Publications

BACKGROUND

Numerous agents are available for moderate sedation in endoscopy.

OBJECTIVE

Our purpose was to compare efficacy, safety, and efficiency of agents used for moderate sedation in EGD or colonoscopy.

DESIGN

Systematic review of computerized bibliographic databases for randomized trials of moderate sedation that compared 2 active regimens or 1 active regimen with placebo or no sedation.

PATIENTS

Unselected adults undergoing EGD or colonoscopy with a goal of moderate sedation.

MAIN OUTCOME MEASUREMENTS

Sedation-related complications, patient assessments (satisfaction, pain, memory, willingness to repeat examination), physician assessments (satisfaction, level of sedation, patient cooperation, examination quality), and procedure-related efficiency outcomes (sedation, procedure, or recovery time).

RESULTS

Thirty-six studies (N = 3918 patients) were included. Sedation improved patient satisfaction (relative risk [RR] = 2.29, range 1.16-4.53) and willingness to repeat EGD (RR = 1.25, range 1.13-1.38) versus no sedation. Midazolam provided superior patient satisfaction to diazepam (RR = 1.18, range 1.07-1.29) and less frequent memory of EGD (RR = 0.57, range 0.50-0.60) versus diazepam. Adverse events and patient/physician assessments were not significantly different for midazolam (with or without narcotics) versus propofol except for slightly less patient satisfaction (RR = 0.90, range 0.83-0.97) and more frequent memory (RR = 3.00, range 1.25-7.21) with midazolam plus narcotics. Procedure times were similar, but sedation and recovery times were shorter with propofol than midazolam-based regimens.

LIMITATIONS

Marked variability in design, regimens tested, and outcomes assessed; relatively poor methodologic quality (Jadad score

CONCLUSIONS

Moderate sedation provides a high level of physician and patient satisfaction and a low risk of serious adverse events with all currently available agents. Midazolam-based regimens have longer sedation and recovery times than does propofol.

BACKGROUND

HIV infection and antiretroviral therapy are associated with dyslipidemia, but the association between regional adipose tissue depots and lipid levels is not defined.

METHODS

The association of magnetic resonance imaging-measured visceral adipose tissue (VAT) and regional subcutaneous adipose tissue (SAT) volume with fasting lipid parameters was analyzed by multivariable linear regression in 737 HIV-infected and 145 control men from the study of Fat Redistribution and Metabolic Change in HIV Infection.

RESULTS

HIV-infected men had higher median triglycerides (170 mg/dL vs. 107 mg/dL; P < 0.0001), lower high-density lipoprotein cholesterol (HDL-C; 38 mg/dL vs. 46 mg/dL; P < 0.0001), and lower low-density lipoprotein cholesterol (LDL-C; 105 mg/dL vs. 125 mg/dL; P < 0.0001) than controls. After adjustment, greater VAT was associated with higher triglycerides and lower HDL-C in HIV-infected and control men, whereas greater leg SAT was associated with lower triglycerides in HIV-infected men with a similar trend in controls. More upper trunk SAT was associated with higher LDL-C and lower HDL-C in controls, whereas more lower trunk SAT was associated with higher triglycerides in controls. After adjustment, HIV infection remained strongly associated (P < 0.0001) with higher triglycerides (+76%, 95% confidence interval [CI]: 53 to 103), lower LDL-C (-19%, 95% CI: -25 to -12), and lower HDL-C (-18%, 95% CI: -22 to -12).

CONCLUSIONS

HIV-infected men are more likely than controls to have higher triglycerides and lower HDL-C, which promote atherosclerosis, but also lower LDL-C. Less leg SAT and more VAT are important factors associated with high triglycerides and low HDL-C in HIV-infected men. The reduced leg SAT in HIV-infected men with lipoatrophy places them at increased risk for proatherogenic dyslipidemia.

OBJECTIVES

To assess long-term changes in subcutaneous tissue among antiretroviral-naive persons initiating 1 of 3 nucleoside reverse transcriptase inhibitor (NRTI)-containing regimens.

METHODS

We compared changes in 308 participants initiating stavudine plus lamivudine (d4T+3TC; N = 63), zidovudine plus lamivudine (ZDV+3TC; N = 192), and abacavir plus lamivudine (ABC+3TC; N = 53), along with protease inhibitors and/or non-NRTIs. Anthropometric measurements (skinfolds) were performed at baseline and 4-month intervals. Rates of change (mm/y) over 36 months, for the early period (months 4 through 12) and late period (months 16 through 36), were calculated.

RESULTS

The rates were negative (tissue loss) for the abdomen and thigh (d4T+3TC, ZDV+3TC) and triceps (ZDV+3TC) skinfolds. For ABC+3TC, most rates were positive (tissue gain). No differences among regimens were seen for the rates of change in the subscapular or suprascapular skinfolds. Rates in the early period were generally positive. The late period rates were negative for d4T+3TC and ZDV+3TC and significantly different from 0 for the abdomen and thigh (d4T+3TC, ZDV+3TC) and triceps (ZDV+3TC) skinfolds, whereas ABC+3TC had less loss in the late period. Most early versus late differences were significant for d4T+3TC and ZDV+3TC; only the triceps skinfold was significant for ABC+3TC.

CONCLUSIONS

In this prospective nonrandomized evaluation, subcutaneous tissue changes varied by regimen. Similar losses were demonstrated for d4T+3TC and ZDV+3TC, whereas ABC+3TC had gains. Temporal differences in rates for d4T+3TC and ZDV+3TC suggest initial recovery followed by long-term treatment effect.

Homozygous loss-of-function mutations in AIRE cause autoimmune polyglandular syndrome type 1 (APS 1), which manifests in a classic triad of hypoparathyroidism, adrenal insufficiency, and candidiasis. Interestingly, a kindred with a specific G228W AIRE variant presented with an autosomal dominant autoimmune phenotype distinct from APS 1. We utilized a novel G228W-knockin mouse model to show that this variant acted in a dominant-negative manner to cause a unique autoimmunity syndrome. In addition, the expression of a large number of Aire-regulated thymic antigens was partially inhibited in these animals, demonstrating the importance of quantitative changes in thymic antigen expression in determining organ-specific autoimmunity. Furthermore, the dominant-negative effect of the G228W variant was exerted through recruitment of WT Aire away from active sites of transcription in the nucleus of medullary thymic epithelial cells in vivo. Together, these results may demonstrate a mechanism by which autoimmune predisposition to phenotypes distinct from APS 1 can be mediated in a dominant-negative fashion by Aire.

BACKGROUND

The purpose of this study was to describe asthma medication adherence behavior and to identify predictors of inhaled corticosteroid (ICS) underuse and inhaled beta-agonist (IBA) overuse.

METHODS

Self-reported medication adherence, spirometry, various measures of status, and blood for immunoglobulin E measurement were collected on 158 subjects from a larger cohort of adults with asthma and rhinitis who were prescribed an ICS, an IBA, or both.

RESULTS

There was a positive association between ICS underuse and higher forced expiratory volume in one second percent (FEV1%) predicted (P = .01) and a negative association with lower income (P = 0.04). IBA overuse was positively associated with greater perceived severity of asthma (P = 0.004) and negatively with higher education level (P = 0.02).

CONCLUSIONS

Nonadherence to prescribed asthma therapy seems to be influenced by socioeconomic factors and by perceived and actual severity of disease. These factors are important to assess when trying to estimate the degree of medication adherence and its relationship to clinical presentation.