A Trial of Automated Outbreak Detection to Reduce Hospital Pathogen Spread.

BACKGROUND: Detection and containment of hospital outbreaks currently depend on variable and personnel-intensive surveillance methods. Whether automated statistical surveillance for outbreaks of health care-associated pathogens allows earlier containment efforts that would reduce the size of outbreaks is unknown. METHODS: We conducted a cluster-randomized trial in 82 community hospitals within a larger health care system. All hospitals followed an outbreak response protocol when outbreaks were detected by their infection prevention programs. Half of the hospitals additionally used statistical surveillance of microbiology data, which alerted infection prevention programs to outbreaks. Statistical surveillance was also applied to microbiology data from control hospitals without alerting their infection prevention programs. The primary outcome was the number of additional cases occurring after outbreak detection. Analyses assessed differences between the intervention period (July 2019 to January 2022) versus baseline period (February 2017 to January 2019) between randomized groups. A post hoc analysis separately assessed pre-coronavirus disease 2019 (Covid-19) and Covid-19 pandemic intervention periods. RESULTS: Real-time alerts did not significantly reduce the number of additional outbreak cases (intervention period versus baseline: statistical surveillance relative rate [RR]=1.41, control RR=1.81; difference-in-differences, 0.78; 95% confidence interval [CI], 0.40 to 1.52; P=0.46). Comparing only the prepandemic intervention with baseline periods, the statistical outbreak surveillance group was associated with a 64.1% reduction in additional cases (statistical surveillance RR=0.78, control RR=2.19; difference-in-differences, 0.36; 95% CI, 0.13 to 0.99). There was no similarly observed association between the pandemic versus baseline periods (statistical surveillance RR=1.56, control RR=1.66; difference-in-differences, 0.94; 95% CI, 0.46 to 1.92). CONCLUSIONS: Automated detection of hospital outbreaks using statistical surveillance did not reduce overall outbreak size in the context of an ongoing pandemic. (Funded by the Centers for Disease Control and Prevention; ClinicalTrials.gov number, NCT04053075. Support for HCA Healthcare's participation in the study was provided in kind by HCA.).

Stewardship Prompts to Improve Antibiotic Selection for Urinary Tract Infection: The INSPIRE Randomized Clinical Trial.

Importance: Urinary tract infection (UTI) is the second most common infection leading to hospitalization and is often associated with gram-negative multidrug-resistant organisms (MDROs). Clinicians overuse extended-spectrum antibiotics although most patients are at low risk for MDRO infection. Safe strategies to limit overuse of empiric antibiotics are needed. Objective: To evaluate whether computerized provider order entry (CPOE) prompts providing patient- and pathogen-specific MDRO risk estimates could reduce use of empiric extended-spectrum antibiotics for treatment of UTI. Design, Setting, and Participants: Cluster-randomized trial in 59 US community hospitals comparing the effect of a CPOE stewardship bundle (education, feedback, and real-time and risk-based CPOE prompts; 29 hospitals) vs routine stewardship (n = 30 hospitals) on antibiotic selection during the first 3 hospital days (empiric period) in noncritically ill adults (≥18 years) hospitalized with UTI with an 18-month baseline (April 1, 2017-September 30, 2018) and 15-month intervention period (April 1, 2019-June 30, 2020). Interventions: CPOE prompts recommending empiric standard-spectrum antibiotics in patients ordered to receive extended-spectrum antibiotics who have low estimated absolute risk (<10%) of MDRO UTI, coupled with feedback and education. Main Outcomes and Measures: The primary outcome was empiric (first 3 days of hospitalization) extended-spectrum antibiotic days of therapy. Secondary outcomes included empiric vancomycin and antipseudomonal days of therapy. Safety outcomes included days to intensive care unit (ICU) transfer and hospital length of stay. Outcomes were assessed using generalized linear mixed-effect models to assess differences between the baseline and intervention periods. Results: Among 127 403 adult patients (71 991 baseline and 55 412 intervention period) admitted with UTI in 59 hospitals, the mean (SD) age was 69.4 (17.9) years, 30.5% were male, and the median Elixhauser Comorbidity Index count was 4 (IQR, 2-5). Compared with routine stewardship, the group using CPOE prompts had a 17.4% (95% CI, 11.2%-23.2%) reduction in empiric extended-spectrum days of therapy (rate ratio, 0.83 [95% CI, 0.77-0.89]; P < .001). The safety outcomes of mean days to ICU transfer (6.6 vs 7.0 days) and hospital length of stay (6.3 vs 6.5 days) did not differ significantly between the routine and intervention groups, respectively. Conclusions and Relevance: Compared with routine stewardship, CPOE prompts providing real-time recommendations for standard-spectrum antibiotics for patients with low MDRO risk coupled with feedback and education significantly reduced empiric extended-spectrum antibiotic use among noncritically ill adults admitted with UTI without changing hospital length of stay or days to ICU transfers. Trial Registration: ClinicalTrials.gov Identifier: NCT03697096.

Stewardship Prompts to Improve Antibiotic Selection for Pneumonia: The INSPIRE Randomized Clinical Trial.

Importance: Pneumonia is the most common infection requiring hospitalization and is a major reason for overuse of extended-spectrum antibiotics. Despite low risk of multidrug-resistant organism (MDRO) infection, clinical uncertainty often drives initial antibiotic selection. Strategies to limit empiric antibiotic overuse for patients with pneumonia are needed. Objective: To evaluate whether computerized provider order entry (CPOE) prompts providing patient- and pathogen-specific MDRO infection risk estimates could reduce empiric extended-spectrum antibiotics for non-critically ill patients admitted with pneumonia. Design, Setting, and Participants: Cluster-randomized trial in 59 US community hospitals comparing the effect of a CPOE stewardship bundle (education, feedback, and real-time MDRO risk-based CPOE prompts; n = 29 hospitals) vs routine stewardship (n = 30 hospitals) on antibiotic selection during the first 3 hospital days (empiric period) in non-critically ill adults (≥18 years) hospitalized with pneumonia. There was an 18-month baseline period from April 1, 2017, to September 30, 2018, and a 15-month intervention period from April 1, 2019, to June 30, 2020. Intervention: CPOE prompts recommending standard-spectrum antibiotics in patients ordered to receive extended-spectrum antibiotics during the empiric period who have low estimated absolute risk (<10%) of MDRO pneumonia, coupled with feedback and education. Main Outcomes and Measures: The primary outcome was empiric (first 3 days of hospitalization) extended-spectrum antibiotic days of therapy. Secondary outcomes included empiric vancomycin and antipseudomonal days of therapy and safety outcomes included days to intensive care unit (ICU) transfer and hospital length of stay. Outcomes compared differences between baseline and intervention periods across strategies. Results: Among 59 hospitals with 96 451 (51 671 in the baseline period and 44 780 in the intervention period) adult patients admitted with pneumonia, the mean (SD) age of patients was 68.1 (17.0) years, 48.1% were men, and the median (IQR) Elixhauser comorbidity count was 4 (2-6). Compared with routine stewardship, the group using CPOE prompts had a 28.4% reduction in empiric extended-spectrum days of therapy (rate ratio, 0.72 [95% CI, 0.66-0.78]; P < .001). Safety outcomes of mean days to ICU transfer (6.5 vs 7.1 days) and hospital length of stay (6.8 vs 7.1 days) did not differ significantly between the routine and CPOE intervention groups. Conclusions and Relevance: Empiric extended-spectrum antibiotic use was significantly lower among adults admitted with pneumonia to non-ICU settings in hospitals using education, feedback, and CPOE prompts recommending standard-spectrum antibiotics for patients at low risk of MDRO infection, compared with routine stewardship practices. Hospital length of stay and days to ICU transfer were unchanged. Trial Registration: ClinicalTrials.gov Identifier: NCT03697070.

Reducing Hospitalizations and Multidrug-Resistant Organisms via Regional Decolonization in Hospitals and Nursing Homes.

Importance: Infections due to multidrug-resistant organisms (MDROs) are associated with increased morbidity, mortality, length of hospitalization, and health care costs. Regional interventions may be advantageous in mitigating MDROs and associated infections. Objective: To evaluate whether implementation of a decolonization collaborative is associated with reduced regional MDRO prevalence, incident clinical cultures, infection-related hospitalizations, costs, and deaths. Design, Setting, and Participants: This quality improvement study was conducted from July 1, 2017, to July 31, 2019, across 35 health care facilities in Orange County, California. Exposures: Chlorhexidine bathing and nasal iodophor antisepsis for residents in long-term care and hospitalized patients in contact precautions (CP). Main Outcomes and Measures: Baseline and end of intervention MDRO point prevalence among participating facilities; incident MDRO (nonscreening) clinical cultures among participating and nonparticipating facilities; and infection-related hospitalizations and associated costs and deaths among residents in participating and nonparticipating nursing homes (NHs). Results: Thirty-five facilities (16 hospitals, 16 NHs, 3 long-term acute care hospitals [LTACHs]) adopted the intervention. Comparing decolonization with baseline periods among participating facilities, the mean (SD) MDRO prevalence decreased from 63.9% (12.2%) to 49.9% (11.3%) among NHs, from 80.0% (7.2%) to 53.3% (13.3%) among LTACHs (odds ratio [OR] for NHs and LTACHs, 0.48; 95% CI, 0.40-0.57), and from 64.1% (8.5%) to 55.4% (13.8%) (OR, 0.75; 95% CI, 0.60-0.93) among hospitalized patients in CP. When comparing decolonization with baseline among NHs, the mean (SD) monthly incident MDRO clinical cultures changed from 2.7 (1.9) to 1.7 (1.1) among participating NHs, from 1.7 (1.4) to 1.5 (1.1) among nonparticipating NHs (group × period interaction reduction, 30.4%; 95% CI, 16.4%-42.1%), from 25.5 (18.6) to 25.0 (15.9) among participating hospitals, from 12.5 (10.1) to 14.3 (10.2) among nonparticipating hospitals (group × period interaction reduction, 12.9%; 95% CI, 3.3%-21.5%), and from 14.8 (8.6) to 8.2 (6.1) among LTACHs (all facilities participating; 22.5% reduction; 95% CI, 4.4%-37.1%). For NHs, the rate of infection-related hospitalizations per 1000 resident-days changed from 2.31 during baseline to 1.94 during intervention among participating NHs, and from 1.90 to 2.03 among nonparticipating NHs (group × period interaction reduction, 26.7%; 95% CI, 19.0%-34.5%). Associated hospitalization costs per 1000 resident-days changed from $64 651 to $55 149 among participating NHs and from $55 151 to $59 327 among nonparticipating NHs (group × period interaction reduction, 26.8%; 95% CI, 26.7%-26.9%). Associated hospitalization deaths per 1000 resident-days changed from 0.29 to 0.25 among participating NHs and from 0.23 to 0.24 among nonparticipating NHs (group × period interaction reduction, 23.7%; 95% CI, 4.5%-43.0%). Conclusions and Relevance: A regional collaborative involving universal decolonization in long-term care facilities and targeted decolonization among hospital patients in CP was associated with lower MDRO carriage, infections, hospitalizations, costs, and deaths.

National validation of the Centers for Medicare & Medicaid Services strategy for identifying potential surgical-site infections following colon surgery and abdominal hysterectomy.

OBJECTIVE: National validation of claims-based surveillance for surgical-site infections (SSIs) following colon surgery and abdominal hysterectomy. DESIGN: Retrospective cohort study. SETTING: US hospitals selected for data validation by Centers for Medicare & Medicaid Services (CMS). PARTICIPANTS: The study included 550 hospitals performing colon surgery and 458 hospitals performing abdominal hysterectomy in federal fiscal year 2013. METHODS: We requested 1,200 medical records from hospitals selected for validation as part of the CMS Hospital Inpatient Quality Reporting program. For colon surgery, we sampled 60% with a billing code suggestive of SSI during their index admission and/or readmission within 30 days and 40% who were readmitted without one of these codes. For abdominal hysterectomy, we included all patients with an SSI code during their index admission, all patients readmitted within 30 days, and a sample of those with a prolonged surgical admission (length of stay > 7 days). We calculated sensitivity and positive predictive value for the different groups. RESULTS: We identified 142 colon-surgery SSIs (46 superficial SSIs and 96 deep and organ-space SSIs) and 127 abdominal-hysterectomy SSIs (58 superficial SSIs and 69 deep and organ-space SSIs). Extrapolating to the full CMS data validation cohort, we estimated an SSI rate of 8.3% for colon surgery and 3.0% for abdominal hysterectomy. Our colon-surgery surveillance codes identified 93% of SSIs, with 1 SSI identified for every 2.6 patients reviewed. Our abdominal-hysterectomy surveillance codes identified 73% of SSIs, with 1 SSI identified for every 1.6 patients reviewed. CONCLUSIONS: Using claims to target record review for SSI validation performed well in a national sample.

Nasal Iodophor Antiseptic vs Nasal Mupirocin Antibiotic in the Setting of Chlorhexidine Bathing to Prevent Infections in Adult ICUs: A Randomized Clinical Trial.

Importance: Universal nasal mupirocin plus chlorhexidine gluconate (CHG) bathing in intensive care units (ICUs) prevents methicillin-resistant Staphylococcus aureus (MRSA) infections and all-cause bloodstream infections. Antibiotic resistance to mupirocin has raised questions about whether an antiseptic could be advantageous for ICU decolonization. Objective: To compare the effectiveness of iodophor vs mupirocin for universal ICU nasal decolonization in combination with CHG bathing. Design, Setting, and Participants: Two-group noninferiority, pragmatic, cluster-randomized trial conducted in US community hospitals, all of which used mupirocin-CHG for universal decolonization in ICUs at baseline. Adult ICU patients in 137 randomized hospitals during baseline (May 1, 2015-April 30, 2017) and intervention (November 1, 2017-April 30, 2019) were included. Intervention: Universal decolonization involving switching to iodophor-CHG (intervention) or continuing mupirocin-CHG (baseline). Main Outcomes and Measures: ICU-attributable S aureus clinical cultures (primary outcome), MRSA clinical cultures, and all-cause bloodstream infections were evaluated using proportional hazard models to assess differences from baseline to intervention periods between the strategies. Results were also compared with a 2009-2011 trial of mupirocin-CHG vs no decolonization in the same hospital network. The prespecified noninferiority margin for the primary outcome was 10%. Results: Among the 801 668 admissions in 233 ICUs, the participants' mean (SD) age was 63.4 (17.2) years, 46.3% were female, and the mean (SD) ICU length of stay was 4.8 (4.7) days. Hazard ratios (HRs) for S aureus clinical isolates in the intervention vs baseline periods were 1.17 for iodophor-CHG (raw rate: 5.0 vs 4.3/1000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 4.1 vs 4.0/1000 ICU-attributable days) (HR difference in differences significantly lower by 18.4% [95% CI, 10.7%-26.6%] for mupirocin-CHG, P < .001). For MRSA clinical cultures, HRs were 1.13 for iodophor-CHG (raw rate: 2.3 vs 2.1/1000 ICU-attributable days) and 0.99 for mupirocin-CHG (raw rate: 2.0 vs 2.0/1000 ICU-attributable days) (HR difference in differences significantly lower by 14.1% [95% CI, 3.7%-25.5%] for mupirocin-CHG, P = .007). For all-pathogen bloodstream infections, HRs were 1.00 (2.7 vs 2.7/1000) for iodophor-CHG and 1.01 (2.6 vs 2.6/1000) for mupirocin-CHG (nonsignificant HR difference in differences, -0.9% [95% CI, -9.0% to 8.0%]; P = .84). Compared with the 2009-2011 trial, the 30-day relative reduction in hazards in the mupirocin-CHG group relative to no decolonization (2009-2011 trial) were as follows: S aureus clinical cultures (current trial: 48.1% [95% CI, 35.6%-60.1%]; 2009-2011 trial: 58.8% [95% CI, 47.5%-70.7%]) and bloodstream infection rates (current trial: 70.4% [95% CI, 62.9%-77.8%]; 2009-2011 trial: 60.1% [95% CI, 49.1%-70.7%]). Conclusions and Relevance: Nasal iodophor antiseptic did not meet criteria to be considered noninferior to nasal mupirocin antibiotic for the outcome of S aureus clinical cultures in adult ICU patients in the context of daily CHG bathing. In addition, the results were consistent with nasal iodophor being inferior to nasal mupirocin. Trial Registration: ClinicalTrials.gov Identifier: NCT03140423.

Decolonization in Nursing Homes to Prevent Infection and Hospitalization.

BACKGROUND: Nursing home residents are at high risk for infection, hospitalization, and colonization with multidrug-resistant organisms. METHODS: We performed a cluster-randomized trial of universal decolonization as compared with routine-care bathing in nursing homes. The trial included an 18-month baseline period and an 18-month intervention period. Decolonization entailed the use of chlorhexidine for all routine bathing and showering and administration of nasal povidone-iodine twice daily for the first 5 days after admission and then twice daily for 5 days every other week. The primary outcome was transfer to a hospital due to infection. The secondary outcome was transfer to a hospital for any reason. An intention-to-treat (as-assigned) difference-in-differences analysis was performed for each outcome with the use of generalized linear mixed models to compare the intervention period with the baseline period across trial groups. RESULTS: Data were obtained from 28 nursing homes with a total of 28,956 residents. Among the transfers to a hospital in the routine-care group, 62.2% (the mean across facilities) were due to infection during the baseline period and 62.6% were due to infection during the intervention period (risk ratio, 1.00; 95% confidence interval [CI], 0.96 to 1.04). The corresponding values in the decolonization group were 62.9% and 52.2% (risk ratio, 0.83; 95% CI, 0.79 to 0.88), for a difference in risk ratio, as compared with routine care, of 16.6% (95% CI, 11.0 to 21.8; P<0.001). Among the discharges from the nursing home in the routine-care group, transfer to a hospital for any reason accounted for 36.6% during the baseline period and for 39.2% during the intervention period (risk ratio, 1.08; 95% CI, 1.04 to 1.12). The corresponding values in the decolonization group were 35.5% and 32.4% (risk ratio, 0.92; 95% CI, 0.88 to 0.96), for a difference in risk ratio, as compared with routine care, of 14.6% (95% CI, 9.7 to 19.2). The number needed to treat was 9.7 to prevent one infection-related hospitalization and 8.9 to prevent one hospitalization for any reason. CONCLUSIONS: In nursing homes, universal decolonization with chlorhexidine and nasal iodophor led to a significantly lower risk of transfer to a hospital due to infection than routine care. (Funded by the Agency for Healthcare Research and Quality; Protect ClinicalTrials.gov number, NCT03118232.).

Childhood Sugar-Sweetened Beverage Consumption: an Agent-Based Model of Context-Specific Reduction Efforts.

INTRODUCTION: Despite widespread recognition among public health experts that childhood sugar-sweetened beverage consumption should be reduced, doing so has proven to be a challenge. An agent-based model of early childhood sugar-sweetened beverage consumption was applied to data from three high-quality, longitudinal cohort studies to gain insight into potentially effective intervention strategies across contexts. METHODS: From 2021 to 2023, a single agent-based model design was applied to data sets derived from three separate cohorts of children followed from infancy to childhood, with very different populations and environments (participants recruited in 1999-2002; 2003-2010; and 2009-2014). After assessing its ability to reproduce observed consumption patterns across cohorts, it was used to simulate potential impacts of multiple intervention strategies across contexts. RESULTS: Interventions reducing home availability of sugar-sweetened beverages consistently had the largest potential effects. Impact differed between cohort settings: a complete decrease in availability resulted in an estimated 87% decrease in overall early childhood consumption for one of the cohorts, compared with 61% and 54% in the others. Reducing availability in center-based child care resulted in substantially greater reduction in one cohort relative to the other two. CONCLUSIONS: There is untapped potential for strategies targeting children's sugar-sweetened beverage consumption in the home, but in some instances, other approaches might also yield meaningful effects. Tailoring approach to setting may be important, and agent-based models can be informative for doing so. This agent-based model has broad generalizability and potential to serve as a tool for designing effective, context-specific strategies to reduce childhood sugar-sweetened beverage consumption.

Combined laparoscopic and open colon surgery rankings fail to accurately rank hospitals by surgical-site infection rate.

OBJECTIVE: To compare strategies for hospital ranking based on colon surgical-site infection (SSI) rate by combining all colon procedures versus stratifying by surgical approach (ie, laparoscopic vs open). DESIGN: Retrospective cohort study. METHODS: We identified SSIs among Medicare beneficiaries undergoing colon surgery from 2009 through 2013 using previously validated methods. We created a risk prediction model for SSI using age, sex, race, comorbidities, surgical approach (laparoscopy vs open), and concomitant colon and noncolon procedures. Adjusted SSI rates were used to rank hospitals. Subanalyses were performed for common colon procedures and procedure types for which there were both open and laparoscopic procedures. We generated ranks using only open and only laparoscopic procedures, overall and for each subanalysis. Rankings were compared using a Spearman correlation coefficient. RESULTS: In total, 694,813 colon procedures were identified among 508,135 Medicare beneficiaries. The overall SSI rate was 7.6%. The laparoscopic approach was associated with lower SSI risk (OR, 0.5; 95% CI, 0.4-0.5), and higher SSI risk was associated with concomitant abdominal surgeries (OR, 1.4; 95% CI, 1.4-1.5) and higher Elixhauser score (OR, 1.1; 95% CI, 1.0-1.1). Hospital rankings for laparascopic procedures were poorly correlated with rankings for open procedures (r = 0.23). CONCLUSIONS: Hospital rankings based on total colon procedures fail to account for differences in SSI risk from laparoscopic vs open procedures. Stratifying rankings by surgical approach yields a more equitable comparison of surgical performance.

An agent-based model of child sugar-sweetened beverage consumption: implications for policies and practices.

BACKGROUND: A strong body of evidence links young children's intake of sugar-sweetened beverages (SSBs) with myriad negative outcomes. OBJECTIVES: Our research provides insight into whether and to what extent potential intervention strategies can reduce young children's consumption of SSBs. METHODS: We built an agent-based model (ABM) of SSB consumption representing participants in the Project Viva longitudinal study between ages 2 and 7 y. In addition to extensive data from Project Viva, our model used nationally representative data as well as recent, high-quality literature. We tested the explanatory power of the model through comparison to consumption patterns observed in the Project Viva cohort. Then, we applied the model to simulate the potential impact of interventions that would reduce SSB availability in 1 or more settings or affect how families receive and respond to pediatrician advice. RESULTS: Our model produced age-stratified trends in beverage consumption that closely match those observed in Project Viva cohort data. Among the potential interventions we simulated, reducing availability in the home-where young children spend the greatest amount of time-resulted in the largest consumption decrease. Removing access to all SSBs in the home resulted in them consuming 1.23 (95% CI: 1.21, 1.24) fewer servings of SSBs per week on average between the ages of 2 and 7 y, a reduction of ∼60%. By comparison, removing all SSB availability outside of the home (i.e., in schools and childcare) had a smaller impact (0.77; CI: 0.75, 0.78), a reduction of ∼40%. CONCLUSIONS: These results suggest that interventions reducing SSB availability in the home would have the strongest effects on SSB consumption.

Correction: Racial and geographic variation in effects of maternal education and neighborhood-level measures of socioeconomic status on gestational age at birth: Findings from the ECHO cohorts.

[This corrects the article DOI: 10.1371/journal.pone.0245064.].

The Impact of Coronavirus Disease 2019 (COVID-19) on Healthcare-Associated Infections.

BACKGROUND: The profound changes wrought by coronavirus disease 2019 (COVID-19) on routine hospital operations may have influenced performance on hospital measures, including healthcare-associated infections (HAIs). We aimed to evaluate the association between COVID-19 surges and HAI and cluster rates. METHODS: In 148 HCA Healthcare-affiliated hospitals, from 1 March 2020 to 30 September 2020, and a subset of hospitals with microbiology and cluster data through 31 December 2020, we evaluated the association between COVID-19 surges and HAIs, hospital-onset pathogens, and cluster rates using negative binomial mixed models. To account for local variation in COVID-19 pandemic surge timing, we included the number of discharges with a laboratory-confirmed COVID-19 diagnosis per staffed bed per month. RESULTS: Central line-associated blood stream infections (CLABSI), catheter-associated urinary tract infections (CAUTI), and methicillin-resistant Staphylococcus aureus (MRSA) bacteremia increased as COVID-19 burden increased. There were 60% (95% confidence interval [CI]: 23-108%) more CLABSI, 43% (95% CI: 8-90%) more CAUTI, and 44% (95% CI: 10-88%) more cases of MRSA bacteremia than expected over 7 months based on predicted HAIs had there not been COVID-19 cases. Clostridioides difficile infection was not significantly associated with COVID-19 burden. Microbiology data from 81 of the hospitals corroborated the findings. Notably, rates of hospital-onset bloodstream infections and multidrug resistant organisms, including MRSA, vancomycin-resistant enterococcus, and Gram-negative organisms, were each significantly associated with COVID-19 surges. Finally, clusters of hospital-onset pathogens increased as the COVID-19 burden increased. CONCLUSIONS: COVID-19 surges adversely impact HAI rates and clusters of infections within hospitals, emphasizing the need for balancing COVID-related demands with routine hospital infection prevention.

Temporal trends of concentrations of per- and polyfluoroalkyl substances among adults with overweight and obesity in the United States: Results from the Diabetes Prevention Program and NHANES.

BACKGROUND: Understanding the temporal trends and change of concentrations of per- and polyfluoroalkyl substances (PFAS) is important to evaluate the health impact of PFAS at both the individual- and population-level, however, limited information is available for pre-diabetic adults in the U.S. OBJECTIVES: Determine trends and rate of change of plasma PFAS concentrations in overweight or obese U.S. adults and evaluate variation by sex, race/ethnicity, and age. METHODS: We described temporal trends of plasma PFAS concentrations using samples collected in 1996-1998, 1999-2001, and 2011-2012 from 957 pre-diabetic adults enrolled in the Diabetes Prevention Program (DPP) trial and Outcomes Study (DPPOS) and compared to serum concentrations from the National Health and Nutrition Examination Survey (NHANES 1999-2000, 2003-2016, adults with BMI ≥ 24 kg/m2). We examined associations between participants' characteristics and PFAS concentrations and estimated the rate of change using repeated measures in DPP/DPPOS assuming a first-order elimination model. RESULTS: Longitudinal measures of PFAS concentrations in DPP/DPPOS individuals were comparable to NHANES cross-sectional populational means. Plasma concentrations of perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid, perfluorohexanesulfonic acid (PFHxS), N-ethyl-perfluorooctane sulfonamido acetic acid (EtFOSAA), and N-methylperfluorooctane sulfonamido acetic acid (MeFOSAA) started to decline after the year 2000 and concentrations of perfluorononanoic acid (PFNA) increased after 2000 and, for NHANES, decreased after 2012. We consistently observed higher PFOS, PFHxS and PFNA among male, compared to female, and higher PFOS and PFNA among Black, compared to white, participants. The estimated time for concentrations to decrease by half ranged from 3.39 years for EtFOSAA to 17.56 years for PFHxS. DISCUSSION: We observed a downward temporal trend in plasma PFOS concentrations that was consistent with the timing for U.S. manufacturers' phaseout. Male and Black participants consistently showed higher PFOS and PFNA than female and white participants, likely due to differences in exposure patterns, metabolism or elimination kinetics.

Matching in cluster randomized trials using the Goldilocks Approach.

In group or cluster-randomized trials (GRTs), matching is a technique that can be used to improve covariate balance. When baseline data are available, we suggest a strategy that can be used to achieve the desired balance between treatment and control groups across numerous potential confounding variables. This strategy minimizes the overall within-pair Mahalanobis distance; and involves iteratively: 1) making pairs that minimize the distance between pairs of clusters with respect to potentially confounding variables; 2) visually assessing the potential effects of these pairs and resulting possible randomizations; and 3) reweighting variables of selecting weights to make pairs of clusters. In step 2, we plot the between-arm differences with a parallel-coordinates plot. Investigators can compare plots of different weighting schemes to determine the one that best suits their needs prior to the actual, final, randomization. We demonstrate application of the approach with the Mupirocin-Iodophor Swap Out trial. A webapp is provided.

Type I error control for cluster randomized trials under varying small sample structures.

BACKGROUND: Linear mixed models (LMM) are a common approach to analyzing data from cluster randomized trials (CRTs). Inference on parameters can be performed via Wald tests or likelihood ratio tests (LRT), but both approaches may give incorrect Type I error rates in common finite sample settings. The impact of different combinations of cluster size, number of clusters, intraclass correlation coefficient (ICC), and analysis approach on Type I error rates has not been well studied. Reviews of published CRTs find that small sample sizes are not uncommon, so the performance of different inferential approaches in these settings can guide data analysts to the best choices. METHODS: Using a random-intercept LMM stucture, we use simulations to study Type I error rates with the LRT and Wald test with different degrees of freedom (DF) choices across different combinations of cluster size, number of clusters, and ICC. RESULTS: Our simulations show that the LRT can be anti-conservative when the ICC is large and the number of clusters is small, with the effect most pronouced when the cluster size is relatively large. Wald tests with the between-within DF method or the Satterthwaite DF approximation maintain Type I error control at the stated level, though they are conservative when the number of clusters, the cluster size, and the ICC are small. CONCLUSIONS: Depending on the structure of the CRT, analysts should choose a hypothesis testing approach that will maintain the appropriate Type I error rate for their data. Wald tests with the Satterthwaite DF approximation work well in many circumstances, but in other cases the LRT may have Type I error rates closer to the nominal level.

Using a Microsimulation of Energy Balance to Explore the Influence of Prenatal Sugar-Sweetened Beverage Intake on Child BMI.

OBJECTIVE: Experiments with animals suggest that high sugar consumption during pregnancy may predispose offspring to obesity, but few human studies have examined this relationship. This study explored the association between the consumption of sugar-sweetened beverages (SSBs) during pregnancy and caloric intake through childhood. METHODS: Using cohort data on child weight, height, and physical activity levels, a lab-validated microsimulation model of energy balance was employed to infer the caloric intake of children through age 11 years. Random effects models were then employed to explore the relationships between prenatal maternal consumption and inferred caloric intake during childhood. RESULTS: An additional daily serving of SSBs during the second trimester of pregnancy was associated with an increase in child consumption of 13 kcal/d (95% CI: 1.2-26.8). Age-stratified models adjusting for maternal and child covariates suggested that this association was strongest for children aged 2.5 to 5.5 years. The consumption of SSBs during the first trimester was not found to have a consistently positive relationship to caloric intake. CONCLUSIONS: These findings suggest that SSB consumption during the second trimester of pregnancy is associated with child energy intake and may influence anthropometry in early childhood, which is consistent with and suggestive of the presence of biological causal pathways alongside likely simultaneous contributions of social and environmental influences.

Per- and polyfluoroalkyl substances and calcifications of the coronary and aortic arteries in adults with prediabetes: Results from the diabetes prevention program outcomes study.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are endocrine disrupting chemicals that have been associated with cardiovascular risk factors including elevated body weight and hypercholesterolemia. Therefore, PFAS may contribute to the development of atherosclerosis and cardiovascular disease (CVD). However, no previous study has evaluated associations between PFAS exposure and arterial calcification. METHODS AND RESULTS: This study used data from 666 prediabetic adults enrolled in the Diabetes Prevention Program trial who had six PFAS quantified in plasma at baseline and two years after randomization, as well as measurements of coronary artery calcium (CAC) and ascending (AsAC) and descending (DAC) thoracic aortic calcification 13-14 years after baseline. We performed multinomial regression to test associations between PFAS and CAC categorized according to Agatston score [low (<10), moderate (11-400) and severe (>400)]. We used logistic regression to assess associations between PFAS and presence of AsAC and DAC. We adjusted models for baseline sex, age, BMI, race/ethnicity, cigarette smoking, education, treatment assignment (placebo or lifestyle intervention), and statin use. PFAS concentrations were similar to national means; 53.9% of participants had CAC > 11, 7.7% had AsAC, and 42.6% had DAC. Each doubling of the mean sum of plasma concentrations of linear and branched isomers of perfluorooctane sulfonic acid (PFOS) was associated with 1.49-fold greater odds (95% CI: 1.01, 2.21) of severe versus low CAC. This association was driven mainly by the linear (n-PFOS) isomer [1.54 (95% CI: 1.05, 2.25) greater odds of severe versus low CAC]. Each doubling of mean plasma N-ethyl-perfluorooctane sulfonamido acetic acid concentration was associated with greater odds of CAC in a dose-dependent manner [OR = 1.26 (95% CI:1.08, 1.47) for moderate CAC and OR = 1.37 (95% CI:1.07, 1.74) for severe CAC, compared to low CAC)]. Mean plasma PFOS and n-PFOS were also associated with greater odds of AsAC [OR = 1.67 (95% CI:1.10, 2.54) and OR = 1.70 (95% CI:1.13, 2.56), respectively], but not DAC. Other PFAS were not associated with outcomes. CONCLUSIONS: Prediabetic adults with higher plasma concentrations of select PFAS had higher risk of coronary and thoracic aorta calcification. PFAS exposure may be a risk factor for adverse cardiovascular health among high-risk populations.

Racial and geographic variation in effects of maternal education and neighborhood-level measures of socioeconomic status on gestational age at birth: Findings from the ECHO cohorts.

Preterm birth occurs at excessively high and disparate rates in the United States. In 2016, the National Institutes of Health (NIH) launched the Environmental influences on Child Health Outcomes (ECHO) program to investigate the influence of early life exposures on child health. Extant data from the ECHO cohorts provides the opportunity to examine racial and geographic variation in effects of individual- and neighborhood-level markers of socioeconomic status (SES) on gestational age at birth. The objective of this study was to examine the association between individual-level (maternal education) and neighborhood-level markers of SES and gestational age at birth, stratifying by maternal race/ethnicity, and whether any such associations are modified by US geographic region. Twenty-six ECHO cohorts representing 25,526 mother-infant pairs contributed to this disseminated meta-analysis that investigated the effect of maternal prenatal level of education (high school diploma, GED, or less; some college, associate's degree, vocational or technical training [reference category]; bachelor's degree, graduate school, or professional degree) and neighborhood-level markers of SES (census tract [CT] urbanicity, percentage of black population in CT, percentage of population below the federal poverty level in CT) on gestational age at birth (categorized as preterm, early term, full term [the reference category], late, and post term) according to maternal race/ethnicity and US region. Multinomial logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CIs). Cohort-specific results were meta-analyzed using a random effects model. For women overall, a bachelor's degree or above, compared with some college, was associated with a significantly decreased odds of preterm birth (aOR 0.72; 95% CI: 0.61-0.86), whereas a high school education or less was associated with an increased odds of early term birth (aOR 1.10, 95% CI: 1.00-1.21). When stratifying by maternal race/ethnicity, there were no significant associations between maternal education and gestational age at birth among women of racial/ethnic groups other than non-Hispanic white. Among non-Hispanic white women, a bachelor's degree or above was likewise associated with a significantly decreased odds of preterm birth (aOR 0.74 (95% CI: 0.58, 0.94) as well as a decreased odds of early term birth (aOR 0.84 (95% CI: 0.74, 0.95). The association between maternal education and gestational age at birth varied according to US region, with higher levels of maternal education associated with a significantly decreased odds of preterm birth in the Midwest and South but not in the Northeast and West. Non-Hispanic white women residing in rural compared to urban CTs had an increased odds of preterm birth; the ability to detect associations between neighborhood-level measures of SES and gestational age for other race/ethnic groups was limited due to small sample sizes within select strata. Interventions that promote higher educational attainment among women of reproductive age could contribute to a reduction in preterm birth, particularly in the US South and Midwest. Further individual-level analyses engaging a diverse set of cohorts are needed to disentangle the complex interrelationships among maternal education, neighborhood-level factors, exposures across the life course, and gestational age at birth outcomes by maternal race/ethnicity and US geography.

Per- and polyfluoroalkyl substances and kidney function: Follow-up results from the Diabetes Prevention Program trial.

Per- and polyfluoroalkyl substances (PFAS) are ubiquitously detected in populations worldwide and may hinder kidney function. The objective of the study was to determine longitudinal associations of plasma PFAS concentrations with estimated glomerular filtration rate (eGFR) and evaluate whether a lifestyle intervention modify the associations. We studied 875 participants initially randomized to the lifestyle or placebo arms in the Diabetes Prevention Program (DPP, 1996-2002) trial and Outcomes Study (DPPOS, 2002-2014). We ran generalized linear mixed models accounting a priori covariates to evaluate the associations between baseline PFAS concentrations and repeated measures of eGFR, separately, for six PFAS (PFOS, PFOA, PFHxS, EtFOSAA, MeFOSAA, PFNA); then used quantile-based g-computation to evaluate the effects of the six PFAS chemicals as a mixture. The cohort was 64.9% female; 73.4% 40-64 years-old; 29.4% with hypertension; 50.5% randomized to lifestyle intervention and 49.5% to placebo and had similar plasma PFAS concentrations as the general U.S. population in 1999-2000. Most participants had normal kidney function (eGFR > 90 mL/min/1.73 m2) over the approximately 14 years of follow-up. We found that plasma PFAS concentrations during DPP were inversely associated with eGFR during DPPOS follow-up. Each quartile increase in baseline plasma concentration of the 6 PFAS as a mixture was associated with 2.26 mL/min/1.73 m2 lower eGFR (95% CI: -4.12, -0.39) at DPPOS Year 5, approximately 9 years since DPP randomization and PFAS measurements. The lifestyle intervention did not modify associations, but inverse associations were stronger among participants with hypertension at baseline. Among prediabetic adults, we found inverse associations between baseline plasma PFAS concentrations and measures of eGFR throughout 14 years of follow-up. The lifestyle intervention of diet, exercise and behavioral changes did not modify the associations, but persons with hypertension may have heightened susceptibility.

Automated outbreak detection of hospital-associated pathogens: Value to infection prevention programs.

OBJECTIVE: To assess the utility of an automated, statistically-based outbreak detection system to identify clusters of hospital-acquired microorganisms. DESIGN: Multicenter retrospective cohort study. SETTING: The study included 43 hospitals using a common infection prevention surveillance system. METHODS: A space-time permutation scan statistic was applied to hospital microbiology, admission, discharge, and transfer data to identify clustering of microorganisms within hospital locations and services. Infection preventionists were asked to rate the importance of each cluster. A convenience sample of 10 hospitals also provided information about clusters previously identified through their usual surveillance methods. RESULTS: We identified 230 clusters in 43 hospitals involving Gram-positive and -negative bacteria and fungi. Half of the clusters progressed after initial detection, suggesting that early detection could trigger interventions to curtail further spread. Infection preventionists reported that they would have wanted to be alerted about 81% of these clusters. Factors associated with clusters judged to be moderately or highly concerning included high statistical significance, large size, and clusters involving Clostridioides difficile or multidrug-resistant organisms. Based on comparison data provided by the convenience sample of hospitals, only 9 (18%) of 51 clusters detected by usual surveillance met statistical significance, and of the 70 clusters not previously detected, 58 (83%) involved organisms not routinely targeted by the hospitals' surveillance programs. All infection prevention programs felt that an automated outbreak detection tool would improve their ability to detect outbreaks and streamline their work. CONCLUSIONS: Automated, statistically-based outbreak detection can increase the consistency, scope, and comprehensiveness of detecting hospital-associated transmission.