Recent Publications by CFE Educators

BACKGROUND

Glycoprotein (GP) IIb/IIIa inhibitors are beneficial in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS); their safe use in women, however, remains a concern. The contribution of dosing to the observed sex-related differences in bleeding is unknown.

METHODS AND RESULTS

We explored the relationship between patient sex, GP IIb/IIIa inhibitor use, dose, and bleeding in 32 601 patients with NSTE ACS across 400 CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines) hospitals, of whom 18 436 were treated. GP IIb/IIIa inhibitor dose was defined as excessive if not reduced when creatinine clearance was 50 mL/min for eptifibatide or 30 mL/min for tirofiban. Major bleeding was defined as a hematocrit drop > or = 0.12, need for transfusion, or intracranial bleeding. Major bleeding was adjusted for clinical factors and antithrombotic dose. The risk for bleeding attributable to excess GP IIb/IIIa dose was determined by sex using prevalence and adjusted odds ratios (ORs). Women had higher rates of major bleeding than men among those treated with GP IIb/IIIa inhibitors (15.7% versus 7.3%, P0.0001) and among those not treated (8.5% versus 5.4%, P0.0001). Despite similar serum creatinine levels, creatinine clearance averaged 20 points lower among treated women than men. Treated women were also more likely to receive excess GP IIb/IIIa doses than men (46.4% versus 17.2%, P0.0001; adjusted OR 3.81, 95% confidence interval [CI] 3.39 to 4.27). Excess dosing was associated with increased risk of bleeding in women (OR 1.72, 95% CI 1.30 to 2.28) and men (OR 1.27, 95% CI 0.97 to 1.66); however, bleeding risk attributable to dosing was much higher in women (25.0% versus 4.4%).

CONCLUSIONS

Women experience more bleeding than men whether or not they are treated with GP IIb/IIIa inhibitors; however, because of frequent excessive dosing in women, up to one fourth of this sex-related risk difference in bleeding is avoidable. Appropriate dosing will improve care of all patients with NSTE ACS, with a particular benefit for women.

PURPOSE OF REVIEW

The purpose of this review is to discuss the classification, diagnosis and management of juvenile-onset spondyloarthritis.

RECENT FINDINGS

There have been changes in the classification criteria for juvenile-onset spondyloarthritis and magnetic resonance imaging has allowed for earlier detection of disease. Additionally, tumor necrosis factor-alpha blockers have been shown to be effective in the treatment of ankylosing spondylitis. There is evidence to suggest that early treatment may lead to better response. A high percentage of patients with enthesitis-related arthritis progress to develop ankylosing spondylitis within 10 years after presentation. Patients with juvenile-onset ankylosing spondylitis appear to have poorer functional outcomes.

SUMMARY

Juvenile-onset spondyloarthritis has variable clinical features that may lead to significant impairments. Improved classification criteria exist, but better techniques that are more sensitive are needed to diagnose disease earlier. New therapies appear to improve outcomes, but randomized controlled trials are needed in this population of patients.

OBJECTIVE

To examine the relationship between gestational weight gain and adverse neonatal outcomes among infants born at term (37 weeks or more).

METHODS

This was a retrospective cohort study of 20,465 nondiabetic, term, singleton births. We performed univariable and multivariable analyses of the associations between gestational weight gain and neonatal outcomes. We categorized gestational weight gain by the Institute of Medicine guidelines as well as extremes of gestational weight gain (less than 7 kg and more than 18 kg).

RESULTS

Gestational weight gain above the Institute of Medicine guidelines was more common than gestational weight gain below (43.3% compared with 20.1%). In multivariable analyses, gestational weight gain above guidelines was associated with a low 5-minute Apgar score (adjusted odds ratio [AOR] 1.33, 95% confidence interval [CI] 1.01-1.76), seizure (AOR 6.50, 95% CI 1.43-29.65), hypoglycemia (AOR 1.52, 95% CI 1.06-2.16), polycythemia (AOR 1.44, 95% CI 1.06-1.94), meconium aspiration syndrome (AOR 1.79, 95% CI 1.12-2.86), and large for gestational age (AOR 1.98, 95% CI 1.74-2.25) compared with women within weight gain guidelines. Gestational weight gain below guidelines was associated with decreased odds of neonatal intensive care unit admission (AOR 0.66, 95% CI 0.46-0.96) and increased odds of small for gestational age (SGA; AOR 1.66, 95% CI 1.44-1.92). Gestational weight gain less than 7 kg was associated with increased risk of seizure, hospital stay more than 5 days, and SGA. Gestational weight gain more than 18 kg was associated with assisted ventilation, seizure, hypoglycemia, polycythemia, meconium aspiration syndrome, and large for gestational age.

CONCLUSION

Gestational weight gain above guidelines was common and associated with multiple adverse neonatal outcomes, whereas gestational weight gain below guidelines was only associated with SGA status. Public health efforts among similar populations should emphasize prevention of excessive gestational weight gain.

OBJECTIVE

The purpose of this study was to examine the lengths of the first and second stages of labor among different racial/ethnic groups to determine whether different norms should be established.

STUDY DESIGN

This was a retrospective cohort study of all laboring, term, singleton, vertex deliveries in a single academic institution. Median lengths of first and second stages of labor were compared among 4 racial/ethnic groups: black, Asian, white, and Latina. Kruskal-Wallis, Wilcoxon rank sum tests, and multivariate linear and logistic regression models were performed.

RESULTS

In 27,521 births, the lengths of first stage of labor did not differ significantly among groups in the multivariate analysis. In the second stage of labor, black women had shorter labors, both overall and stratified by epidural use. In the multivariate analysis, when controlled for demographics, parity, epidural, chorioamnionitis, birthweight, delivery year, and labor management, black women had a shorter second stage than did white women (nulliparous women, 22 minutes; multiparous women, 7.5 minutes; P .001) and lower rates of prolonged second stage (odds ratio, 0.6; P .001). Nulliparous Asian women had a significantly longer second stage and higher rates of prolonged second stage, and nulliparous Latina women had a shorter second stage, compared with nulliparous white women.

CONCLUSION

When data are controlled for confounding factors, black women had a shorter length of second stage of labor than did women in other ethnic groups. These differences appear to be clinically significant. This contributes to the support of a multifactorial redefinition of labor curves, which are used widely in the management of labor.

Our previous recordings from dorsal root ganglion and spinal lamina V neurons from TRPV1-mutant mice showed dramatic decreases in responses to temperatures near the activation threshold of this channel (43-49 degrees C). Somewhat unexpectedly, we only observed behavioral deficits in these mice at higher temperatures (50-58 degrees C). In the present study, we tested the hypothesis that the noxious heat-evoked pain behavior that persists in TRPV1-mutant mice reflects residual responsiveness of neurons in the superficial, but not deep, dorsal horn. To this end, we performed in vivo extracellular recordings of spinal nociresponsive neurons in laminae I and V in wild type (WT) and TRPV1 mutant mice. Neurons in WT and mutant mice from both laminae did not differ in their spontaneous activity or evoked responses to mechanical or cold stimuli. By contrast, most lamina I neurons from mutant mice responded to noxious heat with significantly higher thresholds than in WT mice. In contrast, lamina V neurons from mutant mice were virtually unresponsive to noxious heat before and after topical mustard oil-induced tissue injury. Interestingly, lamina I neurons in mutant mice displayed thermal sensitization following tissue injury, comparable in magnitude, but of shorter duration, than in WT mice. We conclude that TRPV1 is necessary for noxious heat-evoked responses of lamina V neurons, both before and after tissue injury. It is also an essential contributor to the normal activation threshold of lamina I neurons to noxious heat and for the full duration of thermal sensitization of lamina I neurons following injury. Finally, our results suggest that the processing of noxious thermal messages by neurons in lamina I involves convergent inputs from a heterogeneous population of primary afferent thermal nociceptors.

Although CXCR4-tropic viruses are relatively uncommon among untreated human immunodeficiency virus (HIV)-infected individuals except during advanced immunodeficiency, the prevalence of CXCR4-tropic viruses among treated patients with detectable viremia is unknown. To address this issue, viral coreceptor usage was measured with a single-cycle recombinant-virus phenotypic entry assay in treatment-naive and treated HIV-infected participants with detectable viremia sampled from 2 clinic-based cohorts. Of 182 treated participants, 75 (41%) harbored dual/mixed or X4-tropic viruses, compared with 178 (18%) of the 976 treatment-naive participants (P.001). This difference remained significant after adjustment for CD4+ T cell count and CCR5 Delta 32 genotype. Enrichment for dual/mixed/X4-tropic viruses among treated participants was largely but incompletely explained by lower pretreatment nadir CD4 + T cell counts. CCR5 inhibitors may thus be best strategically used before salvage therapy and before significant CD4 + T cell depletion.

CONTEXT

Due to the Chornobyl accident, millions were exposed to radioactive isotopes of iodine and some received appreciable iodine 131 (131I) doses. A subsequent increase in thyroid cancer has been largely attributed to this exposure, but evidence concerning autoimmune thyroiditis (AIT) remains inconclusive.

OBJECTIVE

The objective of the study was to quantify risk of AIT after 131I exposure.

DESIGN/SETTING/PARTICIPANTS

Baseline data were collected from the first screening cycle (1998-2000) of a large cohort of radiation-exposed individuals (n = 12,240), residents of contaminated, iodine-deficient territories of Ukraine. Study individuals were under the age of 18 yr on April 26, 1986, and had thyroid radioactivity measurements made shortly after the accident.

OUTCOMES

AIT was defined a priori based on various combinations of elevated antibodies to thyroid peroxidase (ATPO), TSH, and clinical findings; elevated ATPO were considered to be an indicator of thyroid autoimmunity.

RESULTS

No significant association was found between 131I thyroid dose estimates and AIT, but prevalence of elevated ATPO demonstrated a modest, significant association with 131I that was well described by several concave models. This relationship was apparent in individuals with moderately elevated ATPO and euthyroid, thyroid disease-free individuals.

CONCLUSIONS

Twelve to 14 yr after the Chornobyl accident, no radiation-related increase in prevalence of AIT was found in a large cohort study, the first in which 131I thyroid doses were estimated using individual radioactivity measurements. However, a dose-response relationship with ATPO prevalence raises the possibility that clinically important changes may occur over time. Thus, further follow-up and analysis of prospective data in this cohort are necessary.

The anti-migraine action of "triptan" drugs involves the activation of serotonin subtype 1D (5-HT1D) receptors expressed on "pain-responsive" trigeminal primary afferents. In the central terminals of these nociceptors, the receptor is concentrated on peptidergic dense core vesicles (DCVs) and is notably absent from the plasma membrane. Based on this arrangement, we hypothesized that in the resting state the receptor is not available for binding by a triptan, but that noxious stimulation of these afferents could trigger vesicular release of DCVs, thus externalizing the receptor. Here we report that within 5 min of an acute mechanical stimulus to the hindpaw of the rat, there is a significant increase of 5-HT1D-immunoreactivity (IR) in the ipsilateral dorsal horn of the spinal cord. We suggest that these rapid immunohistochemical changes reflect redistribution of sequestered receptor to the plasma membrane, where it is more readily detected. We also observed divergent changes in 5-HT1D-IR in inflammatory and nerve-injury models of persistent pain, occurring at least in part through the regulation of 5-HT1D-receptor gene expression. Finally, we found that 5-HT1D-IR is unchanged in the spinal cord dorsal horn of mice with a deletion of the gene encoding the neuropeptide substance P. This result differs from that reported for the partial differential-opioid receptor, which is also sorted to DCVs, but is greatly reduced in preprotachykinin mutant mice. We suggest that a "pain"-triggered regulation of 5-HT1D-receptor expression underlies the effectiveness of triptans for the treatment of migraine. Moreover, the widespread expression of 5-HT1D receptor in somatic nociceptive afferents suggests that triptans could, in certain circumstances, treat pain in nontrigeminal regions of the body.