Rapid Diagnosis of Infection in the Critically Ill, a Multicenter Study of Molecular Detection in Bloodstream Infections, Pneumonia, and Sterile Site Infections.

OBJECTIVE: Early identification of causative microorganism(s) in patients with severe infection is crucial to optimize antimicrobial use and patient survival. However, current culture-based pathogen identification is slow and unreliable such that broad-spectrum antibiotics are often used to insure coverage of all potential organisms, carrying risks of overtreatment, toxicity, and selection of multidrug-resistant bacteria. We compared the results obtained using a novel, culture-independent polymerase chain reaction/electrospray ionization-mass spectrometry technology with those obtained by standard microbiological testing and evaluated the potential clinical implications of this technique. DESIGN: Observational study. SETTING: Nine ICUs in six European countries. PATIENTS: Patients admitted between October 2013 and June 2014 with suspected or proven bloodstream infection, pneumonia, or sterile fluid and tissue infection were considered for inclusion. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We tested 616 bloodstream infection, 185 pneumonia, and 110 sterile fluid and tissue specimens from 529 patients. From the 616 bloodstream infection samples, polymerase chain reaction/electrospray ionization-mass spectrometry identified a pathogen in 228 cases (37%) and culture in just 68 (11%). Culture was positive and polymerase chain reaction/electrospray ionization-mass spectrometry negative in 13 cases, and both were negative in 384 cases, giving polymerase chain reaction/electrospray ionization-mass spectrometry a sensitivity of 81%, specificity of 69%, and negative predictive value of 97% at 6 hours from sample acquisition. The distribution of organisms was similar with both techniques. Similar observations were made for pneumonia and sterile fluid and tissue specimens. Independent clinical analysis of results suggested that polymerase chain reaction/electrospray ionization-mass spectrometry technology could potentially have resulted in altered treatment in up to 57% of patients. CONCLUSIONS: Polymerase chain reaction/electrospray ionization-mass spectrometry provides rapid pathogen identification in critically ill patients. The ability to rule out infection within 6 hours has potential clinical and economic benefits.

Cost-effectiveness of a fourth-generation combination immunoassay for human immunodeficiency virus (HIV) antibody and p24 antigen for the detection of HIV infections in the United States.

PURPOSE: The US Food and Drug Administration recently approved the first 4th-generation HIV test. This study evaluated the cost-effectiveness of the 4th-generation assay versus a 3rd-generation test in screening for HIV infections in the United States. METHODS: An exploratory microsimulation model was developed that follows hypothetical individuals and simulates the course of HIV/AIDS, treatment with highly active antiretroviral therapy, and transmissions. RESULTS: With a 1% HIV prevalence, screening 1.5 million individuals with the 4th- versus 3rd-generation assay resulted in detection of 266 additional HIV cases at an incremental cost per additional HIV case detected of $63,763, an additional 489 life years and 395 quality-adjusted life years (QALYs), and 26 HIV transmissions prevented. Although lifetime costs were increased by $33.6 million, the incremental cost/QALY gained was $85,206. The 4th-generation test was more cost-effective in high incidence settings. The number needed to screen to detect one additional HIV case was 5,635. CONCLUSIONS: Screening using the 4th-generation assay may be cost-effective for HIV detection in appropriate settings, resulting in increased case identification, fewer transmissions, extended life, and increased quality of life. With early and accurate detection, this 4th-generation test may provide a suitable alternative to current 3rd-generation tests.

Association between critical care physician management and patient mortality in the intensive care unit.

BACKGROUND: Critically ill patients admitted to intensive care units (ICUs) are thought to gain an added survival benefit from management by critical care physicians, but evidence of this benefit is scant. OBJECTIVE: To examine the association between hospital mortality in critically ill patients and management by critical care physicians. DESIGN: Retrospective analysis of a large, prospectively collected database of critically ill patients. SETTING: 123 ICUs in 100 U.S. hospitals. PATIENTS: 101,832 critically ill adults. MEASUREMENTS: Through use of a random-effects logistic regression, investigators compared hospital mortality between patients cared for entirely by critical care physicians and patients cared for entirely by non-critical care physicians. An expanded Simplified Acute Physiology Score was used to adjust for severity of illness, and a propensity score was used to adjust for differences in the probability of selective referral of patients to critical care physicians. RESULTS: Patients who received critical care management (CCM) were generally sicker, received more procedures, and had higher hospital mortality rates than those who did not receive CCM. After adjustment for severity of illness and propensity score, hospital mortality rates were higher for patients who received CCM than for those who did not. The difference in adjusted hospital mortality rates was less for patients who were sicker and who were predicted by propensity score to receive CCM. LIMITATION: Residual confounders for illness severity and selection biases for CCM might exist that were inadequately assessed or recognized. CONCLUSION: In a large sample of ICU patients in the United States, the odds of hospital mortality were higher for patients managed by critical care physicians than those who were not. Additional studies are needed to further evaluate these results and clarify the mechanisms by which they might occur.

Cost-effectiveness of three different strategies for the treatment of first recurrent Clostridium difficile infection diagnosed in a community setting.

OBJECTIVE: A significant portion of patients with Clostridium difficile infections (CDI) experience recurrence, and there is little consensus on its treatment. With the availability of newer agents for CDI and the added burdens of recurrent disease, a cost-effectiveness analysis may provide insight on the most efficient use of resources. DESIGN: A decision-tree analysis was created to compare the cost-effectiveness of 3 possible treatments for patients with first CDI recurrence: oral vancomycin, fidaxomicin, or bezlotoxumab plus vancomycin. The model was performed from a payer's perspective with direct cost inputs and a timeline of 1 year. A systematic review of literature was performed to identify clinical, utility, and cost data. Quality-adjusted life years (QALY) and incremental cost-effectiveness ratios were calculated. The willingness-to-pay (WTP) threshold was set at $100,000 per QALY gained. The robustness of the model was tested using one-way sensitivity analyses and probabilistic sensitivity analysis. RESULTS: Vancomycin had the lowest cost ($15,692) and was associated with a QALY gain of 0.8019 years. Bezlotoxumab plus vancomycin was a dominated strategy. Fidaxomicin led to a higher QALY compared to vancomycin, at an incremental cost of $500,975 per QALY gained. Based on our WTP threshold, vancomycin alone was the most cost-effective regimen for treating the first recurrence of CDI. Sensitivity analyses demonstrated the model's robustness. CONCLUSIONS: Vancomycin alone appears to be the most cost-effective regimen for the treatment of first recurrence of CDI. Fidaxomicin alone led to the highest QALY gained, but at a cost beyond what is considered cost-effective.

Falling towers, crumbling levees, and viral mutations.

Hurricanes Katrina and Rita destroyed an entire beloved city and shattered a large part of the US Gulf Coast. Unlike the destruction of 9/11, it is difficult to say at the time of this writing whether or not this region will ever be fully restored. In light of these and other man-made and natural disasters, the world needs to revisit its approach to disaster planning and preparedness to insure that we can best meet the needs of those likely to be affected by future calamities.

Decision analysis models and simulations in critical care medicine.

Because clinical trials have frequently not been performed for many clinical problems in critical care and other clinical disciplines, models and simulations are often used to quantitatively assess important diagnostic, therapeutic, and cost-effectiveness issues. This article presents a brief overview of decision analysis models, one of the most common methodologies used to develop disease models and simulations, and their applications to problems in critical care medicine.

Physician and nurse satisfaction with an Electronic Medical Record system.

Electronic Medical Records (EMRs) are intended to support clinical activity, improve efficiency, and reduce error. Reluctance to use EMRs may exist among clinicians. The purpose of this study was to assess physician and nurse satisfaction with an Emergency Department (ED) EMR. We surveyed Emergency Medicine (EM) physicians and nurses at a large urban teaching hospital after implementation of an Emergency Department EMR. The questionnaire assessed: 1) computer background and experience; 2) perceptions regarding EMR use; and 3) concerns about impact upon quality of patient care. The clinicians find the EMR easy to use and are generally satisfied with the impact on their work. However, they report that the EMR has no positive impact on patient care. They report confusion in following the sequence of screens, and are concerned with the amount of time it takes to use the EMR and the confidentiality of patient information. Similar results were found between physicians and nurses. Nurses, but not physicians, report that they are able to finish work much faster than before implementation (p < 0.05). We were unable to correlate computer background and experience with satisfaction with an EMR. This survey suggests that EM physicians and nurses favor the use of an EMR and suggests opportunities for EMR enhancement.

Cost-effectiveness of a FISH assay for the diagnosis of melanoma in the USA.

OBJECTIVE: The authors evaluated the cost-effectiveness of a FISH assay in melanoma diagnosis in the USA. METHOD: A model was developed simulating the addition of FISH to the diagnosis of suspected melanoma. A decision analytic module simulated diagnosis using microscopic assessment alone versus addition of FISH (sensitivity: 92%; specificity: 94%). The authors simulated a clinical setting in which an initial excisional biopsy microscopic assessment (sensitivity: 73%; specificity: 78%) was followed by dermatopathologist assessment (sensitivity: 89%; specificity: 79%) for inconclusive results. Diagnostic strategies 1 and 2 added FISH to the initial and dermatopathologist assessments, respectively. A Markov outcomes module simulated patients' remaining lifetime, including treatment. RESULTS: In diagnostic strategies 1 and 2, the cost per quality-adjusted life year gained was US$14,930 and 43,925, respectively, versus no FISH. Cost per misdiagnosis avoided was US$3292 and 3759, respectively. Sensitivity and specificity without FISH were both ≥88%; however, addition of FISH exceeded US$100,000/quality-adjusted life year. CONCLUSION: In specific clinical settings, FISH could be cost effective for melanoma diagnosis.

The economic impact and cost-effectiveness of urinary neutrophil gelatinase-associated lipocalin after cardiac surgery.

BACKGROUND: Acute kidney injury (AKI) is common after cardiac surgery, and expeditious recognition with specific biomarkers may help improve outcome. OBJECTIVE: Because the economic impact of a biomarker-based diagnostic strategy is unknown, we assessed the cost-effectiveness of using urinary neutrophil gelatinase-associated lipocalin (NGAL) for the diagnosis of AKI after cardiac surgery compared with current diagnostic methods. METHODS: A decision analysis model was developed using the societal perspective to evaluate the cost-effectiveness of NGAL. Cost per quality-adjusted life-year (QALY) was determined for NGAL and standard strategies. The base case was a 67-year-old male patient undergoing coronary artery bypass graft surgery in the United Kingdom. Multiple sensitivity analyses were performed to determine how cost-effectiveness would vary with changes in the underlying clinical and economic variables. RESULTS: The base case yielded expected costs of £4244 and 11.86 QALYs for the NGAL strategy compared with £4672 and 11.79 QALYs for the standard therapy. The cost-effectiveness ratio for the NGAL strategy was £358/QALY compared with £396/QALY for the standard regimen. Cost-effectiveness increased as the treatment effect-defined as the ability to prevent progression of established AKI (kidney injury or failure)-for the therapy triggered by an elevated NGAL level rose. Sensitivity analysis demonstrated that the model was most responsive to the probability of developing AKI and least sensitive to the test cost for NGAL. Probabilistic sensitivity analysis supported the NGAL strategy as the most cost-effective option. Because this study was a decision analysis model incorporating a nonspecific treatment for AKI (as opposed to an observational study or controlled trial), model structural assumptions may therefore have underestimated mortality and the likelihood of developing AKI, although these were tested in multiple sensitivity analyses. Indirect costs were also not explicitly factored. CONCLUSION: The use of urinary NGAL after cardiac surgery appears to be cost-effective in the early diagnosis of AKI.

Impact of delayed transfer of critically ill patients from the emergency department to the intensive care unit.

OBJECTIVE: Numerous factors can cause delays in transfer to an intensive care unit for critically ill emergency department patients. The impact of delays is unknown. We aimed to determine the association between emergency department "boarding" (holding admitted patients in the emergency department pending intensive care unit transfer) and outcomes for critically ill patients. DESIGN: This was a cross-sectional analytical study using the Project IMPACT database (a multicenter U.S. database of intensive care unit patients). Patients admitted from the emergency department to the intensive care unit (2000-2003) were included and divided into two groups: emergency department boarding >or=6 hrs (delayed) vs. emergency department boarding <6 hrs (nondelayed). Demographics, intensive care unit procedures, length of stay, and mortality were analyzed. Groups were compared using chi-square, Mann-Whitney, and unpaired Student's t-tests. SETTING: Emergency department and intensive care unit. PATIENTS: Patients admitted from the emergency department to the intensive care unit (2000-2003). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Main outcomes were intensive care unit and hospital survival and intensive care unit and hospital length of stay. During the study period, 50,322 patients were admitted. Both groups (delayed, n = 1,036; nondelayed, n = 49,286) were similar in age, gender, and do-not-resuscitate status, along with Acute Physiology and Chronic Health Evaluation II score in the subgroup for which it was recorded. Among hospital survivors, the median hospital length of stay was 7.0 (delayed) vs. 6.0 days (nondelayed) (p < .001). Intensive care unit mortality was 10.7% (delayed) vs. 8.4% (nondelayed) (p < .01). In-hospital mortality was 17.4% (delayed) vs. 12.9% (nondelayed) (p < .001). In the stepwise logistic model, delayed admission, advancing age, higher Acute Physiology and Chronic Health Evaluation II score, male gender, and diagnostic categories of trauma, intracerebral hemorrhage, and neurologic disease were associated with lower hospital survival (odds ratio for delayed admission, 0.709; 95% confidence interval, 0.561-0.895). CONCLUSIONS: Critically ill emergency department patients with a >or=6-hr delay in intensive care unit transfer had increased hospital length of stay and higher intensive care unit and hospital mortality. This suggests the need to identify factors associated with delayed transfer as well as specific determinants of adverse outcomes.