Publications

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.

This document presents the proceedings from the American Thoracic Society Climate Change and Respiratory Health Workshop that was held on May 15, 2010, in New Orleans, Louisiana. The purpose of the one-day meeting was to address the threat to global respiratory health posed by climate change. Domestic and international experts as well as representatives of international respiratory societies and key U.S. federal agencies convened to identify necessary research questions concerning climate change and respiratory health and appropriate mechanisms and infrastructure needs for answering these questions. After much discussion, a breakout group compiled 27 recommendations for physicians, researchers, and policy makers. These recommendations are listed under main issues that the workshop participants deemed of key importance to respiratory health. Issues include the following: (1) the health impacts of climate change, with specific focus on the effect of heat waves, air pollution, and natural cycles; (2) mitigation and adaptation measures to be taken, with special emphasis on recommendations for the clinical and research community; (3) recognition of challenges specific to low-resource countries when coping with respiratory health and climate change; and (4) priority research infrastructure needs, with special discussion of international needs for cooperating with present and future environmental monitoring and alert systems.

OBJECTIVE

To determine the validity of standardized screening assessments of cognitive functioning to detect neuropsychological impairment evaluated using a comprehensive battery in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

METHODS

This is a cross-sectional study using a combined cohort of 139 persons with SLE and 82 persons with RA. Screening cut points were empirically derived using receiver operating characteristic curves and threshold selection methods. Screening measures included the Hopkins Verbal Learning Test-Revised (HVLT-R) learning and delayed recall indices and phonemic fluency, a composite measure of the 3 cognitive screening tests, and the Perceived Deficits Questionnaire-Short Form (PDQ-SF), a self-report measure of cognitive symptoms. A comprehensive neuropsychological battery was administered as the "gold standard" index of neuropsychological impairment.

RESULTS

Rates of neuropsychological impairment were 27% and 15% for the SLE and RA cohorts, respectively. Optimal threshold estimations were derived for 5 screening techniques. The HVLT-R learning and phonemic fluency indices yielded the greatest sensitivity at 81%. The PDQ-SF yielded the lowest sensitivity at 52%. All measures were significantly associated with neuropsychological impairment after controlling for relevant sociodemographic covariates and depression.

CONCLUSION

These results suggest that telephone-administered screening techniques may be useful measures to identify persons with neuropsychological impairment. Specifically, measures of phonemic fluency and verbal learning appeared to be most sensitive and least likely to misclassify impaired individuals as cognitively intact. Self-reported questionnaires may have relatively decreased sensitivity compared to standardized interviewer-administered cognitive measures.

OBJECTIVE

To examine associations between CSF biomarkers, initial neurologic dysfunction, and long-term ambulatory outcome in dogs with acute intervertebral disk herniation (IVDH).

DESIGN

Prospective clinical study.

ANIMALS

54 dogs with acute thoracolumbar IVDH and 16 clinically normal dogs.

PROCEDURES

For each dog, variables, including CSF myelin basic protein (MBP), lactate, calcium, glucose, and total protein concentrations; nucleated cell count; and creatine kinase (CK) and aspartate aminotransferase activities, were measured. For dogs with thoracolumbar IVDH, initial neurologic function was characterized by use of a modified Frankel score (MFS; determined on a scale of 0 to 5, where 0 represented paraplegia with no deep nociception and 5 represented paraspinal hyperesthesia only). Long-term follow-up was assessed.

RESULTS

Among dogs with thoracolumbar IVDH, those with CSF CK activity ≤ 38 U/L had a 35-fold increase in the odds of long-term ambulation, compared with the odds in dogs with CSF CK activity > 38 U/L, adjusting for neurologic functioning at the evaluation. The CSF lactate, calcium, and glucose concentrations and aspartate aminotransferase activity were not predictive of long-term ambulatory outcome. Data analysis revealed that long-term functional recovery was > 98% for affected dogs, regardless of their initial MFS, when CSF CK activity was ≤ 38 U/L and MBP concentration was ≤ 3 ng/mL.

CONCLUSIONS AND CLINICAL RELEVANCE

In dogs with acute thoracolumbar IVDH, CSF CK activity and MBP concentration appeared to be prognostic indicators and, along with initial MFS, can be used to predict long-term ambulatory outcome.