≥18 years old and continuous VHA users for at least 24 months after entry into expert care. Retention measures included: Annual Appointments (≥2 appointments annually at least 60 days apart), Missed Appointments (missed ≥25% of appointments), Infrequent Appointments (>6 months without an appointment), and Missed or Infrequent Appointments (missed ≥25% of appointments or >6 months without an appointment). Multivariable nominal logistic regression models were used to determine associations between retention measures and outcomes. Overall, 8,845 patients met study criteria. At baseline, 64% of patients were virologically suppressed and 37% had a CD4 cell count >500 cells/mm3. At 24 months, 82% were virologically suppressed and 46% had a CD4 cell count >500 cells/mm3. During follow-up, 13% progressed to AIDS, 48% visited the emergency department (ED), 28% were hospitalized, and 0.3% died. All four retention measures were associated with virologic suppression and antiretroviral therapy initiation at 24 months follow-up. Annual Appointments correlated positively with CD4 cell count >500 cells/mm3. Missed Appointments was predictive of all primary and secondary outcomes, including CD4 cell count ≤500 cells/mm3, progression to AIDS, ED visit, and hospitalization. Missed Appointments was the only measure to predict all primary and secondary outcomes. This finding could be useful to health care providers and public health organizations as they seek ways to optimize the health of HIV patients.

Impact of cancer supportive care pathways compliance on emergency department visits and hospitalizations.

PURPOSE: To evaluate the effects of compliance to cancer supportive care pathways on emergency department (ED) visits and hospitalizations as a result of neutropenia, anemia, and chemotherapy-induced nausea and vomiting (CINV). METHODS: CareFirst claims database was used to evaluate data spanning 2 years of the clinical pathways program. Frequency of ED visits/hospitalizations for neutropenia, anemia, and CINV were compared between compliant and noncompliant pathway utilization of granulocyte colony-stimulating factors (G-CSFs), erythropoiesis-stimulating agents (ESAs), and antiemetics, respectively. Logistic regression analysis was used to control for drug expenditures and cancer types. RESULTS: A total of 4,144 lines of therapy were received by 3,191 patients from 46 practices across three states. Overall, there were 472 ED visits/hospitalizations for neutropenia, 34 visits for anemia, and 799 visits for CINV. G-CSF pathway-compliant treatment was associated with a significant reduction in neutropenia ED visits/hospitalizations compared with noncompliant treatment (odds ratio [OR] = 0.34; 95% CI, 0.25 to 0.45; P < .001). Adjusting for cancer type and G-CSF drug expenditures, a similar reduction in neutropenia ED visits/hospitalizations was observed (OR = 0.42; 95% CI 0.30 to 0.58; P < .001). Analogous analyses did not demonstrate a significant association between ESA and antiemetic pathway compliance and ED visits/hospitalizations for anemia (P = .069) and CINV (P = .106), respectively. G-CSF therapy pathway compliance was also associated with an average decrease of $1,085 in ED visit/hospitalization costs per line of therapy (P < .001). CONCLUSION: G-CSF pathway compliance was associated with a significant decrease in the rate of neutropenia ED visits/hospitalizations and resulting costs.

Treatment failure and costs in patients with methicillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infections: a South Texas Ambulatory Research Network (STARNet) study.

OBJECTIVE: To measure the incidence of treatment failure and associated costs in patients with methicillin-resistant Staphylococcus aureus skin and soft tissue infections (SSTIs). METHODS: This was a prospective, observational study in 13 primary care clinics. Primary care providers collected clinical data, wound swabs, and 90-day follow-up information. Patients were considered to have "moderate or complicated" SSTIs if they had a lesion ≥5 cm in diameter or diabetes mellitus. Treatment failure was evaluated within 90 days of the initial visit. Cost estimates were obtained from federal sources. RESULTS: Overall, treatment failure occurred in 21% of patients (21 of 98) at a mean additional cost of $1,933.71 per patient. In a subgroup analysis of patients who received incision and drainage, those with moderate or complicated SSTIs had higher rates of treatment failure than those with mild or uncomplicated SSTIs (36% vs. 10%; P=.04). CONCLUSIONS: One in 5 patients presenting to a primary care clinic for a methicillin-resistant S. aureus SSTI will likely require additional interventions at an associated cost of almost $2,000 per patient. Baseline risk stratification and new treatment approaches are needed to reduce treatment failures and costs in the primary care setting.

Documenting the benefits and cost savings of a large multistate cancer pathway program from a payer's perspective.

PURPOSE: Clinical pathways are viewed as valuable practice tools leading to presumed cost savings. CareFirst BlueCross BlueShield partnering with P4 Pathways implemented a multistate oncology clinical pathways program in 2008. This is the first comprehensive evaluation to our knowledge of a pathways program implemented on a broad scale. METHODS: This study used a retrospective single-group, pretest-post-test design. Data representing preclinical pathways (year -1) and 2 years after program initiation (years +1 and +2) were obtained from claims data. Participating sites with ≥one claim for breast, lung, or colorectal cancer treatment from each year were included in the evaluation. Compliance was defined as site attainment of prespecified annual thresholds for the use of chemotherapy and supportive care. Savings were determined by comparing per-patient changes in drug and hospital costs through year +2 with the projected annual expenditure increases of 12% and 7%, respectively. RESULTS: Forty-six sites representing 4,713 patients met inclusion criteria. The unadjusted site compliance rate for chemotherapy was 83% and 54% for years +1 and +2, respectively; supportive care site compliance was 74% for both years. Per-patient drug costs increased from $16,494 in year -1 to $16,906 in year +2 (P=.587), whereas hospitalization costs decreased from $2,502 to $1,064 (P=.004). Compared with projected cost increases, pathways resulted in $10.3 million in savings by participant sites ($7.0 million from drugs and $3.3 million from hospitalizations) or $30.9 million when extrapolated to the entire health plan. CONCLUSION: Broadly implemented clinical pathways can achieve reasonable physician compliance, resulting in substantial cost savings.

Fenofibrate-associated nephrotoxicity: a review of current evidence.

PURPOSE: The literature describing fenofibrate-associated nephrotoxicity was reviewed. SUMMARY: Fenofibrate-associated nephrotoxicity is an underrecognized adverse effect that is being reported with increasing frequency in the medical literature. A MEDLINE search identified articles describing fenofibrate-associated nephrotoxicity. Two retrospective chart reviews reported this adverse reaction in transplant recipients and patients with renal insufficiency. A case series of six patients noted that the adverse reaction also occurred in patients without a predisposition to renal injury. Two small prospective studies have examined fenofibrate-associated nephrotoxicity, with conflicting findings regarding the mechanism. Finally, a large retrospective review and a population-based cohort study found that patients with preexisting renal disease or taking high-dosage fenofibrate have a higher risk of developing fenofibrate-associated nephrotoxicity. Fenofibrate-associated nephrotoxicity was shown to be reversible with both discontinuation and continued use of fenofibrate, though one study found that the elevations in serum creatinine (SCr) levels were permanent in study participants. Some argue that SCr elevations described in these articles were not due to renal toxicity but may be attributed to reversible mechanisms. While several mechanisms may be biologically plausible, none of the theories have been tested in clinical trials. A possible mechanism for the increase in SCr levels may include changes in renal hemodynamics causing volume depletion and the impairment of generation of vasodilatory prostaglandins, leading to renal vasoconstriction. CONCLUSION: Fenofibrate-associated nephrotoxicity is an underrecognized adverse drug reaction. Several published reports have detailed possible etiologies; however, data detailing the true incidence of fenofibrate-associated nephrotoxicity and its associated risk factors are limited.