Reliability at the Lower Limits of HIV-1 RNA Quantification in Clinical Samples: A Comparison of RT-PCR versus bDNA Assays

INTRODUCTION:To explore whether an assay change was responsible for an increasing proportion of patients with undetectable HIV viral loads at our urban HIV clinic, we selected highly stable patients, examining their viral loads before and after changing assays. We compared the proportion with detectable viremia during RT-PCR vs. bDNA periods. METHODOLOGY/PRINCIPAL FINDINGS:We selected patients with > or =1 viral loads assessed during both RT-PCR and bDNA periods. We included patients with stable CD4 counts, excluding patients with viral loads > or =1,000 copies/ml or any significant changes in therapy. Out of 4500 clinic patients, 419 patients (1588 viral loads) were included. 39% of viral loads were reported as detectable by RT-PCR vs. 5% reported as detectable by bDNA. The mean coefficient of variation was higher before vs. after assay change. We found an odds' ratio of 16.7 for having a viral load >75 copies/ml during the RT-PCR vs. bDNA periods. DISCUSSION:These data support previous reports, suggesting that bDNA may more reliably discriminate between viral suppression and low level viremia in stable patients on therapy. Low-level viremia, noted more with RT-PCR, may promote unneeded testing, while differences in viral load reliability may impact antiretroviral trial and quality assurance endpoints. Commonly used plasma separator tubes may differentially affect RT-PCR and bDNA results

Wasserstein Distributionally Robust Look-Ahead Economic Dispatch

We consider the problem of look-ahead economic dispatch (LAED) with uncertain renewable energy generation. The goal of this problem is to minimize the cost of conventional energy generation subject to uncertain operational constraints. The risk of violating these constraints must be below a given threshold for a family of probability distributions with characteristics similar to observed past data or predictions. We present two data-driven approaches based on two novel mathematical reformulations of this distributionally robust decision problem. The first one is a tractable convex program in which the uncertain constraints are defined via the distributionally robust conditional-value-at-risk. The second one is a scalable robust optimization program that yields an approximate distributionally robust chance-constrained LAED. Numerical experiments on the IEEE 39-bus system with real solar production data and forecasts illustrate the effectiveness of these approaches. We discuss how system operators should tune these techniques in order to seek the desired robustness-performance trade-off and we compare their computational scalability

A multicenter study of Clostridium difficile infection-related colectomy, 2000-2006

BACKGROUND: The incidence of Clostridium difficile infection (CDI) has been increasing. Previous studies report that the number of colectomies for CDI is also rising. Outside of a few notable outbreaks, there are few published data documenting increasing severity of CDI. The specific aims of this multiyear, multicenter study were to assess CDI-related colectomy rates and compare CDI-related colectomy rates by CDI surveillance definition. METHODS: Cases of CDI and patients who underwent colectomy were identified electronically from 5 US tertiary-care centers from July 2000 through June 2006. Chart review was performed to determine if a colectomy was for CDI. Monthly CDI-related colectomy rates were calculated as the number of CDI-related colectomies per 1,000 CDI cases. Data between observational groups were compared using χ(2) and Mann-Whitney U tests. Logistic regression was performed to evaluate risk factors for CDI-related colectomy. RESULTS: 8569 cases of CDI were identified and 75 patients had CDI-related colectomy. The overall colectomy rate was 8.7/1,000 CDI cases. The CDI-related colectomy rate ranged from 0 to 23 per 1,000 CDI episodes across hospitals. The colectomy rates for healthcare facility (HCF)-onset CDI was 4.3/1000 CDI cases and 16.5 /1000 CDI cases for community-onset CDI (p <.05). There were significantly more CDI-related colectomies at hospitals B and C (p<.05). CONCLUSIONS: The overall CDI-related colectomy rate was low, and there was no significant change in the CDI-related colectomy rate over time. Onset of disease outside of the study hospital was an independent risk factor for colectomy

Multicenter evaluation of computer automated versus traditional surveillance of hospital-acquired bloodstream infections

Objective.Central line–associated bloodstream infection (BSI) rates are a key quality metric for comparing hospital quality and safety. Traditional BSI surveillance may be limited by interrater variability. We assessed whether a computer-automated method of central line–associated BSI detection can improve the validity of surveillance.Design.Retrospective cohort study.Setting.Eight medical and surgical intensive care units (ICUs) in 4 academic medical centers.Methods.Traditional surveillance (by hospital staff) and computer algorithm surveillance were each compared against a retrospective audit review using a random sample of blood culture episodes during the period 2004–2007 from which an organism was recovered. Episode-level agreement with audit review was measured with κ statistics, and differences were assessed using the test of equal κ coefficients. Linear regression was used to assess the relationship between surveillance performance (κ) and surveillance-reported BSI rates (BSIs per 1,000 central line–days).Results.We evaluated 664 blood culture episodes. Agreement with audit review was significantly lower for traditional surveillance (κ [95% confidence interval (CI)] = 0.44 [0.37–0.51]) than computer algorithm surveillance (κ [95% CI] [0.52–0.64]; P = .001). Agreement between traditional surveillance and audit review was heterogeneous across ICUs (P = .001); furthermore, traditional surveillance performed worse among ICUs reporting lower (better) BSI rates (P = .001). In contrast, computer algorithm performance was consistent across ICUs and across the range of computer-reported central line–associated BSI rates.Conclusions.Compared with traditional surveillance of bloodstream infections, computer automated surveillance improves accuracy and reliability, making interfacility performance comparisons more valid.Infect Control Hosp Epidemiol 2014;35(12):1483–1490</jats:sec

Multicenter study of the impact of community-onset Clostridium difficile infection on surveillance for C. difficile infection

OBJECTIVE: To evaluate the influence of community-onset/healthcare facility-associated cases on Clostridium difficile infection (CDI) incidence and outbreak detection. DESIGN: Retrospective cohort. SETTING: Five acute-care healthcare facilities in the United States. METHODS: Positive stool C. difficile toxin assays from July 2000 through June 2006 and healthcare facility exposure information were collected. CDI cases were classified as hospital-onset (HO) if they were diagnosed > 48 hours after admission or community-onset/healthcare facility-associated if they were diagnosed ≤ 48 hours from admission and had recently been discharged from the healthcare facility. Four surveillance definitions were compared: HO cases only and HO plus community-onset/healthcare facility-associated cases diagnosed within 30 (HCFA-30), 60 (HCFA-60) and 90 (HCFA-90) days after discharge from the study hospital. Monthly CDI rates were compared. Control charts were used to identify potential CDI outbreaks. RESULTS: The HCFA-30 rate was significantly higher than the HO rate at two healthcare facilities (p<0.01). The HCFA-30 rate was not significantly different from the HCFA-60 or HCFA-90 rates at any healthcare facility. The correlations between each healthcare facility’s monthly rates of HO and HCFA-30 CDI were almost perfect (range, 0.94–0.99, p<0.001). Overall, 12 time points had a CDI rate >3 SD above the mean, including 11 by the HO definition and 9 by the HCFA-30 definition, with discordant results at 4 time points (κ = 0.794, p<0.001). CONCLUSIONS: Tracking community-onset/healthcare facility-associated cases in addition to HO cases captures significantly more CDI cases but surveillance of HO CDI alone is sufficient to detect an outbreak

Staphylococcus aureus bacteriuria as a prognosticator for outcome of Staphylococcus aureus bacteremia: a case-control study

<p>Abstract</p> <p>Background</p> <p>When <it>Staphylococcus aureus </it>is isolated in urine, it is thought to usually represent hematogenous spread. Because such spread might have special clinical significance, we evaluated predictors and outcomes of <it>S. aureus </it>bacteriuria among patients with <it>S. aureus </it>bacteremia.</p> <p>Methods</p> <p>A case-control study was performed at John H. Stroger Jr. Hospital of Cook County among adult inpatients during January 2002-December 2006. Cases and controls had positive and negative urine cultures, respectively, for <it>S. aureus</it>, within 72 hours of positive blood culture for <it>S. aureus</it>. Controls were sampled randomly in a 1:4 ratio. Univariate and multivariable logistic regression analyses were done.</p> <p>Results</p> <p>Overall, 59% of patients were African-American, 12% died, 56% of infections had community-onset infections, and 58% were infected with methicillin-susceptible <it>S. aureus </it>(MSSA). Among 61 cases and 247 controls, predictors of <it>S. aureus </it>bacteriuria on multivariate analysis were urological surgery (OR = 3.4, p = 0.06) and genitourinary infection (OR = 9.2, p = 0.002). Among patients who died, there were significantly more patients with bacteriuria than among patients who survived (39% vs. 17%; p = 0.002). In multiple Cox regression analysis, death risks in bacteremic patients were bacteriuria (hazard ratio 2.9, CI 1.4-5.9, p = 0.004), bladder catheter use (2.0, 1.0-4.0, p = 0.06), and Charlson score (1.1, 1.1-1.3, p = 0.02). Neither length of stay nor methicillin-resistant <it>Staphylococcus aureus </it>(MRSA) infection was a predictor of <it>S. aureus </it>bacteriuria or death.</p> <p>Conclusions</p> <p>Among patients with <it>S. aureus </it>bacteremia, those with <it>S. aureus </it>bacteriuria had 3-fold higher mortality than those without bacteriuria, even after adjustment for comorbidities. Bacteriuria may identify patients with more severe bacteremia, who are at risk of worse outcomes.</p

Study protocol for the Innovative Support for Patients with SARS-COV-2 Infections Registry (INSPIRE): A longitudinal study of the medium and long-term sequelae of SARS-CoV-2 infection

Background: Reports on medium and long-term sequelae of SARS-CoV-2 infections largely lack quantification of incidence and relative risk. We describe the rationale and methods of the Innovative Support for Patients with SARS-CoV-2 Registry (INSPIRE) that combines patient-reported outcomes with data from digital health records to understand predictors and impacts of SARS-CoV-2 infection. Methods: INSPIRE is a prospective, multicenter, longitudinal study of individuals with symptoms of SARS-CoV-2 infection in eight regions across the US. Adults are eligible for enrollment if they are fluent in English or Spanish, reported symptoms suggestive of acute SARS-CoV-2 infection, and if they are within 42 days of having a SARS-CoV-2 viral test (i.e., nucleic acid amplification test or antigen test), regardless of test results. Recruitment occurs in-person, by phone or email, and through online advertisement. A secure online platform is used to facilitate the collation of consent-related materials, digital health records, and responses to self-administered surveys. Participants are followed for up to 18 months, with patient-reported outcomes collected every three months via survey and linked to concurrent digital health data; follow-up includes no in-person involvement. Our planned enrollment is 4,800 participants, including 2,400 SARS-CoV-2 positive and 2,400 SARS-CoV-2 negative participants (as a concurrent comparison group). These data will allow assessment of longitudinal outcomes from SARS-CoV-2 infection and comparison of the relative risk of outcomes in individuals with and without infection. Patient-reported outcomes include self-reported health function and status, as well as clinical outcomes including health system encounters and new diagnoses. Results: Participating sites obtained institutional review board approval. Enrollment and follow-up are ongoing. Conclusions: This study will characterize medium and long-term sequelae of SARS-CoV-2 infection among a diverse population, predictors of sequelae, and their relative risk compared to persons with similar symptomatology but without SARS-CoV-2 infection. These data may inform clinical interventions for individuals with sequelae of SARS-CoV-2 infection

Association of Initial SARS-CoV-2 Test Positivity With Patient-Reported Well-being 3 Months After a Symptomatic Illness.

IMPORTANCE: Long-term sequelae after symptomatic SARS-CoV-2 infection may impact well-being, yet existing data primarily focus on discrete symptoms and/or health care use. OBJECTIVE: To compare patient-reported outcomes of physical, mental, and social well-being among adults with symptomatic illness who received a positive vs negative test result for SARS-CoV-2 infection. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was a planned interim analysis of an ongoing multicenter prospective longitudinal registry study (the Innovative Support for Patients With SARS-CoV-2 Infections Registry [INSPIRE]). Participants were enrolled from December 11, 2020, to September 10, 2021, and comprised adults (aged ≥18 years) with acute symptoms suggestive of SARS-CoV-2 infection at the time of receipt of a SARS-CoV-2 test approved by the US Food and Drug Administration. The analysis included the first 1000 participants who completed baseline and 3-month follow-up surveys consisting of questions from the 29-item Patient-Reported Outcomes Measurement Information System (PROMIS-29; 7 subscales, including physical function, anxiety, depression, fatigue, social participation, sleep disturbance, and pain interference) and the PROMIS Short Form-Cognitive Function 8a scale, for which population-normed T scores were reported. EXPOSURES: SARS-CoV-2 status (positive or negative test result) at enrollment. MAIN OUTCOMES AND MEASURES: Mean PROMIS scores for participants with positive COVID-19 tests vs negative COVID-19 tests were compared descriptively and using multivariable regression analysis. RESULTS: Among 1000 participants, 722 (72.2%) received a positive COVID-19 result and 278 (27.8%) received a negative result; 406 of 998 participants (40.7%) were aged 18 to 34 years, 644 of 972 (66.3%) were female, 833 of 984 (84.7%) were non-Hispanic, and 685 of 974 (70.3%) were White. A total of 282 of 712 participants (39.6%) in the COVID-19-positive group and 147 of 275 participants (53.5%) in the COVID-19-negative group reported persistently poor physical, mental, or social well-being at 3-month follow-up. After adjustment, improvements in well-being were statistically and clinically greater for participants in the COVID-19-positive group vs the COVID-19-negative group only for social participation (β = 3.32; 95% CI, 1.84-4.80; P \u3c .001); changes in other well-being domains were not clinically different between groups. Improvements in well-being in the COVID-19-positive group were concentrated among participants aged 18 to 34 years (eg, social participation: β = 3.90; 95% CI, 1.75-6.05; P \u3c .001) and those who presented for COVID-19 testing in an ambulatory setting (eg, social participation: β = 4.16; 95% CI, 2.12-6.20; P \u3c .001). CONCLUSIONS AND RELEVANCE: In this study, participants in both the COVID-19-positive and COVID-19-negative groups reported persistently poor physical, mental, or social well-being at 3-month follow-up. Although some individuals had clinically meaningful improvements over time, many reported moderate to severe impairments in well-being 3 months later. These results highlight the importance of including a control group of participants with negative COVID-19 results for comparison when examining the sequelae of COVID-19