Hospitalized patients who are colonized with methicillin-resistant Staphylococcus aureus (MRSA) are at high risk for infection after discharge.
We conducted a multicenter, randomized, controlled ...trial of postdischarge hygiene education, as compared with education plus decolonization, in patients colonized with MRSA (carriers). Decolonization involved chlorhexidine mouthwash, baths or showers with chlorhexidine, and nasal mupirocin for 5 days twice per month for 6 months. Participants were followed for 1 year. The primary outcome was MRSA infection as defined according to Centers for Disease Control and Prevention (CDC) criteria. Secondary outcomes included MRSA infection determined on the basis of clinical judgment, infection from any cause, and infection-related hospitalization. All analyses were performed with the use of proportional-hazards models in the per-protocol population (all participants who underwent randomization, met the inclusion criteria, and survived beyond the recruitment hospitalization) and as-treated population (participants stratified according to adherence).
In the per-protocol population, MRSA infection occurred in 98 of 1063 participants (9.2%) in the education group and in 67 of 1058 (6.3%) in the decolonization group; 84.8% of the MRSA infections led to hospitalization. Infection from any cause occurred in 23.7% of the participants in the education group and 19.6% of those in the decolonization group; 85.8% of the infections led to hospitalization. The hazard of MRSA infection was significantly lower in the decolonization group than in the education group (hazard ratio, 0.70; 95% confidence interval CI, 0.52 to 0.96; P=0.03; number needed to treat to prevent one infection, 30; 95% CI, 18 to 230); this lower hazard led to a lower risk of hospitalization due to MRSA infection (hazard ratio, 0.71; 95% CI, 0.51 to 0.99). The decolonization group had lower likelihoods of clinically judged infection from any cause (hazard ratio, 0.83; 95% CI, 0.70 to 0.99) and infection-related hospitalization (hazard ratio, 0.76; 95% CI, 0.62 to 0.93); treatment effects for secondary outcomes should be interpreted with caution owing to a lack of prespecified adjustment for multiple comparisons. In as-treated analyses, participants in the decolonization group who adhered fully to the regimen had 44% fewer MRSA infections than the education group (hazard ratio, 0.56; 95% CI, 0.36 to 0.86) and had 40% fewer infections from any cause (hazard ratio, 0.60; 95% CI, 0.46 to 0.78). Side effects (all mild) occurred in 4.2% of the participants.
Postdischarge MRSA decolonization with chlorhexidine and mupirocin led to a 30% lower risk of MRSA infection than education alone. (Funded by the AHRQ Healthcare-Associated Infections Program and others; ClinicalTrials.gov number, NCT01209234 .).
Claims-based analyses report that the incidence of sepsis-associated organ dysfunction is increasing. We examined whether coding practices for acute organ dysfunction are changing over time and if ...so, whether this is biasing estimates of rising severe sepsis incidence and severity.
We assessed trends from 2005 to 2013 in the annual sensitivity and incidence of discharge ICD-9-CM codes for organ dysfunction (shock, respiratory failure, acute kidney failure, acidosis, hepatitis, coagulopathy, and thrombocytopenia) relative to standardized clinical criteria (use of vasopressors/inotropes, mechanical ventilation for ≥ 2 consecutive days, rise in baseline creatinine, low pH, elevated transaminases or bilirubin, abnormal international normalized ratio or low fibrinogen, and decline in platelets). We studied all adult patients with suspected infection (defined by ≥ 1 blood culture order) at two US academic hospitals.
Acute organ dysfunction codes were present in 57,273 of 191,695 (29.9%) hospitalizations with suspected infection, most commonly acute kidney failure (60.2% of cases) and respiratory failure (28.9%). The sensitivity of all organ dysfunction codes except thrombocytopenia increased significantly over time. This was most pronounced for acute kidney failure codes, which increased in sensitivity from 59.3% in 2005 to 87.5% in 2013 relative to a fixed definition for changes in creatinine (p = 0.019 for linear trend). Acute kidney failure codes were increasingly assigned to patients with smaller creatinine changes: the average peak creatinine change associated with a code was 1.99 mg/dL in 2005 versus 1.49 mg/dL in 2013 (p <0.001 for linear decline). The mean number of dysfunctional organs in patients with suspected infection increased from 0.32 to 0.59 using discharge codes versus 0.69 to 0.79 using clinical criteria (p < 0.001 for both trends and comparison of the two trends). The annual incidence of hospitalizations with suspected infection and any dysfunctional organ rose an average of 5.9% per year (95% CI 4.3, 7.4%) using discharge codes versus only 1.1% (95% CI 0.1, 2.0 %) using clinical criteria.
Coding for acute organ dysfunction is becoming increasingly sensitive and the clinical threshold to code patients for certain kinds of organ dysfunction is decreasing. This accounts for much of the apparent rise in severe sepsis incidence and severity imputed from claims.
The clinical research enterprise is not producing the evidence decision makers arguably need in a timely and cost effective manner; research currently involves the use of labor-intensive parallel ...systems that are separate from clinical care. The emergence of pragmatic clinical trials (PCTs) poses a possible solution: these large-scale trials are embedded within routine clinical care and often involve cluster randomization of hospitals, clinics, primary care providers, etc. Interventions can be implemented by health system personnel through usual communication channels and quality improvement infrastructure, and data collected as part of routine clinical care. However, experience with these trials is nascent and best practices regarding design operational, analytic, and reporting methodologies are undeveloped.
To strengthen the national capacity to implement cost-effective, large-scale PCTs, the Common Fund of the National Institutes of Health created the Health Care Systems Research Collaboratory (Collaboratory) to support the design, execution, and dissemination of a series of demonstration projects using a pragmatic research design.
In this article, we will describe the Collaboratory, highlight some of the challenges encountered and solutions developed thus far, and discuss remaining barriers and opportunities for large-scale evidence generation using PCTs.
A planning phase is critical, and even with careful planning, new challenges arise during execution; comparisons between arms can be complicated by unanticipated changes. Early and ongoing engagement with both health care system leaders and front-line clinicians is critical for success. There is also marked uncertainty when applying existing ethical and regulatory frameworks to PCTS, and using existing electronic health records for data capture adds complexity.
The CDC introduced ventilator-associated event (VAE) definitions in January 2013. Little is known about VAE prevention. We hypothesized that daily, coordinated spontaneous awakening trials (SATs) and ...spontaneous breathing trials (SBTs) might prevent VAEs.
To assess the preventability of VAEs.
We nested a multicenter quality improvement collaborative within a prospective study of VAE surveillance among 20 intensive care units between November 2011 and May 2013. Twelve units joined the collaborative and implemented an opt-out protocol for nurses and respiratory therapists to perform paired daily SATs and SBTs. The remaining eight units conducted surveillance alone. We measured temporal trends in VAEs using generalized mixed effects regression models adjusted for patient-level unit, age, sex, reason for intubation, Sequential Organ Failure Assessment score, and comorbidity index.
We tracked 5,164 consecutive episodes of mechanical ventilation: 3,425 in collaborative units and 1,739 in surveillance-only units. Within collaborative units, significant increases in SATs, SBTs, and percentage of SBTs performed without sedation were mirrored by significant decreases in duration of mechanical ventilation and hospital length-of-stay. There was no change in VAE risk per ventilator day but significant decreases in VAE risk per episode of mechanical ventilation (odds ratio OR, 0.63; 95% confidence interval CI, 0.42-0.97) and infection-related ventilator-associated complications (OR, 0.35; 95% CI, 0.17-0.71) but not pneumonias (OR, 0.51; 95% CI, 0.19-1.3). Within surveillance-only units, there were no significant changes in SAT, SBT, or VAE rates.
Enhanced performance of paired, daily SATs and SBTs is associated with lower VAE rates. Clinical trial registered with www.clinicaltrials.gov (NCT 01583413).
Concerns regarding both the limited generalizability and the slow pace of traditional randomized trials have led to calls for greater use of real‐world evidence (RWE) in the evaluation of new ...treatments or products. RWE studies often rely on real‐world data (RWD), including data extracted from healthcare records or data captured by mobile phones or other consumer devices. Global assessments of RWD sources are not helpful in assessing whether any specific RWD element is fit for any specific purpose. Instead, evidence generators and evidence consumers should clearly identify the specific health state or clinical phenomenon of interest and then consider each step between that clinical phenomenon and its representation in a research database. We propose specific questions regarding potential error or bias affecting each of those steps: Would a person experiencing this clinical phenomenon present for care in this setting or interact with this recording device? Would this clinical phenomenon be accurately recognized or assessed? How might the recording environment or tools affect accurate and consistent recording of this clinical phenomenon? Can data elements from different sources be harmonized, both technically (same format) and semantically (same meaning)? Can the original data elements be consistently reduced to a useful clinical phenotype? Addressing these questions requires a range of clinical, organizational, and technical expertise. Transparency regarding each step in the creation of RWD is essential if evidence consumers are to rely on RWE studies.
Ventilator-associated pneumonia (VAP) surveillance is time consuming, subjective, inaccurate, and inconsistently predicts outcomes. Shifting surveillance from pneumonia in particular to complications ...in general might circumvent the VAP definition's subjectivity and inaccuracy, facilitate electronic assessment, make interfacility comparisons more meaningful, and encourage broader prevention strategies. We therefore evaluated a novel surveillance paradigm for ventilator-associated complications (VAC) defined by sustained increases in patients' ventilator settings after a period of stable or decreasing support.
We assessed 600 mechanically ventilated medical and surgical patients from three hospitals. Each hospital contributed 100 randomly selected patients ventilated 2-7 days and 100 patients ventilated >7 days. All patients were independently assessed for VAP and for VAC. We compared incidence-density, duration of mechanical ventilation, intensive care and hospital lengths of stay, hospital mortality, and time required for surveillance for VAP and for VAC. A subset of patients with VAP and VAC were independently reviewed by a physician to determine possible etiology.
Of 597 evaluable patients, 9.3% had VAP (8.8 per 1,000 ventilator days) and 23% had VAC (21.2 per 1,000 ventilator days). Compared to matched controls, both VAP and VAC prolonged days to extubation (5.8, 95% CI 4.2-8.0 and 6.0, 95% CI 5.1-7.1 respectively), days to intensive care discharge (5.7, 95% CI 4.2-7.7 and 5.0, 95% CI 4.1-5.9), and days to hospital discharge (4.7, 95% CI 2.6-7.5 and 3.0, 95% CI 2.1-4.0). VAC was associated with increased mortality (OR 2.0, 95% CI 1.3-3.2) but VAP was not (OR 1.1, 95% CI 0.5-2.4). VAC assessment was faster (mean 1.8 versus 39 minutes per patient). Both VAP and VAC events were predominantly attributable to pneumonia, pulmonary edema, ARDS, and atelectasis.
Screening ventilator settings for VAC captures a similar set of complications to traditional VAP surveillance but is faster, more objective, and a superior predictor of outcomes.
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