Publications

BACKGROUND

Prior studies have indicated that the magnitude of risk association of microvolt T-wave alternans (MTWA) testing appears to vary with the population studied. We performed a meta-analysis to determine the ability of MTWA to modify risk assessment of ventricular tachyarrhythmic events (VTEs) and sudden cardiac death (SCD) across a series of patient risk profiles using likelihood ratio (LR) testing, a measure of test performance independent of disease prevalence.

METHODS

We identified original research articles published from January 1990 to January 2011 that investigate spectrally derived MTWA. Ventricular tachyarrhythmic event was defined as the total and arrhythmic mortality and nonfatal sustained or implantable cardioverter-defibrillator-treated ventricular tachyarrhythmias. Summary estimates were created for positive and nonnegative MTWA results using a random-effects model and were expressed as positive (LR+) and negative (LR-) LRs.

RESULTS

Of 1,534 articles, 20 prospective cohort studies met our inclusion criteria, consisting of 5,945 subjects predominantly with prior myocardial infarction or left ventricular dysfunction. Although there was a modest association between positive MTWA and VTE (relative risk 2.45, 1.58-3.79) and nonnegative MTWA and VTE (3.68, 2.23-6.07), test performance was poor (positive MTWA: LR+ 1.78, LR- 0.43; nonnegative MTWA: LR+ 1.38, LR- 0.56). Subgroup analyses of subjects classified as prior VTE, post-myocardial infarction, SCD-HeFT type, and MADIT-II type had a similar poor test performance. A negative MTWA result would decrease the annualized risk of VTE from 8.85% to 6.37% in MADIT-II-type patients and from 5.91% to 2.60% in SCD-HeFT-type patients.

CONCLUSIONS

Despite a modest association, results of spectrally derived MTWA testing do not sufficiently modify the risk of VTE to change clinical decisions.

BACKGROUND

Tandem colonoscopy is regarded as the reference standard for the evaluation of the adenoma detection rate (ADR) and adenoma miss rate (AMR) during colonoscopy. Pooled results from previous tandem studies yield AMRs of 22%. The AMR of trainees is important to estimate the number of colonoscopies required to develop competence in screening for colorectal neoplasms.

OBJECTIVE

To measure the ADR and AMR of trainees as a function of experience.

METHODS

Prospective tandem colonoscopy study at an academic VA medical center. A trainee initially attempted colonoscopy. If the trainee was able to intubate the cecum, the trainee performed the withdrawal, and the colonoscopy was then repeated by the attending physician to assess the AMR.

RESULTS

Twelve trainee endoscopists were included in the study. Trainees had between 0 and 33 months of previous endoscopic experience and had done between 0 and 605 previous colonoscopies. A total of 230 patients were evaluated for the study, and 218 patients were enrolled. Complete tandem colonoscopy was performed in 147 patients. There was a 54% ADR. The mean (standard deviation) size of the adenomas in the cohort was 5.9 (5.3) mm. Significant variables in multivariate logistic regression analysis for missed adenomas were trainee experience (P = .011) and patient age (P < .001). The AMR decreased with increasing experience, and it is estimated that 450 colonoscopies are required to attain AMRs of less than 25% in a 60-year-old patient.

LIMITATIONS

Single-center study; the attending physician performing the second pass was not blinded to the first pass. The AMR was only analyzed for cases in which the trainee was able to reach the cecum with no or minimal assistance.

CONCLUSIONS

Our tandem colonoscopy study demonstrates that the AMR decreases as the experience of trainees increases and is a late competency attained during training. Future training may need to incorporate these findings to serve as a basis for determining appropriate training guidelines.

Viruses and hosts are involved in a continuing 'arms race'. The body deploys multiple defenses; however, viruses utilize generally superior and more rapidly evolving tactics for negating host immune surveillance and viral clearance. In the case of the two major pathogenic human retroviruses, human immunodeficiency virus-1 (HIV-1) and human T-lymphotrophic virus-I (HTLV-I), the nuclear factor-κB (NF-κB) transcription factor plays a key role in the host's anti-viral responses involving both the innate and adaptive arms of the immune response. Similarly, these retroviruses capably exploit NF-κB for their replication, spread, and pathogenic functions. In this review, we discuss the dynamic and intimate interplay that occurs between NF-κB and the HTLV-I and HIV-1 retroviral pathogens.

BACKGROUND

Adenosine exerts actions in multiple organ systems, and adenosine receptors are a therapeutic target in many development programmes.

OBJECTIVE

The aim of this analysis was to evaluate the safety of rolofylline, an adenosine A(1)-receptor antagonist, in patients with acute heart failure.

METHODS

The effect of rolofylline was investigated in patients hospitalized for acute heart failure with impaired renal function. Intravenous rolofylline 30 mg or placebo was infused over 4 hours daily for up to 3 days. Adverse events (AEs) and serious AEs (SAEs) were recorded from baseline through 7 and 14 days, respectively, and clinical events were adjudicated through 60 days.

RESULTS

Of 2033 patients enrolled, 2002 received study drug randomized 2 : 1 to rolofylline or placebo. Rolofylline and placebo were associated with a similar risk of pre-specified groups of AEs or SAEs, other than selected neurological events. Investigator-reported seizures occurred in 11 (0.8%) rolofylline-treated patients and zero patients receiving placebo (p = 0.02). Stroke occurred in 21 (1.6%) patients assigned to rolofylline compared with 3 (0.5%) placebo-treated patients through 60 days with a greater risk for stroke in the rolofylline group (hazard ratio 3.49; 95% CI 1.04, 11.71; p = 0.043). There was no temporal relation to rolofylline administration and no specific stroke subtype or clinical characteristics that predicted stroke in the rolofylline group.

CONCLUSIONS

Rolofylline treatment was associated with an increased seizure rate, an anticipated complication of A(1)-receptor antagonists. An unanticipated, disproportionate increase in strokes in the rolofylline-treated patients emerged, although no clear temporal relation, aetiology, stroke subtype or interacting factor suggestive of a causal mechanism was identified. Further research into stroke as a potential complication of adenosine-modulating therapies is required. Additionally, this study underscores the value of longer follow-up durations for AEs, even for agents with short treatment periods, such as in acute heart failure.

BACKGROUND

Paranasal sinuses are reservoirs for nitric oxide (NO), and humming facilitates nasal diffusion of NO. The nasal NO response to humming has previously been shown to be blunted with chronic sinusitis and nasal polyposis. We hypothesized that the nasal NO response to humming will be proportional to radiographic osteomeatal patency when comparing allergic rhinitis (AR) patients (without chronic sinusitis) with normal controls.

METHODS

Nonsmoking subjects completed questionnaires and skin-prick testing. Subjects underwent sinus CT scanning, followed by exhaled (oral) and nasal NO sampling (with and without humming). Humming-to-quiet (H/Q) nasal NO ratios were calculated. Three-dimensional reconstructions were used to trace the osteomeatal complex (OMC) and measure minimum cross-sectional area. Lund-Mackay scores were also documented.

RESULTS

A total of 33 subjects (22 women; mean age, 35.5 years) completed the study. Seventeen AR patients (5 IAR and 12 PAR) participated, as did 16 nonallergic controls. Among controls, quiet nasal NO levels--corrected for fractional exhaled NO--rose significantly with OMC area and fell significantly with Lund-Mackay scores (p < 0.05). However, we observed no proportionality between H/Q ratio and radiographic OMC patency.

CONCLUSION

Analysis of nasal NO samples taken under quiet conditions from normal controls was consistent with the paranasal sinuses acting as a reservoir of nasal NO and with OMC patency acting as a significant factor in NO diffusion. However, our results did not support a relationship between the nasal NO response to humming and radiographic OMC patency in a sample excluding subjects with severe rhinosinusitis.