Last data update: May 13, 2024. (Total: 46773 publications since 2009)
Records 1-30 (of 49 Records) |
Query Trace: Kleinman N[original query] |
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Stewardship prompts to improve antibiotic selection for pneumonia: The INSPIRE Randomized Clinical Trial
Gohil SK , Septimus E , Kleinman K , Varma N , Avery TR , Heim L , Rahm R , Cooper WS , Cooper M , McLean LE , Nickolay NG , Weinstein RA , Burgess LH , Coady MH , Rosen E , Sljivo S , Sands KE , Moody J , Vigeant J , Rashid S , Gilbert RF , Smith KN , Carver B , Poland RE , Hickok J , Sturdevant SG , Calderwood MS , Weiland A , Kubiak DW , Reddy S , Neuhauser MM , Srinivasan A , Jernigan JA , Hayden MK , Gowda A , Eibensteiner K , Wolf R , Perlin JB , Platt R , Huang SS . Jama 2024 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. |
Stewardship prompts to improve antibiotic selection for urinary tract infection: The INSPIRE Randomized Clinical Trial
Gohil SK , Septimus E , Kleinman K , Varma N , Avery TR , Heim L , Rahm R , Cooper WS , Cooper M , McLean LE , Nickolay NG , Weinstein RA , Burgess LH , Coady MH , Rosen E , Sljivo S , Sands KE , Moody J , Vigeant J , Rashid S , Gilbert RF , Smith KN , Carver B , Poland RE , Hickok J , Sturdevant SG , Calderwood MS , Weiland A , Kubiak DW , Reddy S , Neuhauser MM , Srinivasan A , Jernigan JA , Hayden MK , Gowda A , Eibensteiner K , Wolf R , Perlin JB , Platt R , Huang SS . Jama 2024 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. |
Reducing hospitalizations and multidrug-resistant organisms via regional decolonization in hospitals and nursing homes
Gussin GM , McKinnell JA , Singh RD , Miller LG , Kleinman K , Saavedra R , Tjoa T , Gohil SK , Catuna TD , Heim LT , Chang J , Estevez M , He J , O'Donnell K , Zahn M , Lee E , Berman C , Nguyen J , Agrawal S , Ashbaugh I , Nedelcu C , Robinson PA , Tam S , Park S , Evans KD , Shimabukuro JA , Lee BY , Fonda E , Jernigan JA , Slayton RB , Stone ND , Janssen L , Weinstein RA , Hayden MK , Lin MY , Peterson EM , Bittencourt CE , Huang SS . Jama 2024 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. |
Large-scale scientific study led by a professional organization during the COVID-19 pandemic: Operations, best practices, and lessons learned
Ondracek CR , Melanson SEF , Doan L , Schulz KM , Kleinman S , Zhao Z , Kumanovics A , Wu AHB , Wiencek J , Meng QH , Apple FS , Koch D , Vesper H , Pokuah F , Bryksin J , Myers GL , Christenson RH , Zhang YV . J Appl Lab Med 2023 In 2021, the Association for Diagnostics & Laboratory Medicine (ADLM) (formerly the American Association for Clinical Chemistry [AACC]) developed a scientific study that aimed to contribute to the understanding of SARS-CoV-2 immunity during the evolving course of the pandemic. This study was led by a group of expert member volunteers and resulted in survey data from 975 individuals and blood collection from 698 of those participants. This paper describes the formulation and execution of this large-scale scientific study, encompassing best practices and insights gained throughout the endeavor. |
Leveraging donor populations to study the epidemiology and pathogenesis of transfusion-transmitted and emerging infectious diseases
Bloch EM , Busch MP , Corash LM , Dodd R , Hailu B , Kleinman S , O'Brien S , Petersen L , Stramer SL , Katz L . Transfus Med Rev 2023 37 (4) 150769 The tragedy of transfusion-associated hepatitis and HIV spurred a decades-long overhaul of the regulatory oversight and practice of blood transfusion. Consequent to improved donor selection, testing, process control, clinical transfusion practice and post-transfusion surveillance, transfusion in the United States and other high-income countries is now a very safe medical procedure. Nonetheless, pathogens continue to emerge and threaten the blood supply, highlighting the need for a proactive approach to blood transfusion safety. Blood donor populations and the global transfusion infrastructure are under-utilized resources for the study of infectious diseases. Blood donors are large, demographically diverse subsets of general populations for whom cross-sectional and longitudinal samples are readily accessible for serological and molecular testing. Blood donor collection networks span diverse geographies, including in low- and middle-income countries, where agents, especially zoonotic pathogens, are able to emerge and spread, given limited tools for recognition, surveillance and control. Routine laboratory storage and transportation, coupled with data capture, afford access to rich epidemiological data to assess the epidemiology and pathogenesis of established and emerging infections. Subsequent to the State of the Science in Transfusion Medicine symposium in 2022, our working group (WG), "Emerging Infections: Impact on Blood Science, the Blood Supply, Blood Safety, and Public Health" elected to focus on "leveraging donor populations to study the epidemiology and pathogenesis of transfusion-transmitted and emerging infectious diseases." The 5 landmark studies span (1) the implication of hepatitis C virus in post-transfusion hepatitis, (2) longitudinal evaluation of plasma donors with incident infections, thus informing the development of a widely used staging system for acute HIV infection, (3) explication of the dynamics of early West Nile Virus infection, (4) the deployment of combined molecular and serological donor screening for Babesia microti, to characterize its epidemiology and infectivity and facilitate routine donor screening, and (5) national serosurveillance for SARS-CoV-2 during the COVID-19 pandemic. The studies highlight the interplay between infectious diseases and transfusion medicine, including the imperative to ensure blood transfusion safety and the broader application of blood donor populations to the study of infectious diseases. |
Nasal iodophor antiseptic vs nasal mupirocin antibiotic in the setting of chlorhexidine bathing to prevent infections in adult ICUs: A randomized clinical trial
Huang SS , Septimus EJ , Kleinman K , Heim LT , Moody JA , Avery TR , McLean L , Rashid S , Haffenreffer K , Shimelman L , Staub-Juergens W , Spencer-Smith C , Sljivo S , Rosen E , Poland RE , Coady MH , Lee CH , Blanchard EJ , Reddish K , Hayden MK , Weinstein RA , Carver B , Smith K , Hickok J , Lolans K , Khan N , Sturdevant SG , Reddy SC , Jernigan JA , Sands KE , Perlin JB , Platt R . JAMA 2023 330 (14) 1337-1347 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
Miller LG , McKinnell JA , Singh RD , Gussin GM , Kleinman K , Saavedra R , Mendez J , Catuna TD , Felix J , Chang J , Heim L , Franco R , Tjoa T , Stone ND , Steinberg K , Beecham N , Montgomery J , Walters D , Park S , Tam S , Gohil SK , Robinson PA , Estevez M , Lewis B , Shimabukuro JA , Tchakalian G , Miner A , Torres C , Evans KD , Bittencourt CE , He J , Lee E , Nedelcu C , Lu J , Agrawal S , Sturdevant SG , Peterson E , Huang SS . N Engl J Med 2023 389 (19) 1766-1777 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.). |
Use of U.S. Blood Donors for National Serosurveillance of SARS-CoV-2 Antibodies: Basis for an Expanded National Donor Serosurveillance Program (preprint)
Stone M , Di Germanio C , Wright DJ , Sulaeman H , Dave H , Fink RV , Notari EP , Green V , Strauss D , Kessler D , Destree M , Saa P , Williamson PC , Simmons G , Stramer SL , Opsomer J , Jones JM , Kleinman S , Busch MP . medRxiv 2021 2021.05.01.21255576 Introduction The REDS-IV-P Epidemiology, Surveillance and Preparedness of the Novel SARS-CoV-2 Epidemic (RESPONSE) seroprevalence study conducted monthly cross-sectional testing for SARS-CoV-2 antibodies on blood donors in six U.S. metropolitan regions to estimate the extent of SARS-COV-2 infections over time.Study Design/Methods During March-August 2020, approximately ≥1,000 serum specimens were collected monthly from each region and tested for SARS-CoV-2 antibodies using a well-validated algorithm. Regional seroprevalence estimates were weighted based on demographic differences with the general population. Seroprevalence was compared with reported COVID-19 case rates over time.Results/Findings For all regions, seroprevalence was <1.0% in March 2020. New York experienced the biggest increase (peak seroprevalence, 15.8 % in May). All other regions experienced modest increases in seroprevalence(1-2% in May-June to 2-4% in July-August). Seroprevalence was higher in younger, non-Hispanic Black, and Hispanic donors. Temporal increases in donor seroprevalence correlated with reported case rates in each region. In August, 1.3-5.6 estimated cumulative infections (based on seroprevalence data) per COVID-19 case reported to CDC.Conclusion Increases in seroprevalence were found in all regions, with the largest increase in New York. Seroprevalence was higher in non-Hispanic Black and Hispanic blood donors than in non-Hispanic White blood donors. SARS-CoV-2 antibody testing of blood donor samples can be used to estimate the seroprevalence in the general population by region and demographic group. The methods derived from the RESPONSE seroprevalence study served as the basis for expanding SARS-CoV-2 seroprevalence surveillance to all 50 states and Puerto Rico.Summary SARS-CoV-2 serosurveillance data from blood donors in 6 US regions were used to estimate population weighted seroprevalence. Seroprevelance rates were higher in case rates. The study was expanded to a national donor serosurveillance program.Disclaimer The content is solely the responsibility of the authors and does not represent the policy of the National Institutes of Health or the Department of Health and Human Services. Any specific brandnames included in this manuscript are for identification purposes only and are not intended to represent an endorsement by CDC. The findings and conclusions in this report are those of the authorsand do not necessarily represent the official position of the Centers of Disease Control and Prevention.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThe authors were supported by research contracts from the National Heart, Lung, and Blood Institute (NHLBI Contracts HHSN 75N92019D00032 and HHSN 75N92019D00033) as well as with funding support from the National Institute of Allergies and Infectious Diseases (NIAID), NIH.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:The study was reviewed by the UCSF Committee for Human Research and determined to meet the definition of research as defined in 46.102(l) but did not involve human subjects based on anonymization of data and routine consent for blood donation testing that includes use of residual samples for research purposes (as defined in 46.103(e)(1) consistent with applicable federal law and CDC policy (45 C.F.R. part 46; 21 C.F.R. part 56; 42 U.S.C. p241(d), 5 U.S.C. p552a, 44 U.S.C. p3501)).All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a pros ective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThe data is not being made publicly available for privacy reasons related to federal regulations but a limited dataset may be made available upon request after formal review by NHLBI and CDC's privacy office before release. |
Evaluation of commercially available high-throughput SARS-CoV-2 serological assays for serosurveillance and related applications (preprint)
Stone M , Grebe E , Sulaeman H , Di Germanio C , Dave H , Kelly K , Biggerstaff BJ , Crews BO , Tran N , Jerome KR , Denny TN , Hogema B , Destree M , Jones JM , Thornburg N , Simmons G , Krajden M , Kleinman S , Dumont LJ , Busch MP . medRxiv 2021 2021.09.04.21262414 SARS-CoV-2 serosurveys can estimate cumulative incidence for monitoring epidemics but require characterization of employed serological assays performance to inform testing algorithm development and interpretation of results. We conducted a multi-laboratory evaluation of 21 commercial high-throughput SARS-CoV-2 serological assays using blinded panels of 1,000 highly-characterized blood-donor specimens. Assays demonstrated a range of sensitivities (96%-63%), specificities (99%-96%) and precision (IIC 0.55-0.99). Durability of antibody detection in longitudinal samples was dependent on assay format and immunoglobulin target, with anti-spike, direct, or total Ig assays demonstrating more stable, or increasing reactivity over time than anti-nucleocapsid, indirect, or IgG assays. Assays with high sensitivity, specificity and durable antibody detection are ideal for serosurveillance. Less sensitive assays demonstrating waning reactivity are appropriate for other applications, including characterizing antibody responses after infection and vaccination, and detection of anamnestic boosting by reinfections and vaccine breakthrough infections. Assay performance must be evaluated in the context of the intended use.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis work was supported by research contracts from the Centers for Disease Control and Prevention (CDC Contract 75D30120C08170).Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:All blood donors consented to use of de-identified, residual specimens for further research purposes. UCSF IRB provided explicit approval for VRI self-certification that use of the de-identified CCP donations in this study does not meet the criteria for human subjects research. CDC investigators reviewed and relied on this determination as consistent with applicable federal law and CDC policy (45 C.F.R. part 46, 21 C.F.R. part 56; 42 U.S.C. Sect. 241(d); 5 U.S.C. Sect. 552a; 44 U.S.C. Sect. 3501).All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThe analytic data set is available upon request. |
Evaluation of Ortho VITROS and Roche Elecsys S and NC immunoassays for SARS-CoV-2 serosurveillance applications
Sulaeman H , Grebe E , Dave H , McCann L , Di Germanio C , Sanghavi A , Sclar V , Bougie DW , Chatelain G , Biggerstaff BJ , Jones JM , Thornburg NJ , Kleinman S , Stone M , Busch MP . Microbiol Spectr 2023 11 (4) e0323422 SARS-CoV-2 seroprevalence studies are instrumental in monitoring epidemic activity and require well-characterized, high-throughput assays, and appropriate testing algorithms. The U.S. Nationwide Blood Donor Seroprevalence Study performed monthly cross-sectional serological testing from July 2020 to December 2021, implementing evolving testing algorithms in response to changes in pandemic activity. With high vaccine uptake, anti-Spike (S) reactivity rates reached >80% by May 2021, and the study pivoted from reflex Roche anti-nucleocapsid (NC) testing of Ortho S-reactive specimens to parallel Ortho S/NC testing. We evaluated the performance of the Ortho NC assay as a replacement for the Roche NC assay and compared performance of parallel S/NC testing on both platforms. Qualitative and quantitative agreement of Ortho NC with Roche NC assays was evaluated on preselected S/NC concordant and discordant specimens. All 190 Ortho S+/Roche NC+ specimens were reactive on the Ortho NC assay; 34% of 367 Ortho S+/Roche NC- specimens collected prior to vaccine availability and 43% of 37 Ortho S-/Roche NC+ specimens were reactive on the Ortho NC assay. Performance of parallel S/NC testing using Ortho and Roche platforms was evaluated on 200 specimens collected in 2019 and 3,903 study specimens collected in 2021. All 200 pre-COVID-19 specimens tested negative on the four assays. Cross-platform agreement between Roche and Ortho platforms was 96.4% (3,769/3,903); most discordant results had reactivity close to the cutoffs on the alternate assays. These findings, and higher efficiency and throughput, support the use of parallel S/NC testing on either Roche or Ortho platforms for large serosurveillance studies. IMPORTANCE Seroprevalence studies like the U.S. Nationwide Blood Donor Seroprevalence Study (NBDS) have been critical in monitoring SARS-CoV-2 epidemic activity. These studies rely on serological assays to detect antibodies indicating prior infection. It is critical that the assays and testing algorithms used in seroprevalence studies have adequate performance (high sensitivity, high specificity, ability to discriminate vaccine-induced and infection-induced antibodies, etc.), as well as appropriate characteristics to support large-scale studies, such as high throughput and low cost. In this study we evaluated the performance of Ortho's anti-nucleocapsid assay as a replacement for the Roche anti-nucleocapsid assay and compared performance of parallel anti-spike and anti-nucleocapsid testing on both platforms. These data demonstrate similar performance of the Ortho and Roche anti-nucleocapsid assays and that parallel anti-spike and anti-nucleocapsid testing on either platform could be used for serosurveillance applications. |
Population-weighted seroprevalence from SARS-CoV-2 infection, vaccination, and hybrid immunity among U.S. blood donations from January-December 2021.
Busch MP , Stramer SL , Stone M , Yu EA , Grebe E , Notari E , Saa P , Ferg R , Manrique IM , Weil N , Fink RV , Levy M , Green V , Cyrus S , Williamson PC , Haynes J , Groves J , Krysztof D , Custer B , Kleinman S , Biggerstaff BJ , Opsomer JD , Jones JM . Clin Infect Dis 2022 75 S254-S263 BACKGROUND: Previous SARS-CoV-2 infection and coronavirus disease 2019 (COVID-19) vaccination, independently and combined ("hybrid immunity"), result in partial protection from subsequent infection and strong protection from severe disease. Proportions of the U.S. population that have been infected, vaccinated, or with hybrid immunity remain unclear, posing a challenge for assessing effective pandemic mitigation strategies. METHODS: In this serial cross-sectional study, nationwide blood donor specimens collected during January-December 2021 were tested for spike and nucleocapsid antibodies, and donor COVID-19 vaccination history of ≥1 dose was collected. Monthly seroprevalence induced from SARS-CoV-2 infection, COVID-19 vaccination, or both, were estimated. Estimates were weighted to account for demographic differences from the general population, and were compared temporally and by demographic factors. RESULTS: Overall, 1,123,855 blood samples were assayed. From January to December 2021, the weighted percentage of donations with seropositivity due to: vaccination without previous infection increased from 3.5% (95% CI, 3.4%-3.7%) to 64.0%, (95% CI, 63.5%-64.5%); previous infection without vaccination decreased from 15.6% (95% CI, 15.2%-16.0%) to 11.7% (95% CI, 11.4%-12.0%); hybrid immunity increased from 0.7% (95% CI, 0.6%-0.7%) to 18.9% (95% CI, 18.5%-19.3%); and from infection, vaccination, or both increased from 19.8% (95% CI (19.3-20.2) to 94.5% (95% CI, 93.5%-94.0% 0.1%). Infection- and vaccination-induced antibody responses varied significantly by age, race-ethnicity, and region, but not by gender. CONCLUSIONS: Our results indicate substantial increases in population humoral immunity from SARS-CoV-2 infection, COVID-19 vaccination, and hybrid immunity during 2021. These findings are important to consider in future COVID-19 studies and long-term pandemic mitigation efforts. |
Evaluation of Commercially Available High-Throughput SARS-CoV-2 Serologic Assays for Serosurveillance and Related Applications.
Stone M , Grebe E , Sulaeman H , Di Germanio C , Dave H , Kelly K , Biggerstaff BJ , Crews BO , Tran N , Jerome KR , Denny TN , Hogema B , Destree M , Jones JM , Thornburg N , Simmons G , Krajden M , Kleinman S , Dumont LJ , Busch MP . Emerg Infect Dis 2022 28 (3) 672-683 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serosurveys can estimate cumulative incidence for monitoring epidemics, requiring assessment of serologic assays to inform testing algorithm development and interpretation of results. We conducted a multilaboratory evaluation of 21 commercial high-throughput SARS-CoV-2 serologic assays using blinded panels of 1,000 highly characterized specimens. Assays demonstrated a range of sensitivities (96%-63%), specificities (99%-96%), and precision (intraclass correlation coefficient 0.55-0.99). Durability of antibody detection was dependent on antigen and immunoglobulin targets; antispike and total Ig assays demonstrated more stable longitudinal reactivity than antinucleocapsid and IgG assays. Assays with high sensitivity, specificity, and durable antibody detection are ideal for serosurveillance, but assays demonstrating waning reactivity are appropriate for other applications, including correlation with neutralizing activity and detection of anamnestic boosting by reinfections. Assay performance must be evaluated in context of intended use, particularly in the context of widespread vaccination and circulation of SARS-CoV-2 variants. |
Dietary and complementary feeding practices of U.S. infants, 6-12 months: A narrative review of the Federal nutrition monitoring data
Bailey RL , Stang JS , Davis TA , Naimi TS , Schneeman BO , Dewey KG , Donovan SM , Novotny R , Kleinman RE , Taveras EM , Bazzano L , Snetselaar LG , de Jesus J , Casavale KO , Stoody EE , Goldman JD , Moshfegh AJ , Rhodes DG , Herrick KA , Koegel K , Perrine CG , Pannucci T . J Acad Nutr Diet 2021 122 (12) 2337-2345 e1 Complementary foods and beverages (CFB) are key components of an infant's diet in the second 6 months of life. This manuscript summarizes nutrition and feeding practices examined by the 2020 Dietary Guidelines Advisory Committees during the CFB life stage. Breastfeeding initiation is high (84%), but exclusive breastfeeding at 6 months (26%) is below the Healthy People 2030 goal (42%). Most infants (51%) are introduced to CFB sometime before 6 months. The primary mode of feeding (i.e., human milk fed [HMF]; infant formula or mixed formula and human milk fed [FMF]) at the initiation of CFB is associated with the timing of introduction and types of CFB reported. FMF infants (42%) are more likely to be introduced to CFB before 4 months compared to HMF infants (19%). Different dietary patterns, such as higher prevalence of consumption and mean amounts, were observed including fruit, grains, dairy, proteins, and solid fats. Compared to HMF infants of the same age, FMF infants consume more total energy (845 vs. 631 kcal) and protein (22 vs. 12 g) from all sources, and more energy (345 vs. 204 kcal) and protein (11 vs. 6 g) from CFB alone. HMF infants have a higher prevalence of risk of inadequate intakes of iron (77% vs. 7%), zinc (54% vs. <3%), and protein (27% vs. <3%). FMF infants are more likely to have early introduction (<12 months) to fruit juice (45% vs. 20%) and cow's milk (36% vs. 24%). Dietitians and nutritional professionals should consider tailoring their advice to caregivers on dietary and complementary feeding practices, taking into account the primary mode of milk feeding during this life stage to support infants' nutrient adequacy. National studies that address the limitations of this analysis, including small sample sizes and imputed breast milk volume, could further refine findings from this analysis. |
Estimated US Infection- and Vaccine-Induced SARS-CoV-2 Seroprevalence Based on Blood Donations, July 2020-May 2021.
Jones JM , Stone M , Sulaeman H , Fink RV , Dave H , Levy ME , Di Germanio C , Green V , Notari E , Saa P , Biggerstaff BJ , Strauss D , Kessler D , Vassallo R , Reik R , Rossmann S , Destree M , Nguyen KA , Sayers M , Lough C , Bougie DW , Ritter M , Latoni G , Weales B , Sime S , Gorlin J , Brown NE , Gould CV , Berney K , Benoit TJ , Miller MJ , Freeman D , Kartik D , Fry AM , Azziz-Baumgartner E , Hall AJ , MacNeil A , Gundlapalli AV , Basavaraju SV , Gerber SI , Patton ME , Custer B , Williamson P , Simmons G , Thornburg NJ , Kleinman S , Stramer SL , Opsomer J , Busch MP . JAMA 2021 326 (14) 1400-1409 IMPORTANCE: People who have been infected with or vaccinated against SARS-CoV-2 have reduced risk of subsequent infection, but the proportion of people in the US with SARS-CoV-2 antibodies from infection or vaccination is uncertain. OBJECTIVE: To estimate trends in SARS-CoV-2 seroprevalence related to infection and vaccination in the US population. DESIGN, SETTING, AND PARTICIPANTS: In a repeated cross-sectional study conducted each month during July 2020 through May 2021, 17 blood collection organizations with blood donations from all 50 US states; Washington, DC; and Puerto Rico were organized into 66 study-specific regions, representing a catchment of 74% of the US population. For each study region, specimens from a median of approximately 2000 blood donors were selected and tested each month; a total of 1 594 363 specimens were initially selected and tested. The final date of blood donation collection was May 31, 2021. EXPOSURE: Calendar time. MAIN OUTCOMES AND MEASURES: Proportion of persons with detectable SARS-CoV-2 spike and nucleocapsid antibodies. Seroprevalence was weighted for demographic differences between the blood donor sample and general population. Infection-induced seroprevalence was defined as the prevalence of the population with both spike and nucleocapsid antibodies. Combined infection- and vaccination-induced seroprevalence was defined as the prevalence of the population with spike antibodies. The seroprevalence estimates were compared with cumulative COVID-19 case report incidence rates. RESULTS: Among 1 443 519 specimens included, 733 052 (50.8%) were from women, 174 842 (12.1%) were from persons aged 16 to 29 years, 292 258 (20.2%) were from persons aged 65 years and older, 36 654 (2.5%) were from non-Hispanic Black persons, and 88 773 (6.1%) were from Hispanic persons. The overall infection-induced SARS-CoV-2 seroprevalence estimate increased from 3.5% (95% CI, 3.2%-3.8%) in July 2020 to 20.2% (95% CI, 19.9%-20.6%) in May 2021; the combined infection- and vaccination-induced seroprevalence estimate in May 2021 was 83.3% (95% CI, 82.9%-83.7%). By May 2021, 2.1 SARS-CoV-2 infections (95% CI, 2.0-2.1) per reported COVID-19 case were estimated to have occurred. CONCLUSIONS AND RELEVANCE: Based on a sample of blood donations in the US from July 2020 through May 2021, vaccine- and infection-induced SARS-CoV-2 seroprevalence increased over time and varied by age, race and ethnicity, and geographic region. Despite weighting to adjust for demographic differences, these findings from a national sample of blood donors may not be representative of the entire US population. |
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
Lin PD , Cardenas A , Hauser R , Gold DR , Kleinman KP , Hivert MF , Calafat AM , Webster TF , Horton ES , Oken E . Environ Int 2021 157 106789 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/m(2)). 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. |
Incidence of Multisystem Inflammatory Syndrome in Children Among US Persons Infected With SARS-CoV-2.
Payne AB , Gilani Z , Godfred-Cato S , Belay ED , Feldstein LR , Patel MM , Randolph AG , Newhams M , Thomas D , Magleby R , Hsu K , Burns M , Dufort E , Maxted A , Pietrowski M , Longenberger A , Bidol S , Henderson J , Sosa L , Edmundson A , Tobin-D'Angelo M , Edison L , Heidemann S , Singh AR , Giuliano JSJr , Kleinman LC , Tarquinio KM , Walsh RF , Fitzgerald JC , Clouser KN , Gertz SJ , Carroll RW , Carroll CL , Hoots BE , Reed C , Dahlgren FS , Oster ME , Pierce TJ , Curns AT , Langley GE , Campbell AP , Balachandran N , Murray TS , Burkholder C , Brancard T , Lifshitz J , Leach D , Charpie I , Tice C , Coffin SE , Perella D , Jones K , Marohn KL , Yager PH , Fernandes ND , Flori HR , Koncicki ML , Walker KS , Di Pentima MC , Li S , Horwitz SM , Gaur S , Coffey DC , Harwayne-Gidansky I , Hymes SR , Thomas NJ , Ackerman KG , Cholette JM . JAMA Netw Open 2021 4 (6) e2116420 IMPORTANCE: Multisystem inflammatory syndrome in children (MIS-C) is associated with recent or current SARS-CoV-2 infection. Information on MIS-C incidence is limited. OBJECTIVE: To estimate population-based MIS-C incidence per 1 000 000 person-months and to estimate MIS-C incidence per 1 000 000 SARS-CoV-2 infections in persons younger than 21 years. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used enhanced surveillance data to identify persons with MIS-C during April to June 2020, in 7 jurisdictions reporting to both the Centers for Disease Control and Prevention national surveillance and to Overcoming COVID-19, a multicenter MIS-C study. Denominators for population-based estimates were derived from census estimates; denominators for incidence per 1 000 000 SARS-CoV-2 infections were estimated by applying published age- and month-specific multipliers accounting for underdetection of reported COVID-19 case counts. Jurisdictions included Connecticut, Georgia, Massachusetts, Michigan, New Jersey, New York (excluding New York City), and Pennsylvania. Data analyses were conducted from August to December 2020. EXPOSURES: Race/ethnicity, sex, and age group (ie, ≤5, 6-10, 11-15, and 16-20 years). MAIN OUTCOMES AND MEASURES: Overall and stratum-specific adjusted estimated MIS-C incidence per 1 000 000 person-months and per 1 000 000 SARS-CoV-2 infections. RESULTS: In the 7 jurisdictions examined, 248 persons with MIS-C were reported (median [interquartile range] age, 8 [4-13] years; 133 [53.6%] male; 96 persons [38.7%] were Hispanic or Latino; 75 persons [30.2%] were Black). The incidence of MIS-C per 1 000 000 person-months was 5.1 (95% CI, 4.5-5.8) persons. Compared with White persons, incidence per 1 000 000 person-months was higher among Black persons (adjusted incidence rate ratio [aIRR], 9.26 [95% CI, 6.15-13.93]), Hispanic or Latino persons (aIRR, 8.92 [95% CI, 6.00-13.26]), and Asian or Pacific Islander (aIRR, 2.94 [95% CI, 1.49-5.82]) persons. MIS-C incidence per 1 000 000 SARS-CoV-2 infections was 316 (95% CI, 278-357) persons and was higher among Black (aIRR, 5.62 [95% CI, 3.68-8.60]), Hispanic or Latino (aIRR, 4.26 [95% CI, 2.85-6.38]), and Asian or Pacific Islander persons (aIRR, 2.88 [95% CI, 1.42-5.83]) compared with White persons. For both analyses, incidence was highest among children aged 5 years or younger (4.9 [95% CI, 3.7-6.6] children per 1 000 000 person-months) and children aged 6 to 10 years (6.3 [95% CI, 4.8-8.3] children per 1 000 000 person-months). CONCLUSIONS AND RELEVANCE: In this cohort study, MIS-C was a rare complication associated with SARS-CoV-2 infection. Estimates for population-based incidence and incidence among persons with infection were higher among Black, Hispanic or Latino, and Asian or Pacific Islander persons. Further study is needed to understand variability by race/ethnicity and age group. |
Use of U.S. Blood Donors for National Serosurveillance of SARS-CoV-2 Antibodies: Basis for an Expanded National Donor Serosurveillance Program.
Stone M , Di Germanio C , Wright DJ , Sulaeman H , Dave H , Fink RV , Notari EP , Green V , Strauss D , Kessler D , Destree M , Saa P , Williamson PC , Simmons G , Stramer SL , Opsomer J , Jones JM , Kleinman S , Busch MP . Clin Infect Dis 2021 74 (5) 871-881 INTRODUCTION: The REDS-IV-P Epidemiology, Surveillance and Preparedness of the Novel SARS-CoV-2 Epidemic (RESPONSE) seroprevalence study conducted monthly cross-sectional testing for SARS-CoV-2 antibodies on blood donors in six U.S. metropolitan regions to estimate the extent of SARS-COV-2 infections over time. STUDY DESIGN/METHODS: During March-August 2020, approximately ≥1,000 serum specimens were collected monthly from each region and tested for SARS-CoV-2 antibodies using a well-validated algorithm. Regional seroprevalence estimates were weighted based on demographic differences with the general population. Seroprevalence was compared with reported COVID-19 case rates over time. RESULTS/FINDINGS: For all regions, seroprevalence was <1.0% in March 2020. New York experienced the biggest increase (peak seroprevalence, 15.8 % in May). All other regions experienced modest increases in seroprevalence(1-2% in May-June to 2-4% in July-August). Seroprevalence was higher in younger, non-Hispanic Black, and Hispanic donors. Temporal increases in donor seroprevalence correlated with reported case rates in each region. In August, 1.3-5.6 estimated cumulative infections (based on seroprevalence data) per COVID-19 case reported to CDC. CONCLUSION: Increases in seroprevalence were found in all regions, with the largest increase in New York. Seroprevalence was higher in non-Hispanic Black and Hispanic blood donors than in non-Hispanic White blood donors. SARS-CoV-2 antibody testing of blood donor samples can be used to estimate the seroprevalence in the general population by region and demographic group. The methods derived from the RESPONSE seroprevalence study served as the basis for expanding SARS-CoV-2 seroprevalence surveillance to all 50 states and Puerto Rico. |
Neurologic Involvement in Children and Adolescents Hospitalized in the United States for COVID-19 or Multisystem Inflammatory Syndrome.
LaRovere KL , Riggs BJ , Poussaint TY , Young CC , Newhams MM , Maamari M , Walker TC , Singh AR , Dapul H , Hobbs CV , McLaughlin GE , Son MBF , Maddux AB , Clouser KN , Rowan CM , McGuire JK , Fitzgerald JC , Gertz SJ , Shein SL , Munoz AC , Thomas NJ , Irby K , Levy ER , Staat MA , Tenforde MW , Feldstein LR , Halasa NB , Giuliano JS Jr , Hall MW , Kong M , Carroll CL , Schuster JE , Doymaz S , Loftis LL , Tarquinio KM , Babbitt CJ , Nofziger RA , Kleinman LC , Keenaghan MA , Cvijanovich NZ , Spinella PC , Hume JR , Wellnitz K , Mack EH , Michelson KN , Flori HR , Patel MM , Randolph AG . JAMA Neurol 2021 78 (5) 536-547 IMPORTANCE: Coronavirus disease 2019 (COVID-19) affects the nervous system in adult patients. The spectrum of neurologic involvement in children and adolescents is unclear. OBJECTIVE: To understand the range and severity of neurologic involvement among children and adolescents associated with COVID-19. SETTING, DESIGN, AND PARTICIPANTS: Case series of patients (age <21 years) hospitalized between March 15, 2020, and December 15, 2020, with positive severe acute respiratory syndrome coronavirus 2 test result (reverse transcriptase-polymerase chain reaction and/or antibody) at 61 US hospitals in the Overcoming COVID-19 public health registry, including 616 (36%) meeting criteria for multisystem inflammatory syndrome in children. Patients with neurologic involvement had acute neurologic signs, symptoms, or diseases on presentation or during hospitalization. Life-threatening involvement was adjudicated by experts based on clinical and/or neuroradiologic features. EXPOSURES: Severe acute respiratory syndrome coronavirus 2. MAIN OUTCOMES AND MEASURES: Type and severity of neurologic involvement, laboratory and imaging data, and outcomes (death or survival with new neurologic deficits) at hospital discharge. RESULTS: Of 1695 patients (909 [54%] male; median [interquartile range] age, 9.1 [2.4-15.3] years), 365 (22%) from 52 sites had documented neurologic involvement. Patients with neurologic involvement were more likely to have underlying neurologic disorders (81 of 365 [22%]) compared with those without (113 of 1330 [8%]), but a similar number were previously healthy (195 [53%] vs 723 [54%]) and met criteria for multisystem inflammatory syndrome in children (126 [35%] vs 490 [37%]). Among those with neurologic involvement, 322 (88%) had transient symptoms and survived, and 43 (12%) developed life-threatening conditions clinically adjudicated to be associated with COVID-19, including severe encephalopathy (n = 15; 5 with splenial lesions), stroke (n = 12), central nervous system infection/demyelination (n = 8), Guillain-Barré syndrome/variants (n = 4), and acute fulminant cerebral edema (n = 4). Compared with those without life-threatening conditions (n = 322), those with life-threatening neurologic conditions had higher neutrophil-to-lymphocyte ratios (median, 12.2 vs 4.4) and higher reported frequency of D-dimer greater than 3 μg/mL fibrinogen equivalent units (21 [49%] vs 72 [22%]). Of 43 patients who developed COVID-19-related life-threatening neurologic involvement, 17 survivors (40%) had new neurologic deficits at hospital discharge, and 11 patients (26%) died. CONCLUSIONS AND RELEVANCE: In this study, many children and adolescents hospitalized for COVID-19 or multisystem inflammatory syndrome in children had neurologic involvement, mostly transient symptoms. A range of life-threatening and fatal neurologic conditions associated with COVID-19 infrequently occurred. Effects on long-term neurodevelopmental outcomes are unknown. |
Per- and polyfluoroalkyl substances and calcifications of the coronary and aortic arteries in adults with prediabetes: Results from the Diabetes Prevention Program Outcomes Study
Osorio-Yáñez C , Sanchez-Guerra M , Cardenas A , Lin PD , Hauser R , Gold DR , Kleinman KP , Hivert MF , Fleisch AF , Calafat AM , Webster TF , Horton ES , Oken E . Environ Int 2021 151 106446 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. |
Per- and polyfluoroalkyl substances and kidney function: Follow-up results from the Diabetes Prevention Program trial
Lin PD , Cardenas A , Hauser R , Gold DR , Kleinman KP , Hivert MF , Calafat AM , Webster TF , Horton ES , Oken E . Environ Int 2021 148 106375 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 m(2)) 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 m(2) 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. |
Evolving viral and serological stages of Zika virus RNA-positive blood donors and estimation of incidence of infection during the 2016 Puerto Rican Zika epidemic: an observational cohort study.
Williamson PC , Biggerstaff BJ , Simmons G , Stone M , Winkelman V , Latoni G , Alsina J , Bakkour S , Newman C , Pate LL , Galel SA , Kleinman S , Busch MP . Lancet Infect Dis 2020 20 (12) 1437-1445 BACKGROUND: Puerto Rico began screening blood donations for Zika virus RNA with nucleic acid amplification tests (NAATs) on April 3, 2016, because of an emerging Zika virus outbreak. We followed up positive donors to assess the dynamics of viral and serological markers during the early stages of Zika virus infection and update the estimate of infection incidence in the Puerto Rican population during the outbreak. METHODS: Blood donations from volunteer donors in Puerto Rico were screened for the presence of Zika virus RNA using the cobas Zika NAAT. Positive donations were further tested to confirm infection, estimate viral load, and identify Zika virus-specific IgM antibodies. Individuals with positive blood donations were invited to attend follow-up visits. Donations with confirmed infection (defined as detection of Zika virus RNA or IgM on additional testing of index or follow-up samples) were assessed for stage of infection according to Zika virus RNA detectability in simulated minipools, viral load, and Zika virus IgM status. A three-step process was used to estimate the mean duration of NAAT reactivity of Zika virus in human plasma from individuals identified pre-seroconversion with at least one follow up visit and to update the 2016 incidence estimate of Zika virus infection. FINDINGS: Between April 3 and Dec 31, 2016, 53 112 blood donations were screened for Zika virus, of which 351 tested positive, 339 had confirmed infections, and 319 could be staged. Compared with IgM-positive index donations (n=110), IgM-negative index donations (n=209) had higher mean viral loads (1.1 x 10(6)vs 8.3 x 10(4) international units per mL) and were more likely to be detected in simulated minipools (93% [n=194] vs 26% [n=29]). The proportions of donations with confirmed infections that had viral RNA detected only in individual-donation NAATs (ie, not in simulated minipools) and were IgM positive increased as the epidemic evolved. The estimated mean duration of NAAT detectability in the 140 donors included in the follow-up study was 11.70 days (95% CI 10.06-14.36). Applying this detection period to the observed proportion of donations that were confirmed NAAT positive yielded a Zika virus seasonal incidence estimate of 21.1% (95% CI 18.1-24.1); 768 101 infections in a population of 3 638 773 in 2016. INTERPRETATION: Characterisation of early Zika virus infection has implications for blood safety because infectivity of blood donations and utility of screening methods likely correlate with viral load and serological stage of infection. Our findings also have implications for diagnostic testing, public health surveillance, and epidemiology, and we estimate that around 21% of the Puerto Rican population was infected during the 2016 outbreak. FUNDING: Biomedical Advanced Research and Development Authority, National Heart, Lung, and Blood Institute. |
Sharing the cure: Building primary care and public health infrastructure to improve the hepatitis C care continuum in Maryland
Irvin R , Ntiri-Reid B , Kleinman M , Agee T , Hitt J , Anaedozie O , Arowolo T , Cassidy-Stewart H , Bush C , Wilson LE , Millman AJ , Nelson NP , Canary L , Brinkley S , Moon J , Falade-Nwulia O , Sulkowski MS , Thomas DL , Melia MT . J Viral Hepat 2020 27 (12) 1388-1395 In 2014, trained health care provider capacity was insufficient to deliver care to an estimated 70,000 persons in Maryland with chronic hepatitis C virus (HCV) infection. The goal of Maryland Community Based Programs to Test and Cure Hepatitis C, a public health implementation project, was to improve HCV treatment access by expanding the workforce. Sharing the Cure (STC) was a package of services deployed 10/1/14 to 9/30/18 that included enhanced information technology and public health infrastructure, primary care provider training, and practice transformation. Nine primary care sites enrolled. HCV clinical outcomes were documented among individuals who presented for care at sites and met criteria for HCV testing including risk factor or birth cohort (born between 1945 and 1965) based testing. Fifty-three providers completed the STC training. STC providers identified 3,237 HCV antibody positive patients of which 2,624 (81%) were RNA+. Of those HCV RNA+, 1,739 (66%) were staged, 932 (36%) were prescribed treatment, 838 (32%) started treatment, 721 (28%) completed treatment, and 543 (21%) achieved cure. Among 1,739 patients staged, 693 (40%) patients had a liver fibrosis assessment score < F2, rendering them ineligible for treatment under Maryland Medicaid guidelines. HCV RNA testing among HCV antibody positive people increased from 40% (baseline) to 95% amongst STC providers. Of 554 patients with virologic data reported, 543 (98%) achieved cure. Primary care practices can effectively serve as HCV treatment centers to expand treatment access. However, criteria by insurance providers in Maryland was a major barrier to treatment. |
Multisystem Inflammatory Syndrome in U.S. Children and Adolescents.
Feldstein LR , Rose EB , Horwitz SM , Collins JP , Newhams MM , Son MBF , Newburger JW , Kleinman LC , Heidemann SM , Martin AA , Singh AR , Li S , Tarquinio KM , Jaggi P , Oster ME , Zackai SP , Gillen J , Ratner AJ , Walsh RF , Fitzgerald JC , Keenaghan MA , Alharash H , Doymaz S , Clouser KN , Giuliano JS Jr , Gupta A , Parker RM , Maddux AB , Havalad V , Ramsingh S , Bukulmez H , Bradford TT , Smith LS , Tenforde MW , Carroll CL , Riggs BJ , Gertz SJ , Daube A , Lansell A , Coronado Munoz A , Hobbs CV , Marohn KL , Halasa NB , Patel MM , Randolph AG . N Engl J Med 2020 383 (4) 334-346 BACKGROUND: Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19) is important, given the clinical and public health implications of the syndrome. METHODS: We conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States. The case definition included six criteria: serious illness leading to hospitalization, an age of less than 21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with Covid-19 in the past month. Clinicians abstracted the data onto standardized forms. RESULTS: We report on 186 patients with MIS-C in 26 states. The median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing, and 164 (88%) were hospitalized after April 16, 2020. Organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%). The median duration of hospitalization was 7 days (interquartile range, 4 to 10); 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support, and 4 (2%) died. Coronary-artery aneurysms (z scores >/=2.5) were documented in 15 patients (8%), and Kawasaki's disease-like features were documented in 74 (40%). Most patients (171 [92%]) had elevations in at least four biomarkers indicating inflammation. The use of immunomodulating therapies was common: intravenous immune globulin was used in 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%). CONCLUSIONS: Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents. (Funded by the Centers for Disease Control and Prevention.). |
High prevalence of multidrug-resistant organism colonization in 28 nursing homes: An "iceberg effect"
McKinnell JA , Miller LG , Singh RD , Gussin G , Kleinman K , Mendez J , Laurner B , Catuna TD , Heim L , Saavedra R , Felix J , Torres C , Chang J , Estevez M , Mendez J , Tchakalian G , Bloomfield L , Ceja S , Franco R , Miner A , Hurtado A , Hean R , Varasteh A , Robinson PA , Park S , Tam S , Tjoa T , He J , Agrawal S , Yamaguchi S , Custodio H , Nguyen J , Bittencourt CE , Evans KD , Mor V , McConeghy K , Weinstein RA , Hayden MK , Stone ND , Steinberg K , Beecham N , Montgomery J , DeAnn W , Peterson EM , Huang SS . J Am Med Dir Assoc 2020 21 (12) 1937-1943 e2 OBJECTIVE: Determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp. (VRE), extended-spectrum beta-lactamase producing organisms (ESBLs), and carbapenem-resistant Enterobacteriaceae (CRE) among residents and in the environment of nursing homes (NHs). DESIGN: Point prevalence sampling of residents and environmental sampling of high-touch objects in resident rooms and common areas. SETTING: Twenty-eight NHs in Southern California from 2016 to 2017. PARTICIPANTS: NH participants in Project PROTECT, a cluster-randomized trial of enhanced bathing and decolonization vs routine care. METHODS: Fifty residents were randomly sampled per NH. Twenty objects were sampled, including 5 common room objects plus 5 objects in each of 3 rooms (ambulatory, total care, and dementia care residents). RESULTS: A total of 2797 swabs were obtained from 1400 residents in 28 NHs. Median prevalence of multidrug-resistant organism (MDRO) carriage per NH was 50% (range: 24%-70%). Median prevalence of specific MDROs were as follows: MRSA, 36% (range: 20%-54%); ESBL, 16% (range: 2%-34%); VRE, 5% (range: 0%-30%); and CRE, 0% (range: 0%-8%). A median of 45% of residents (range: 24%-67%) harbored an MDRO without a known MDRO history. Environmental MDRO contamination was found in 74% of resident rooms and 93% of common areas. CONCLUSIONS AND IMPLICATIONS: In more than half of the NHs, more than 50% of residents were colonized with MDROs of clinical and public health significance, most commonly MRSA and ESBL. Additionally, the vast majority of resident rooms and common areas were MDRO contaminated. The unknown submerged portion of the iceberg of MDRO carriers in NHs may warrant changes to infection prevention and control practices, particularly high-fidelity adoption of universal strategies such as hand hygiene, environmental cleaning, and decolonization. |
Dietary characteristics associated with plasma concentrations of per- and polyfluoroalkyl substances among adults with pre-diabetes: Cross-sectional results from the Diabetes Prevention Program Trial
Lin PD , Cardenas A , Hauser R , Gold DR , Kleinman KP , Hivert MF , Fleisch AF , Calafat AM , Sanchez-Guerra M , Osorio-Yanez C , Webster TF , Horton ES , Oken E . Environ Int 2020 137 105217 Diet is assumed to be the main source of exposure to per- and polyfluoroalkyl substances (PFAS) in non-occupationally exposed populations, but studies on the diet-PFAS relationship in the United States are scarce. We extracted multiple dietary variables, including daily intakes of food group, diet scores, and dietary patterns, from self-reported dietary data collected at baseline (1996-1999) from adults with pre-diabetes enrolled in the Diabetes Prevention Program, and used linear regression models to evaluate relationships of each dietary variable with plasma concentrations of six PFAS (perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), 2-(N-ethyl-perfluorooctane sulfonamido) acetic acid (EtFOSAA), 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (MeFOSAA), perfluorononanoic acid (PFNA) adjusting for covariates. Participants (N=941, 65% female, 58% Caucasian, 68% married, 75% with higher education, 95% nonsmoker) had similar PFAS concentrations compared to the general U.S. population during 1999-2000. Using a single food group approach, fried fish, other fish/shellfish, meat and poultry had positive associations with most PFAS plasma concentrations. The strongest effect estimate detected was between fried fish and PFNA [13.6% (95% CI: 7.7, 19.9) increase in median concentration per SD increase]. Low-carbohydrate and high protein diet score had positive association with plasma PFHxS. Some food groups, mostly vegetables and fruits, and the Dietary Approaches to Stop Hypertension diet score had inverse associations with PFOS and MeFOSAA. A vegetable diet pattern was associated with lower plasma concentrations of MeFOSAA, while high-fat meat and low-fiber and high-fat grains diet patterns were associated with higher plasma concentrations of PFOS, PFHxS, MeFOSAA and PFNA. We summarized four major dietary characteristics associated with variations in PFAS plasma concentrations in this population. Specifically, consuming more meat/fish/shellfish (especially fried fish, and excluding Omega3-rich fish), low-fiber and high-fat bread/cereal/rice/pasta, and coffee/tea was associated with higher plasma concentrations while dietary patterns of vegetables, fruits and Omega-3 rich fish were associated with lower plasma concentrations of some PFAS. |
Per- and polyfluoroalkyl substances and blood pressure in pre-diabetic adults-cross-sectional and longitudinal analyses of the Diabetes Prevention Program Outcomes Study
Lin PD , Cardenas A , Hauser R , Gold DR , Kleinman KP , Hivert MF , Calafat AM , Webster TF , Horton ES , Oken E . Environ Int 2020 137 105573 The relationship of plasma concentration of per- and polyfluoroalkyl substances (PFAS) with blood pressure (BP) is uncertain. This study examined cross-sectional and prospective associations of PFAS with BP and hypertension. We quantified plasma PFAS concentrations from 957 participants enrolled in the lifestyle and placebo arms of the Diabetes Prevention Program (DPP), a randomized controlled trial with approximately 15 years of follow-up. We used multivariable linear and logistic regressions to test cross-sectional associations of six PFAS, including perfluorooctanesulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), N-ethyl-perfluorooctane sulfonamido acetic acid (EtFOSAA), N-methyl-perfluorooctane sulfonamido acetic acid (MeFOSAA), and perfluorononanoic acid (PFNA), with BP and hypertension prevalence, respectively, at baseline. We used generalized linear mixed models to estimate longitudinal associations between baseline PFAS and the rate of BP changes, and Cox-Proportional hazard models to estimate risk of developing hypertension relative to baseline PFAS. Models were adjusted for baseline age, sex, race/ethnicity, treatment arm, educational attainment, income, marital status, smoking habit, alcohol drinking, and diet. We tested for effect modification by the treatment arm and sex, and accounted for multiple comparisons using the False-Discovery Rate (FDR). PFAS concentrations and hypertension prevalence within the study population (65.3% female, 57.7% White, 65.3% aged 40-59 years) were comparable to the general U.S. population. Cross-sectionally, we found small but statistically significant associations of baseline plasma concentrations of PFOA with systolic BP (beta per doubling: 1.49 mmHg, 95% CI: 0.29, 2.70); and MeFOSAA with hypertension (RR = 1.09 per doubling, 95% CI: 1.01, 1.19). Estimates were not statistically significant after FDR adjustment. Longitudinally, we observed null associations in the placebo arm, but some inverse associations of baseline PFOS and MeFOSAA with systolic BP in the lifestyle arm, perhaps due to regression toward the mean. Baseline PFAS concentrations also were not prospectively associated with hypertension risk. Overall, there were modest and mostly null associations of plasma PFAS concentrations with BP and hypertension. |
Associations of perfluoroalkyl and polyfluoroalkyl substances with incident diabetes and microvascular disease
Cardenas A , Hivert MF , Gold DR , Hauser R , Kleinman KP , Lin PD , Fleisch AF , Calafat AM , Ye X , Webster TF , Horton ES , Oken E . Diabetes Care 2019 42 (9) 1824-1832 OBJECTIVE: Perfluoroalkyl and polyfluoroalkyl substances (PFASs) are suspected endocrine disruptors widely detected across populations. We examine the extent to which PFASs are associated with diabetes incidence and microvascular disease. Secondarily, we tested whether a lifestyle intervention modifies associations and decreases concentrations. RESEARCH DESIGN AND METHODS: We analyzed data from a prospective cohort of 957 participants from the Diabetes Prevention Program (DPP) trial and Outcomes Study (DPPOS). At baseline, participants were randomized to an intensive lifestyle intervention of diet, physical activity, and behavior modification or a placebo medication. We quantified plasma concentrations of six PFASs at baseline and 2 years after randomization. Participants were monitored for approximately 15 years, repeatedly tested for diabetes, and evaluated for microvascular disease at the end of the follow-up. RESULTS: A doubling in baseline Sb-PFOA concentration was associated with a 14% increase in diabetes risk for the placebo (hazard ratio [HR] 1.14, 95% CI 1.04, 1.25) but not in the lifestyle intervention group (HR 1.01, 95% CI 0.92, 1.11, P interaction = 0.11). Mean change in plasma baseline branched perfluorooctanoic acid concentration was greater for the placebo (0.96 ng/mL; 95% CI 0.71, 1.22) compared with the lifestyle intervention group (0.31 ng/mL; 95% CI 0.14, 0.48) 2 years after randomization. Each doubling in N-ethyl-perfluorooctane sulfonamido acetic acid was associated with 17% greater odds of prevalent microvascular disease (OR 1.17, 95% CI 1.05, 1.31), and a similar association was observed for perfluorodimethylhexane sulfonic acid (OR 1.18, 95% CI 1.04, 1.35), regardless of treatment. CONCLUSIONS: Some plasma PFASs were associated with diabetes and microvascular disease. Our results suggest that exercise and diet may attenuate the diabetogenic association of PFASs. |
Per- and polyfluoroalkyl substances and blood lipid levels in pre-diabetic adults-longitudinal analysis of the diabetes prevention program outcomes study
Lin PD , Cardenas A , Hauser R , Gold DR , Kleinman KP , Hivert MF , Fleisch AF , Calafat AM , Webster TF , Horton ES , Oken E . Environ Int 2019 129 343-353 Exposure to per- and polyfluoroalkyl substances (PFASs) may interfere with lipid regulation. However, most previous studies were cross-sectional with the risk of reverse causation, suggesting a need for long-term prospective studies. We examined the relationship of baseline plasma PFAS concentrations with repeated measures of blood lipids. We included 888 prediabetic adults from the Diabetes Prevention Program (DPP) and DPP Outcomes Study, who had measurements of 6 plasma PFAS concentrations at baseline (1996-1999) and repeated measures of blood lipids over 15years of follow-up, and were initially randomized to placebo or a lifestyle intervention. We used linear regression to examine cross-sectional associations of PFAS concentrations and lipid levels at baseline, and evaluated prospective risks of hypercholesterolemia and hypertriglyceridemia using Cox proportional hazard models, and tested for effect modification by study arm. Participants (65.9% female, 57.0% White, 65.9% aged 40-59years) had comparable PFAS concentrations [e.g., median (IQR) perfluorooctanoic acid (PFOA) 4.9ng/mL (3.2)] with the general U.S. population in 1999-2000. We observed higher total cholesterol at baseline per doubling of PFOA (beta: 6.1mg/dL, 95% CI: 3.1, 9.04), perfluorohexane sulfonic acid (PFHxS, beta: 2.2mg/dL, 95% CI: 0.2, 4.3), and perfluorononanoic acid (PFNA, beta: 2.9mg/dL, 95% CI: 0.7, 5.0). Prospectively, baseline concentrations of several PFASs, including PFOA, PFOS, PFHxS and PFNA, predicted higher risks of incident hypercholesterolemia and hypertriglyceridemia, but only in the placebo group and not the lifestyle intervention group. For example, participants in the placebo group with PFOA concentration>median (4.9ng/mL) were almost twice as likely (HR: 1.90, 95% CI: 1.25, 2.88) to develop hypertriglyceridemia compared to those </=median. Findings suggest adverse effects of some PFASs on lipid profiles in prediabetic adults. However, the detrimental effect was attenuated with a lifestyle intervention. |
Chlorhexidine versus routine bathing to prevent multidrug-resistant organisms and all-cause bloodstream infections in general medical and surgical units (ABATE Infection trial): a cluster-randomised trial
Huang SS , Septimus E , Kleinman K , Moody J , Hickok J , Heim L , Gombosev A , Avery TR , Haffenreffer K , Shimelman L , Hayden MK , Weinstein RA , Spencer-Smith C , Kaganov RE , Murphy MV , Forehand T , Lankiewicz J , Coady MH , Portillo L , Sarup-Patel J , Jernigan JA , Perlin JB , Platt R . Lancet 2019 393 (10177) 1205-1215 BACKGROUND: Universal skin and nasal decolonisation reduces multidrug-resistant pathogens and bloodstream infections in intensive care units. The effect of universal decolonisation on pathogens and infections in non-critical-care units is unknown. The aim of the ABATE Infection trial was to evaluate the use of chlorhexidine bathing in non-critical-care units, with an intervention similar to one that was found to reduce multidrug-resistant organisms and bacteraemia in intensive care units. METHODS: The ABATE Infection (active bathing to eliminate infection) trial was a cluster-randomised trial of 53 hospitals comparing routine bathing to decolonisation with universal chlorhexidine and targeted nasal mupirocin in non-critical-care units. The trial was done in hospitals affiliated with HCA Healthcare and consisted of a 12-month baseline period from March 1, 2013, to Feb 28, 2014, a 2-month phase-in period from April 1, 2014, to May 31, 2014, and a 21-month intervention period from June 1, 2014, to Feb 29, 2016. Hospitals were randomised and their participating non-critical-care units assigned to either routine care or daily chlorhexidine bathing for all patients plus mupirocin for known methicillin-resistant Staphylococcus aureus (MRSA) carriers. The primary outcome was MRSA or vancomycin-resistant enterococcus clinical cultures attributed to participating units, measured in the unadjusted, intention-to-treat population as the HR for the intervention period versus the baseline period in the decolonisation group versus the HR in the routine care group. Proportional hazards models assessed differences in outcome reductions across groups, accounting for clustering within hospitals. This trial is registered with ClinicalTrials.gov, number NCT02063867. FINDINGS: There were 189 081 patients in the baseline period and 339 902 patients (156 889 patients in the routine care group and 183 013 patients in the decolonisation group) in the intervention period across 194 non-critical-care units in 53 hospitals. For the primary outcome of unit-attributable MRSA-positive or VRE-positive clinical cultures (figure 2), the HR for the intervention period versus the baseline period was 0.79 (0.73-0.87) in the decolonisation group versus 0.87 (95% CI 0.79-0.95) in the routine care group. No difference was seen in the relative HRs (p=0.17). There were 25 (<1%) adverse events, all involving chlorhexidine, among 183 013 patients in units assigned to chlorhexidine, and none were reported for mupirocin. INTERPRETATION: Decolonisation with universal chlorhexidine bathing and targeted mupirocin for MRSA carriers did not significantly reduce multidrug-resistant organisms in non-critical-care patients. FUNDING: National Institutes of Health. |
The SHIELD Orange County Project - multi drug-resistant organism (MDRO) prevalence in 21 nursing homes and long term acute care facilities in southern California
McKinnell JA , Singh RD , Miller LG , Kleinman K , Gussin G , He J , Saavedra R , Dutciuc TD , Estevez M , Chang J , Heim L , Yamaguchi S , Custodio H , Gohil SK , Park S , Tam S , Robinson PA , Tjoa T , Nguyen J , Evans KD , Bittencourt CE , Lee BY , Mueller LE , Bartsch SM , Jernigan JA , Slayton RB , Stone ND , Zahn M , Mor V , McConeghy K , Baier RR , Janssen L , O'Donnell K , Weinstein RA , Hayden MK , Coady MH , Bhattarai M , Peterson EM , Huang SS . Clin Infect Dis 2019 69 (9) 1566-1573 Background: Multidrug-resistant organisms (MDROs) spread between hospitals, nursing homes (NH), and long-term acute care facilities (LTACs) via patient transfers. SHIELD OC is a regional public health collaborative involving decolonization at 38 healthcare facilities selected based upon their high degree of patient sharing. We report baseline MDRO prevalence in 21 NH/LTACs. Methods: A random sample of 50 adults for 21 NH/LTACs (18 NHs, 3 LTACs) were screened for methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp. (VRE), extended-spectrum beta-lactamase producing organisms (ESBL), and carbapenem-resistant Enterobacteriaceae (CRE) using nares, skin (axilla/groin), and peri-rectal swabs. Facility and resident characteristics associated with MDRO carriage were assessed using multivariable models clustering by person and facility. Results: Prevalence of MDROs was 65% in NHs and 80% in LTACs. The most common MDROs in NHs were MRSA (42%) and ESBL (34%); in LTACs they were VRE (55%) and ESBL (38%). CRE prevalence was higher in facilities that manage ventilated LTAC patients and NH residents (8% vs. <1%, p<0.001). MDRO status was known for 18% of NH residents and 49% of LTAC patients. MDRO colonized adults commonly harbored additional MDROs (54% MDRO+ NH residents and 62% MDRO+ LTACs patients). History of MRSA [OR=1.7 C.I. (1.2, 2.4),p=0.004], VRE [OR=2.1 C.I.(1.2, 3.8),p=0.01], ESBL [OR=1.6 C.I.(1.1, 2.3),p=0.03] and diabetes [OR=1.3 C.I.(1.0, 1.7),p=0.03] were associated with any MDRO carriage. Conclusions: The majority of NH residents and LTACs patients harbor MDROs. MDRO status is frequently unknown to the facility. The high MDRO prevalence highlights the need for prevention efforts in NH/LTACs as part of regional efforts to control MDRO spread. |
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