Matching in Cluster Randomized Trials Using the Goldilocks Approach

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

The impact of HIV-associated lipodystrophy on healthcare utilization and costs

BackgroundHIV disease itself is associated with increased healthcare utilization and healthcare expenditures. HIV-infected persons with lipodystrophy have been shown to have poor self-perceptions of health. We evaluated whether lipodystrophy in the HIV-infected population was associated with increased utilization of healthcare services and increased healthcare costs.ObjectiveTo examine utilization of healthcare services and associated costs with respect to presence of lipodystrophy among HIV-infected patients.MethodsHealthcare utilization and cost of healthcare services were collected from computerized accounting records for participants in a body image study among HIV-infected patients treated at a tertiary care medical center. Lipodystrophy was assessed by physical examination, and effects of lipodystrophy were assessed via body image surveys. Demographic and clinical characteristics were also ascertained. Analysis of healthcare utilization and cost outcomes was performed via between-group analyses. Multivariate modeling was used to determine predictors of healthcare utilization and associated costs.ResultsOf the 181 HIV-infected participants evaluated in the study, 92 (51%) had clinical evidence of HIV-associated lipodystrophy according to physician examination. Total healthcare utilization, as measured by the number of medical center visits over the study period, was notably increased among HIV-infected subjects with lipodystrophy as compared to HIV-infected subjects without lipodystrophy. Similarly, total healthcare expenditures over the study period were $1,718 more for HIV-infected subjects with lipodystrophy than for HIV-infected subjects without lipodystrophy. Multivariate modeling demonstrated strong associations between healthcare utilization and associated costs, and lipodystrophy score as assessed by a clinician. Healthcare utilization and associated costs were not related to body image survey scores among HIV-infected patients with lipodystrophy.ConclusionPatients with HIV-associated lipodystrophy demonstrate an increased utilization of healthcare services with associated increased healthcare costs as compared to HIV-infected patients without lipodystrophy. The economic and healthcare service burdens of HIV-associated lipodystrophy are significant and yet remain inadequately addressed by the medical community

Frequent hospital readmissions for Clostridium difficile infection and the impact on estimates of hospital-associated C. difficile burden

ObjectiveClostridium difficile infection (CDI) is associated with hospitalization and may cause readmission following admission for any reason. We aimed to measure the incidence of readmissions due to CDI.DesignRetrospective cohort study.PatientsAdult inpatients in Orange County, California, who presented with new-onset CDI within 12 weeks of discharge.MethodsWe assessed mandatory 2000-2007 hospital discharge data for trends in hospital-associated CDI (HA-CDI) incidence, with and without inclusion of postdischarge CDI (PD-CDI) events resulting in rehospitalization within 12 weeks of discharge. We measured the effect of including PD-CDI events on hospital-specific CDI incidence, a mandatory reporting measure in California, and on relative hospital ranks by CDI incidence.ResultsFrom 2000 to 2007, countywide hospital-onset CDI (HO-CDI) incidence increased from 15 per 10,000 to 22 per 10,000 admissions. When including PD-CDI events, HA-CDI incidence doubled (29 per 10,000 in 2000 and 52 per 10,000 in 2007). Overall, including PD-CDI events resulted in significantly higher hospital-specific CDI incidence, although hospitals had disproportionate amounts of HA-CDI occurring postdischarge. This resulted in substantial shifts in some hospitals' rankings by CDI incidence. In multivariate models, both HO and PD-CDI were associated with increasing age, higher length of stay, and select comorbidities. Race and Hispanic ethnicity were predictive of PD-CDI but not HO-CDI.ConclusionsPD-CDI events associated with rehospitalization are increasingly common. The majority of HA-CDI cases may be occurring postdischarge, raising important questions about both accurate reporting and effective prevention strategies. Some risk factors for PD-CDI may be different than those for HO-CDI, allowing additional identification of high-risk groups before discharge

Proteomic differences between Listeria monocytogenes isolates from food and clinical environments

Listeria monocytogenes is an organism associated with a wide range of foods. It causes listeriosis, a severe illness that mainly affects people with weakened immune systems. Proteomic profiles of three different L. monocytogenes isolates were studied using 1D SDS PAGE, 2DE and mass spectrometry. The protein banding patterns generated by 1D SDS PAGE of three strains of L. monocytogenes were found to be similar. Visual observations from 2DE gel maps revealed that certain spots appeared to have intensity differences. Key differences in proteins synthesis of three strains of L. monocytogenes were found using the PDQest TM 2DE Analysis software. Comparison showed that the clinical isolate (strain SB92/844) had 53.4% and 53.9% protein profile similarity with dairy isolate (strain V7) and seafood isolate (SB92/870), respectively. The identity of selected protein spots was achieved using MALDI-TOF and ion trap mass spectrometry. It was found that certain identified proteins (i.e., a major cold shock protein and superoxide dismutase) were expressed differently between two local strains of L. monocytogenes (SB92/844, SB92/870) and one strain from overseas (V7)

The Potential Trajectory of Carbapenem-Resistant Enterobacteriaceae, an Emerging Threat to Health-Care Facilities, and the Impact of the Centers for Disease Control and Prevention Toolkit.

Carbapenem-resistant Enterobacteriaceae (CRE), a group of pathogens resistant to most antibiotics and associated with high mortality, are a rising emerging public health threat. Current approaches to infection control and prevention have not been adequate to prevent spread. An important but unproven approach is to have hospitals in a region coordinate surveillance and infection control measures. Using our Regional Healthcare Ecosystem Analyst (RHEA) simulation model and detailed Orange County, California, patient-level data on adult inpatient hospital and nursing home admissions (2011-2012), we simulated the spread of CRE throughout Orange County health-care facilities under 3 scenarios: no specific control measures, facility-level infection control efforts (uncoordinated control measures), and a coordinated regional effort. Aggressive uncoordinated and coordinated approaches were highly similar, averting 2,976 and 2,789 CRE transmission events, respectively (72.2% and 77.0% of transmission events), by year 5. With moderate control measures, coordinated regional control resulted in 21.3% more averted cases (n = 408) than did uncoordinated control at year 5. Our model suggests that without increased infection control approaches, CRE would become endemic in nearly all Orange County health-care facilities within 10 years. While implementing the interventions in the Centers for Disease Control and Prevention's CRE toolkit would not completely stop the spread of CRE, it would cut its spread substantially, by half

Making Sense of the Legendre Transform

The Legendre transform is an important tool in theoretical physics, playing a critical role in classical mechanics, statistical mechanics, and thermodynamics. Yet, in typical undergraduate or graduate courses, the power of motivation and elegance of the method are often missing, unlike the treatments frequently enjoyed by Fourier transforms. We review and modify the presentation of Legendre transforms in a way that explicates the formal mathematics, resulting in manifestly symmetric equations, thereby clarifying the structure of the transform algebraically and geometrically. Then we bring in the physics to motivate the transform as a way of choosing independent variables that are more easily controlled. We demonstrate how the Legendre transform arises naturally from statistical mechanics and show how the use of dimensionless thermodynamic potentials leads to more natural and symmetric relations.Comment: 11 pages, 3 figure

Successful strategies for high participation in three regional healthcare surveys: an observational study

<p>Abstract</p> <p>Background</p> <p>Regional healthcare facility surveys to quantitatively assess nosocomial infection rates are important for confirming standardized data collection and assessing health outcomes in the era of mandatory reporting. This is particularly important for the assessment of infection control policies and healthcare associated infection rates among hospitals. However, the success of such surveys depends upon high participation and representativeness of respondents.</p> <p>Methods</p> <p>This descriptive paper provides methodologies that may have contributed to high participation in a series of administrative, infection control, and microbiology laboratory surveys of all 31 hospitals in a large southern California county. We also report 85% (N = 72) countywide participation in an administrative survey among nursing homes in this same area.</p> <p>Results</p> <p>Using in-person recruitment, 48% of hospitals and nursing homes were recruited within one quarter, with 75% recruited within three quarters.</p> <p>Conclusions</p> <p>Potentially useful strategies for successful recruitment included in-person recruitment, partnership with the local public health department, assurance of anonymity when presenting survey results, and provision of staff labor for the completion of detailed survey tables on the rates of healthcare associated pathogens. Data collection assistance was provided for three-fourths of surveys. High compliance quantitative regional surveys require substantial recruitment time and study staff support for high participation.</p

Attributable healthcare utilization and cost of pneumonia due to drug-resistant streptococcus pneumonia: a cost analysis

Background: The burden of disease due to S. pneumoniae (pneumococcus), particularly pneumonia, remains high despite the widespread use of vaccines. Drug resistant strains complicate clinical treatment and may increase costs. We estimated the annual burden and incremental costs attributable to antibiotic resistance in pneumococcal pneumonia. Methods: We derived estimates of healthcare utilization and cost (in 2012 dollars) attributable to penicillin, erythromycin and fluoroquinolone resistance by taking the estimate of disease burden from a previously described decision tree model of pneumococcal pneumonia in the U.S. We analyzed model outputs assuming only the existence of susceptible strains and calculating the resulting differences in cost and utilization. We modeled the cost of resistance from delayed resolution of illness and the resulting additional health services. Results: Our model estimated that non-susceptibility to penicillin, erythromycin and fluoroquinolones directly caused 32,398 additional outpatient visits and 19,336 hospitalizations for pneumococcal pneumonia. The incremental cost of antibiotic resistance was estimated to account for 4% ($91 million) of direct medical costs and 5$233 million) of total costs including work and productivity loss. Most of the incremental medical cost ($82 million) was related to hospitalizations resulting from erythromycin non-susceptibility. Among patients under age 18 years, erythromycin non-susceptibility was estimated to cause 17$38 million in costs, or 39% of pneumococcal pneumonia costs attributable to resistance. Conclusions: We estimate that antibiotic resistance in pneumococcal pneumonia leads to substantial healthcare utilization and cost, with more than one-third driven by macrolide resistance in children. With 5% of total pneumococcal costs directly attributable to resistance, strategies to reduce antibiotic resistance or improve antibiotic selection could lead to substantial savings

Antibiotic Resistance Patterns of Bacterial Isolates from Blood in San Francisco County, California, 1996-1999

Countywide antibiotic resistance patterns may provide additional information from that obtained from national sampling or individual hospitals. We reviewed susceptibility patterns of selected bacterial strains isolated from blood in San Francisco County from January 1996 to March 1999. We found substantial hospital-to-hospital variability in proportional resistance to antibiotics in multiple organisms. This variability was not correlated with hospital indices such as number of intensive care unit or total beds, annual admissions, or average length of stay. We also found a significant increase in methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and proportional resistance to multiple antipseudomonal antibiotics. We describe the utility, difficulties, and limitations of countywide surveillance