Comparison of real-world clinical and economic outcomes in patients receiving oral anticoagulants: A retrospective claims analysis.

BACKGROUND: Direct oral anticoagulants (DOACs) have become widely used for the prevention of stroke in nonvalvular atrial fibrillation (AF) and for the treatment of venous thromboembolism (VTE). Warfarin, the standard of care prior to DOACs, requires monitoring and dose adjustment to ensure patients remain appropriately anticoagulated. DOACs do not require monitoring but are significantly more expensive. We sought to examine real-world effectiveness and costs of DOACs and warfarin in patients with AF and VTE. OBJECTIVE: To examine clinical and economic outcomes. The clinical objectives were to determine the bleeding and thrombotic event rates associated with DOACs vs warfarin. The economic objectives were to determine the cost associated with these events, as well as the all-cause medical and pharmacy costs associated with DOACs vs warfarin. METHODS: This analysis was an observational, propensity-matched comparison of retrospective medical and pharmacy claims data for members enrolled in an integrated health plan between October 1, 2015, and September 30, 2020. Members who were older than 18 years of age with at least 1 30-day supply of warfarin or a DOAC filled within 30 days of a new diagnosis of VTE or nonvalvular AF were eligible for the analysis. Cox hazard ratios were used to compare differences in clinical outcomes, where paired t-tests were used to evaluate economic outcomes. RESULTS: After matching, there were 893 patients in each group. Among matched members, warfarin was associated with increased risk of nonmajor bleeds relative to apixaban (hazard ratio [HR] = 1.526; P = 0.0048) and increased risk of pulmonary embolism relative to both DOACs (apixaban: HR = 1.941 [P = 0.0328]; rivaroxaban: HR = 1.833 [P = 0.0489]). No statistically significant difference was observed in hospitalizations or in length of stay between warfarin and either DOAC. The difference-in-difference (DID) in total costs of care per member per month for apixaban and rivaroxaban relative to warfarin were $801.64 (P = 0.0178) and $534.23 (P = 0.0998) more, respectively. DID in VTE-related cost for apixaban was $177.09 less, relative to warfarin (P = 0.0098). DID in all-cause pharmacy costs for apixaban and rivaroxaban relative to warfarin were $342.47 (P < 0.0001) and $386.42 (P < 0.001) more, respectively. CONCLUSIONS: Warfarin use was associated with a significant decrease in total cost of care despite a significant increase in VTE-related costs vs apixaban. Warfarin was also associated with a significant increase in other nonmajor bleeds relative to apixaban, as well as a significant increase in pulmonary embolism relative to both DOACs. Warfarin was associated with a significant reduction in all-cause pharmacy cost compared with either DOAC. DISCLOSURES: The authors of this study have nothing to disclose.

Factors associated with ciprofloxacin-resistant Escherichia coli urinary tract infections in discharged ED patients.

BACKGROUND: We sought to identify factors associated with Escherichia coli resistance to ciprofloxacin among discharged emergency department (ED) patient visits treated for a urinary tract infection (UTI). We hypothesized that specific historical factors available upon ED presentation would be associated with increased odds of ciprofloxacin resistance in this population. METHODS: We conducted a retrospective, observational cohort study of consecutive discharged adult ED patient visits with a primary diagnosis of UTI caused by E coli to a single center from 2011 to 2014. Two investigators separately abstracted to a preconstructed data collection form the following independent variables on each included visit: patient age, sex, residence, active immunosuppressive condition or medication, chronic indwelling Foley catheter, hospitalization or antibiotic use within 90 days prior to presentation, and history of recurrent UTIs. We used multivariable logistic regression after taking into account colinearity to identify those independent variables associated with increased odds of ciprofloxacin resistance and report descriptive characteristics of the study cohort, odds ratios (ORs) with 95% confidence interval (CI) and model strength. RESULTS: Age at least 65 years (OR, 3.15; 95% CI, 1.44-6.87; P=.004), recurrent UTI (OR, 6.23; 95% CI, 2.38-16.30; P<.001), and recent hospitalization (OR, 3.99; 95% CI, 1.56-10.23; P=.004) were significantly associated with ciprofloxacin-resistant E coli UTIs in relevant visits. CONCLUSION: In this single-center study, age at least 65 years, recurrent UTI, and recent hospitalization were most clearly associated with increased odds of ciprofloxacin-resistant UTIs in discharged adult ED patient visits. If validated, these factors should suggest that alternative antimicrobial agents should be considered in the treatment of this condition among discharged adult ED patients.

High frequency of nonadherence to Clostridium difficile treatment guidelines.

OBJECTIVES: The 2010 Infectious Diseases Society of America/Society for Healthcare Epidemiology of America treatment guidelines for Clostridium difficile infections (CDI) recommend oral metronidazole for mild-to-moderate disease and oral vancomycin for severe disease. Given that disease severity is easily determined by the peripheral white blood cell count and serum creatinine level, a computerized decision support (CDS) pathway to guide treatment is inherently appealing. Because providers often override or ignore the computer-based alerts, the proposed CDS pathway should be justified before implementation. METHODS: We undertook this study to ascertain the frequency of nonadherence to CDI guidelines. Between October 1, 2007 and September 30, 2008, a total of 229 cases were screened and 78 cases were included in the study, which took place at a 661-bed acute tertiary care teaching hospital. RESULTS: During the year-long study of CDI cases at our tertiary care hospital, 61.5% (48/78) of the patients received an antibiotic regimen that was not recommended by the 2010 guidelines. Among the 35 patients with mild-to-moderate CDI, 85.7% (30/35) received the recommended treatment of oral metronidazole monotherapy; in contrast, among the 43 patients with severe disease, none (0/43) received the recommended treatment of oral vancomycin monotherapy (P < 0.01). Moreover, 17.9% (14/78) of patients received concurrent oral metronidazole and vancomycin, a regimen that is not recommended anywhere in the Infectious Diseases Society of America/Society for Healthcare Epidemiology of America guidelines and which may be associated with a poor outcome. Patients who received combination oral metronidazole and vancomycin were not more likely to have comorbidities or severe CDI compared with those who received a single antibiotic agent. CONCLUSIONS: As a result of this study, we plan to educate our providers on the treatment of CDI through a CDS pathway in an effort to increase guideline adherence, decrease inappropriate antibiotic use, and potentially improve patient outcomes.

Pharmacist addition to the post-ED visit review of discharge antimicrobial regimens.

OBJECTIVE: Our objective was to evaluate whether pharmacist addition to the postvisit review of discharged adult emergency department (ED) visits' prescriptions/cultures would reduce the prevalence of revised antimicrobial regimen inappropriateness. METHODS: We conducted a retrospective observational study of discharged adult ED visits to a single center with positive cultures requiring antimicrobial regimen revision (May 1 to October 31, 2012, nurse process; February 1 to July 31, 2013, nurse/pharmacist process). Investigators abstracted cohorts' medical records for demographic, ED diagnosis, original/revised antibiotic regimen, culture result, medical history, medications, and patient instruction data and determined whether the revised regimen was inappropriate based on Infectious Diseases Society of America/Centers for Disease Control and Prevention and clinical guidelines. We used the large sample z-test to compare the prevalence of revised antimicrobial regimen inappropriateness between the 2 cohorts. RESULTS: In the prepharmacist cohort, there were 411 positive ED discharge cultures. Seventy-three (17.8%; 95% confidence interval [CI], 14.1%-21.5%) required antimicrobial regimen revision; 34 of these met 1 or more level of inappropriateness (46.6%; 95% CI, 35.1%-58.0%). In the postpharmacist cohort, there were 459 positive ED discharge cultures. Seventy-five (16.3%; 95% CI, 13.0%-19.7%) required revision; 11 of these met 1 or more level of inappropriateness (14.7%; 95% CI, 6.7%-22.7%; z = 4.2; P < .0001 for comparison). CONCLUSION: In this single-center study, pharmacist addition to the postvisit review of discharged adult ED patients' prescriptions/cultures reduced the prevalence of revised antimicrobial regimen inappropriateness.

Macroglobulin complement-related encodes a protein required for septate junction organization and paracellular barrier function in Drosophila.

Polarized epithelia play crucial roles as barriers to the outside environment and enable the formation of specialized compartments for organs to carry out essential functions. Barrier functions are mediated by cellular junctions that line the lateral plasma membrane between cells, principally tight junctions in vertebrates and septate junctions (SJs) in invertebrates. Over the last two decades, more than 20 genes have been identified that function in SJ biogenesis in Drosophila, including those that encode core structural components of the junction such as Neurexin IV, Coracle and several claudins, as well as proteins that facilitate the trafficking of SJ proteins during their assembly. Here we demonstrate that Macroglobulin complement-related (Mcr), a gene previously implicated in innate immunity, plays an essential role during embryonic development in SJ organization and function. We show that Mcr colocalizes with other SJ proteins in mature ectodermally derived epithelial cells, that it shows interdependence with other SJ proteins for SJ localization, and that Mcr mutant epithelia fail to form an effective paracellular barrier. Tissue-specific RNA interference further demonstrates that Mcr is required cell-autonomously for SJ organization. Finally, we show a unique interdependence between Mcr and Nrg for SJ localization that provides new insights into the organization of the SJ. Together, these studies demonstrate that Mcr is a core component of epithelial SJs and also highlight an interesting relationship between innate immunity and epithelial barrier functions.

Biomechanical evaluation of the docking plus ulnar collateral ligament reconstruction technique compared with the docking technique.

BACKGROUND: Surgical techniques for ulnar collateral ligament (UCL) reconstruction have evolved since first described by Jobe. A modified reconstruction technique has been developed, called the docking plus technique, and the authors biomechanically compared it to the commonly performed docking technique. HYPOTHESIS: The docking plus technique for UCL reconstruction will demonstrate greater ligament stiffness than the docking technique. STUDY DESIGN: Controlled laboratory study. METHODS: Ten matched pairs of human cadaveric specimens (mean age ± SD, 52 ± 6 years) were loaded to failure at an elbow flexion angle of 30° at a compressive rate of 14 mm/s. The specimens underwent reconstruction with an autologous graft using the docking plus or docking technique. The reconstructed and native specimens were loaded to failure at the same parameters. RESULTS: The most common mode of failure in the native UCL was midsubstance rupture and avulsion from the ulnar ligament insertion, while the docking plus group failed by suture rupture and the docking group by suture pullout and midsubstance rupture. The mean ± SD stiffness of the native UCL was 21.0 ± 9.0 N/mm, docking plus technique was 11.2 ± 6.6 N/mm, and docking technique was 5.3 ± 1.5 N/mm. The mean stiffness of the docking plus reconstruction was statistically greater (P = .004) than that of the docking technique. The mean ± SD ultimate moment for the native UCL was 35.0 ± 14.0 N·m, docking plus technique was 20.6 ± 7.3 N·m, and docking technique was 8.6 ± 5.1 N·m. The moment across the elbow joint at failure of the docking plus reconstruction was statistically greater (P = .002) than that of the docking technique. CONCLUSION: The docking plus technique reproduces greater ligament stiffness and demonstrates a higher failure moment immediately after reconstruction than does the docking technique. CLINICAL RELEVANCE: The docking plus technique allows greater stiffness and a higher moment to failure immediately after reconstruction and describes a way to maintain constant graft tension during fixation, resulting in a biomechanically stronger UCL reconstruction.

Pharmacotherapy for acute heart failure syndromes.

PURPOSE: Drug therapies for patients with acute heart failure syndromes (AHFS) are reviewed, including clinical practice guideline recommendations for the treatment of hospitalized patients with heart failure (HF). SUMMARY: AHFS may be defined as new-onset, gradual, or rapidly worsening HF signs and symptoms that require urgent therapy. Clinical practice guidelines from the American College of Cardiology Foundation-American Heart Association, Heart Failure Society of America, and European Society of Cardiology offer recommendations for the management of AHFS, addressing the role of diuretics, vasodilators, and inotropes. The guidelines emphasize the utility of vasodilators for patients with signs and symptoms of pulmonary congestion, including pulmonary edema or severe hypertension or both, who have not responded to diuretics. The early initiation of vasoactive medications, including diuretics and vasodilators, has been linked to improved outcomes in some reports. Conversely, the use of inotropes is de-emphasized, particularly as part of the routine management of these patients. Newer agents, including vasopressin antagonists, have also been approved recently but are not addressed by the clinical practice guidelines. The guidelines address the importance of initiating and optimizing evidence-based oral medications for long-term use, including angiotensin-converting-enzyme (ACE) inhibitors, angiotensin-receptor blockers, ß-blockers, and aldosterone antagonists, during the patient's hospital stay in an effort to address long-term outcomes. CONCLUSION: Drug therapy of AHFS may include diuretics, vasodilators, morphine, ACE inhibitors, digoxin, inotropes, and vasopressin antagonists. Clinical practice guidelines for patients with AHFS provide a useful mechanism to incorporate available evidence and standards of practice into patient care.

Postnatal growth of the clavicle: birth to 18 years of age.

BACKGROUND: The purpose of our study was to perform a large cross-sectional study aimed at determining the postnatal growth pattern of the clavicle from birth to 18 years of age. METHODS: We analyzed the digital chest radiographs of a convenience sample of 961 individuals between birth and 18 years of age. Malrotated radiographs were excluded. Right and left clavicle lengths were measured in millimeters from the most lateral ossified border to the most medial ossified border of each clavicle. Study patients were divided into 19 subgroups with the first group being labeled as "birth to 11 months of age" followed by 1-year-olds, 2-year olds, etc. Patients were also grouped by sex. There was a minimum of 25 patients in each group. RESULTS: At 18 years of age the mean+/-SD clavicle length for females was 149+/-12 mm and for males it was 161+/-11 mm. Although a statistically significant difference (P=0.049) was noted between the length of right and left clavicles it was not clinically significant (0.036 mm). A steady growth rate was noted for both genders from birth to the age of 12 years (8.4 mm/y). Above the age of 12 years there were significant differences in the growth of the clavicles of girls (2.6 mm/y) versus boys (5.4 mm/y) (P<0.001). Our data suggest that females achieve 80% of their clavicle length by 9 years of age and boys by 12 years of age. CONCLUSION: This cross-sectional study establishes that relatively little clavicle growth (20%) remains for girls beyond age 9 years and for boys beyond 12 years. The length of one clavicle may be properly judged by comparing it with the contralateral clavicle. CLINICAL RELEVANCE: Remodeling of the clavicle shaft fractures is currently believed to be proportional to remaining growth. Our study questions the capacity of the clavicle to re-establish normal length beyond the age thresholds we have identified.