Metformin Use Is Associated With Lower Mortality in Veterans With Diabetes Hospitalized With Pneumonia.

BACKGROUND: Recent studies suggest that metformin use may be associated with improved infectious disease-related outcomes, whereas other papers suggest potentially worse outcomes in serious bacterial infections. Our purpose was to examine the association of prior outpatient prescription of metformin on 30- and 90-day mortality for older veterans with pre-existing diabetes hospitalized with pneumonia. METHODS: We conducted a retrospective cohort study using national Department of Veterans Affairs data of patients ≥65 years with a prior history of diabetes who were hospitalized with pneumonia over a 10-year period (fiscal years 2002-2012.) For our primary analysis, we created a propensity score and matched metformin users to nonusers 1:1. RESULTS: We identified 34 759 patients who met the inclusion criteria, 20.3% of whom were prescribed metformin. Unadjusted 30-day mortality was 9.6% for those who received metformin versus 13.9% in nonusers (P < .003), and 90-day mortality was 15.8% for those who received metformin versus 23.0% for nonusers (P < .0001). For the propensity score model, we matched 6899 metformin users to 6899 nonusers. After propensity matching, both 30-day (relative risk [RR]: .86; 95% confidence interval [CI]: .78-.95) and 90-day (RR: .85; 95% CI: .79-.92) mortality was significantly lower for metformin users. CONCLUSIONS: Prior receipt of metformin was associated with significantly lower mortality after adjusting for potential confounders. Additional research is needed to examine the safety and potential benefits of metformin use in patients with respiratory infections.

Transcriptomic responses in the blood and sputum of cigarette smokers compared to e-cigarette vapers.

RATIONALE: Electronic (e)-cigarettes are popular among youth and cigarette smokers attempting to quit. Studies to date have focused on the utility of e-cigarettes as a smoking cessation tool, but the biological effects are largely unknown. OBJECTIVES: To identify transcriptomic differences in the blood and sputum of e-cigarette users compared to conventional cigarettes smokers and healthy controls and describe biological pathways affected by these tobacco products. METHODS: Cross-sectional analysis of whole blood and sputum RNA-sequencing data from 8 smokers, 9 e-cigarette users (e-cigs) and 4 controls. Weighted gene co-network analysis (WGCNA) identified gene module associations. Ingenuity Pathway Analysis (IPA) identified canonical pathways associated with tobacco products. MAIN RESULTS: In blood, a three-group comparison showed 16 differentially expressed genes (DEGs); pair-wise comparison showed 7 DEGs between e-cigs and controls, 35 DEGs between smokers and controls, and 13 DEGs between smokers and e-cigs. In sputum, 438 DEGs were in the three-group comparison. In pair-wise comparisons, there were 2 DEGs between e-cigs and controls, 270 DEGs between smokers and controls, and 468 DEGs between smokers and e-cigs. Only 2 genes in the smokers vs. control comparison overlapped between blood and sputum. Most gene modules identified through WGCNA associated with tobacco product exposures also were associated with cotinine and exhaled CO levels. IPA showed more canonical pathways altered by conventional cigarette smoking than by e-cigarette use. CONCLUSION: Cigarette smoking and e-cigarette use led to transcriptomic changes in both blood and sputum. However, conventional cigarettes induced much stronger transcriptomic responses in both compartments.

Effectiveness of Beta-Lactam plus Doxycycline for Patients Hospitalized with Community-Acquired Pneumonia.

BACKGROUND: Despite clinical practice guideline recommendations to use doxycycline as part of combination therapy for some patients hospitalized with pneumonia, there is minimal evidence supporting this recommendation. Our aim was to examine the association between beta-lactam plus doxycycline and mortality for patients hospitalized with community-acquired pneumonia. METHODS: We identified patients >65 years of age admitted to any US Department of Veterans Affairs hospital in fiscal years 2002-2012 with a discharge diagnosis of pneumonia. We excluded those patients who did not receive antibiotic therapy concordant with the 2019 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) clinical practice guidelines. Using propensity score matching, we examined the association of doxycycline with 30- and 90-day mortality. RESULTS: Our overall cohort was comprised of 70533 patients and 5282 (7.49%) received doxycycline. Unadjusted 30-day mortality was 6.4% for those who received a beta-lactam plus doxycycline versus 9.1% in those who did not (P < .0001), and 90-day mortality was 13.8% for those who received a beta-lactam + doxycycline versus 16.8% for those who did not (P < .0001). In the propensity score matched models, both 30- (odds ratio 0.72, 95% confidence interval [CI], .63-.84) and 90-day (0.83, 95% CI, .74-.92) mortality were significantly lower for those who received doxycycline. CONCLUSIONS: In this retrospective observational cohort study, we found that doxycycline use, as part of guideline-concordant antibiotic therapy, was associated with lower 30- and 90-day mortality than regimens without doxycycline. While this supports the safety and effectiveness of antibiotic regimes that include doxycycline, additional studies, especially randomized clinical trials, are needed to confirm this.

The inflammatory biomarker YKL-40 is elevated in the serum, but not the sputum, of E-cigarette users.

METHODS: We conducted a cross-sectional study of adults between 18 and 55 years old. Inclusion criteria were: exclusive e-cigarette use or cigarette smoking for ≥ 1 year or no history of tobacco use. Participants with a history of pulmonary illness, atopy, medications (except birth control pills), marijuana, and illegal substance use were excluded. Custom Multiplex ELISA was used to measure YKL-40 and other biomarker levels in the serum and induced sputum of the participants. Multivariable linear regression was used to compare the levels of YLK-40 in healthy participants, e-cigarette, and cigarette users after adjusting for age, sex, and BMI. RESULTS: We recruited 20 healthy controls, 23 cigarette smokers, and 22 exclusive e-cigarette users. Serum YKL-40 (ng/ml) was significantly higher in e-cigarette users (Median 21.2 [IQR 12.1-24.0] ng/ml) when compared to controls (12.2 [IQR 8.7-18.1] ng/ml, p = 0.016) but comparable to cigarette smokers (21.6 [IQR 11.62-51.7] ng/ml, p = 0.31). No significant differences were found in the serum or sputum of the other biomarkers tested. CONCLUSION: The inflammatory biomarker, YKL-40 is elevated in the serum but not the sputum of e-cigarette users with no reported pulmonary disease. Further research is necessary to characterize this association.

Comparison of patient-reported outcomes measurement information system and legacy instruments in multiple domains among older veterans with chronic back pain.

BACKGROUND: Chronic low back pain (cLBP) results in significant physical, psycho-social and socioeconomic burden. Identifying efficient and reliable patient reported outcome measures is critical for research and clinical purposes. The NIH's Patient Reported Outcomes Measurement Information System (PROMIS) instruments have not been compared to validated "legacy" instruments in older adults with cLBP. This study evaluates construct (convergent and discriminant) validity and time to complete (TTC) PROMIS as compared to legacy instruments. METHODS: We enrolled older Veterans (age 60+) with cLBP with/without leg pain scheduled for lumbar epidural steroid injections. Subjects completed PROMIS computer adaptive test item banks and corresponding legacy instruments in the following domains: pain intensity, interference, and behavior; functional status; depression and anxiety; fatigue; sleep and social functioning. Convergent and discriminant validity between PROMIS and legacy instruments was evaluated using Spearman rank order correlations; Mann-Whitney U tests compared TTC. RESULTS: Of the 71 Veterans recruited, the median (IQR) age was 67 (63-71) years old, 94% were men, 76% were White, 17% Black, and 96% were Non-Hispanic. Spearman correlations between PROMIS and legacy instruments showed moderate to very strong convergent validity in all domains (r = 0.4-1.0), except for social functioning and pain behavior (PROMIS Pain Behavior with Fear Avoidance Belief Questionnaire). The total median TTC for all PROMIS items was significantly shorter than legacy items, 8 min 50 s vs 29 min 14 s respectively, p < 0.001. CONCLUSIONS: Given time efficiency of using PROMIS, along with strong construct validity, PROMIS instruments are a practical choice for measuring multidimensional PROs in older Veterans with cLBP for both research and clinical purposes.

Statins in survivors of traumatic brain injury: a propensity score-matched analysis.

BACKGROUND: Several in-vitro and animal studies suggest that statins may have beneficial effects on clinical outcomes of traumatic brain injury (TBI), however, clinical data are scarce. OBJECTIVES: To examine the association of statin use with TBI clinical outcomes among patients with TBI. METHODS: A retrospective cohort study of Tricare beneficiaries who had a TBI diagnosis, as defined by the Barbell injury diagnosis matrix. Outcomes were defined using ICD-9 codes and included: post-concussion syndrome, neurological disorders, substance dependence or abuse, and psychiatric disorders. Statin-users and non-users were propensity score (PS)-matched using 103 baseline characteristics. RESULTS: Out of 1187 adult patients with a TBI diagnosis (172 statin-users and 1015 nonusers), we PS-matched 70 statin-users to 70 non-users. There were no statistically significant differences in the PS-matched cohort of statin-users in comparison to nonusers for post-concussion syndrome (odds ratio [OR]: 0.24, 95% confidence interval [CI]: 0.03-2.20), neurological disorders (OR: 0.60, CI: 0.31-1.16); substance dependence or abuse (OR: 0.80, CI: 0.40-1.60), or psychiatric disorders (OR 0.80, CI: 0.41-1.55). CONCLUSION: This study did not show benefit or harm for statins among survivors of TBI. Our findings do not support the evidence from some animal studies and small randomized controlled trials. Further studies utilizing larger sample sizes are warranted.

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.

Streptococcus pneumoniae translocates into the myocardium and forms unique microlesions that disrupt cardiac function.

Hospitalization of the elderly for invasive pneumococcal disease is frequently accompanied by the occurrence of an adverse cardiac event; these are primarily new or worsened heart failure and cardiac arrhythmia. Herein, we describe previously unrecognized microscopic lesions (microlesions) formed within the myocardium of mice, rhesus macaques, and humans during bacteremic Streptococcus pneumoniae infection. In mice, invasive pneumococcal disease (IPD) severity correlated with levels of serum troponin, a marker for cardiac damage, the development of aberrant cardiac electrophysiology, and the number and size of cardiac microlesions. Microlesions were prominent in the ventricles, vacuolar in appearance with extracellular pneumococci, and remarkable due to the absence of infiltrating immune cells. The pore-forming toxin pneumolysin was required for microlesion formation but Interleukin-1ß was not detected at the microlesion site ruling out pneumolysin-mediated pyroptosis as a cause of cell death. Antibiotic treatment resulted in maturing of the lesions over one week with robust immune cell infiltration and collagen deposition suggestive of long-term cardiac scarring. Bacterial translocation into the heart tissue required the pneumococcal adhesin CbpA and the host ligands Laminin receptor (LR) and Platelet-activating factor receptor. Immunization of mice with a fusion construct of CbpA or the LR binding domain of CbpA with the pneumolysin toxoid L460D protected against microlesion formation. We conclude that microlesion formation may contribute to the acute and long-term adverse cardiac events seen in humans with IPD.

Association of Statin Therapy and Risks of Cholelithiasis, Biliary Tract Diseases, and Gallbladder Procedures: Retrospective Cohort Analysis of a US Population.

BACKGROUND: Gallstone disease is a leading cause of morbidity in Western countries and carries a high economic burden. Statin medications decrease hepatic cholesterol biosynthesis and may, therefore, lower the risk of cholesterol cholelithiasis by reducing the cholesterol concentration in the bile. Population-based evidence, however, is sparse. OBJECTIVE: To assess the risk of gallbladder diseases among statin users compared with nonusers in an American patient cohort. METHODS: We performed a retrospective cohort study of patients enrolled in the San Antonio Tricare health system using data between October 2003 and March 2012. We defined 2 groups: statin users (use for 90 days or greater) and nonusers (no prior statin). A propensity score based on 82 variables was generated to match statin users and nonusers 1:1. Outcomes included incidence of cholelithiasis, biliary tract diseases, and gallbladder procedures. RESULTS: A total of 43 438 patients were identified; 13 626 (31.4%) were statin users, and 29 812 (68.6%) were nonusers. We matched 6342 pairs of statin users and nonusers based on propensity score. The odds ratios (ORs) in statin users in comparison to nonusers were similar for cholelithiasis (OR = 0.86; 95% CI = 0.73, 1.02), biliary tract disease (OR = 0.85; 95% CI = 0.67-1.08), and gall bladder procedures (OR = 0.85; 95% CI = 0.69, 1.04). CONCLUSIONS: Statin use was not significantly associated with either an increased or decreased risk of cholelithiasis or gallbladder disease.

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.

A retrospective cohort study of comorbidity trajectories associated with traumatic brain injury in veterans of the Iraq and Afghanistan wars.

OBJECTIVES: To identify and validate trajectories of comorbidity associated with traumatic brain injury in male and female Iraq and Afghanistan war Veterans (IAV). METHODS: Derivation and validation cohorts were compiled of IAV who entered the Department of Veterans Affairs (VA) care and received 3 years of VA care between 2002-2011. Chronic disease and comorbidities associated with deployment including TBI were identified using diagnosis codes. A latent class analysis (LCA) of longitudinal comorbidity data was used to identify trajectories of comorbidity. RESULTS: LCA revealed five trajectories that were similar for women and men: (1) Healthy, (2) Chronic Disease, (3) Mental Health, (4) Pain and (5) Polytrauma Clinical Triad (PCT: pain, mental health and TBI). Two additional classes found in men were 6) Minor Chronic and 7) PCT with chronic disease. Among these gender-stratified trajectories, it was found that women were more likely to experience headache (Pain trajectory) and depression (Mental Health trajectory), while men were more likely to experience lower back pain (Pain trajectory) and substance use disorder (Mental Health trajectory). The probability of TBI was highest in the PCT-related trajectories, with significantly lower probabilities in other trajectories. CONCLUSIONS: It was found that TBI was most common in PCT-related trajectories, indicating that TBI is commonly comorbid with pain and mental health conditions for both men and women. The relatively young age of this cohort raises important questions regarding how disease burden, including the possibility of neurodegenerative sequelae, will accrue alongside normal age-related decline in individuals with TBI. Additional 'big data' methods and a longer observation period may allow the development of predictive models to identify individuals with TBI that are at-risk for adverse outcomes.

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.

Risk factors and antibiotic therapy in P. aeruginosa community-acquired pneumonia.

BACKGROUND AND OBJECTIVE: Current guidelines recommend empirical treatment against Pseudomonas aeruginosa in community-acquired pneumonia (CAP) patients with specific risk factors. However, evidence to support these recommendations is limited. We evaluate the risk factors and the impact of antimicrobial therapy in patients hospitalized with CAP due to P. aeruginosa. METHODS: We performed a retrospective population-based study of >150 hospitals. Patients were included if they had a diagnosis of CAP and P. aeruginosa was identified as the causative pathogen. Univariate and multivariate analyses were performed using the presence of risk factors and 30-day mortality as the dependent measures. RESULTS: Seven hundred eighty-one patients with P. aeruginosa pneumonia were identified in a cohort of 62 689 patients with pneumonia (1.1%). Of these, 402 patients (0.6%) were included in the study and 379 (0.5%) were excluded due to health care-associated pneumonia or immunosuppression. In patients with CAP due to P. aeruginosa, 272 (67.8%) had no documented risk factors. These patients had higher rates of dementia and cerebrovascular disease. Empirical antibiotic therapy against P. aeruginosa within the first 48 h of presentation was independently associated with lower 30-day mortality in patients with CAP due to P. aeruginosa (hazard ratio (HR) 0.42, 95% confidence interval (CI): 0.23-0.76) and in patients without risk factors for P. aeruginosa CAP (HR 0.40, 95% CI: 0.21-0.76). CONCLUSIONS: Risk factor recommended by current guidelines only detect one third of the patients admitted with CAP due to P. aeruginosa. Risk factors did not define the whole benefit observed due to empirical therapy covering P. aeruginosa.

Association of skeletal muscle relaxers and antihistamines on mortality, hospitalizations, and emergency department visits in elderly patients: a nationwide retrospective cohort study.

BACKGROUND: High-risk medication exposure in the elderly is common and associated with increased mortality, hospitalizations, and emergency department (ED) visits. Skeletal muscle relaxants and antihistamines are high-risk medications commonly prescribed in elderly patients. The objective of this study was to determine the association between skeletal muscle relaxants or antihistamines and mortality, hospitalizations, and emergency department visits. METHODS: This study used a new-user, retrospective cohort design using national Veteran Affairs (VA) data from 128 hospitals. Veterans ≥65 years of age on October 1, 2005 who received VA inpatient/outpatient care at least once in each of fiscal year (FY) 2005 and FY 2006 were included. Exposure to skeletal muscle relaxants and antihistamines was defined by the National Committee for Quality Assurance Healthcare Effectiveness Data and Information Set measures for high-risk medications in the elderly. Primary outcomes identified within one year of exposure were death, ED visit, or hospitalization; ED visits or hospitalizations due to falls and fracture were also assessed. Propensity score matching (1 to 1 match) was used to balance covariates between exposed patients and non-exposed patients. RESULTS: In this cohort of 1,807,404 patients 55,566 patients were included in the propensity-matched cohort for skeletal muscle relaxants and 60,058 patients were included in the propensity-matched cohort for anti-histamines. Mortality was lower in skeletal muscle relaxants-exposed patients (adjusted odds ratio [AOR] 0.87, 95% CI 0.81-0.94), but risk of emergency care (AOR 2.25, 95% CI 2.16-2.33) and hospitalization (AOR 1.56, 95% CI 1.48-1.65) was higher for patients prescribed skeletal muscle relaxants. Similar findings were observed for emergency and hospital care for falls or fractures. Mortality (AOR 1.93, 95% CI 1.82-2.04), ED visits (AOR 2.35, 95% CI 2.27-2.43), and hospitalizations (AOR 2.21, 95% CI 2.11-2.32) were higher in the antihistamine-exposed group, with similar findings for falls and fractures outcomes. CONCLUSION: Skeletal muscle relaxants and antihistamines are associated with an increased risk of ED visits and hospitalizations in elderly patients. Antihistamines were also associated with an increased risk of death, further validating the classification of these drug classes as "high risk".

Serious mental illnesses associated with receipt of surgery in retrospective analysis of patients in the Veterans Health Administration.

BACKGROUND: The STOPP study (Surgical Treatment Outcomes for Patients with Psychiatric Disorders) analyzed variation in rates and types of major surgery by serious mental illness status among patients treated in the Veterans Health Administration (VA). VA patients are veterans of United States military service who qualify for federal care by reason of disability, special service experiences, or poverty. METHODS: STOPP conducted a secondary data analysis of medical record extracts for seven million VA patients treated Oct 2005-Sep 2009. The retrospective study aggregated inpatient surgery events, comorbid diagnoses, demographics, and postoperative 30-day mortality. RESULTS: Serious mental illness -- schizophrenia, bipolar disorder, posttraumatic stress disorder, or major depressive disorder, was identified in 12 % of VA patients. Over the 4-year study period, 321,131 patients (4.5 %) underwent surgery with same-day preoperative or immediate post-operative admission including14 % with serious mental illness. Surgery patients were older (64 vs. 61 years) and more commonly African-American, unmarried, impoverished, highly disabled (24 % vs 12 % were Priority 1), obese, with psychotic disorder (4.3 % vs 2.9 %). Among surgery patients, 3.7 % died within 30 days postop. After covariate adjustment, patients with pre-existing serious mental illness were relatively less likely to receive surgery (adjusted odds ratios 0.4-0.7). CONCLUSIONS: VA patients undergoing major surgery appeared, in models controlling for comorbidity and demographics, to disproportionately exclude those with serious mental illness. While VA preferentially treats the most economically and medically disadvantaged veterans, the surgery subpopulation may be especially ill, potentially warranting increased postoperative surveillance.

Prior cardiovascular disease increases long-term mortality in COPD patients with pneumonia.

There is controversy regarding the impact of chronic obstructive pulmonary disease (COPD) in clinical outcomes in elderly patients with pneumonia. Comorbidities such as cardiovascular disease have been reported to play an important role in patients with acute exacerbations of COPD. However, limited data are available regarding the impact of cardiovascular disease in elderly COPD patients who require hospitalisation for pneumonia. We examined a cohort of subjects with pneumonia and pre-existing COPD. Prior cardiovascular disease was defined as history of myocardial infarction, congestive heart failure, cardiac arrhythmia, unstable angina or stroke. Outcomes examined included 30-day, 90-day, 6-month and 1-year mortality. We included 17,140 elderly COPD patients who were hospitalised for pneumonia. Prior cardiovascular disease was present in 10 240 (59.7%) patients. Prior cardiovascular disease was independently associated with 90-day mortality (21.3% versus 19.4%; hazard ratio (HR) 1.29, 95% CI 1.02-1.17), 6-month mortality (29.0% versus 26.1%; HR 1.28, 95% CI 1.07-1.50) and 12-month mortality (39.2% versus 34.5%; HR 1.33, 95% CI 1.15-1.54) when compared to no prior cardiovascular disease. The temporal differential effect between groups increases from 1.0% at 30 days to 4.7% at 1 year. Prior cardiovascular disease is associated with increased long-term mortality in elderly COPD patients with pneumonia. Differences in mortality rates increased over time.