'Naïve' and 'memory' CD4+ T-cells and T-cell receptor (TCR) V beta repertoire dynamics are independent of the levels of viremia following HIV seroconversion

The progression of 'naive' and 'memory' T-cells and the T-cell receptor Vbeta (TCR Vbeta) repertoire dynamics within the peripheral CD4+ T-cell compartment were studied in individuals following HIV seroconversion. Profound TCR Vbeta repertoire perturbations were observed within the CD4+ T-cell pool in treatment-naive patients regardless of their levels of viremia during the first 6-8 months after seroconversion. The ratio of 'naive' to 'memory' CD4+ T-cells as well as the TCR Vbeta repertoire dynamics did not appear to correlate with absolute numbers of CD4 T-cells.     

Antiretroviral drug resistance testing in adult HIV-1 infection: recommendations of an International AIDS Society-USA Panel

Martin S. Hirsch, MD; Françoise Brun-Vézinet, MD; Richard T. D'Aquila, MD; Scott M. Hammer, MD; Victoria A. Johnson, MD; Daniel R. Kuritzkes, MD; Clive Loveday, MD, PhD; John W. Mellors, MD; Bonaventura Clotet, MD, PhD; Brian Conway, MD; Lisa M. Demeter, MD; Stefano Vella, MD; Donna M. Jacobsen; Douglas D. Richman, MD

JAMA. 2000;283:2417-2426.

Objective  Assays for drug resistance testing in human immunodeficiency virus type 1 (HIV-1) infection are now available and clinical studies suggest that viral drug resistance is correlated with poor virologic response to new therapy. The International AIDS Society–USA sought to update prior recommendations to provide guidance for clinicians regarding indications for HIV-1 resistance testing.

Participants  An International AIDS Society–USA 13-member physician panel with expertise in basic science, clinical research, and patient care involving HIV resistance to antiretroviral drugs was reconvened to provide recommendations for the clinical use of drug resistance testing.

Evidence and Consensus Process  The full panel met regularly between January and October 1999. Resistance and resistance testing data appearing in the last decade through April 2000 and presentations at national and international research conferences were reviewed. Recommendations and considerations were developed by 100% group consensus, acknowledging that definitive data to support final recommendations are not yet available.

Conclusions  Emerging data indicate that despite limitations, resistance testing should be incorporated into patient management in some settings. Resistance testing is recommended to help guide the choice of new regimens after treatment failure and for guiding therapy for pregnant women. It should be considered in treatment-naive patients with established infection, but cannot be firmly recommended in this setting. Testing also should be considered prior to initiating therapy in patients with acute HIV infection, although therapy should not be delayed pending the results. Expert interpretation is recommended given the complexity of results and assay limitations.

     

Rates of in-hospital arrests, deaths and intensive care admissions: the effect of a medical emergency team

OBJECTIVES: To evaluate the effectiveness of a medical emergency team (MET) in reducing the rates of selected adverse events. DESIGN: Cohort comparison study after casemix adjustment. PATIENTS AND SETTING: All adult (> or = 14 years) patients admitted to three Australian public hospitals from 8 July to 31 December 1996. INTERVENTION STUDIED: At Hospital 1, a medical emergency team (MET) could be called for abnormal physiological parameters or staff concern. Hospitals 2 and 3 had conventional cardiac arrest teams. MAIN OUTCOME MEASURES: Casemix-adjusted rates of cardiac arrest, unanticipated admission to intensive care unit (ICU), death, and the subgroup of deaths where there was no pre-existing "do not resuscitate" (DNR) order documented. RESULTS: There were 1510 adverse events identified among 50 942 admissions. The rate of unanticipated ICU admissions was less at the intervention hospital in total (casemix-adjusted odds ratios: Hospital 1, 1.00; Hospital 2, 1.59 [95% CI, 1.24-2.04]; Hospital 3, 1.73 [95% CI, 1.37-2.16]). There was no significant difference in the rates of cardiac arrest or total deaths between the three hospitals. However, one of the hospitals with a conventional cardiac arrest team had a higher death rate among patients without a DNR order. CONCLUSIONS: The MET hospital had fewer unanticipated ICU/HDU admissions, with no increase in in-hospital arrest rate or total death rate. The non-DNR deaths were lower compared with one of the other hospitals; however, we did not adjust for DNR practices. We suggest that the MET concept is worthy of further study.     

Alosetron versus traditional pharmacotherapy in clinical practice: effects on resource use,health-related quality of life,safety and symptom improvement in women with severe diarrhea-predominant irritable bowel syndrome

Objective: Severe diarrhea-predominant irritable bowel syndrome (IBS-D) is associated with decreased health-related quality of life (HRQOL) and increased health care costs. Treatment recommendations for IBS-D often start with traditional pharmacotherapy (TP), with escalation to alosetron, rifaximin or eluxadoline if there is no success. There has been no previous head-to-head clinical trial comparing IBS-D treatment outcome for alosetron versus TP. This study, GSK protocol S3B30020, evaluated resource use, work productivity, health-related quality of life and global symptom response in women with IBS-D who were treated with alosetron or TP.

Methods: A total of 1956 patients who met criteria for severe IBS-D were randomized to treatment with alosetron 1?mg twice daily (BID) or only TP for up to 24 weeks. Work productivity and resource use were evaluated by standard questionnaires, HRQOL by the IBSQOL instrument and IBS symptoms by the Global Improvement Scale (GIS).

Results: Compared to only TP, alosetron-treated patients reported: (1) fewer clinic/office visits for any health problem (p?=?.0181) or for IBS-D (p?=?.0004); (2) reduced use of over-the-counter medications for IBS-D (p < .0001); (3) fewer days of lost work productivity (p < .0001); (4) decreased restriction of social and outdoor activities (p < .0001); and (5) greater global improvement in IBS-D symptoms (p < .0001). Alosetron treatment improved HRQOL scores for all domains (p < .0001). Incidence of adverse events during alosetron use was not remarkable and was similar to that previously reported.

Conclusions: Alosetron 1?mg BID significantly reduced health care utilization and lost productivity, and significantly improved global IBS symptoms, HRQOL, and participation in outdoor and social activities compared with treatment response to TP.