Frequency Of Development Of Connective Tissue Disease In Statin-Users Versus Nonusers

Statins have pleiotropic properties that may affect the development of connective tissue diseases (CTD). The objective of this study was to compare the risk of CTD diagnoses in statin users and nonusers. This study was a propensity score-matched analysis of adult patients (30 to 85 years old) in the San Antonio military medical community. The study was divided into baseline (October 1, 2003 to September 30, 2005), and follow-up (October 1, 2005 to March 5, 2010) periods. Statin users received a statin prescription during fiscal year 2005. Nonusers did not receive a statin at any time during the study. The outcome measure was the occurrence of 3 diagnosis codes of the International Classification of Diseases, 9th Revision, Clinical Modification consistent with CTD. We described co-morbidities during the baseline period using the Charlson Comorbidity Index. We created a propensity score based on 41 variables. We then matched statin users and nonusers 1:1, using a caliper of 0.001. Of 46,488 patients who met study criteria (13,640 statin users and 32,848 nonusers), we matched 6,956 pairs of statin users and nonusers. Matched groups were similar in terms of patient age, gender, incidence of co-morbidities, total Charlson Comorbidity Index, health care use, and medication use. The odds ratio for CTD was lower in statin users than nonusers (odds ratio: 0.80; 95% confidence interval: 0.64 to 0.99; p = 0.05). Secondary analysis and sensitivity analysis confirmed these results. In conclusion, statin use was associated with a lower risk of CTD. Published by Elsevier Inc.Pharmac

Non-unique factorization of polynomials over residue class rings of the integers

We investigate non-unique factorization of polynomials in Z_{p^n}[x] into irreducibles. As a Noetherian ring whose zero-divisors are contained in the Jacobson radical, Z_{p^n}[x] is atomic. We reduce the question of factoring arbitrary non-zero polynomials into irreducibles to the problem of factoring monic polynomials into monic irreducibles. The multiplicative monoid of monic polynomials of Z_{p^n}[x] is a direct sum of monoids corresponding to irreducible polynomials in Z_p[x], and we show that each of these monoids has infinite elasticity. Moreover, for every positive integer m, there exists in each of these monoids a product of 2 irreducibles that can also be represented as a product of m irreducibles.Comment: 11 page

Micafungin in the treatment of invasive candidiasis and invasive aspergillosis

Micafungin is an echinocandin antifungal agent available for clinical use in Japan, Europe, and the United States. Through inhibition of β-1,3-glucan production, an essential component of the fungal cell wall, micafungin exhibits potent antifungal activity against key pathogenic fungi, including Candida and Aspergillus species, while contributing minimal toxicity to mammalian cells. This activity is maintained against polyene and azole-resistant isolates. Pharmacokinetic and pharmacodynamic studies have demonstrated linear kinetics both in adults and children with concentration-dependent activity observed both in vitro and in vivo. Dosage escalation studies have also demonstrated that doses much higher than those currently recommended may be administered without serious adverse effects. Clinically, micafungin has been shown to be efficacious for the treatment of invasive candidiasis and invasive aspergillosis. Furthermore, the clinical effectiveness of micafungin against these infections occurs without the drug interactions that occur with the azoles and the nephrotoxicity observed with amphotericin B formulations. This review will focus on the pharmacology, clinical microbiology, mechanisms of resistance, safety, and clinical efficacy of micafungin in the treatment of invasive candidiasis and invasive aspergillosis

Delirium Associations With Antibiotics: A Pharmacovigilance Study of the FDA Adverse Event Reporting System (FAERS)

Background Ertapenem, cefepime, imipenem, ofloxacin, ceftazidime, clarithromycin, cefaclor, levofloxacin, linezolid, moxifloxacin, azithromycin, piperacillin-tazobactam, trimethoprim-sulfamethoxazole, metronidazole, ciprofloxacin, and cefuroxime are known to be associated with delirium. Other antibiotics may also lead to delirium, but no study has systemically compared delirium associations for many available antibiotics. Objective The objective of this study was to evaluate the association between delirium and antibiotics using the FDA Adverse Event Reporting System (FAERS). Methods FAERS reports from January 1, 2004 to December 31, 2018 were included in the study. Reporting odds ratios (RORs) and corresponding 95% confidence intervals (95% CI) for the association between antibiotics and delirium were calculated. 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 10,015,622 reports (including 16,982 delirium reports) were considered, after inclusion criteria were applied. Statistically significant delirium RORs (95% CI) for antibiotics were: ertapenem 21.07 (16.38-27.10), cefepime 9.8 (6.37-15.09), imipenem 9.68 (6.75-13.89), ofloxacin 7.73 (4.00-14.92), ceftazidime 6.09 (2.73-13.62), clarithromycin 5.34 (4.37-6.53), cefaclor 5.32 (1.71-16.58), ampicillin-sulbactam 4.49 (2.13-9.45), levofloxacin 4.47 (3.88-5.16), linezolid 4.33 (3.28-5.72), moxifloxacin 3.51 (2.81-4.38), azithromycin 2.76 (2.09-3.64), piperacillin-tazobactam 2.41 (1.47-3.93), trimethoprim-sulfamethoxazole 2.36 (1.61-3.47), metronidazole 1.85 (1.31-2.60), ciprofloxacin 1.83 (1.44-2.33), and cefuroxime 1.81 (1.03-3.20). Conclusion This study found statistically significant increased risk of reporting delirium with ertapenem, cefepime, imipenem, ofloxacin, ceftazidime, clarithromycin, cefaclor, ampicillin-sulbactam, levofloxacin, linezolid, moxifloxacin, azithromycin, piperacillin-tazobactam, trimethoprim-sulfamethoxazole, metronidazole, ciprofloxacin, and cefuroxime

Brief Overview of Approaches and Challenges in New Antibiotic Development: A Focus On Drug Repurposing

Drug repurposing, or identifying new uses for existing drugs, has emerged as an alternative to traditional drug discovery processes involving de novo synthesis. Drugs that are currently approved or under development for non-antibiotic indications may possess antibiotic properties, and therefore may have repurposing potential, either alone or in combination with an antibiotic. They might also serve as “antibiotic adjuvants” to enhance the activity of certain antibiotics

Non-invasive mechanical ventilation and mortality in elderly immunocompromised patients hospitalized with pneumonia: a retrospective cohort study

Christopher S. Johnson and Eric M. Mortensen are with the University of Texas Southwestern Medical Center and the VA North Texas Health Care System, Dallas VA Medical Center -- Christopher R. Frei and Antonio R. Anzueto are with the South Texas Veterans Health Care System and the University of Texas Health Science Center at San Antonio -- Christopher R. Frei is with the University of Texas at Austin, -- Mark L Metersky is with the University of Connecticut School of MedicineBackground: Mortality after pneumonia in immunocompromised patients is higher than for immunocompetent patients. The use of non-invasive mechanical ventilation for patients with severe pneumonia may provide beneficial outcomes while circumventing potential complications associated with invasive mechanical ventilation. The aim of our study was to determine if the use of non-invasive mechanical ventilation in elderly immunocompromised patients with pneumonia is associated with higher all-cause mortality. Methods: In this retrospective cohort study, data were obtained from the Department of Veterans Affairs administrative databases. We included veterans age ≥65 years who were immunocompromised and hospitalized due to pneumonia. Multilevel logistic regression analysis was used to determine the relationship between the use of invasive versus non-invasive mechanical ventilation and 30-day and 90-day mortality. Results: Of 1,946 patients in our cohort, 717 received non-invasive mechanical ventilation and 1,229 received invasive mechanical ventilation. There was no significant association between all-cause 30-day mortality and non-invasive versus invasive mechanical ventilation in our adjusted model (odds ratio (OR) 0.85, 95% confidence interval (CI) 0.66-1.10). However, those patients who received non-invasive mechanical ventilation had decreased 90-day mortality (OR 0.66, 95% CI 0.52-0.84). Additionally, receipt of guideline-concordant antibiotics in our immunocompromised cohort was significantly associated with decreased odds of 30-day mortality (OR 0.31, 95% CI 0.24-0.39) and 90-day mortality (OR 0.41, 95% CI 0.31-0.53). Conclusions: Our findings suggest that physicians should consider the use of non-invasive mechanical ventilation, when appropriate, for elderly immunocompromised patients hospitalized with [email protected]

Brief Overview of Approaches and Challenges in New Antibiotic Development: A Focus on Drug Repurposing

Drug repurposing, or identifying new uses for existing drugs, has emerged as an alternative to traditional drug discovery processes involving de novo synthesis. Drugs that are currently approved or under development for non-antibiotic indications may possess antibiotic properties, and therefore may have repurposing potential, either alone or in combination with an antibiotic. They might also serve as “antibiotic adjuvants” to enhance the activity of certain antibiotics

Antibiotic prescribing by age, sex, race, and ethnicity for patients admitted to the hospital with community-acquired bacterial pneumonia (CABP) in the All of Us database

Abstract Purpose: To assess the proportion of inpatients who received guideline-concordant antibiotics for community-acquired bacterial pneumonia (CABP) in special populations of the All of Us database. Background: CABP contributes significantly to healthcare burden worldwide. The American Thoracic Society and Infectious Disease Society of America jointly published guidelines for the treatment of CABP. Guideline-concordant antibiotics for CABP are associated with better patient and cost outcomes. Methods: This was a retrospective cohort study of patients with pneumonia (n = 1608; SNOMED 233604007) from 10/1/2018 to 1/01/22 in the All of Us database. Cases were excluded for treatment setting other than inpatient, prior (within 90 days) pneumonia, receipt of intravenous antibiotics, respiratory isolation of methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa, and/or other non-community-acquired types of pneumonia. Patients were grouped based on patient age, sex, race, and ethnicity. The proportion of patients on guideline-concordant therapy was compared within groups using chi-square statistics. Significant associations were assessed using multivariate logistic regression models. Results: A total of 1608 cases were included, and 45% of these patients received guideline-concordant antibiotics. Non-Hispanic White (NHW) patients vs. Black patients were associated with a 36% higher likelihood for receiving guideline-concordant antibiotics (adjusted OR, 1.36; 95% CI 1.02–1.81), whereas NHW vs. Hispanic patients were associated with a 34% lower likelihood for receiving guideline-concordant antibiotics (aOR 0.66; 0.48–0.91). Conclusion: Black patients with CABP in the All of Us database were less likely to receive guideline-concordant antibiotics, and Hispanic patients were more likely to receive guideline-concordant antibiotics, than NHW patients

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