Rates of resistance to ceftazidime-avibactam and ceftolozane-tazobactam among patients treated for multidrug-resistant Pseudomonas aeruginosa bacteremia or pneumonia.

Among consecutive patients with multidrug-resistant Pseudomonas aeruginosa bacteremia or pneumonia we found those treated with ceftazidime-avibactam were more likely to develop resistance (defined as ≥4-fold increased MIC) than those treated with ceftolozane-tazobactam (40% vs. 10%; P=0.002). Ceftazidime-avibactam resistance was associated with new mutations in ampC and efflux regulatory pathways.

Association of Frailty with Healthcare Utilization for Patients over One Year Following Surgical Evaluation.

OBJECTIVE: Characterize the distribution of healthcare utilization associated with pre-operative frailty in the year following evaluation by a surgeon. SUMMARY BACKGROUND DATA: Frailty is associated with increased morbidity, mortality, and costs for surgical patients. However, the total financial burden for frail patients beyond the index surgery and inpatient stay remains unknown. METHODS: Prospective cohort assembled from February 2016 to December 2020 within a multi-hospital integrated healthcare delivery and finance system (IDFS), from patients evaluated with the Risk Analysis Index (RAI) of frailty. Inclusion criteria: age greater than 18, valid RAI, membership in the IDFS Health Plan. Data were stratified by frailty and surgical status. RESULTS: The mean (SD) age was 54.7 (16.1) and 58.2% female of the cohort (n=86,572). For all patients with reimbursement for surgery (n=53,856), frail and very frail patients incurred respective increases of 8% ( P =0.027) and 29% ( P <0.001) on utilization relative to the normal group. Robust patients saw a 52% ( P <0.001) decrease. This pattern was more pronounced in the cohort without surgery (n=32,716). The increase over normal utilization for frail and very frail patients increased to 23% ( P =0.004) and 68% ( P <0.001), respectively. Utilization among robust patients decreased 62% ( P <0.001). Increases among the frail were primarily due to increased inpatient medical and post-acute care services (all P <0.001). CONCLUSIONS: Patient frailty is associated with increased total healthcare utilization, primarily via increased inpatient medical and post-acute care following surgery. Quantifying these frailty-related financial burdens may inform clinical decision making as well as the design of value-based reimbursement strategies.

Carbapenem combination therapy versus standard of care for persistent methicillin-susceptible Staphylococcus aureus bacteraemia.

BACKGROUND: Successful use of carbapenems in combination with cefazolin or oxacillin for treatment of MSSA bacteraemia has been described; however, comparative data to standard treatment approaches are lacking. METHODS: This was a multicentre, retrospective study of adult patients with MSSA bacteraemia for >48 h. Standard treatment was considered monotherapy with cefazolin, oxacillin or nafcillin. Combination therapy was defined as the addition of ertapenem or meropenem to standard treatment for at least 24 h. The primary outcome was duration of bacteraemia defined as time from administration of an antibiotic with in vitro activity to first negative blood culture. Time to blood culture sterilization was compared through risk-set matching with aid of a propensity score. RESULTS: Overall, 238 patients were included; 66% (157/238) received standard treatment and 34% (81/238) received combination therapy. The median (IQR) time to carbapenem initiation was 4.7 (3.63-6.5) days. Patients who received combination therapy were younger (P = 0.012), more likely to have endocarditis (P = 0.034) and had longer median duration of bacteraemia (P < 0.001). After applying risk-set matching, patients who received combination therapy experienced faster time to blood culture sterilization compared with control patients [HR = 1.618 (95% CI; 1.119-2.339) P = 0.011]. Using a paired hazard model, 90 day mortality rates were not statistically different among patients who received combination therapy versus matched controls [HR = 1.267 (95% CI; 0.610-2.678), P = 0.608]. DISCUSSION: Carbapenem combination therapy resulted in faster time to blood culture sterilization, but no differences in overall mortality rates. Randomized trials are critical to determine the utility of carbapenem combination therapy.

Trajectory Analysis of Healthcare Utilization Before and After Major Surgery.

OBJECTIVE: To characterize patterns of healthcare utilization before and after surgery and determine any association with pre-operative frailty. SUMMARY BACKGROUND DATA: Frail patients experience worse post-operative outcomes and increased costs during the surgical encounter. Evidence is comparatively lacking for longer-term effects of frailty on post-operative healthcare utilization. METHODS: Retrospective, longitudinal cohort analysis of adult patients undergoing any elective surgical procedure following pre-operative frailty assessment with the Risk Analysis Index (RAI) from 02/2016-12/2020 at a large integrated healthcare delivery and financing system. Group-based trajectory modeling of claims data estimated distinct clusters of patients with discrete utilization trajectories. Multivariable regression predicted membership in trajectories of interest using preoperative characteristics, including frailty. RESULTS: Among 29,067 surgical encounters, four distinct utilization trajectories emerged in longitudinal data from the 12 months before and after surgery. All cases exhibited a surge in utilization during the surgical month, after which most patients returned to "low" [25,473 (87.6%)], "medium" [1,403 (4.8%)], or "high" [528 (1.8%)] baseline utilization states established before surgery. The fourth trajectory identified 1,663 (5.7%) cases where surgery occasioned a transition from "low" utilization before surgery to "high" utilization afterward. RAI score alone did not effectively predict membership in this transition group, but a multivariable model with other preoperative variables was effective (c=0.859, max re-scaled R-squared 0.264). CONCLUSIONS AND RELEVANCE: Surgery occasions the transition from low to high healthcare utilization for a substantial subgroup of surgical patients. Multivariable modeling may effectively discriminate this utilization trajectory, suggesting an opportunity to tailor care processes for these patients.

Examining Causes of Racial Disparities in General Surgical Mortality: Hospital Quality Versus Patient Risk.

BACKGROUND: Racial disparities in general surgical outcomes are known to exist but not well understood. OBJECTIVES: To determine if black-white disparities in general surgery mortality for Medicare patients are attributable to poorer health status among blacks on admission or differences in the quality of care provided by the admitting hospitals. RESEARCH DESIGN: Matched cohort study using Tapered Multivariate Matching. SUBJECTS: All black elderly Medicare general surgical patients (N=18,861) and white-matched controls within the same 6 states or within the same 838 hospitals. MEASURES: Thirty-day mortality (primary); others include in-hospital mortality, failure-to-rescue, complications, length of stay, and readmissions. RESULTS: Matching on age, sex, year, state, and the exact same procedure, blacks had higher 30-day mortality (4.0% vs. 3.5%, P<0.01), in-hospital mortality (3.9% vs. 2.9%, P<0.0001), in-hospital complications (64.3% vs. 56.8% P<0.0001), and failure-to-rescue rates (6.1% vs. 5.1%, P<0.001), longer length of stay (7.2 vs. 5.8 d, P<0.0001), and more 30-day readmissions (15.0% vs. 12.5%, P<0.0001). Adding preoperative risk factors to the above match, there was no significant difference in mortality or failure-to-rescue, and all other outcome differences were small. Blacks matched to whites in the same hospital displayed no significant differences in mortality, failure-to-rescue, or readmissions. CONCLUSIONS: Black and white Medicare patients undergoing the same procedures with closely matched risk factors displayed similar mortality, suggesting that racial disparities in general surgical mortality are not because of differences in hospital quality. To reduce the observed disparities in surgical outcomes, the poorer health of blacks on presentation for surgery must be addressed.

Racial disparities in colon cancer survival: a matched cohort study.

BACKGROUND: Differences in colon cancer survival by race are a recognized problem among Medicare beneficiaries. OBJECTIVE: To determine to what extent the racial disparity in survival is due to disparity in presentation characteristics at diagnosis or disparity in subsequent treatment. DESIGN: Black patients with colon cancer were matched with 3 groups of white patients: a "demographic characteristics" match controlling for age, sex, diagnosis year, and Survey, Epidemiology, and End Results (SEER) site; a "presentation" match controlling for demographic characteristics plus comorbid conditions and tumor characteristics, including stage and grade; and a "treatment" match, including presentation variables plus details of surgery, radiation, and chemotherapy. SETTING: 16 U.S. SEER sites. PATIENTS: 7677 black patients aged 65 years or older diagnosed between 1991 and 2005 in the SEER-Medicare database and 3 sets of 7677 matched white patients, followed until 31 December 2009. MEASUREMENTS: 5-year survival. RESULTS: The absolute difference in 5-year survival between black and white patients was 9.9% (95% CI, 8.3% to 11.4%; P<0.001) in the demographic characteristics match. This disparity remained unchanged between 1991 and 2005. After matching for presentation characteristics, the difference decreased to 4.9% (CI, 3.6% to 6.1%; P<0.001). After additional matching for treatment, this difference decreased to 4.3% (CI, 2.9% to 5.5%; P<0.001). The disparity in survival attributed to treatment differences made up only an absolute 0.6% of the overall 9.9% survival disparity. LIMITATION: An observational study limited to elderly Medicare fee-for-service beneficiaries living in selected geographic areas. CONCLUSION: Racial disparities in colon cancer survival did not decrease among patients diagnosed between 1991 and 2005. This persistent disparity seemed to be more related to presentation characteristics at diagnosis than to subsequent treatment differences. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality and National Science Foundation.

Anesthesia technique, mortality, and length of stay after hip fracture surgery.

IMPORTANCE: More than 300,000 hip fractures occur each year in the United States. Recent practice guidelines have advocated greater use of regional anesthesia for hip fracture surgery. OBJECTIVE: To test the association of regional (ie, spinal or epidural) anesthesia vs general anesthesia with 30-day mortality and hospital length of stay after hip fracture. DESIGN, SETTING, AND PATIENTS: We conducted a matched retrospective cohort study involving patients 50 years or older who were undergoing surgery for hip fracture at general acute care hospitals in New York State between July 1, 2004, and December 31, 2011. Our main analysis was a near-far instrumental variable match that paired patients who lived at different distances from hospitals that specialized in regional or general anesthesia. Supplementary analyses included a within-hospital match that paired patients within the same hospital and an across-hospital match that paired patients at different hospitals. EXPOSURES: Spinal or epidural anesthesia; general anesthesia. MAIN OUTCOMES AND MEASURES: Thirty-day mortality and hospital length of stay. Because the distribution of length of stay had long tails, we characterized this outcome using the Huber M estimate with Huber weights, a robust estimator similar to a trimmed mean. RESULTS: Of 56,729 patients, 15,904 (28%) received regional anesthesia and 40,825 (72%) received general anesthesia. Overall, 3032 patients (5.3%) died. The M estimate of the length of stay was 6.2 days (95% CI, 6.2 to 6.2). The near-far matched analysis showed no significant difference in 30-day mortality by anesthesia type among the 21,514 patients included in this match: 583 of 10,757 matched patients (5.4%) who lived near a regional anesthesia-specialized hospital died vs 629 of 10,757 matched patients (5.8%) who lived near a general anesthesia-specialized hospital (instrumental variable estimate of risk difference, -1.1%; 95% CI, -2.8 to 0.5; P = .20). Supplementary analyses of within and across hospital patient matches yielded mortality findings to be similar to the main analysis. In the near-far match, regional anesthesia was associated with a 0.6-day shorter length of stay than general anesthesia (95% CI, -0.8 to -0.4, P < .001). Supplementary analyses also showed regional anesthesia to be associated with shorter length of stay, although the observed association was smaller in magnitude than in the main analysis. CONCLUSIONS AND RELEVANCE: Among adults in acute care hospitals in New York State undergoing hip repair, the use of regional anesthesia compared with general anesthesia was not associated with lower 30-day mortality but was associated with a modestly shorter length of stay. These findings do not support a mortality benefit for regional anesthesia in this setting.

Racial disparities in operative procedure time: the influence of obesity.

BACKGROUND: Using Pennsylvania Medicare claims from 1995 to 1996, the authors previously reported that anesthesia procedure length appears longer in blacks than whites. In a new study using a different and larger data set, the authors now examine whether body mass index (BMI), not available in Medicare claims, explains this difference. The authors also examine the relative contributions of surgical and anesthesia times. METHODS: The Obesity and Surgical Outcomes Study of 47 hospitals throughout Illinois, New York, and Texas abstracted chart information including BMI on elder Medicare patients (779 blacks and 14,596 whites) undergoing hip and knee replacement and repair, colectomy, and thoracotomy between 2002 and 2006. The authors matched all black Medicare patients to comparable whites and compared procedure lengths. RESULTS: Mean BMI in the black and white populations was 30.24 and 28.96 kg/m, respectively (P<0.0001). After matching on age, sex, procedure, comorbidities, hospital, and BMI, mean white BMI in the comparison group was 30.1 kg/m (P=0.94). The typical matched pair difference (black-white) in anesthesia (induction to recovery room) procedure time was 7.0 min (P=0.0019), of which 6 min reflected the surgical (cut-to-close) time difference (P=0.0032). Within matched pairs, where the difference in procedure times was greater than 30 min between patients, blacks more commonly had longer procedure times (Odds=1.39; P=0.0008). CONCLUSIONS: Controlling for patient characteristics, BMI, and hospital, elder black Medicare patients experienced slightly but significantly longer procedure length than their closely matched white controls. Procedure length difference was almost completely due to surgery, not anesthesia.

Characteristics associated with differences in survival among black and white women with breast cancer.

IMPORTANCE: Difference in breast cancer survival by race is a recognized problem among Medicare beneficiaries. OBJECTIVE: To determine if racial disparity in breast cancer survival is primarily attributable to differences in presentation characteristics at diagnosis or subsequent treatment. DESIGN, SETTING, AND PATIENTS: Comparison of 7375 black women 65 years and older diagnosed between 1991 to 2005 and 3 sets of 7375 matched white control patients selected from 99,898 white potential controls, using data for 16 US Surveillance, Epidemiology and End Results (SEER) sites in the SEER-Medicare database. All patients received follow-up through December 31, 2009, and the black case patients were matched to 3 white control populations on demographics (age, year of diagnosis, and SEER site), presentation (demographics variables plus patient comorbid conditions and tumor characteristics such as stage, size, grade, and estrogen receptor status), and treatment (presentation variables plus details of surgery, radiation therapy, and chemotherapy). MAIN OUTCOMES AND MEASURES: 5-Year survival. RESULTS: The absolute difference in 5-year survival (blacks, 55.9%; whites, 68.8%) was 12.9% (95% CI, 11.5%-14.5%; P < .001) in the demographics match. This difference remained unchanged between 1991 and 2005. After matching on presentation characteristics, the absolute difference in 5-year survival was 4.4% (95% CI, 2.8%-5.8%; P < .001) and was 3.6% (95% CI, 2.3%-4.9%; P < .001) lower for blacks than for whites matched also on treatment. In the presentation match, fewer blacks received treatment (87.4% vs 91.8%; P < .001), time from diagnosis to treatment was longer (29.2 vs 22.8 days; P < .001), use of anthracyclines and taxols was lower (3.7% vs 5.0%; P < .001), and breast-conserving surgery without other treatment was more frequent (8.2% vs 7.3%; P = .04). Nevertheless, differences in survival associated with treatment differences accounted for only 0.81% of the 12.9% survival difference. CONCLUSIONS AND RELEVANCE: In the SEER-Medicare database, differences in breast cancer survival between black and white women did not substantially change among women diagnosed between 1991 and 2005. These differences in survival appear primarily related to presentation characteristics at diagnosis rather than treatment differences.

Clindamycin Plus Vancomycin Versus Linezolid for Treatment of Necrotizing Soft Tissue Infection.

Background: Necrotizing soft tissue infections (NSTIs) are life-threatening infections. The aim of this study is to evaluate the safety of clindamycin plus vancomycin versus linezolid as empiric treatment of NSTIs. Methods: This was a retrospective, single-center, quasi-experimental study of patients admitted from 1 June 2018 to 30 June 2019 (preintervention) and 1 May 2020 to 15 October 2021 (postintervention). Patients who received surgical management within 24 hours of NSTI diagnosis and at least 1 dose of linezolid or clindamycin were included. The primary endpoint was death at 30 days. The secondary outcomes included rates of acute kidney injury (AKI) and Clostridioides difficile infection (CDI). Results: A total of 274 patients were identified by admission diagnosis code for NSTI or Fournier gangrene; 164 patients met the inclusion criteria. Sixty-two matched pairs were evaluated. There was no difference in rates of 30-day mortality (8.06% vs 6.45%; hazard ratio [HR], 1.67 [95% confidence interval {CI}, .32-10.73]; P = .65). There was no difference in CDI (6.45% vs 1.61%; HR, Infinite [Inf], [95% CI, .66-Inf]; P = .07) but more AKI in the preintervention group (9.68% vs 1.61%; HR, 6 [95% CI, .73-276]; P = .05). Conclusions: In this small, retrospective, single-center, quasi-experimental study, there was no difference in 30-day mortality in patients receiving treatment with clindamycin plus vancomycin versus linezolid in combination with standard gram-negative and anaerobic therapy and surgical debridement for the treatment of NSTIs. A composite outcome of death, AKI, or CDI within 30 days was more common in the clindamycin plus vancomycin group.

Comparative effectiveness of regional versus general anesthesia for hip fracture surgery in adults.

BACKGROUND: Hip fracture is a common, morbid, and costly event among older adults. Data are inconclusive as to whether epidural or spinal (regional) anesthesia improves outcomes after hip fracture surgery. METHODS: The authors examined a retrospective cohort of patients undergoing surgery for hip fracture in 126 hospitals in New York in 2007 and 2008. They tested the association of a record indicating receipt of regional versus general anesthesia with a primary outcome of inpatient mortality and with secondary outcomes of pulmonary and cardiovascular complications using hospital fixed-effects logistic regressions. Subgroup analyses tested the association of anesthesia type and outcomes according to fracture anatomy. RESULTS: Of 18,158 patients, 5,254 (29%) received regional anesthesia. In-hospital mortality occurred in 435 (2.4%). Unadjusted rates of mortality and cardiovascular complications did not differ by anesthesia type. Patients receiving regional anesthesia experienced fewer pulmonary complications (359 [6.8%] vs. 1,040 [8.1%], P < 0.005). Regional anesthesia was associated with a lower adjusted odds of mortality (odds ratio: 0.710, 95% CI 0.541, 0.932, P = 0.014) and pulmonary complications (odds ratio: 0.752, 95% CI 0.637, 0.887, P < 0.0001) relative to general anesthesia. In subgroup analyses, regional anesthesia was associated with improved survival and fewer pulmonary complications among patients with intertrochanteric fractures but not among patients with femoral neck fractures. CONCLUSIONS: Regional anesthesia is associated with a lower odds of inpatient mortality and pulmonary complications among all hip fracture patients compared with general anesthesia; this finding may be driven by a trend toward improved outcomes with regional anesthesia among patients with intertrochanteric fractures.

Strengthening the Impact of Digital Cognitive Behavioral Interventions Through a Dual Intervention: Proficient Motivational Interviewing-Based Health Coaching Plus In-Application Techniques.

BACKGROUND: The COVID-19 pandemic has accelerated the adoption of digital tools to support individuals struggling with their mental health. The use of a digital intervention plus human coaching ("dual" intervention) is gaining momentum in increasing overall engagement in digital cognitive behavioral interventions (dCBIs). However, there is limited insight into the methodologies and coaching models used by those deploying dual interventions. To achieve a deeper understanding, we need to identify and promote effective engagement that leads to clinical outcomes versus simply monitoring engagement metrics. Motivational interviewing (MI) is a collaborative, goal-oriented communication approach that pays particular attention to the language of change and is an effective engagement approach to help people manage mental health issues. However, this approach has been traditionally used for in-person or telephonic interventions, and less is known about the application of MI to digital interventions. OBJECTIVE: We sought to provide a dual intervention approach and address multiple factors across two levels of engagement to operationalize a dCBI that combined cognitive behavioral therapy-based techniques and MI-based interactions between the digital health coach (DHC) and user. METHODS: We reviewed hundreds of digital exchanges between DHCs and users to identify and improve training and quality assurance activities for digital interventions. RESULTS: We tested five hypotheses and found that: (1) users of a dual digital behavioral health intervention had greater engagement levels than users of a noncoached intervention (P<.001); (2) DHCs with a demonstrated competency in applying MI to digital messages had more engaged users, as measured by the DHC-to-user message exchange ratio (P<.001); (3) the DHC-to-user message exchange ratio was correlated with more engagement in app activities (r=0.28, 95% CI 0.23-0.33); (4) DHCs with demonstrated MI proficiency elicited a greater amount of "change talk" from users than did DHCs without MI proficiency (H=25.12, P<.001); and (5) users who were engaged by DHCs with MI proficiency had better clinical outcomes compared to users engaged by DHCs without MI proficiency (P=.02). CONCLUSIONS: To our knowledge, this pilot was the first of its kind to test the application of MI to digital coaching protocols, and it demonstrated the value of MI proficiency in digital health coaching for enhanced engagement and health improvement. Further research is needed to establish coaching models in dCBIs that incorporate MI to promote effective engagement and optimize positive behavioral outcomes.

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.

Identification, Shiga toxin subtypes and prevalence of minor serogroups of Shiga toxin-producing Escherichia coli in feedlot cattle feces.

Shiga toxin-producing Escherichia coli (STEC) are foodborne pathogens that cause illnesses in humans ranging from mild to hemorrhagic enteritis with complications of hemolytic uremic syndrome and even death. Cattle are a major reservoir of STEC, which reside in the hindgut and are shed in the feces, a major source of food and water contaminations. Seven serogroups, O26, O45, O103, O111, O121, O145 and O157, called 'top-7', are responsible for the majority of human STEC infections in North America. Additionally, 151 serogroups of E. coli are known to carry Shiga toxin genes (stx). Not much is known about fecal shedding and prevalence and virulence potential of STEC other than the top-7. Our primary objectives were to identify serogroups of STEC strains, other than the top-7, isolated from cattle feces and subtype stx genes to assess their virulence potential. Additional objective was to develop and validate a novel multiplex PCR assay to detect and determine prevalence of six serogroups, O2, O74, O109, O131, O168, and O171, in cattle feces. A total of 351 strains, positive for stx gene and negative for the top-7 serogroups, isolated from feedlot cattle feces were used in the study. Of the 351 strains, 291 belonged to 16 serogroups and 60 could not be serogrouped. Among the 351 strains, 63 (17.9%) carried stx1 gene and 300 (82.1%) carried stx2, including 12 strains positive for both. The majority of the stx1 and stx2 were of stx1a (47/63; 74.6%) and stx2a subtypes (234/300; 78%), respectively, which are often associated with human infections. A novel multiplex PCR assay developed and validated to detect six serogroups, O2, O74, O109, O131, O168, and O171, which accounted for 86.9% of the STEC strains identified, was utilized to determine their prevalence in fecal samples (n = 576) collected from a commercial feedlot. Four serogroups, O2, O109, O168, and O171 were identified as the dominant serogroups prevalent in cattle feces. In conclusion, cattle shed in the feces a number of STEC serogroups, other than the top-7, and the majority of the strains isolated possessed stx2, particularly of the subtype 2a, suggesting their potential risk to cause human infections.

Multiplex PCR Assays for the Detection of One Hundred and Thirty Seven Serogroups of Shiga Toxin-Producing Escherichia coli Associated With Cattle.

Escherichia coli carrying prophage with genes that encode for Shiga toxins are categorized as Shiga toxin-producing E. coli (STEC) pathotype. Illnesses caused by STEC in humans, which are often foodborne, range from mild to bloody diarrhea with life-threatening complications of renal failure and hemolytic uremic syndrome and even death, particularly in children. As many as 158 of the total 187 serogroups of E. coli are known to carry Shiga toxin genes, which makes STEC a major pathotype of E. coli. Seven STEC serogroups, called top-7, which include O26, O45, O103, O111, O121, O145, and O157, are responsible for the majority of the STEC-associated human illnesses. The STEC serogroups, other than the top-7, called "non-top-7" have also been associated with human illnesses, more often as sporadic infections. Ruminants, particularly cattle, are principal reservoirs of STEC and harbor the organisms in the hindgut and shed in the feces, which serves as a major source of food and water contaminations. A number of studies have reported on the fecal prevalence of top-7 STEC in cattle feces. However, there is paucity of data on the prevalence of non-top-7 STEC serogroups in cattle feces, generally because of lack of validated detection methods. The objective of our study was to develop and validate 14 sets of multiplex PCR (mPCR) assays targeting serogroup-specific genes to detect 137 non-top-7 STEC serogroups previously reported to be present in cattle feces. Each assay included 7-12 serogroups and primers were designed to amplify the target genes with distinct amplicon sizes for each serogroup that can be readily identified within each assay. The assays were validated with 460 strains of known serogroups. The multiplex PCR assays designed in our study can be readily adapted by most laboratories for rapid identification of strains belonging to the non-top-7 STEC serogroups associated with cattle.

Dose-dependent effects of adenosine antagonists on tacrine-induced tremulous jaw movements.

The present study examines the effect of three adenosine receptor antagonists on tremulous jaw movements (TJMs), an animal model of tremor. Forty-five rats were pre-treated with one adenosine antagonist: caffeine (0.0, 5.0, or 10.0 mg/kg; non-selective adenosine receptor antagonist), 8-cyclopentyltheophylline (CPT; 0.0, 5.0, or 10.0 mg/kg; selective adenosine A1 receptor antagonist), or SCH 58261 (0.0 or 8.0 mg/kg; selective adenosine A2A receptor antagonist) followed by TJM induction with tacrine (0.0, 0.75, or 2.5 mg/kg; acetylcholinesterase inhibitor). CPT and SCH 58261 both significantly reduced TJMs while caffeine did not. Unexpectedly, both SCH 58261 and CPT reduced TJMs even in the absence of tacrine. Also, CPT showed a robust reduction of TJMs, achieved at both (5.0 mg/kg) and (10.0 mg/kg) doses and regardless of tacrine dose. In conclusion, this study shows adenosine receptor antagonism to generally suppress low-dose tacrine-induced TJMs. In concert with two prior studies, these results are suggestive of behavioral evidence for a biphasic effect of adenosine A2A receptor antagonists (caffeine and SCH 58261) that is modulated by tacrine, and a model of this effect is proposed.

Comparative genomics reveals differences in mobile virulence genes of Escherichia coli O103 pathotypes of bovine fecal origin.

Escherichia coli O103, harbored in the hindgut and shed in the feces of cattle, can be enterohemorrhagic (EHEC), enteropathogenic (EPEC), or putative non-pathotype. The genetic diversity particularly that of virulence gene profiles within O103 serogroup is likely to be broad, considering the wide range in severity of illness. However, virulence descriptions of the E. coli O103 strains isolated from cattle feces have been primarily limited to major genes, such as Shiga toxin and intimin genes. Less is known about the frequency at which other virulence genes exist or about genes associated with the mobile genetic elements of E. coli O103 pathotypes. Our objective was to utilize whole genome sequencing (WGS) to identify and compare major and putative virulence genes of EHEC O103 (positive for Shiga toxin gene, stx1, and intimin gene, eae; n = 43), EPEC O103 (negative for stx1 and positive for eae; n = 13) and putative non-pathotype O103 strains (negative for stx and eae; n = 13) isolated from cattle feces. Six strains of EHEC O103 from human clinical cases were also included. All bovine EHEC strains (43/43) and a majority of EPEC (12/13) and putative non-pathotype strains (12/13) were O103:H2 serotype. Both bovine and human EHEC strains had significantly larger average genome sizes (P < 0.0001) and were positive for a higher number of adherence and toxin-based virulence genes and genes on mobile elements (prophages, transposable elements, and plasmids) than EPEC or putative non-pathotype strains. The genome size of the three pathotypes positively correlated (R2 = 0.7) with the number of genes carried on mobile genetic elements. Bovine strains clustered phylogenetically by pathotypes, which differed in several key virulence genes. The diversity of E. coli O103 pathotypes shed in cattle feces is likely reflective of the acquisition or loss of virulence genes carried on mobile genetic elements.

Using Appendicitis to Improve Estimates of Childhood Medicaid Participation Rates.

OBJECTIVE: Administrative data are often used to estimate state Medicaid/Children's Health Insurance Program duration of enrollment and insurance continuity, but they are generally not used to estimate participation (the fraction of eligible children enrolled) because administrative data do not include reasons for disenrollment and cannot observe eligible never-enrolled children, causing estimates of eligible unenrolled to be inaccurate. Analysts are therefore forced to either utilize survey information that is not generally linkable to administrative claims or rely on duration and continuity measures derived from administrative data and forgo estimating claims-based participation. We introduce appendectomy-based participation (ABP) to estimate statewide participation rates using claims by taking advantage of a natural experiment around statewide appendicitis admissions to improve the accuracy of participation rate estimates. METHODS: We used Medicaid Analytic eXtract (MAX) for 2008-2010; and the American Community Survey for 2008-2010 from 43 states to calculate ABP, continuity ratio, duration, and participation based on the American Community Survey (ACS). RESULTS: In the validation study, median participation rate using ABP was 86% versus 87% for ACS-based participation estimates using logical edits and 84% without logical edits. Correlations between ABP and ACS with or without logical edits was 0.86 (P < .0001). Using regression analysis, ABP alone was a significant predictor of ACS (P < .0001) with or without logical edits, and adding duration and/or the continuity ratio did not significantly improve the model. CONCLUSION: Using the ABP rate derived from administrative claims (MAX) is a valid method to estimate statewide public insurance participation rates in children.

Auditing Practice Style Variation in Pediatric Inpatient Asthma Care.

IMPORTANCE: Asthma is the most prevalent chronic illness among children, remaining a leading cause of pediatric hospitalizations and representing a major financial burden to many health care systems. OBJECTIVE: To implement a new auditing process examining whether differences in hospital practice style may be associated with potential resource savings or inefficiencies in treating pediatric asthma admissions. DESIGN, SETTING, AND PARTICIPANTS: A retrospective matched-cohort design study, matched for asthma severity, compared practice patterns for patients admitted to Children's Hospital Association hospitals contributing data to the Pediatric Hospital Information System (PHIS) database. With 3 years of PHIS data on 48 887 children, an asthma template was constructed consisting of representative children hospitalized for asthma between April 1, 2011, and March 31, 2014. The template was matched with either a 1:1, 2:1, or 3:1 ratio at each of 37 tertiary care children's hospitals, depending on available sample size. EXPOSURE: Treatment at each PHIS hospital. MAIN OUTCOMESS AND MEASURES: Cost, length of stay, and intensive care unit (ICU) utilization. RESULTS: After matching patients (n = 9100; mean [SD] age, 7.1 [3.6] years; 3418 [37.6%] females) to the template (n = 100, mean [SD] age, 7.2 [3.7] years; 37 [37.0%] females), there was no significant difference in observable patient characteristics at the 37 hospitals meeting the matching criteria. Despite similar characteristics of the patients, we observed large and significant variation in use of the ICUs as well as in length of stay and cost. For the same template-matched populations, comparing utilization between the 12.5th percentile (lower eighth) and 87.5th percentile (upper eighth) of hospitals, median cost varied by 87% ($3157 vs $5912 per patient; P < .001); total hospital length of stay varied by 47% (1.5 vs 2.2 days; P < .001); and ICU utilization was 254% higher (6.5% vs 23.0%; P < .001). Furthermore, the patterns of resource utilization by patient risk differed significantly across hospitals. For example, as patient risk increased one hospital displayed significantly increasing costs compared with their matched controls (comparative cost difference: lowest risk, -34.21%; highest risk, 53.27%; P < .001). In contrast, another hospital displayed significantly decreasing costs relative to their matched controls as patient risk increased (comparative cost difference: lowest risk, -10.12%; highest risk, -16.85%; P = .01). CONCLUSIONS AND RELEVANCE: For children with asthma who had similar characteristics, we observed different hospital resource utilization; some values differed greatly, with important differences by initial patient risk. Through the template matching audit, hospitals and stakeholders can better understand where this excess variation occurs and can help to pinpoint practice styles that should be emulated or avoided.