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OBJECTIVES/SPECIFIC AIMS: Previous studies suggest that genetic variants in the oxytocin receptor (OXTR) may alter oxytocin dose requirement for labor induction and may increase risk for preterm labor and neurodevelopmental disorders. However, the mechanisms of actions of these variants remain unknown. The goal of this study was to functionally characterize common missense and noncoding variants in OXTR. First, we aimed to determine the effects of missense variants on two major aspects of receptor function: calcium signaling and β-arrestin recruitment. Second, we used allelic expression imbalance assays in an effort to identify regulatory single nucleotide polymorphisms (SNPs) in noncoding regions of OXTR that alter OXTR mRNA expression. METHODS/STUDY POPULATION: We used the Exome Aggregation Consortium database to identify the 12 most prevalent missense single nucleotide variants in OXTR. To determine the functional effects of these variants, we transfected human embryonic kidney cells (a common model system used to study receptor function) with wild type OXTR, variant OXTR, or empty vector control. We used the calcium-sensitive dye Fluo4 to quantify intracellular calcium flux in response to oxytocin treatment, and used bioluminescence resonance energy transfer assays to measure recruitment of the signaling partner β-arrestin to the receptor. To investigate potential effects of noncoding SNPs on OXTR mRNA expression, we quantified allele-specific expression of OXTR in human uterine tissue obtained from participants at the time of Cesarean section. We used next-generation sequencing (Illumina MiSeq) to count alleles of a reporter SNP in OXTR exon 3. RESULTS/ANTICIPATED RESULTS: Of the 12 most prevalent missense single nucleotide variants, four were predicted to be deleterious by PolyPhen variant annotation software. We anticipate that these variants will alter receptor signaling through calcium or β-arrestin pathways. We further observed that a reporter SNP in OXTR exon 3 exhibits significant allelic expression imbalance in a subset of our myometrial tissue samples, indicating that OXTR expression may be regulated by a functional SNP. Our current work focuses on discovering the functional SNPs in OXTR responsible for the pattern of allelic expression imbalance seen in mRNA. In the future, we will seek to explore the effects of these variants on uterine function by using genome editing of uterine smooth muscle cells. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results suggest that both missense and noncoding variants may affect OXTR expression and function. Future studies may suggest that OXTR sequencing, genotyping, or expression analysis would be useful to identify individuals likely to respond or fail to respond to safe doses of oxytocin for labor induction. Personalizing approaches for labor induction in this way would increase the safety of oxytocin and potentially reduce maternal morbidity and mortality.
National policies target healthcare-associated infections using medical claims and National Healthcare Safety Network surveillance data. We found low concordance between the 2 data sources in rates and rankings for surgical site infection following colon surgery in 155 hospitals, underscoring the limitations in evaluating hospital quality by claims data.
To assess variability in antimicrobial use and associations with infection testing in pediatric ventilator-associated events (VAEs).
Descriptive retrospective cohort with nested case-control study.
Pediatric intensive care units (PICUs), cardiac intensive care units (CICUs), and neonatal intensive care units (NICUs) in 6 US hospitals.
Children≤18 years ventilated for≥1 calendar day.
We identified patients with pediatric ventilator-associated conditions (VACs), pediatric VACs with antimicrobial use for≥4 days (AVACs), and possible ventilator-associated pneumonia (PVAP, defined as pediatric AVAC with a positive respiratory diagnostic test) according to previously proposed criteria.
Among 9,025 ventilated children, we identified 192 VAC cases, 43 in CICUs, 70 in PICUs, and 79 in NICUs. AVAC criteria were met in 79 VAC cases (41%) (58% CICU; 51% PICU; and 23% NICU), and varied by hospital (CICU, 20–67%; PICU, 0–70%; and NICU, 0–43%). Type and duration of AVAC antimicrobials varied by ICU type. AVAC cases in CICUs and PICUs received broad-spectrum antimicrobials more often than those in NICUs. Among AVAC cases, 39% had respiratory infection diagnostic testing performed; PVAP was identified in 15 VAC cases. Also, among AVAC cases, 73% had no associated positive respiratory or nonrespiratory diagnostic test.
Antimicrobial use is common in pediatric VAC, with variability in spectrum and duration of antimicrobials within hospitals and across ICU types, while PVAP is uncommon. Prolonged antimicrobial use despite low rates of PVAP or positive laboratory testing for infection suggests that AVAC may provide a lever for antimicrobial stewardship programs to improve utilization.
This study finds a positive, economically meaningful impact of generalist chief executive officers (CEOs) on shareholder value using 164 sudden deaths and 345 non-sudden exogenous turnovers. The higher a departing CEO’s general ability index (GAI), independently and relative to her successor, the lower is the abnormal stock return to turnover announcements. Returns reflect post-turnover changes in operating performance. Further, CEOs’ and successors’ GAIs are significantly positively related, but only for non-sudden turnovers. Consistently, for sudden deaths, we find positive stock returns to appointments of generalist successors. The results provide a market-based explanation for the generalist pay premium.
In 2008, the Centers for Medicare and Medicaid Services (CMS) stopped reimbursing for hospital-acquired conditions (HACs) not present on admission (POA). We sought to understand why this policy did not impact central line–associated bloodstream infection (CLABSI) and catheter-associated urinary tract infection (CAUTI) trends.
Retrospective cohort study.
Acute-care hospitals in the United States.
Fee-for-service Medicare patients discharged January 1, 2007, through December 31, 2011.
Using inpatient Medicare claims data, we analyzed billing practices before and after the HAC policy was implemented, including the use and POA designation of codes for CLABSI or CAUTI. For the 3-year period following policy implementation, we determined the impact on diagnosis-related groups (DRG) determining reimbursement as well as hospital characteristics associated with the reimbursement impact.
During the study period, 65,205,607 Medicare fee-for-service hospitalizations occurred at 3,291 acute-care, nonfederal US hospitals. Based on coding, CLABSI and CAUTI affected 0.23% and 0.06% of these hospitalizations, respectively. In addition, following the HAC policy, 82% of the CLABSI codes and 91% of the CAUTI codes were marked POA, which represented a large increase in the use of this designation. Finally, for the small numbers of CLABSI and CAUTI coded as not POA, financial impacts were detected on only 0.4% of the hospitalizations with a CLABSI code and 5.7% with a CAUTI code.
Part of the reason the HAC policy did not have its intended impact is that billing codes for CLABSI and CAUTI were rarely used, were commonly listed as POA in the postpolicy period, and infrequently impacted hospital reimbursement.
In 2012, the Centers for Medicare and Medicaid Services expanded a 2008 program that eliminated additional Medicare payment for mediastinitis following coronary artery bypass graft (CABG) to include Medicaid. We aimed to evaluate the impact of this Medicaid program on mediastinitis rates reported by the National Healthcare Safety Network (NHSN) compared with the rates of a condition not targeted by the program, deep-space surgical site infection (SSI) after knee replacement.
Interrupted time series with comparison group.
We included surveillance data from nonfederal acute-care hospitals participating in the NHSN and reporting CABG or knee replacement outcomes from January 2009 through June 2017. We examined the Medicaid program’s impact on NHSN-reported infection rates, adjusting for secular trends. The data analysis used generalized estimating equations with robust sandwich variance estimators.
During the study period, 196 study hospitals reported 273,984 CABGs to the NHSN, resulting in 970 mediastinitis cases (0.35%), and 294 hospitals reported 555,395 knee replacements, with 1,751 resultant deep-space SSIs (0.32%). There was no significant change in incidence of either condition during the study. Mediastinitis models showed no effect of the 2012 Medicaid program on either secular trend during the postprogram versus preprogram periods (P=.70) or an immediate program effect (P=.83). Results were similar in sensitivity analyses when adjusting for hospital characteristics, restricting to hospitals with consistent NHSN reporting or incorporating a program implementation roll-in period. Knee replacement models also showed no program effect.
The 2012 Medicaid program to eliminate additional payments for mediastinitis following CABG had no impact on reported mediastinitis rates.
The objective of this study was to assess determinants of poor sleep quality which is an under-diagnosed and under-treated problem in elderly patients with diabetes mellitus, hyperlipidemia and hypertension.
Poor sleep quality is linked to decreased quality of life, increased morbidity and mortality. Poor sleep quality is common in the elderly population with associated cardiometabolic risk factors such as diabetes, hyperlipidemia and hypertension.
This is a cross-sectional study undertaken in the primary healthcare setting (Singhealth Polyclinics-Outram) in Singapore. Singaporeans aged 65 years and above who had at least one of the three cardiometabolic risk factors (diabetes, hypertension and hyperlipidemia) were identified. Responders’ sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) questionnaire and were divided into those with good quality sleep and those with poor quality sleep, based on the PSQI score. Information on demographics, co-morbidities and lifestyle practices were collected. Descriptive and multivariate analyses of determinants of poor sleep were determined.
There were 199 responders (response rate 88.1%). Nocturia (adjusted prevalence rate ratio 1.54, 95% confidence interval 1.06–2.26) was found to be associated with an increased risk of poor sleep quality in elderly patients with diabetes mellitus, hypertension and hyperlipidaemia. Nocturia, a prevalent problem in the Asian elderly population, has been found to be associated with poor sleep quality in our study. Hence, it is imperative to identify and treat patients with nocturia to improve sleep quality among them.
Adult ventilator-associated event (VAE) definitions include ventilator-associated conditions (VAC) and subcategories for infection-related ventilator-associated complications (IVAC) and possible ventilator-associated pneumonia (PVAP). We explored these definitions for children.
Pediatric, cardiac, or neonatal intensive care units (ICUs) in 6 US hospitals
Patients ≤18 years old ventilated for ≥1 day
We identified patients with pediatric VAC based on previously proposed criteria. We applied adult temperature, white blood cell count, antibiotic, and culture criteria for IVAC and PVAP to these patients. We matched pediatric VAC patients with controls and evaluated associations with adverse outcomes using Cox proportional hazards models.
In total, 233 pediatric VACs (12,167 ventilation episodes) were identified. In the cardiac ICU (CICU), 62.5% of VACs met adult IVAC criteria; in the pediatric ICU (PICU), 54.2% of VACs met adult IVAC criteria; and in the neonatal ICU (NICU), 20.2% of VACs met adult IVAC criteria. Most patients had abnormal white blood cell counts and temperatures; we therefore recommend simplifying surveillance by focusing on “pediatric VAC with antimicrobial use” (pediatric AVAC). Pediatric AVAC with a positive respiratory diagnostic test (“pediatric PVAP”) occurred in 8.9% of VACs in the CICU, 13.3% of VACs in the PICU, and 4.3% of VACs in the NICU. Hospital mortality was increased, and hospital and ICU length of stay and duration of ventilation were prolonged among all pediatric VAE subsets compared with controls.
We propose pediatric AVAC for surveillance related to antimicrobial use, with pediatric PVAP as a subset of AVAC. Studies on generalizability and responsiveness of these metrics to quality improvement initiatives are needed, as are studies to determine whether lower pediatric VAE rates are associated with improvements in other outcomes.
We conducted a content analysis of public comments to understand the key framing approaches used by private industry v. public health sector, with the goal of informing future public health messaging, framing and advocacy in the context of policy making.
Comments to the proposed menu-labelling policy were extracted from Regulations.gov and analysed. A framing matrix was used to organize and code key devices and themes. Documents were analysed using content analysis with Dedoose software.
Recent national nutrition-labelling regulations in the USA provide a timely opportunity to understand message framing in relation to obesity prevention and policy.
We examined a total of ninety-seven documents submitted on behalf of organizations (private industry, n 64; public health, n 33).
Public health focused on positive health consequences of the policy, used a social justice frame and supported its arguments with academic data. Industry was more critical of the policy; it used a market justice frame that emphasized minimal regulation, depicted its members as small, family-run businesses, and illustrated points with humanizing examples.
Public health framing should counter and consider engaging directly with non-health-related arguments made by industry. Public health should include more powerful framing devices to convey their messages, including metaphors and humanizing examples.
Recent neuroimaging research on disorders of consciousness provides direct evidence of covert consciousness otherwise not detected clinically in a subset of severely brain-injured patients. These findings have motivated strategic development of binary communication paradigms, from which researchers interpret voluntary modulations in brain activity to glean information about patients’ residual cognitive functions and emotions. The discovery of such responsiveness raises ethical and legal issues concerning the exercise of autonomy and capacity for decisionmaking on matters such as healthcare, involvement in research, and end of life. These advances have generated demands for access to the technology against a complex background of continued scientific advancement, questions about just allocation of healthcare resources, and unresolved legal issues. Interviews with professionals whose work is relevant to patients with disorders of consciousness reveal priorities concerning further basic research, legal and policy issues, and clinical considerations.
Administrative and surveillance data are used frequently in healthcare epidemiology and antimicrobial stewardship (HE&AS) research because of their wide availability and efficiency. However, data quality issues exist, requiring careful consideration and potential validation of data. This methods paper presents key considerations for using administrative and surveillance data in HE&AS, including types of data available and potential use, data limitations, and the importance of validation. After discussing these issues, we review examples of HE&AS research using administrative data with a focus on scenarios when their use may be advantageous. A checklist is provided to help aid study development in HE&AS using administrative data.
There is a growing body of literature describing the characteristics of patients who plan for the end of life, but little research has examined how caregivers influence patients' advance care planning (ACP). The purpose of this study was to examine how patient and caregiver characteristics are associated with advance directive (AD) completion among patients diagnosed with a terminal illness. We defined AD completion as having completed a living will and/or identified a healthcare power of attorney.
A convenience sample of 206 caregiver–patient dyads was included in the study. All patients were diagnosed with an advanced life-limiting illness. Trained research nurses administered surveys to collect information on patient and caregiver demographics (i.e., age, sex, race, education, marital status, and individual annual income) and patients' diagnoses and completion of AD. Multivariate logistic regression was employed to model predictors for patients' AD completion.
Over half of our patient sample (59%) completed an AD. Patients who were older, diagnosed with amyotrophic lateral sclerosis, and with a caregiver who was Caucasian or declined to report an income level were more likely to have an AD in place.
Significance of results:
Our results suggest that both patient and caregiver characteristics may influence patients' decisions to complete an AD at the end of life. When possible, caregivers should be included in advance care planning for patients who are terminally ill.
In October 2008, Medicare ceased additional payment for hospital-acquired conditions not present on admission. We evaluated the policy’s differential impact in hospitals with high vs low operating margins. Medicare’s payment policy may have had an impact on reducing central line–associated bloodstream infections in hospitals with low operating margins.
Infect. Control Hosp. Epidemiol. 2015;37(1):100–103
This study aims to develop an expedited radiotherapy (RT) process and evaluate its time savings in women requiring whole breast RT.
Material and methods
An inter-professional RT team streamlined the computed tomography (CT) simulation and treatment pathway for a ‘QuickStart’ process. Target delineation was performed by an advanced practice radiation therapist and approved by the radiation oncologist (RO) for planning. Automated breast planning software was used for treatment planning and standard quality checks were performed. To assess time savings, the initial 25 QuickStart patients were matched with women who underwent whole breast simulation on the same day (±3 days), treated using the conventional process.
A total of 73 post-lumpectomy women were treated through the QuickStart process; the median consent-to-RT was 2 days (range: 0–13) and the mean CT simulation-to-RT treatment was 2 hours and 42 minutes (SD 0:30). In the subgroup analysis, QuickStart patients saved an average of 11 days from CT simulation-to-RT and had shorter median wait-times for both surgery/chemotherapy-to-RT (60 versus 38 days; p=0·002) and consultation-to-RT (7 versus 20 days; p<0·001).
Through inter-professional team efforts and the application of automated planning software, we have achieved a process that significantly decreases patient wait-times while maintaining the quality of whole breast RT.
The 2008 Centers for Medicare & Medicaid Services hospital-acquired conditions policy limited additional payment for conditions deemed reasonably preventable.
To examine whether this policy was associated with decreases in billing rates for 2 targeted conditions, vascular catheter-associated infections (VCAI) and catheter-associated urinary tract infections (CAUTI).
Adult Medicare patients admitted to 569 acute care hospitals in California, Massachusetts, or New York and subject to the policy.
We used an interrupted times series design to assess whether the hospital-acquired conditions policy was associated with changes in billing rates for VCAI and CAUTI.
Before the policy, billing rates for VCAI and CAUTI were increasing (prepolicy odds ratio per quarter for VCAI, 1.17 [95% CI, 1.11–1.23]; for CAUTI, 1.19 [1.16–1.23]). The policy was associated with an immediate drop in billing rates for VCAI and CAUTI (odds ratio for change at policy implementation for VCAI, 0.75 [95% CI, 0.69–0.81]; for CAUTI, 0.87 [0.79–0.96]). In the postpolicy period, we observed a decreasing trend in the billing rate for VCAI and a leveling-off in the billing rate for CAUTI (postpolicy odds ratio per quarter for VCAI, 0.98 [95% CI, 0.97–0.99]; for CAUTI, 0.99 [0.97–1.00]).
The Centers for Medicare & Medicaid Services hospital-acquired conditions policy appears to have been associated with immediate reductions in billing rates for VCAI and CAUTI, followed by a slight decreasing trend or leveling-off in rates. These billing rates, however, may not correlate with changes in clinically meaningful patient outcomes and may reflect changes in coding practices.
Infect. Control Hosp. Epidemiol. 2015;36(8):871–877
Policymakers may wish to align healthcare payment and quality of care while minimizing unintended consequences, particularly for safety net hospitals.
To determine whether the 2008 Centers for Medicare and Medicaid Services Hospital-Acquired Conditions policy had a differential impact on targeted healthcare-associated infection rates in safety net compared with non–safety net hospitals.
Interrupted time-series design.
SETTING AND PARTICIPANTS
Nonfederal acute care hospitals that reported central line–associated bloodstream infection and ventilator-associated pneumonia rates to the Centers for Disease Control and Prevention’s National Health Safety Network from July 1, 2007, through December 31, 2013.
We did not observe changes in the slope of targeted infection rates in the postpolicy period compared with the prepolicy period for either safety net (postpolicy vs prepolicy ratio, 0.96 [95% CI, 0.84–1.09]) or non–safety net (0.99 [0.90–1.10]) hospitals. Controlling for prepolicy secular trends, we did not detect differences in an immediate change at the time of the policy between safety net and non–safety net hospitals (P for 2-way interaction, .87).
The Centers for Medicare and Medicaid Services Hospital-Acquired Conditions policy did not have an impact, either positive or negative, on already declining rates of central line–associated bloodstream infection in safety net or non–safety net hospitals. Continued evaluations of the broad impact of payment policies on safety net hospitals will remain important as the use of financial incentives and penalties continues to expand in the United States.
Background: Acquired brain injury is a critical public health and socioeconomic problem in Canada, leaving many patients in vegetative, minimally conscious, or locked-in states, unresponsive and unable to communicate. Recent advances in neuroimaging research have demonstrated residual consciousness in a few exemplary patients with acquired brain injury, suggesting potential misdiagnosis and changes in prognosis. Such progress, in parallel with research using multimodal brain imaging technologies in recent years, has promising implications for clinical translation, notwithstanding the many challenges that impact health care and policy development. This study explored the perspectives of Canadian professionals with expertise either in neuroimaging research, disorders of consciousness, or both, on the potential clinical applications and implications of imaging technology. Methods: Twenty-two professionals from designated communities of neuroimaging researchers, ethicists, lawyers, and practitioners participated in semistructured interviews. Data were analyzed for emergent themes. Results: The five most dominant themes were: (1) validation and calibration of the methods; (2) informed consent; (3) burdens on the health care system; (4) implications for the Canadian health care system; and (5) possibilities for improved prognosis. Conclusions: Movement of neuroimaging from research into clinical care for acquired brain injury will require careful consideration of legal and ethical issues alongside research reliability, responsible distribution of health care resources, and the interaction of technological capabilities with patient outcome.
To create a national policy model to evaluate the projected cost-effectiveness of multiple hospital-based strategies to prevent methicillin-resistant Staphylococcus aureus (MRSA) transmission and infection.
Cost-effectiveness analysis using a Markov microsimulation model that simulates the natural history of MRSA acquisition and infection.
PATIENTS AND SETTING
Hypothetical cohort of 10,000 adult patients admitted to a US intensive care unit.
We compared 7 strategies to standard precautions using a hospital perspective: (1) active surveillance cultures; (2) active surveillance cultures plus selective decolonization; (3) universal contact precautions (UCP); (4) universal chlorhexidine gluconate baths; (5) universal decolonization; (6) UCP + chlorhexidine gluconate baths; and (7) UCP+decolonization. For each strategy, both efficacy and compliance were considered. Outcomes of interest were: (1) MRSA colonization averted; (2) MRSA infection averted; (3) incremental cost per colonization averted; (4) incremental cost per infection averted.
A total of 1989 cases of colonization and 544 MRSA invasive infections occurred under standard precautions per 10,000 patients. Universal decolonization was the least expensive strategy and was more effective compared with all strategies except UCP+decolonization and UCP+chlorhexidine gluconate. UCP+decolonization was more effective than universal decolonization but would cost $2469 per colonization averted and $9007 per infection averted. If MRSA colonization prevalence decreases from 12% to 5%, active surveillance cultures plus selective decolonization becomes the least expensive strategy.
Universal decolonization is cost-saving, preventing 44% of cases of MRSA colonization and 45% of cases of MRSA infection. Our model provides useful guidance for decision makers choosing between multiple available hospital-based strategies to prevent MRSA transmission.
To develop a candidate definition for central line–associated bloodstream infection (CLABSI) in neonates with presumed mucosal barrier injury due to gastrointestinal (MBI-GI) conditions and to evaluate epidemiology and microbiology of MBI-GI CLABSI in infants
Multicenter retrospective cohort study.
Neonatal intensive care units from 14 US children’s hospitals and pediatric facilities.
A multidisciplinary focus group developed a candidate MBI-GI CLABSI definition based on presence of an MBI-GI condition, parenteral nutrition (PN) exposure, and an eligible enteric organism. CLABSI surveillance data from participating hospitals were supplemented by chart review to identify MBI-GI conditions and PN exposure.
During 2009–2012, 410 CLABSIs occurred in 376 infants. MBI-GI conditions and PN exposure occurred in 149 (40%) and 324 (86%) of these 376 neonates, respectively. The distribution of pathogens was similar among neonates with versus without MBI-GI conditions and PN exposure. Fifty-nine (16%) of the 376 initial CLABSI episodes met the candidate MBI-GI CLABSI definition. Subsequent versus initial CLABSIs were more likely to be caused by an enteric organism (22 of 34 [65%] vs 151 of 376 [40%]; P = .009) and to meet the candidate MBI-GI CLABSI definition (19 of 34 [56%] vs 59 of 376 [16%]; P < .01).
While MBI-GI conditions and PN exposure were common, only 16% of initial CLABSIs met the candidate definition of MBI-GI CLABSI. The high proportion of MBI-GI CLABSIs among subsequent infections suggests that infants with MBI-GI CLABSI should be a population targeted for further surveillance and interventional research.
Infect Control Hosp Epidemiol 2014;35(11):1391–1399