Sergey Tarima

Nationwide Trends of Severe Sepsis in the 21st Century (2000–2007)

BACKGROUND Severe sepsis is common and often fatal. The expanding armamentarium of evidence-based therapies has improved the outcomes of persons with this disease. However, the existing national estimates of the frequency and outcomes of severe sepsis were made before many of the recent therapeutic advances. Therefore, it is important to study the outcomes of this disease in an aging US population with rising comorbidities. METHODS We used the Healthcare Costs and Utilization Projects Nationwide Inpatient Sample (NIS) to estimate the frequency and outcomes of severe sepsis hospitalizations between 2000 and 2007. We identified hospitalizations for severe sepsis using International Classification of Diseases, Ninth Revision, Clinical Modification codes indicating the presence of sepsis and organ system failure. Using weights from NIS, we estimated the number of hospitalizations for severe sepsis in each year. We combined these with census data to determine the number of severe sepsis hospitalizations per 100,000 persons. We used discharge status to identify in-hospital mortality and compared mortality rates in 2000 with those in 2007 after adjusting for demographics, number of organ systems failing, and presence of comorbid conditions. RESULTS The number of severe sepsis hospitalizations per 100,000 persons increased from 143 in 2000 to 343 in 2007. The mean number of organ system failures during admission increased from 1.6 to 1.9 (P < .001). The mean length of hospital stay decreased from 17.3 to 14.9 days. The mortality rate decreased from 39% to 27%. However, more admissions ended with discharge to a long-term care facility in 2007 than in 2000 (35% vs 27%, P < .001). CONCLUSIONS An increasing number of admissions for severe sepsis combined with declining mortality rates contribute to more individuals surviving to hospital discharge. Importantly, this leads to more survivors being discharged to skilled nursing facilities and home with in-home care. Increased attention to this phenomenon is warranted.

Allogeneic transplantation for therapy-related myelodysplastic syndrome and acute myeloid leukemia

Therapy-related myelodysplastic syndromes (t-MDSs) and acute myeloid leukemia (t-AML) have a poor prognosis with conventional therapy. Encouraging results are reported after allogeneic transplantation. We analyzed outcomes in 868 persons with t-AML (n = 545) or t-MDS (n = 323) receiving allogeneic transplants from 1990 to 2004. A myeloablative regimen was used for conditioning in 77%. Treatment-related mortality (TRM) and relapse were 41% (95% confidence interval [CI], 38-44) and 27% (24-30) at 1 year and 48% (44-51) and 31% (28-34) at 5 years, respectively. Disease-free (DFS) and overall survival (OS) were 32% (95% CI, 29-36) and 37% (34-41) at 1 year and 21% (18-24) and 22% (19-26) at 5 years, respectively. In multivariate analysis, 4 risk factors had adverse impacts on DFS and OS: (1) age older than 35 years; (2) poor-risk cytogenetics; (3) t-AML not in remission or advanced t-MDS; and (4) donor other than an HLA-identical sibling or a partially or well-matched unrelated donor. Five-year survival for subjects with none, 1, 2, 3, or 4 of these risk factors was 50% (95% CI, 38-61), 26% (20-31), 21% (16-26), 10% (5-15), and 4% (0-16), respectively (P < .001). These data permit a more precise prediction of outcome and identify subjects most likely to benefit from allogeneic transplantation.

Audiometric pattern as a predictor of cardiovascular status: Development of a model for assessment of risk

This study hypothesizes that low‐frequency hearing loss is associated with underlying cardiovascular disease. The objective of this study was to use a mathematical model of hearing thresholds to predict cardiovascular status.

Small- and Moderate-Size Right-to-Left Shunts Identified by Saline Contrast Echocardiography Are Normal and Unrelated to Migraine Headache

BACKGROUND We suspected, based on clinical experience, that the prevalence of both intracardiac and pulmonary arteriovenous malformations (PAVMs) is higher than previously reported in a healthy population when using modern ultrasound technology combined with a rigorous saline contrast echocardiogram (SCE) protocol. We hypothesized the prevalence of right-to-left shunts (RLSs) would be so high when using this sensitive technique that there would be no significant association of RLS with migraine headache. METHODS We recruited 104 healthy volunteers to undergo an SCE followed by completion of a migraine questionnaire. The SCEs were meticulously graded for shunt size and location based on left-sided heart contrast quantity and timing. The migraine headache questionnaire was graded by a neurologist blinded to SCE results. RESULTS One hundred four subjects underwent the study protocol. We found 71% of subjects exhibited evidence of RLS. Patent foramen ovale (PFO) was identified in 40 (38%), PAVM was identified in 29 (28%), and five subjects had evidence of both (5%). Based on questionnaires, 42 (40%) of the subjects had migraine headache (29% with aura). There was no significant association of migraine headache with PFO (OR, 0.59; 95% CI, 0.16-2.12; P = .54) or PAVM (OR, 0.8; 95% CI, 0.34-1.9; P = .67), although only 13 (13%) of the subjects had evidence of large RLS. CONCLUSIONS When using modern ultrasound technology combined with a rigorous SCE technique, the majority of healthy subjects demonstrate some degree of RLS. PAVM in an otherwise healthy population is common. Small- and moderate-size RLSs do not appear to be significantly associated with migraine headache.

SAS and R functions to compute pseudo-values for censored data regression

Recently, in a series of papers, a method based on pseudo-values has been proposed for direct regression modeling of the survival function, the restricted mean and cumulative incidence function with right censored data. The models, once the pseudo-values have been computed, can be fit using standard generalized estimating equation software. Here we present SAS macros and R functions to compute these pseudo-values. We illustrate the use of these routines and show how to obtain regression estimates for a study of bone marrow transplant patients.

Quadratic regression analysis for gene discovery and pattern recognition for non-cyclic short time-course microarray experiments.

BackgroundCluster analyses are used to analyze microarray time-course data for gene discovery and pattern recognition. However, in general, these methods do not take advantage of the fact that time is a continuous variable, and existing clustering methods often group biologically unrelated genes together.ResultsWe propose a quadratic regression method for identification of differentially expressed genes and classification of genes based on their temporal expression profiles for non-cyclic short time-course microarray data. This method treats time as a continuous variable, therefore preserves actual time information. We applied this method to a microarray time-course study of gene expression at short time intervals following deafferentation of olfactory receptor neurons. Nine regression patterns have been identified and shown to fit gene expression profiles better than k-means clusters. EASE analysis identified over-represented functional groups in each regression pattern and each k-means cluster, which further demonstrated that the regression method provided more biologically meaningful classifications of gene expression profiles than the k-means clustering method. Comparison with Peddada et al.s order-restricted inference method showed that our method provides a different perspective on the temporal gene profiles. Reliability study indicates that regression patterns have the highest reliabilities.ConclusionOur results demonstrate that the proposed quadratic regression method improves gene discovery and pattern recognition for non-cyclic short time-course microarray data. With a freely accessible Excel macro, investigators can readily apply this method to their microarray data.

Pulmonary Embolism: The Weekend Effect

BACKGROUND Pulmonary embolism is a common, often fatal condition that requires timely recognition and rapid institution of therapy. Previous studies have documented worse outcomes for weekend admissions for a variety of time-sensitive medical conditions. This phenomenon has not been clearly demonstrated for pulmonary embolism. METHODS We used the Healthcare Cost and Utilization Project Nationwide Inpatient Sample for the years 2000 to 2008 to identify people with a principal discharge diagnosis of pulmonary embolism. We classified admissions as weekend if they occurred between midnight Friday and midnight Sunday. We compared all-cause in-hospital mortality between weekend and weekday admissions and investigated the timing of inferior vena cava (IVC) filter placement and thrombolytic infusion as potential explanations for differences in mortality. RESULTS Unadjusted mortality was higher for weekend admissions than weekday admissions (OR, 1.19; 95% CI, 1.13-1.24). This increase in mortality remained statistically significant after controlling for potential confounding variables (OR, 1.17; 95% CI, 1.11-1.22). Among patients who received an IVC filter, a larger proportion of those admitted on a weekday than on the weekend received it on their first hospital day (38% vs 29%, P < .001). The timing of thrombolytic therapy did not differ between weekday and weekend admissions. CONCLUSIONS Weekend admissions for pulmonary embolism were associated with higher mortality than weekday admissions. Our finding that IVC filter placement occurred later in the hospital course for patients admitted on weekends with pulmonary embolism suggests differences in the timeliness of diagnosis and treatment between weekday and weekend admissions. Regardless of cause, physicians should be aware that weekend admissions for pulmonary embolism have a 20% increased risk of death and warrant closer attention than provided during the week.

The association of robotic surgical technology and hospital prostatectomy volumes: increasing market share through the adoption of technology.

Despite limited and conflicting evidence for the efficacy of newly developed robotic technology for laparoscopic prostatectomy, this technology is spreading rapidly. Because the newer technology is more costly, reasons for this rapid adoption are unclear. The authors of this report sought to determine whether hospital acquisition of robotic technology was associated with volume of prostate cancer surgery.

Preinjury somatization symptoms contribute to clinical recovery after sport-related concussion.

Objective: To determine the degree to which preinjury and acute postinjury psychosocial and injury-related variables predict symptom duration following sport-related concussion. Methods: A total of 2,055 high school and collegiate athletes completed preseason evaluations. Concussed athletes (n = 127) repeated assessments serially (<24 hours and days 8, 15, and 45) postinjury. Cox proportional hazard modeling was used to predict concussive symptom duration (in days). Predictors considered included demographic and history variables; baseline psychological, neurocognitive, and balance functioning; acute injury characteristics; and postinjury clinical measures. Results: Preinjury somatic symptom score (Brief Symptom Inventory–18 somatization scale) was the strongest premorbid predictor of symptom duration. Acute (24-hour) postconcussive symptom burden (Sport Concussion Assessment Tool–3 symptom severity) was the best injury-related predictor of recovery. These 2 predictors were moderately correlated (r = 0.51). Path analyses indicated that the relationship between preinjury somatization symptoms and symptom recovery was mediated by postinjury concussive symptoms. Conclusions: Preinjury somatization symptoms contribute to reported postconcussive symptom recovery via their influence on acute postconcussive symptoms. The findings highlight the relevance of premorbid psychological factors in postconcussive recovery, even in a healthy athlete sample relatively free of psychopathology or medical comorbidities. Future research should elucidate the neurobiopsychosocial mechanisms that explain the role of this individual difference variable in outcome following concussive injury.

The numeracy understanding in medicine instrument: a measure of health numeracy developed using item response theory.

Background: Health numeracy can be defined as the ability to understand and apply information conveyed with numbers, tables and graphs, probabilities, and statistics to effectively communicate with health care providers, take care of one’s health, and participate in medical decisions. Objective: To develop the Numeracy Understanding in Medicine Instrument (NUMi) using item response theory scaling methods. Design: A 20-item test was formed drawing from an item bank of numeracy questions. Items were calibrated using responses from 1000 participants and a 2-parameter item response theory model. Construct validity was assessed by comparing scores on the NUMi to established measures of print and numeric health literacy, mathematic achievement, and cognitive aptitude. Participants: Community and clinical populations in the Milwaukee and Chicago metropolitan areas. Results: Twenty-nine percent of the 1000 respondents were Hispanic, 24% were non-Hispanic white, and 42% were non-Hispanic black. Forty-one percent had no more than a high school education. The mean score on the NUMi was 13.2 (s = 4.6) with a Cronbach α of 0.86. Difficulty and discrimination item response theory parameters of the 20 items ranged from −1.70 to 1.45 and 0.39 to 1.98, respectively. Performance on the NUMi was strongly correlated with the Wide Range Achievement Test–Arithmetic (0.73, P < 0.001), the Lipkus Expanded Numeracy Scale (0.69, P < 0.001), the Medical Data Interpretation Test (0.75, P < 0.001), and the Wonderlic Cognitive Ability Test (0.82, P < 0.001). Performance was moderately correlated to the Short Test of Functional Health Literacy (0.43, P < 0.001). Limitations: The NUMi was found to be most discriminating among respondents with a lower-than-average level of health numeracy. Conclusions: The NUMi can be applied in research and clinical settings as a robust measure of the health numeracy construct.