Recent Publications by CFE Educators

Atopic dermatitis is the most common chronic skin disease, and it primarily affects children. Although atopic dermatitis (AD) has the highest effect on burden of skin disease, no high-level studies have defined optimal therapy for severe disease. Corticosteroids have been used to treat AD since the 1950s and remain the only systemic medication with Food and Drug Administration approval for this indication in children, despite published guidelines of care that recommend against this option. Several clinical trials with level 1 evidence have supported the use of topical treatments for mild to moderate atopic dermatitis in adults and children, but these trials have had little consistency in protocol design. Consensus recommendations will help standardize clinical development and trial design for children. The Food and Drug Administration issues guidance documents for industry as a source for "the Agency's current thinking on a particular subject." Although they are nonbinding, industry considers these documents to be the standard for clinical development and trial design. Our consensus group is the first to specifically address clinical trial design in this population. We developed a draft guidance document for industry, Developing Drugs for Treatment of Atopic Dermatitis in Children (≥3 months to 18 years of age). This draft guidance has been submitted to the Food and Drug Administration based on a provision in the Federal Register (Good Guidance Practices).

Background

The independent contributions of microbial translocation and liver fibrosis to immune activation in human immunodeficiency virus (HIV) and/or hepatitis C virus (HCV)-infected persons are unclear.

Methods

Multivariable linear regression was used to evaluate whether intestinal fatty acid binding protein (I-FABP: a marker of gut epithelial integrity) and transient elastography-measured liver fibrosis might mediate the association of HIV and HCV with the soluble CD14 (sCD14) level in 120 individuals with HIV and HCV coinfection, 262 with HIV monoinfection, 72 with HCV monoinfection, and 170 without infection.

Results

Coinfected individuals, HIV-monoinfected individuals, and HCV-monoinfected individuals had 37%, 21%, and 12% higher sCD14 levels, respectively, than uninfected individuals, after multivariable adjustment. Additional adjustment for I-FABP level modestly attenuated the association of HIV infection, but attenuation occurred to a lesser extent in the HCV-monoinfected group. Adjustment for liver fibrosis substantially attenuated the association of HCV infection, but attenuation occurred to a lesser extent in the HIV-monoinfected group. Relative to the uninfected group, the primary mediator of the sCD14 level was the I-FABP level in the HIV-infected groups and liver fibrosis in the HCV-monoinfected group.

Conclusion

HIV and HCV are independently and additively associated with higher a sCD14 level. Our findings suggest that microbial translocation contributes to an increased sCD14 level during HIV infection, whereas liver fibrosis plays a stronger role during HCV monoinfection. Coinfected persons may be at greatest risk for progression, because of the independent effects of microbial translocation and liver fibrosis on immune activation.

BACKGROUND

Different outcomes among patients hospitalized for bleeding after starting anticoagulation could influence choice of anticoagulant. We compared length of hospitalization, proportion of Intensive Care Unit (ICU) admissions, ICU length of stay, and 30- and 90-day mortality for adults with atrial fibrillation hospitalized for bleeding after starting warfarin, dabigatran, or rivaroxaban.

METHODS

An US commercial database of 38 million members from 1 November 2010 to 31 March 2014 was used to examine adults with atrial fibrillation hospitalized for bleeding after starting warfarin (2,446), dabigatran (442), or rivaroxaban (256). Outcomes included difference in mean total length of hospitalization, proportion of ICU admissions, mean length of ICU stay, and all-cause 30- and 90-day mortality.

RESULTS

Warfarin users were older and had more comorbidities. Multivariable regression modeling with propensity score weighting showed warfarin users were hospitalized 2.0 days longer (95% CI 1.8-2.3; p 0.001) than dabigatran users and 2.6 days longer (95% CI 2.4-2.9; p 0.001) than rivaroxaban users. Dabigatran users were hospitalized 0.6 days longer (95% CI 0.2-1.0; p = 0.001) than rivaroxaban users. There were no differences in the proportion of ICU admissions. Among ICU admissions, warfarin users stayed 3.0 days (95% CI 1.9-3.9; p 0.001) longer than dabigatran users and 2.4 days longer (95% CI 0.9-3.7; p = 0.003) than rivaroxaban users. There was no difference in ICU stay between dabigatran and rivaroxaban users. There were no differences in 30- and 90-day all-cause mortality.

CONCLUSIONS

Rivaroxaban and dabigatran were associated with shorter hospitalizations; however, there were no differences in 30- and 90-day mortality. These findings suggest bleeding associated with the newer agents is not more dangerous than bleeding associated with warfarin.

Meningioma is the most common primary intracranial tumor, but the molecular drivers of aggressive meningioma are incompletely understood. Using 280 human meningioma samples and RNA sequencing, immunohistochemistry, whole-exome sequencing, DNA methylation arrays, and targeted gene expression profiling, we comprehensively define the molecular profile of aggressive meningioma. Transcriptomic analyses identify FOXM1 as a key transcription factor for meningioma proliferation and a marker of poor clinical outcomes. Consistently, we discover genomic and epigenomic factors associated with FOXM1 activation in aggressive meningiomas. Finally, we define a FOXM1/Wnt signaling axis in meningioma that is associated with a mitotic gene expression program, poor clinical outcomes, and proliferation of primary meningioma cells. In summary, we find that multiple molecular mechanisms converge on a FOXM1/Wnt signaling axis in aggressive meningioma.

Tularemia is a rare and potentially life-threatening infection caused by the highly infectious gram-negative coccobacillus Francisella tularensis. We present the case of an 11-year old girl who presented with erythema multiforme minor in the setting of an indolent but progressive soft tissue infection and was found to have tularemia. We review the role of dermatologists in identifying the features of and complications associated with this rare zoonosis and discuss the potential effect of climate change on its incidence.

OBJECTIVE

We sought to explore the relationship between counseling quality, measured by shared decision making and decision satisfaction, and psychological outcomes (anxiety, grief, and posttraumatic stress) after second-trimester abortion for pregnancy complications.

STUDY DESIGN

We conducted a cross-sectional study of women who underwent second-trimester abortion for complications. We recruited participants from Facebook and online support groups and surveyed them about counseling experiences and psychosocial issues. We used multivariate linear regression to evaluate relationships between counseling quality and psychological outcomes.

RESULTS

We analyzed data from 145 respondents. Shared decision making and decision satisfaction scores were positively and strongly correlated in bivariate analysis (r=0.7, p.0001), as were posttraumatic stress and grief scores (r=0.7, p.0001). In the adjusted analysis, higher decision satisfaction was associated with lower grief and posttraumatic stress scores (p=.02 and p=.01, respectively) and higher shared decision making was associated with lower posttraumatic stress scores (p=.01).

CONCLUSIONS

Decision satisfaction and shared decision making have a positive effect on psychological outcomes after second-trimester abortion for pregnancy complications. Counseling quality may be especially important in this setting given the sensitive nature of decisions regarding pregnancy termination for complications.

IMPLICATION

These results highlight the importance of patient-centered counseling for women seeking pregnancy termination.

OBJECTIVE

We sought to qualitatively understand patients' experiences with digoxin as a step before dilation and evacuation (D&E).

STUDY DESIGN

We recruited English-speaking women from one abortion health center where digoxin is routinely used before D&E. We interviewed participants one to three weeks after the D&E about physical and emotional experiences with digoxin and understanding of its purpose. Using grounded theory, we analyzed transcripts iteratively, identifying themes from interviews; we stopped recruitment when we reached thematic saturation.

RESULTS

We conducted 20 interviews and participants described mixed experiences. Three overarching themes from the qualitative interviews were: (1) physical and emotional discomfort; (2) varied understanding of digoxin's purpose and effects; and (3) reassurance. Most participants described significantly negative experiences with digoxin; however, many participants also described positive aspects of the injection intermingled with those negative experiences.

CONCLUSIONS

Participants' experiences with digoxin before D&E were both polarized and nuanced. While participants were largely clear about digoxin's action, they were much less clear about the reason for its use.

IMPLICATIONS

Both the clinical purpose for and patients' experiences with digoxin before D&E are complicated. Providers who continue to use digoxin should consider patient preferences in how they offer digoxin, and consider tools to ensure patient understanding.

OBJECTIVE

To describe the frequency of migraine and predictors of having migraine in sarcoidosis patients.

METHODS

The ID migraine questionnaire was administered to a well-phenotyped observational cohort of sarcoidosis patients (most of whom were seeking specialty care) and healthy controls. Predictors of migraine status were examined using univariate and multivariable logistic regression.

RESULTS

Migraine was seen in 29% of 96 patients with sarcoidosis and 13% of 39 healthy controls, ( p = 0.049). Among those with sarcoidosis, in univariate regression analysis only female sex was predictive of having migraine, and in a multivariable regression female sex remained significant (OR 4.6, 95% CI 1.2-18.2). There was no association between migraine and age, depression, dyspnea, immunosuppression use, or ESR.

CONCLUSIONS

Migraine is a common comorbidity in sarcoidosis patients. As such, better recognition and targeted treatment of migraine has the potential to improve quality of life as part of a comprehensive care plan for sarcoidosis patients.

INTRODUCTION

Sarcoidosis is a systemic inflammatory disease associated with myriad symptoms, including fatigue. It can affect physiological processes like sleep, leading to poor sleep quality and excessive daytime sleepiness. We hypothesized that sarcoidosis patients would report more severe sleep disturbance than healthy controls and that relationships would be found with sleep disturbance and the severity of other symptoms.

METHODS

We enrolled 84 sarcoidosis patients and 30 healthy controls and recorded demographic and clinical characteristics. Self-report measures were used to assess sleep disturbance, psychosocial symptoms, and quality of life at enrollment and longitudinally. Relationships between different self-report outcomes were analyzed using correlation statistics.

RESULTS

Using the General Sleep Disturbance Scale, 54% of sarcoidosis patients reported frequent and occasional sleep disturbance compared to only 17% of healthy controls (p  0.0001). This significant increase in sleep disturbance found in sarcoidosis patients strongly correlated with multiple psychosocial symptoms, including fatigue, depression, and cognitive dysfunction, and negatively impacted quality of life (p  0.01). Traditional measures of sarcoidosis disease severity or activity were not associated with sleep disturbance. Sleep disturbance scores remained stable at follow-up (mean time between first and last administration of questionnaire was 17.3 months) in 56 of the sarcoidosis patients.

CONCLUSIONS

Sarcoidosis patients experienced significant sleep disturbance that correlated with higher levels of fatigue, depression, and cognitive dysfunction, and poorer quality of life. These associations were present regardless of disease severity or activity and result in decrements in quality of life and mental health.