Christopher Schmickl

The accuracy and efficiency of electronic screening for recruitment into a clinical trial on COPD

Participant recruitment is an important process in successful conduct of randomized controlled trials. To facilitate enrollment into a National Institutes of Health-sponsored clinical trial involving patients with chronic obstructive pulmonary disease (COPD), we developed and prospectively validated an automated electronic screening tool based on boolean free-text search of admission notes in electronic medical records. During a 2-week validation period, all patients admitted to prespecified general medical services were screened for eligibility by both the electronic screening tool and a COPD nurse. Group discussion was the gold standard for confirmation of true-positive results. Compared with the gold standard, electronic screening yielded 100% sensitivity, 92% specificity, 100% negative predictive value, and 72% positive predictive value. Compared with traditional manual screening, electronic screening demonstrated time-saving potential of 76%. Thus, the electronic screening tool accurately identifies potential study subjects and improves efficiency of patient accrual for a clinical trial on COPD. This method may be expanded into other institutional and clinical settings.

Male-predominant plasma transfusion strategy for preventing transfusion-related acute lung injury: a systematic review.

Objectives:To assess 1) the effectiveness of male-predominant plasma transfusion strategy for preventing transfusion-related acute lung injury and related mortality; and 2) whether this effect varies across different patient subgroups. Design:Systematic Review and meta-analysis: Data were identified by querying MEDLINE and EMBASE (including proceedings of major conferences on blood transfusions), searching the Internet for hemovigilance reports, reviewing reference lists of eligible articles and contacting experts in the field. Eligible were all studies reporting transfusion-related acute lung injury incidence, all-cause mortality (primary outcomes), hospital length of stay, time to extubation, PaO2/FIO2-ratio or blood pressure changes (secondary outcomes) in recipients of plasma transfusions containing relatively more plasma from individuals at low risk of carrying leukocyte-antibodies (“male plasma”) than those receiving comparator plasma (“control plasma”). No limits were placed on study design, population or language. The only exclusion criteria were non-human subjects and lack of control group. Prespecified study quality indicators (including risk of bias assessment) and potential effect modifiers were tested using Cochran’s Q Test. Final analyses using random-effects models and I2 to assess heterogeneity were performed in the subset of studies judged to provide the best evidence and separately for significantly different subgroups using STATA 12.1 (StataCorp, College Station, TX). Setting:As per primary studies. Patients/Subjects:As per primary studies. Interventions:As per primary studies (generally: exposure to plasma containing relatively more male plasma than comparator plasma). Measurements and Main Results:From a total of 850 retrieved records, we identified 45 eligible studies. For transfusion-related acute lung injury incidence, final analysis was restricted to 13 cohort studies and one randomized controlled trial in which transfusion-related acute lung injury cases only involved plasma transfusions. Risk of transfusion-related acute lung injury and mortality in plasma recipients exposed to men when compared with control plasma were 0.27 (95% CI, 0.20–0.38; p < 0.001; I2 = 0%; n = 14; 286 events) and 0.89 (95% CI, 0.80–1.00; p = 0.04; I2 = 79%; n = 7; 5, 710 events), respectively. No other significant interactions were found. Secondary outcomes showed similar results but were less reported and the studies were more heterogeneous. Sensitivity analyses did not alter the results. There was no evidence of publication bias. Discussion:More than 800 million people in 17 countries are subject to male-predominant plasma transfusion policy and at least three more countries are planning or considering adoption of this strategy. On the basis of most observational data, judged to be of high quality, male-predominant plasma transfusion strategy reduces plasma-related transfusion-related acute lung injury incidence and possibly mortality. There was no evidence that the effect differs across patient subgroups, but power to detect such differences was low.

Decision support tool for early differential diagnosis of acute lung injury and cardiogenic pulmonary edema in medical critically ill patients.

BACKGROUND At the onset of acute hypoxic respiratory failure, critically ill patients with acute lung injury (ALI) may be difficult to distinguish from those with cardiogenic pulmonary edema (CPE). No single clinical parameter provides satisfying prediction. We hypothesized that a combination of those will facilitate early differential diagnosis. METHODS In a population-based retrospective development cohort, validated electronic surveillance identified critically ill adult patients with acute pulmonary edema. Recursive partitioning and logistic regression were used to develop a decision support tool based on routine clinical information to differentiate ALI from CPE. Performance of the score was validated in an independent cohort of referral patients. Blinded post hoc expert review served as gold standard. RESULTS Of 332 patients in a development cohort, expert reviewers (κ, 0.86) classified 156 as having ALI and 176 as having CPE. The validation cohort had 161 patients (ALI = 113, CPE = 48). The score was based on risk factors for ALI and CPE, age, alcohol abuse, chemotherapy, and peripheral oxygen saturation/Fio(2) ratio. It demonstrated good discrimination (area under curve [AUC] = 0.81; 95% CI, 0.77-0.86) and calibration (Hosmer-Lemeshow [HL] P = .16). Similar performance was obtained in the validation cohort (AUC = 0.80; 95% CI, 0.72-0.88; HL P = .13). CONCLUSIONS A simple decision support tool accurately classifies acute pulmonary edema, reserving advanced testing for a subset of patients in whom satisfying prediction cannot be made. This novel tool may facilitate early inclusion of patients with ALI and CPE into research studies as well as improve and rationalize clinical management and resource use.

Comparison of hospital mortality and long-term survival in patients with acute lung injury/ARDS vs cardiogenic pulmonary edema

BACKGROUND Early differential diagnosis of acute lung injury (ALI) vs cardiogenic pulmonary edema (CPE) is important for selecting the most appropriate therapy, but the prognostic implications of this distinction have not been studied. Accurate prognostic information is essential for providing appropriate informed consent prior to initiation of mechanical ventilation. METHODS This is a long-term follow-up study of a previously established population-based cohort of critically ill adult patients with acute pulmonary edema admitted at a tertiary-care center during 2006 to 2009, in which post hoc expert review had established ALI vs CPE diagnosis. Using logistic and Cox regression, hospital mortality and long-term survival were compared in patients with ALI vs patients with CPE. RESULTS Of 328 patients (ALI = 155, CPE = 173), 240 patients (73%) died during a median follow-up of 160 days. After adjusting for confounders, patients with ALI were significantly more likely to die in the hospital (OR = 4.2, 95% CI = 2.3-7.8, n = 325, P < .001), but among hospital survivors the risk of death during follow-up was the same in both groups (hazard ratio = 1.13, 95% CI = 0.79-1.62, n = 229, P = .50). Independent predictors of mortality included age and APACHE (Acute Physiology and Chronic Health Evaluation) III score. Results were similar when restricting patients with ALI to the subset with ARDS (Berlin definition). In post hoc analyses, the mortality rate in hospital survivors compared with the general US population was significantly higher during the first 2 years but essentially converged by year five. CONCLUSIONS Although hospital mortality is higher in patients with ALI/ARDS compared with patients with CPE, long-term survival is similar in hospital survivors from both groups.

Customized Reference Ranges for Laboratory Values Decrease False Positive Alerts in Intensive Care Unit Patients

Background Traditional electronic medical record (EMR) interfaces mark laboratory tests as abnormal based on standard reference ranges derived from healthy, middle-aged adults. This yields many false positive alerts with subsequent alert-fatigue when applied to complex populations like hospitalized, critically ill patients. Novel EMR interfaces using adjusted reference ranges customized for specific patient populations may ameliorate this problem. Objective To compare accuracy of abnormal laboratory value indicators in a novel vs traditional EMR interface. Methods Laboratory data from intensive care unit (ICU) patients consecutively admitted during a two-day period were recorded. For each patient, available laboratory results and the problem list were sent to two mutually blinded critical care experts, who marked the values about which they would like to be alerted. All disagreements were resolved by an independent super-reviewer. Based on this gold standard, we calculated and compared the sensitivity, specificity, positive and negative predictive values (PPV, NPV) of customized vs traditional abnormal value indicators. Results Thirty seven patients with a total of 1341 laboratory results were included. Experts’ agreement was fair (kappa = 0.39). Compared to the traditional EMR, custom abnormal laboratory value indicators had similar sensitivity (77% vs 85%, P = 0.22) and NPV (97.1% vs 98.6%, P = 0.06) but higher specificity (79% vs 61%, P<0.001) and PPV (28% vs 11%, P<0.001). Conclusions Reference ranges for laboratory values customized for an ICU population decrease false positive alerts. Disagreement among clinicians about which laboratory values should be indicated as abnormal limits the development of customized reference ranges.