Estimating local extinction rates over successive time-frames

Blood culture contamination is a common problem in the emergency department (ED) that leads to unnecessary patient morbidity and health care costs. The study objective was to develop and evaluate the effectiveness of a quality improvement (QI) intervention for reducing blood culture contamination in an ED. The authors developed a QI intervention to reduce blood culture contamination in the ED and then evaluated its effectiveness in a prospective interrupted times series study. The QI intervention involved changing the technique of blood culture specimen collection from the traditional clean procedure to a new sterile procedure, with standardized use of sterile gloves and a new materials kit containing a 2% chlorhexidine skin antisepsis device, a sterile fenestrated drape, a sterile needle, and a procedural checklist. The intervention was implemented in a university-affiliated ED and its effect on blood culture contamination evaluated by comparing the biweekly percentages of blood cultures contaminated during a 48-week baseline period (clean technique) and 48-week intervention period (sterile technique), using segmented regression analysis with adjustment for secular trends and first-order autocorrelation. The goal was to achieve and maintain a contamination rate below 3%. During the baseline period, 321 of 7,389 (4.3%) cultures were contaminated, compared to 111 of 6,590 (1.7%) during the intervention period (p < 0.001). In the segmented regression model, the intervention was associated with an immediate 2.9% (95% confidence interval [CI] = 2.2% to 3.2%) absolute reduction in contamination. The contamination rate was maintained below 3% during each biweekly interval throughout the intervention period. A QI assessment of ED blood culture contamination led to development of a targeted intervention to convert the process of blood culture collection from a clean to a fully sterile procedure. Implementation of this intervention led to an immediate and sustained reduction of contamination in an ED with a high baseline contamination rate.

Rationale : Benralizumab has been shown to reduce asthma exacerbations among patients with severe asthma within a clinical trial setting. However there is a dearth of health outcomes data as it pertains to benralizumab adherence. This purpose of study was to examine the relationship between benralizumab adherence, asthma exacerbations, and costs among patients with a diagnosis of severe asthma newly initiating benralizumab in a real-world setting. Methods: This study was a retrospective database analysis of the MORE2 Registry® of commercial, Medicare Advantage, and Managed Medicaid claims, along with the 100% Medicare Fee-for-Service claims databases spanning 2017-2022. Inclusion criteria: 1) prescription claim for benralizumab and ≥1 refill within 90 days (earliest prescription claim=index date), 2) 12 months of health plan enrollment preceding (baseline) and following (follow-up) the index date, 3) ≥1 inpatient or ≥2 outpatient claims with a diagnosis code for asthma during the baseline period, and 4) presence of ≥2 asthma exacerbations during the baseline period. Patients were classified as adherent vs. non-adherent to benralizumab based on the number of treatment claims appearing during follow-up (6+ vs. &amp;lt; 6 benralizumab claims). Asthma exacerbations were assessed during the baseline and follow-up periods, and were defined as any of the following: 1) asthma-related hospitalization, 2) outpatient asthma visit accompanied by a filled prescription for an oral corticosteroid within 7 days, or 3) treatment with mechanical ventilation. Percent change in exacerbation rates and exacerbation related costs were assessed from the baseline to follow-up among the adherence cohorts, with paired t-tests used to examine statistically significant differences across periods. Results: A total of 7,706 patients were included in the study; of these, n=6,067 were classified as adherent (78.7%). The mean±SD age of the sample was 59.8±17.1 years, with the majority being of female sex (n=5,350; 69.4%) and receiving Medicare Fee-for-Service benefits (n=4,213; 54.7%). Following initiation of benralizumab, the annual rate of asthma exacerbations decreased 45.2% for adherent patients, and 33.5% for non-adherent patients (p &amp;lt; 0.001; (Figure 1), while the proportion of patients with ≥4 exacerbations decreased 52.7 and 37.9% for the two cohorts, respectively. Total medical costs associated with exacerbations decreased 49.0% for the adherent cohort ($1,802 to $919; p &amp;lt; 0.001). Conclusion: Patients with severe asthma treated with benralizumab demonstrated meaningful reductions in the rate of asthma exacerbations and associated medical costs in a real-world setting. Promotion of treatment adherence is critical, as effects were strongest among patients who were adherent to therapy.

BackgroundPatients with severe asthma frequently have associated comorbidities, which can compound existing symptoms, complicating asthma management. ObjectiveTo describe the real-world effectiveness of mepolizumab in patients with severe asthma stratified by common overlapping comorbidities. MethodsThis was a retrospective analysis of patients with asthma from the MarketScan Commercial and Medicare Supplemental Database initiating mepolizumab treatment (index date). Eligible patients had more than or equal to 1 claim (excluding claims for diagnostic tests) with a diagnosis code for more than or equal to 1 of 7 comorbidities (atopic disease, nasal polyps, chronic sinusitis, obesity, respiratory infections, chronic obstructive pulmonary disease, and depression/anxiety) during the 12-month preindex baseline period; these were used to stratify patients into 7 nonmutually exclusive subgroups. Outcomes included asthma exacerbations and exacerbation-related health care resource utilization during the 12-month baseline and follow-up periods. Each patient acted as their own control. ResultsOf the 639 patients included, the most common comorbidities were atopic diseases (73.2%), respiratory infections (55.6%), and chronic sinusitis (45.1%). Across all 7 comorbidity subgroups, there were significant (P < .05) reductions of 38% to 55% and 57% to 83% in exacerbations and exacerbations requiring hospitalization, respectively, during the follow-up vs baseline period, except for exacerbations requiring hospitalization in the nasal polyp subgroup, owing to the small subgroup sample size. During the follow-up vs baseline periods, mean number of oral corticosteroids claims was significantly (P < .001) reduced by 29% to 38%; 39% to 47% of patients achieved greater than or equal to 50% oral corticosteroids dose reduction. Significant reductions in exacerbation-related health care resource utilization were also observed. ConclusionMepolizumab treatment provided real-world clinical benefits in patients.

Changes in the rate of protein synthesis during the cell cycle of Chlamydomonas reinhardi have been measured by determining changes in the separate rates of polypeptide chain initiation and elongation and in the rate of incorporation of a radioactive amino acid. The rate of polypeptide chain elongation, determined from the relative rates of labeling of two size classes of polyribosomes, varies only about twofold during the cell cycle. The rate of polypeptide chain initiation, determined from an analysis of the distribution of ribosomes in monoribosomes (and ribosomal subunits) and polyribosomes, varies more than 25-fold. Also, the overall rate of protein synthesis during the cell cycle varies to the same extent as the rate of chain initiation. Measurement of protein synthetic rates using incorporation of a radioactive amino acid ([3H]arginine) underestimates the actual change in the rate of protein synthesis during the cell cycle. The vast changes in the initiation rate during the cell cycle suggest a mechanism for selecting specific messenger RNAs for translation at different cell-cycle stages.

YANG ET AL. RESPOND

Background: Many women with endometriosis experience chronic abdominal pain. Clinical guidelines recommend treatment with analgesics, contraceptive hormones, gonadotropin-releasing hormone analogs, and surgery. Treatment patterns in women with endometriosis are not well characterized. Methods: Data from the IBM® MarketScan® Commercial Database were accessed from 2009 to 2017. One-year baseline and follow-up periods were defined around the date of the first claim with a diagnosis of endometriosis (the index date). Women 18-49 years of age on the index date with a diagnosis of endometriosis, continuous enrollment during baseline and follow-up, and pharmacy benefits were included. The following outcomes were analyzed descriptively: baseline comorbidities; medication use and surgeries; and sequence of treatment utilization in the baseline and the follow-up period. Results: A total of 190,921 women were included. The mean ± (standard deviation) age was 39.0 ± (7.3), and abdominal/pelvic pain (36.0%) and excessive or frequent menstruation (32.0%) were the most prevalent comorbidities. In the baseline period, the utilization of pharmacological treatment was: estrogen/progestin 42.5%, opioids 41.5%, and nonsteroidal anti-inflammatory drugs (NSAIDs) 37.5%. In the follow-up period, utilization of opioids and NSAIDs increased to 68.9% and 51.1%, respectively, whereas the use of estrogen/progestin dropped to 23.8%. Surgeries were infrequent in the baseline period (6.3%). However, in the follow-up period, 27.9% of women underwent laparoscopy and 29.7% had a hysterectomy, with a total of 68.1% of the study population undergoing surgical treatment. Conclusions: A diagnosis of endometriosis is accompanied by an increase in the use of analgesics and surgical procedures. The diversity of treatments suggests a lack of clarity in management guidelines.

BackgroundBelimumab, a B-lymphocyte stimulator, was FDA-approved March 2011 for the treatment of adult patients with active, autoantibody-positive SLE receiving standard of care medications. There is a need to evaluate belimumab's...

PRS29 EVALUATION OF THE REAL-WORLD INCREMENTAL COST BURDEN OF NEWLY TREATED PAH IN THE US

PMU5 IMPACT of Telehealth Utilization during the COVID-19 Pandemic on Health Care Resource Utilization

Background: In controlled clinical studies, mepolizumab has been shown to reduce exacerbation rates and the use of oral corticosteroids as well as improve asthma control and health-related quality of life compared with placebo in patients with severe eosinophilic asthma. However, real-world data on the impact of mepolizumab on clinical outcomes are limited. Objective: To evaluate the effect of mepolizumab on asthma exacerbations and asthma exacerbation-related costs in patients with severe asthma in U.S. clinical practice. Methods: This retrospective cohort study used U.S. administrative claims data from patients ages ≥12 years and with severe asthma at mepolizumab treatment initiation (index date; identification period, January 2015-June 2017) who had received two or more mepolizumab administrations within 180 days of the index date and had no evidence of treatment with another asthma biologic. The exacerbation rate and exacerbation-related costs were assessed in both the 12 months before mepolizumab initiation (baseline period) and the following 12 months (follow-up period). A clinical trial-like cohort was identified, defined as patients with two or more baseline exacerbations and ≥10 administrations during follow-up. Results: A total of 201 patients were included in the overall population and 74 patients in the clinical trial-like cohort. Mepolizumab significantly reduced the exacerbation rate between the baseline and follow-up periods in both the overall population and the clinical trial-like cohort (p < 0.001), which corresponded to 33.6% and 48.6% reductions, respectively. The rate of exacerbations in patients who required hospitalization between the baseline and follow-up periods was also reduced by 35.3% (p = 0.080) and 68.2% (p = 0.015) in the overall population and in the clinical trial-like cohort, respectively. Cost data were inconclusive. Conclusion: This study, which used real-world data, demonstrated that mepolizumab is associated with reductions in asthma exacerbations, in line with the findings from controlled clinical studies. These results provided further evidence of the effectiveness of mepolizumab in a real-world setting.

Using Lean Management to Reduce Blood Culture Contamination

Rationale : Currently, there is a single biologic approved for the treatment of COPD in the U.S. This real-world evidence study sought to evaluate the change in COPD exacerbations following initiation of benralizumab among patients with a diagnosis of asthma and concomitant COPD. Methods: This study was a retrospective database analysis of the MORE2 Registry® of commercial, Medicare Advantage, and Managed Medicaid claims, along with the 100% Medicare Fee-for-Service claims databases spanning 2017-2022. Inclusion criteria were as follows: 1) prescription claim for benralizumab and ≥1 refill within 90 days (earliest prescription claim=index date), 2) 12 months of health plan enrollment preceding (baseline) and following (follow-up) the index date, 3) diagnoses of both asthma and COPD, and 4) presence of ≥2 asthma exacerbations during the baseline period. COPD exacerbations were assessed during the baseline and follow-up periods, and were classified as either 1) moderate, defined as an outpatient COPD visit accompanied by a filled prescription for a course of theophylline, aminophylline, or an oral corticosteroid or oral antibiotic within 7 days of the outpatient visit, or 2) severe, defined as a COPD or related respiratory hospitalization. Percent change in annual moderate, severe, and total COPD exacerbation rates were assessed from the baseline to follow-up, with paired t-tests used to examine statistically significant differences across periods. Subgroup analyses were also conducted among the subset of patients with available blood eosinophil (bEOS) laboratory test result data. Results: A total of 2,894 patients with asthma and concomitant COPD were included in the study. Following initiation of benralizumab, the annual rate of total COPD exacerbations decreased 45.6% (3.6±2.5 to 2.0±2.2 exacerbations per year; p &amp;lt; 0.001), while the proportion of patients with ≥4 COPD exacerbations decreased from 43.0% during baseline to 19.0% during follow-up. Additionally, the total number of severe COPD exacerbations decreased 59.7% following the initiation of benralizumab from 0.16±0.55 to 0.07±0.33; p &amp;lt; 0.001 (see Figure 1). Subgroup analyses based on baseline bEOS groups revealed that greater reductions in total COPD exacerbations were observed post-benralizumab initiation among patients with higher bEOS levels (bEOS &amp;lt; 150/µL; 27.8%; bEOS 150-299/µL, 42.2%; bEOS ≥ 300 /µL, 50.8%). Conclusion: Patients with severe asthma and concomitant COPD treated with benralizumab demonstrated meaningful reductions in the rate of COPD exacerbations, inclusive of severe events, in a real-world setting. The largest reductions were observed among patients with the highest eosinophil levels.

Extinction in the Anthropocene.

test, after a five-minute period of rest, and after withdrawal of 250 ml. and of 500 ml. of blood. The entire phlebotomy was completed within ten minutes. Five minutes after the withdrawal of 500 ml., another electrocardiogram was taken; this was followed immediately by a repetition of the exercise test. Electrocardio­ grams were also taken immediately after the test and five minutes, 15 minutes, and 25 minutes after completion of the test, while the subject was at rest. At the same time blood was taken for determination of the hemoglobin and hema­ tocrit values, erythrocyte and leukocyte counts, concentration of total serum protein and albumin, and prothrombin time. These data were previously re­ ported. 4 In analyzing the electrocardiographic findings, particular attention was directed to changes in rate, alteration in the ST segment levels and T waves, as well as axis deviations in the four standard leads. Altogether 42 donors were tested, each having 10 electrocardiographic tracings, making a total of 420 ob­ servations. Results. No significant changes were found in the ST segments, T waves or axis alteration, which were not easily explained by change in the heart rate. A summary of the statistical analysis of the changes in rate is given in Table 1 The heart rate was significantly greater immediately following the post-phle­ botomy exercise test. Similarily at this time the ST and T wave changes related to the tachycardia were most marked. However, electrocardiographic tracings obtained after five minutes' rest following the post-phlebotomy exercise tolerance test showed a complete reversion of the rate and of the form of the ST segment and T wave to those obtained prior to the first test. When the changes in the heart rates were subjected to statistical analysis, significant differences were found on comparing the rates at rest with those immediately after phlebotomy; the rates immediately after phlebotomy with those five minutes later; and the

Głównym celem tego opracowania jest analiza zmian stopy procentowej NBP w XXI w. Jako narzędzie badawcze wykorzystano regułę Taylora, która często stanowi odniesienie do zmian krótkookresowych stóp procentowych. W wielu przypadkach, mimo relatywnej swojej prostoty, dobrze opisuje faktyczne zmiany stóp procentowych w bankach centralnych. Opracowanie składa się z trzech głównych części. W pierwszej zarysowano współczesną politykę pieniężną, dokonując próby uchwycenia jej konsensu w zakresie celów, instrumentów i strategii. Ukazano przy tym rolę reguł i dyskrecjonalności w polityce pieniężnej. W drugiej części przedstawiono metodykę badania empirycznego zastosowanego w tym opracowaniu. Wskazano główne założenia badawcze oraz omówiono konstrukcję reguły Taylora. Trzecia część artykuł zawiera badania empiryczne, w których przeprowadzono analizę zmian stopy referencyjnej NBP w XXI w. na tle reguły Taylora. Dokonano przy tym oceny wybranych decyzji dotyczących zmiany tej stopy, w szczególności w latach 2015-2020.