Sequential Organ Failure Assessment Score Modified for Recent Infection in Patients With Hematologic Malignant Tumors and Severe Sepsis.

BACKGROUND: Baseline health status influences outcomes of severe sepsis. OBJECTIVE: To determine if recent infection is a marker of poor health in patients with hematologic malignant tumors and severe sepsis by modifying the Sequential Organ Failure Assessment (SOFA) score to account for infection. METHODS: Medical records of the first 50 patients with hematologic malignant tumors and severe sepsis admitted from September 1, 2009 to September 1, 2014, were reviewed to derive a modified SOFA score. The predictive accuracy of the modified score was compared with that of the unmodified score and the Acute Physiology and Chronic Health Evaluation (APACHE) II score for the 196 subsequent patients. RESULTS: The area under the receiver operator characteristic curve was 0.73 (95% CI, 0.66-0.80) for the modified score, 0.68 (95% CI, 0.61-0.76) for the unmodified score, and 0.65 (95% CI, 0.58-0.73) for the APACHE II score. The modified score was better for discriminating survivors from nonsurvivors than the unmodified score (P = .005) and the APACHE II score (P = .04). After adjustments for the modified score and age, only increased days from hospital to intensive care unit admission was significantly associated with 30-day mortality. CONCLUSION: Modifying the SOFA score to account for infections before admission to the intensive care unit improved the prognostic usefulness of the scores for patients with hematologic malignant tumors and severe sepsis.

Short communication: Apoptosis pathways in HIV-1-infected patients before and after highly active antiretroviral therapy: relevance to immune recovery.

Investigations into apoptotic pathways, intrinsic and extrinsic, and the effects of highly active antiretroviral therapy (HAART) on T cell death via those pathways may provide insight into the mechanisms of and barriers to immune recovery. HIV-1-infected patients were enrolled into a randomized, controlled study of the immune effects of a lopinavir/ritonavir (LPV/r)-based versus an efavirenz (EFV)-based HAART regimen in antiretroviral-naive subjects with CD4(+) counts <350 cells/mm(3). Patients were randomized to receive TDF/FTC/EFZ or TDF/FTC plus LPV/r. Fourteen patients were enrolled and 10 patients completed 6 months of therapy as per the protocol. CD4(+) counts were measured before and during HAART therapy. We isolated T cell subsets to measure ex vivo apoptosis by propidium iodide staining. We also assessed caspase activation for the intrinsic and extrinsic pathways of apoptosis, as well as effector caspase activation. We also measured mitochondrial membrane potential. Cells were analyzed by flow cytometry. All patients had increased activation of caspase 8 (extrinsic pathway), caspase 9 (intrinsic pathway), effector caspases 3/7, and low mitochondrial membrane potential at baseline compared to controls. By 4 weeks, there was a decrease in activation of all caspases, but little further decrease by week 24. T cell mitochondrial membrane potential did not increase until week 12, but continued to increase until week 24. The only predictor of CD4(+) count increase was the increase in mitochondrial membrane potential of naive cells at 6 months (r=0.66, p=0.038). This suggests that positive selection of naive CD4(+) T cells in the thymus is the major determinant of CD4(+) recovery.

Procalcitonin-guided antibiotic therapy: a systematic review and meta-analysis.

BACKGROUND: The utility of procalcitonin to manage patients with infections is unclear. A systematic review of comparative studies using procalcitonin-guided antibiotic therapy in patients with infections was performed. METHODS: Randomized, controlled trials comparing procalcitonin-guided initiation, intensification, or discontinuation of antibiotic therapy to clinically guided therapy were included. Outcomes were antibiotic usage, morbidity, and mortality. MEDLINE, EMBASE, the Cochrane Database, National Institute for Clinical Excellence, the National Guideline Clearinghouse, and the Health Technology Assessment Programme were searched from January 1, 1990 to December 16, 2011. RESULTS: Eighteen randomized, controlled trials were included. Data were pooled into clinically similar patient populations. In adult intensive care unit (ICU) patients, procalcitonin-guided discontinuation of antibiotics reduced antibiotic duration by 2.05 days (95% confidence interval [CI]: -2.59 to -1.52) without increasing morbidity or mortality. In contrast, procalcitonin-guided intensification of antibiotics in adult ICU patients increased antibiotic usage and morbidity. In adult patients with respiratory tract infections, procalcitonin guidance significantly reduced antibiotic duration by 2.35 days (95% CI: -4.38 to -0.33), antibiotic prescription rate by 22% (95% CI: -41% to -4%), and total antibiotic exposure without affecting morbidity or mortality. A single, good quality study of neonates with suspected sepsis demonstrated reduced antibiotic duration by 22.4 hours (P = 0.012) and reduced the proportion of neonates on antibiotics for ≥ 72 hours by 27% (P = 0.002) with procalcitonin guidance. CONCLUSION: Procalcitonin guidance can safely reduce antibiotic usage when used to discontinue antibiotic therapy in adult ICU patients and when used to initiate or discontinue antibiotics in adult patients with respiratory tract infections.

A targeted, conventional assay, emergency department HIV testing program integrated with existing clinical procedures.

OBJECTIVE: Various HIV testing models have been described, but widespread implementation has lagged. We describe a clinical HIV testing program notable for its use of conventional (nonrapid) assays, native hospital personnel, and an electronic system to aid targeted patient selection. METHODS: Clinical HIV testing program records and hospital emergency department (ED) and laboratory records were reviewed and linked for the period from January 2007 until November 5, 2008. RESULTS: There were 103,475 visits to the ED, for which 1,258 (1.2%) resulted in HIV testing, and 54 (4.3%) were positive for HIV antibody. Result notification was successful for 52 (96%) individuals with positive test results. After reporting to the health department, it was determined that 28 (2.2%) individuals had received a new diagnosis, of whom 89% were linked with care. Mean baseline CD4 counts for new diagnoses for periods 1 through 3, respectively, were (1) unavailable, (2) 138 cells/µL (95% confidence interval [CI] 34 to 242 cells/µL), and (3) 222 cells/µL (95% CI 119 to 325 cells/µL). Overall, mean calculated to be 180 cells/µL (95% CI 16 to 345 cells/µL). CONCLUSION: This ED HIV testing model successfully expanded new patient identification, result notification, and linkage to care. Although this effort falls short of Centers for Disease Control and Prevention recommendations, the model can be implemented widely without external funding for parallel staffing or rapid assays.

Neutrophil function after bone marrow and hematopoietic stem cell transplant.

Bone marrow and hematopoietic stem cell transplants are life saving procedures for a variety of hematologic malignancies. Unfortunately, long-term survival is significantly impacted by the development of invasive fungal and bacterial infections, in part attributable to innate and adaptive immunologic defects post-transplant. This review focuses specifically on neutrophil function after autologous and allogeneic bone marrow and hematopoietic stem cell transplant.

Do hospitalists or physicians with greater inpatient HIV experience improve HIV care in the era of highly active antiretroviral therapy? Results from a multicenter trial of academic hospitalists.

BACKGROUND: Little is known about the effect of provider type and experience on outcomes, resource use, and processes of care of hospitalized patients with human immunodeficiency virus (HIV) infection. Hospitalists are caring for this population with increasing frequency. METHODS: Data from a natural experiment in which patients were assigned to physicians on the basis of call cycle was used to study the effects of provider type-that is, hospitalist versus nonhospitalist-and HIV-specific inpatient experience on resource use, outcomes, and selected measures of processes of care at 6 academic institutions. Administrative data, inpatient interviews, 30-day follow-up interviews, and the National Death Index were used to measure outcomes. RESULTS: A total of 1207 patients were included in the analysis. There were few differences in resource use, outcomes, and processes of care by provider type and experience with HIV-infected inpatients. Patients who received hospitalist care demonstrated a trend toward increased length of hospital stay compared with patients who did not receive hospitalist care (6.0 days vs. 5.2 days; P = .13). Inpatient providers with moderate experience with HIV-infected patients were more likely to coordinate care with outpatient providers (odds ratio, 2.40; P = .05) than were those with the least experience with HIV-infected patients, but this pattern did not extend to providers with the highest level of experience. CONCLUSION: Provider type and attending physician experience with HIV-infected inpatients had minimal effect on the quality of care of HIV-infected inpatients. Approaches other than provider experience, such as the use of multidisciplinary inpatient teams, may be better targets for future studies of the outcomes, processes of care, and resource use of HIV-infected inpatients.

Characteristics of prospective memory deficits in HIV-seropositive substance-dependent individuals: preliminary observations.

The construct of "prospective memory" (PM) refers to a type of episodic memory for a future intention or "remembering what one must do." This function has been proposed as a candidate mechanism underlying behaviors of critical importance in HIV disease, including adherence with medication regimens and continued engagement in risk behavior. We administered tasks of time-based and event-based prospective memory and control tasks of retrospective and working memory to 31 HIV-seropositive and 35 HIV-seronegative substance-dependent individuals (SDIs). We found that compared with HIV- controls HIV+ participants showed deficits in time-based but not event-based PM. Retrospective, but not working, memory performance correlated significantly with time-based PM performance. In addition, performance on the time-based PM task was a significant predictor of scores on a self-report measure of risky sexual and injection practices. These preliminary data provide new and unique findings regarding the components of executive function mediated by prefrontal cortical systems that are impaired among HIV+ SDIs and their relevance to "real-world" behaviors.

Cognitive impulsivity and HIV serostatus in substance dependent males.

HIV-seropositive (HIV+) drug users show impaired performance on measures of integrity of prefrontal-subcortical systems. The Iowa Gambling Task (GT) is mediated primarily through ventromedial-prefrontal systems, and poor performance on this measure ("cognitive impulsivity") is common among substance dependent individuals (SDIs) as well as patients with disease involving prefrontal-subcortical systems (e.g., Huntington disease). We hypothesized that HIV+ SDIs might be more vulnerable to cognitive impulsivity when compared with HIV-seronegative (HIV-) SDIs because recent studies report evidence of additive effects of HIV serostatus and drug dependence on cognition. Further, working memory is considered a key component of GT performance and is reliably impaired among HIV+ SDIs compared to controls. We administered the GT to 46 HIV+ and 47 well-matched HIV- males with a past or current history of substance dependence. In addition, we evaluated correlations between subjects' scores on the GT and on a delayed nonmatch to sample (DNMS) task in order to test if working memory deficits accounted for cognitive impulsivity among the HIV+ subjects. The HIV+ subjects performed significantly more poorly on the GT compared to the HIV- group but this effect could not be explained by working memory deficits. Implications of these findings for future basic and applied studies of HIV and substance dependence are discussed.

Delayed nonmatch-to-sample performance in HIV-seropositive and HIV-seronegative polydrug abusers.

Working memory (WM) deficits are common in HIV-seropositive (HIV+) individuals and can be amplified by manipulating a variety of task parameters, such as increasing memory load or information complexity. The authors investigated the role of timing in HIV-associated WM defects by varying the amount of time required to maintain information online while holding memory load and information complexity constant. The authors studied 50 HIV+ and 35 HIV-seronegative (HIV-) polydrug abusers abstinent at testing and well-matched on demographic variables. The HIV- group outperformed the HIV+ group across all stimulus-response time delays. HIV-associated WM defects are not critically dependent on the amount of time stimulus representations must be maintained and might be attributed to impaired encoding or retrieval of stimulus representations.