Impact of a pharmacist-led oral chemotherapy monitoring clinic at the South Texas Veterans Health Care System.

As cancer treatments shift from traditional intravenous chemotherapy to inclusion of oral oncolytics, there is a critical need for structured oral chemotherapy monitoring and follow-up programs. To provide continuous care and minimize clinical gaps to Veterans receiving oral chemotherapy, the hematology/oncology clinical pharmacy practitioners designed and initiated a pilot, pharmacist-driven, Oral Chemotherapy Monitoring Clinic at the South Texas Veterans Health Care System supported by an oral chemotherapy certified pharmacy technician. A retrospective evaluation of patients receiving oral chemotherapy at the South Texas Veterans Health Care System was performed before (Phase I) and after (Phase II) pilot implementation to assess the impact of an Oral Chemotherapy Monitoring Clinic on compliance with drug-specific lab and symptom monitoring. Complete monitoring was defined as 100% of recommended labs and symptoms assessed per cycle, partial monitoring was <100%, but >0%, and incomplete monitoring was defined as 0%. The primary outcome assessed the proportion of patients receiving complete monitoring in Phase II compared to Phase I. Most patients were male (94%), with a median age of 72 years. The most common oncolytic was abiraterone acetate. Overall, drug-specific baseline and follow-up laboratory and symptom monitoring was complete at a statistically significantly higher rate in Phase II compared with Phase I (p-value < 0.01). A significantly higher portion of patients in the Phase II cohort had a clinical pharmacy practitioner intervention (44% vs. 90%; p < 0.01). Monitoring for Veterans receiving oral chemotherapy was optimized with clinical pharmacy practitioner and certified pharmacy technician involvement while simultaneously alleviating Oncologist and nurse oral chemotherapy workload.

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.

Clinical utility of methicillin-resistant Staphylococcus aureus nasal PCR to streamline antimicrobial use in treatment of diabetic foot infection with or without osteomyelitis.

BACKGROUND: Diabetic Foot Infection (DFI) guidelines recommend empiric methicillin-resistant Staphylococcus aureus (MRSA)-targeted therapy in settings where there is high prevalence of MRSA infections or in cases of severe infection; however, they do not provide recommendations for de-escalation. This approach has the potential to increase unnecessary use of broad-spectrum antibiotics; therefore, additional strategies are needed to optimize appropriate antibiotic use. This study evaluates the effect of MRSA nasal PCR testing on MRSA-targeted antibiotic use and clinical outcomes in patients with DFI. METHODS: This was a retrospective quasi-experimental study of patients admitted to South Texas Veterans Health Care System for DFI, with or without osteomyelitis (OM), who had an MRSA nasal PCR and culture data. Eligible patients were identified from the Corporate Data Warehouse and reviewed via electronic health record. Patients were allocated into two groups: PRE (5/1/2019-4/30/2020) and POST (12/1/2020-11/30/2021) protocol implementation for de-escalation or avoidance of MRSA-targeted antibiotics. The primary outcome was median (interquartile range [IQR]) hours of empiric inpatient MRSA-targeted antibiotic therapy. A Wilcoxon Rank Sum test was used to assess the difference between the groups for the primary outcome. Secondary outcomes included the proportion of patients needing MRSA coverage added back for MRSA after de-escalation, hospital readmission, length of hospital stay (LOS), patient mortality, and acute kidney injury. RESULTS: A total of 151 patients were included (83 PRE; 68 POST). Most patients were male (98% PRE; 97% POST) with a median age of 64 (IQR, 56-72) years. Incidence of MRSA in DFI in the cohort was 14.7% overall (12% PRE and 17.6% POST). MRSA was detected via nasal PCR in 12% of patients 15.7% PRE and 7.4% POST). After protocol implementation, there was a significant decrease in empiric MRSA-targeted antibiotic therapy use, from a median of 72 (IQR, 27-120) hours in the PRE group, to 24 (IQR, 12-72) hours in the POST group (p < 0.01). No significant differences were found for other secondary outcomes. CONCLUSION: This study of patients presenting to a Veterans Affairs (VA) hospital with DFI identified a statistically significant decrease in median duration of MRSA-targeted antibiotic use post-protocol implementation. This suggests a favorable effect of MRSA nasal PCR for de-escalation or avoidance of MRSA-targeted antibiotics in DFI.

Impact of macrolide treatment on long-term mortality in patients admitted to the ICU due to CAP: a targeted maximum likelihood estimation and survival analysis.

INTRODUCTION: Patients with community-acquired pneumonia (CAP) admitted to the intensive care unit (ICU) have high mortality rates during the acute infection and up to ten years thereafter. Recommendations from international CAP guidelines include macrolide-based treatment. However, there is no data on the long-term outcomes of this recommendation. Therefore, we aimed to determine the impact of macrolide-based therapy on long-term mortality in this population. METHODS: Registered patients in the MIMIC-IV database 16 years or older and admitted to the ICU due to CAP were included. Multivariate analysis, targeted maximum likelihood estimation (TMLE) to simulate a randomised controlled trial, and survival analyses were conducted to test the effect of macrolide-based treatment on mortality six-month (6 m) and twelve-month (12 m) after hospital admission. A sensitivity analysis was performed excluding patients with Pseudomonas aeruginosa or MRSA pneumonia to control for Healthcare-Associated Pneumonia (HCAP). RESULTS: 3775 patients were included, and 1154 were treated with a macrolide-based treatment. The non-macrolide-based group had worse long-term clinical outcomes, represented by 6 m [31.5 (363/1154) vs 39.5 (1035/2621), p < 0.001] and 12 m mortality [39.0 (450/1154) vs 45.7 (1198/2621), p < 0.001]. The main risk factors associated with long-term mortality were Charlson comorbidity index, SAPS II, septic shock, and respiratory failure. Macrolide-based treatment reduced the risk of dying at 6 m [HR (95% CI) 0.69 (0.60, 0.78), p < 0.001] and 12 m [0.72 (0.64, 0.81), p < 0.001]. After TMLE, the protective effect continued with an additive effect estimate of - 0.069. CONCLUSION: Macrolide-based treatment reduced the hazard risk of long-term mortality by almost one-third. This effect remains after simulating an RCT with TMLE and the sensitivity analysis for the HCAP classification.

Comparative-Effectiveness of Oral Beta-Lactams and Fluoroquinolones for Stepdown Therapy in Patients with Enterobacterales Bloodstream Infections: A Retrospective Cohort Study.

Background: This study compares treatment failure for patients who received oral beta-lactams (BLs) and fluoroquinolones (FQs) for stepdown treatment of Enterobacterales bloodstream infections (BSIs). Methods: We conducted a single-center, retrospective, age- and sex-matched, cohort study, at a Veterans Affairs (VA) hospital in South Texas. Eligible patients were at least 18 years of age with a monomicrobial BSI treated with a single oral BL or FQ antibiotic. Treatment failure was defined as recurrence or all-cause mortality within 90 days of documented BSI. Bivariate (chi-square, Fisher's Exact, and Wilcoxon Rank Sum) and multivariate (logistic regression) statistical tests were used to compare groups. Results: A total of 130 patients were included in this study, with 65 patients per group. Groups were well balanced with respect to exact age, sex assigned at birth, Caucasian race, source control, intensive care unit admission, and Charlson Comorbidity Index. Importantly, 60% of patients in the BL group had cultures that were resistant to FQs and 71% were prescribed cefpodoxime. Patients in the BL group had higher median (interquartile range [IQR]) Pitt bacteremia scores than those in the FQ group: 2 (1-4) vs. 1 (1-2), p=0.04. Patients in the BL group also had a higher median (IQR) duration of intravenous (IV) antibiotics than those in the FQ group: 5 (3-7) vs. 4 (3-5), p=0.02. Treatment failure was statistically comparable for patients in the BL and FQ groups: 15% vs. 12%, p=0.61. This finding was consistent in a multivariate logistic regression model with group (BL vs. FQ) as the independent variable, treatment failure as the dependent variable, and Pitt bacteremia score and duration of IV antibiotics as covariates (OR: 0.76, 95% CI: 0.27-2.18). One patient in the FQ group experienced Clostridioides difficile infection. Conclusion: This study suggests that BLs may be as effective as FQs for oral stepdown treatment of Enterobacterales BSI without the potential associated risks. Furthermore, in the setting of FQ-resistant Enterobacterales BSI secondary to urinary source, third generation oral cephalosporins (i.e., cefpodoxime) may be reasonable alternatives.

Incidence of invasive fungal infections in patients with chronic lymphocytic leukemia receiving ibrutinib within the veteran's healthcare administration.

PURPOSE: Ibrutinib is a tyrosine kinase inhibitor that is increasingly prescribed in chronic lymphocytic leukemia (CLL). Invasive fungal infections (IFIs) have been reported early after ibrutinib initiation. Timing of IFIs is within 6 months and commonly reported fungal infections include Cryptococcus, Aspergillus, and Pneumocystis. Currently, there are no recommendations for routine prophylaxis against IFIs in patients receiving ibrutinib for CLL. OBJECTIVE: The objective of this study was to evaluate the incidence of IFIs in patients receiving ibrutinib for CLL in first-line and relapsed/refractory (R/R) settings. METHODS: This was a retrospective, cohort study of patients diagnosed with CLL and initiated on ibrutinib in the Veterans Health Administration (VHA) from October 1, 2013 to March 31, 2018. Patients were included if diagnosed with a proven or probable IFI from the start date of ibrutinib to 30 days after the last dose of ibrutinib. RESULTS: Fourteen out of 1069 patients met inclusion criteria for IFI while on ibrutinib for CLL. All patients included were male with a median age of 78 years. Fifty percent of patients were initiated on ibrutinib within 3 months of last chemotherapy. IFIs occurred within 3 months (50%) and 6 months (71%) of ibrutinib initiation. Seventy-one percent of patients were continued on ibrutinib with concurrent IFI diagnosis. CONCLUSION: The reported IFI incidence of 1.3% is comparable to current estimates of 1.2%. Future studies should examine the relationship of ibrutinib and incidence of IFIs in first-line and R/R settings in addition to identifying clinical risk factors predisposing patients to IFIs.

Rhabdomyolysis Associations with Antibiotics: A Pharmacovigilance Study of the FDA Adverse Event Reporting System (FAERS).

Introduction: Daptomycin, macrolides, trimethoprim-sulfamethoxazole, linezolid, fluoroquinolones, and cefdinir are known to be associated with rhabdomyolysis. Other antibiotics may also lead to rhabdomyolysis, but no study has systemically compared rhabdomyolysis associations for many available antibiotics. Objectives: The objective of this study was to evaluate the association between rhabdomyolysis and many available antibiotics using the FDA Adverse Event Report System (FAERS). Methods: FAERS reports from January 1, 2004 to December 31, 2017 were included in the study. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify rhabdomyolysis cases. Reporting Odds Ratios (RORs) and corresponding 95% confidence intervals (95%CI) for the association between antibiotics and rhabdomyolysis were calculated. An association was considered statistically significant when the lower limit of the 95%CI was greater than 1.0. Results: A total of 2,334,959 reports (including 7,685 rhabdomyolysis reports) were considered, after inclusion criteria were applied. Daptomycin had the greatest proportion of rhabdomyolysis reports, representing 5.5% of all daptomycin reports. Statistically significant rhabdomyolysis RORs (95% CI) for antibiotics were (in descending order): daptomycin 17.94 (14.08-22.85), cefditoren 8.61 (3.54-20.94), cefaclor 7.16 (2.28-22.49), erythromycin 5.93 (3.17-11.10), norfloxacin 4.50 (1.44-14.07), clarithromycin 3.95 (2.77-5.64), meropenem 3.19 (1.51-6.72), azithromycin 2.94 (1.96-4.39), cefdinir 2.84 (1.06-7.62), piperacillin-tazobactam 2.61 (1.48-4.61), trimethoprim-sulfamethoxazole 2.53 (1.52-4.21), linezolid 2.49 (1.47-4.21), ciprofloxacin 2.10 (1.51-2.92). Conclusions: This study confirms prior evidence for rhabdomyolysis associations with daptomycin, macrolides, trimethoprim-sulfamethoxazole, linezolid, fluoroquinolones, and cefdinir. This study also identifies previously unknown rhabdomyolysis associations with meropenem, cefditoren, cefaclor, and piperacillin-tazobactam.

Clostridium difficile Infection Risk with Important Antibiotic Classes: An Analysis of the FDA Adverse Event Reporting System.

Introduction: Antibiotic use is an important risk factor for Clostridium difficile infection (CDI). Prior meta-analyses have identified antibiotics and antibiotic classes that pose the greatest risk for CDI; however, CDI epidemiology is constantly changing and contemporary analyses are needed. Objectives: The objective of this study was to evaluate the association between CDI and important antibiotic classes in recent years using the FDA Adverse Event Report System (FAERS). Methods: FAERS reports from January 1, 2015 to December 31, 2017 were analyzed. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify CDI cases. We computed the Reporting Odds Ratios (RORs) and corresponding 95% confidence intervals (95%CI) for the association between antibiotics and CDI. An association was considered statistically significant when the lower limit of the 95%CI was greater than 1. Results: A total of 2,042,801 reports (including 5,187 CDI reports) were considered, after inclusion criteria were applied. Lincosamides (e.g., clindamycin) had the greatest proportion of CDI reports, representing 10.4% of all lincosamide reports. CDI RORs (95%CI) for the antibiotic classes were (in descending order): lincosamides 46.95 (39.49-55.82), monobactams 29.97 (14.60-61.54), penicillin combinations 20.05 (17.39-23.12), carbapenems 19.16 (15.52-23.67), cephalosporins/ monobactams/carbapenems 17.28 (14.95-19.97), cephalosporins 15.33 (12.60-18.65), tetracyclines 7.54 (5.42-10.50), macrolides 5.80 (4.48-7.51), fluoroquinolones 4.94 (4.20-5.81), and trimethoprim-sulfonamides 3.32 (2.03-5.43). Conclusion: All antibiotic classes included in the study were significantly associated with CDI. Lincosamides (e.g., clindamycin) had the highest CDI ROR among the antibiotics evaluated in this study.

Torsades de pointes and QT prolongation Associations with Antibiotics: A Pharmacovigilance Study of the FDA Adverse Event Reporting System.

Introduction: Macrolides, linezolid, imipenem-cilastatin, fluoroquinolones, penicillin combinations, and ceftriaxone are known to be associated with Torsades de pointes/QT prolongation (TdP/QTP). Other antibiotics may also lead to TdP/QTP, but no study has systemically compared TdP/QTP associations for many available antibiotics. Objectives: The objective of this study was to evaluate the association between TdP/QTP and many available antibiotics using the FDA Adverse Event Report System (FAERS). Methods: FAERS reports from January 1, 2015 to December 31, 2017 were analyzed. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify TdP/QTP cases. We calculated the Reporting Odds Ratios (RORs) and corresponding 95% confidence intervals (95%CI) for the association between antibiotics and TdP/QTP. An association was considered to be statistically significant when the lower limit of the 95%CI was greater than 1.0. Results: A total of 2,042,801 reports (including 3,960 TdP/QTP reports) were considered, after inclusion criteria were applied. Macrolides had the greatest proportion of TdP/QTP reports. Of the 4,092 reports associated with macrolides, 108 reports (2.6%) were associated with TdP/QTP. Significant TdP/QTP RORs (95%CI) for the antibiotics were (in descending order): macrolides 14.32 (11.80-17.38), linezolid 12.41 (8.52-18.08), amikacin 11.80 (5.57-24.97), imipenem-cilastatin 6.61 (3.13-13.94), fluoroquinolones 5.68 (4.78-6.76), penicillin combinations 3.42 (2.35-4.96), and ceftriaxone 2.55 (1.41-4.62). Conclusion: This study confirms prior evidence for TdP/QTP associations with macrolides, linezolid, imipenem-cilastatin, fluoroquinolones, penicillin combinations, and ceftriaxone. This study also identifies a new association between amikacin and TdP/QTP.

Emerging multidrug resistance in community-associated Staphylococcus aureus involved in skin and soft tissue infections and nasal colonization.

Background: Staphylococcus aureus is a major pathogen causing significant morbidity and mortality worldwide. The emergence of MDR S. aureus strains in the community setting has major implications in disease management. However, data regarding the occurrence and patterns of MDR community-associated S. aureus sub-clones is limited. Objectives: To use whole-genome sequences to describe the diversity and distribution of resistance mechanisms among community-associated S. aureus isolates. Methods: S. aureus isolates from skin and soft tissue infections (SSTIs) and nasal colonization were collected from patients within 10 primary care clinics from 2007 to 2015. The Illumina Miseq platform was used to determine the genome sequences for 144 S. aureus isolates. Phylogenetic and bioinformatics analyses were performed using in silico tools. The resistome was assembled and compared with the phenotypically derived antibiogram. Results: Approximately one-third of S. aureus isolates in the South Texas primary care setting were MDR. A higher proportion of SSTI isolates were MDR in comparison with nasal colonization isolates. Individuals with MDR S. aureus SSTIs were more likely to be African American and obese. Furthermore, S. aureus populations are able to acquire and lose antimicrobial resistance genes. USA300 strains were differentiated by a stable chromosomal mutation in gyrA conferring quinolone resistance. The resistomes were highly predictive of antimicrobial resistance phenotypes. Conclusions: These findings highlight the high prevalence and epidemiological factors associated with MDR S. aureus strains in the community setting and demonstrate the utility of next-generation sequencing to potentially quicken antimicrobial resistance detection and surveillance for targeted interventions.

Association of statins with aortic, peripheral, and visceral artery aneurysm development.

Objectives Prior studies examining the effects of statins on arterial aneurysm development and progression yielded conflicting results due to their smaller size and presence of residual confounders. The objective of this study is to examine the association of statins with risk of being diagnosed with aortic, peripheral, and visceral artery aneurysm. Methods This was a retrospective cohort study of Tricare enrollees (from 1 October 2003 to 31 March 2012). Main outcomes were diagnosis of aortic, peripheral, or visceral artery aneurysm and undergoing aortic aneurysm repair procedure during follow-up period. Using 115 baseline characteristics, we generated a propensity score to match statin users and nonusers and examine the odds of outcomes (primary analysis). Secondary analysis examined outcomes at various subcohorts. Results Out of 10,910 statin users and 49,545 nonusers, we propensity score-matched 6728 pairs of statin users and nonusers. Statin users and nonusers had similar odds of being diagnosed with aortic, peripheral, and visceral artery aneurysms (odds ratio [OR]: 1.06, 95% confidence interval [95% CI]: 0.85-1.33) and of undergoing aortic aneurysm repair procedures (OR: 0.54, 95% CI: 0.22-1.35). Secondary analysis showed a tendency toward fewer aortic aneurysm procedures among statin users that did not reach statistical significance. However, high-intensity statin users in comparison to non-intensive statin users had higher adjusted odds of aortic, peripheral, and visceral artery aneurysms (OR: 1.76, 95% CI: 1.37-2.25, p < .0001). Conclusions This study does not support a clinically significant benefit or harm from statins regarding development of arterial aneurysm. However, secondary analyses may support the hypothesis proposed by previous research proposing a bidirectional role for statins.

A prospective observational cohort study in primary care practices to identify factors associated with treatment failure in Staphylococcus aureus skin and soft tissue infections.

BACKGROUND: The incidence of outpatient visits for skin and soft tissue infections (SSTIs) has substantially increased over the last decade. The emergence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) has made the management of S. aureus SSTIs complex and challenging. The objective of this study was to identify risk factors contributing to treatment failures associated with community-associated S. aureus skin and soft tissue infections SSTIs. METHODS: This was a prospective, observational study among 14 primary care clinics within the South Texas Ambulatory Research Network. The primary outcome was treatment failure within 90 days of the initial visit. Univariate associations between the explanatory variables and treatment failure were examined. A generalized linear mixed-effect model was developed to identify independent risk factors associated with treatment failure. RESULTS: Overall, 21% (22/106) patients with S. aureus SSTIs experienced treatment failure. The occurrence of treatment failure was similar among patients with methicillin-resistant S. aureus and those with methicillin-susceptible S. aureus SSTIs (19 vs. 24%; p = 0.70). Independent predictors of treatment failure among cases with S. aureus SSTIs was a duration of infection of ≥7 days prior to initial visit [aOR, 6.02 (95% CI 1.74-19.61)] and a lesion diameter size ≥5 cm [5.25 (1.58-17.20)]. CONCLUSIONS: Predictors for treatment failure included a duration of infection for ≥7 days prior to the initial visit and a wound diameter of ≥5 cm. A heightened awareness of these risk factors could help direct targeted interventions in high-risk populations.

Predictors of Pseudomonas and methicillin-resistant Staphylococcus aureus in hospitalized patients with healthcare-associated pneumonia.

BACKGROUND AND OBJECTIVE: Patients with healthcare-associated pneumonia (HCAP) are at high risk of infection with multidrug-resistant (MDR) pathogens. Factors discriminating infection with MDR Gram-negative (MDR-GN) organism from infection with methicillin-resistant Staphylococcus aureus (MRSA) are not well understood and patients are often treated for both organisms. This study was performed to determine risk factors predicting pneumonia due to Pseudomonas versus MRSA. METHODS: Veterans age ≥65 hospitalized with HCAP between 2002 and 2012 were identified from the Veterans Affairs administrative databases. Patients were identified with Pseudomonas pneumonia, MRSA pneumonia or neither according to the International Classification of Diseases, 9th Revision, Clinical Modification codes. We assessed unadjusted and adjusted associations of patient characteristics and HCAP due to Pseudomonas or MRSA. RESULTS: Of the 61,651 patients with HCAP, 1156 (1.9%) were diagnosed with Pseudomonas pneumonia, 641 (1.0%) with MRSA pneumonia and 59,854 (97.1%) with neither. MRSA pneumonia was positively associated with male gender, age >74, diabetes, chronic obstructive pulmonary disease (COPD), recent nursing home or hospital stay, recent exposure to fluoroquinolone or antibiotics treating Gram-positive organisms, and severe pneumonia. MRSA pneumonia was negatively associated with complicated diabetes. Pseudomonas pneumonia was positively associated with recent hospital stay, immunocompromise, COPD, hemiplegia, recent exposure to inhaled corticosteroids, ß-lactam/cephalosporin/carbapenem antibiotics, antibiotics against Gram-positive organisms, 'other antibiotics' and severe pneumonia. Pseudomonas pneumonia was negatively associated with age >84, higher socioeconomic status, drug abuse and diabetes. CONCLUSIONS: Patient characteristics may assist in identifying patients at risk for HCAP due to Pseudomonas or MRSA.

Statins and New-Onset Diabetes Mellitus and Diabetic Complications: A Retrospective Cohort Study of US Healthy Adults.

BACKGROUND: Statin use is associated with increased incidence of diabetes and possibly with increased body weight and reduced exercise capacity. Data on the long-term effects of these associations in healthy adults, however, are very limited. In addition, the relationship between these effects and diabetic complications has not been adequately studied. OBJECTIVE: To examine the association between statin use and new-onset diabetes, diabetic complications, and overweight/obesity in a cohort of healthy adults. RESEARCH DESIGN: This was a retrospective cohort study. PARTICIPANTS: Subjects were Tricare beneficiaries who were evaluated between October 1, 2003 and March 1, 2012. Patients were divided into statin users and nonusers. INTERVENTION: We excluded patients who, at baseline, had a preexisting disease indicative of cardiovascular diseases, any positive element of the Charlson comorbidity index (including diabetes mellitus), or life-limiting chronic diseases. Using 42 baseline characteristics, we generated a propensity score to match statin users and nonusers. MAIN MEASURES: Outcomes assessed included new-onset diabetes, diabetic complications, and overweight/obesity. KEY RESULTS: A total of 25,970 patients (3982 statin users and 21,988 nonusers) were identified as healthy adults at baseline. Of these, 3351 statins users and 3351 nonusers were propensity score-matched. Statin users had higher odds of new-onset diabetes (odds ratio [OR] 1.87; 95 % confidence interval [95 % CI] 1.67-2.01), diabetes with complications (OR 2.50; 95 % CI 1.88-3.32), and overweight/obesity (OR 1.14; 95 % CI 1.04-1.25). Secondary and sensitivity analyses demonstrated similar findings. CONCLUSIONS: Diabetes, diabetic complications, and overweight/obesity were more commonly diagnosed among statin-users than similar nonusers in a healthy cohort of adults. This study demonstrates that short-term clinical trials might not fully describe the risk/benefit of long-term statin use for primary prevention.

Statins and male sexual health: a retrospective cohort analysis.

INTRODUCTION: Conflicting reports exist regarding the role of statins in male gonadal and sexual function. Some studies report a beneficial effect, particularly for erectile dysfunction (ED), through statins' anti-inflammatory and cardiovascular protective properties. Others suggest that statins might be associated with sexual dysfunction through negative effects on hormone levels. AIM: This study aims to compare the risk of gonadal or sexual dysfunction in statin users vs. nonusers in a single-payer healthcare system. METHODS: This was a retrospective cohort study of all male patients (30-85 years) enrolled in the Tricare San Antonio market. Using 79 baseline characteristics, we created a propensity score-matched cohort of statin users and nonusers. The study duration was divided into a baseline period (October 1, 2003 to September 30, 2005) to describe patient baseline characteristics, and a follow-up period (October 1, 2005 to March 1, 2012) to determine patient outcomes. Statin users were defined as those prescribed a statin for ≥3 months between October 1, 2004 and September 30, 2005. MAIN OUTCOME MEASURES: Outcomes were identified as the occurrence of benign prostatic hypertrophy (BPH), ED, infertility, testicular dysfunction, or psychosexual dysfunction during the follow-up period as identified by inpatient or outpatient International Classification of Diseases, 9th Revision, Clinical Modification codes. Logistic regression was used to determine the association of statin use with patient outcomes. RESULTS: Of 20,731 patients who met study criteria, we propensity score-matched 3,302 statin users with 3,302 nonusers. Statin use in men was not significantly associated with an increased or decreased risk of BPH (odds ratio [OR] 1.08; 95% confidence interval [CI] 0.97-1.19), ED (OR 1.01; 95% CI 0.90-1.13), infertility (OR 1.22; 95% CI 0.66-2.29), testicular dysfunction (OR 0.91; 95% CI 0.73-1.14), or psychosexual dysfunction (OR 1.03; 95% CI 0.94-1.14). CONCLUSIONS: Statin use was not associated with increased risk of being diagnosed with gonadal or sexual dysfunction in men. Further studies using a larger sample may be needed.

The association of statin use and gonado-sexual function in women: a retrospective cohort analysis.

INTRODUCTION: It has been hypothesized that statins reduce sex hormone biosynthesis through hepatic inhibition of cholesterol synthesis, which is a precursor of androstenedione and estradiol. Such a reduction has been associated with menstrual irregularities, menopausal disorders, infertility, and low libido, but studies are conflicting. Few studies have evaluated the clinical effects of statins on gonadal-sexual function in women. AIM: To compare the risk of gonado-sexual dysfunction in statin users vs. nonusers. METHODS: This was a retrospective cohort study of all female, adult patients (30-85 years) enrolled in the Tricare Prime/Plus San Antonio catchment area. Using 79 baseline characteristics, we created a propensity score-matched cohort of statin users and nonusers. The study duration was divided into a baseline period (October 1, 2003 to September 30, 2005) to describe patient baseline characteristics and a follow-up period (October 1, 2005 to March 1, 2012) to determine patient outcomes. Statin users were defined as those prescribed a statin for ≥3 months between October 1, 2004 and September 30, 2005. Logistic regression was used to determine the association of statin use with patient outcomes. MAIN OUTCOME MEASURES: Outcomes included menstrual disorders, menopausal disorders, infertility, and ovarian/sexual dysfunction during the follow-up period. Outcomes were identified using inpatient or outpatient International Classification of Diseases, Ninth Revision, Clinical Modification codes as defined by the Agency for Healthcare Research and Quality's Clinical Classifications Software. RESULTS: Of 22,706 women who met study criteria, we propensity score-matched 2,890 statin users with 2,890 nonusers; mean age 58 ± 12 years. Statin use was not significantly associated with menstrual disorders (OR 0.97; 95% CI 0.81-1.16), menopausal disorders (OR 0.92; 95% CI 0.83-1.02), infertility (OR 0.79; 95% CI 0.36-1.73), or ovarian/sexual dysfunction (OR 1.18; 95% CI 0.83-1.70). CONCLUSIONS: Statin use was not associated with higher risk of gonado-sexual dysfunction in women.

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.

Statin therapy and gastrointestinal hemorrhage: a retrospective cohort study with propensity score-matching.

PURPOSE: Whereas some studies suggest that statins exert a gastroprotective effect against gastrointestinal hemorrhage, others report that statin use is associated with increased risk of gastrointestinal hemorrhage. Aim of report: To investigate the risk of gastrointestinal hemorrhage among statin-users compared with non-users. METHODS: This was a retrospective cohort study using clinical, administrative, and pharmacy data encompassing October 2003 to March 2012 from patients enrolled in the San Antonio military health care system. Two treatment groups were defined: statin-users (use for at least 90 days) and non-users (never received statin). A propensity score-matched cohort was generated to match statin-users and non-users based on 82 variables. Main outcome measures were defined by the International Classification of Diseases, ninth revision-clinical modification diagnoses codes or procedural codes for gastrointestinal hemorrhage, gastritis/doudenitis, gastroduodenal ulcers, endoscopy procedures, and endoscopy procedures related to gastrointestinal hemorrhage. RESULTS: A total of 43,438 patients were identified; 13,626 (31.4%) were statin-users and 29,812 were non-users. We propensity score-matched 6342 non-users with 6342 statin-users. The risk of outcomes was similar between the two groups for gastrointestinal hemorrhage (Odds Ratio [OR]: 1.0; 95% confidence interval [95%CI]: 0.91, 1.11); gastrointestinal ulcers (OR: 0.99; 95%CI [0.80, 1.24]); gastritis/duodenitis (OR: 0.92; 95%CI [0.83, 1.02]); and endoscopic procedures (OR: 1.07; 95%CI [0.98, 1.17]). CONCLUSION: Statin use was not significantly associated with either an increased or decreased risk of gastrointestinal hemorrhage. Choice of statin therapy should not be limited in those patients at risk of gastrointestinal hemorrhage.

Pharmacogenomic diversity of tamoxifen metabolites and estrogen receptor genes in Hispanics and non-Hispanic whites with breast cancer.

Ethnic differences in patient genetics and breast cancer (BC) biology contribute to ethnic disparities in cancer presentation and patient outcome. We prospectively evaluated SNPs within phase I and phase II tamoxifen (TAM) metabolizing enzymes, and the estrogen receptor gene (ESR1), aiming to identify potential pharmacogenomic ethnicity patterns in an ER-positive BC cohort constituted of Hispanic and Non-Hispanic White (NHW) women in South Texas. Plasma concentrations of TAM/metabolites were measured using HPLC. CYP2C9, CYP2D6 and SULT1A1 genotypes were determined by DNA sequencing/Pyrosequencing technology. ESR1 PvuII and XbaI SNPs were genotyped using Applied Biosystems Taqman Allelic Discrimination Assay. Hispanics had higher levels of TAM, 4-hydroxytamoxifen, and endoxifen than NHWs. There was a higher prevalence of CYP2D6 EM within Hispanics than NHWs, which corresponded to higher endoxifen levels, but no differences were verified with regard to CYP2C9 and SULT1A1. We found a higher incidence of the wild type forms of the ESR1 in Hispanics than NHWs. The performance status, the disease stage at diagnosis, and the use of aromatase inhibitors might have overcome the overall favorable pharmacogenomics profile of Hispanics when compared to NHWs in relation to TAM therapy responsiveness. Our data strongly point to ethnical peculiarities related to pharmacogenomics and demographic features of TAM treated Hispanics and NHWs. In the era of pharmacogenomics and its ultimate goal of individualized, efficacious and safe therapy, cancer studies focused on the Hispanic population are warranted because this is the fastest growing major demographic group, and an understudied segment in the U.S.