Helene Chokron Garneau

Rituximab Treatment of Patients with Severe, Corticosteroid-Resistant Thyroid-Associated Ophthalmopathy

PURPOSE To study the effectiveness of anti-CD20 (rituximab [RTX]; Rituxan; Genentech, Inc., South San Francisco, CA) therapy in patients with severe, corticosteroid (CS)-resistant thyroid-associated ophthalmopathy (TAO). DESIGN Retrospective, interventional case series. PARTICIPANTS Six consecutive subjects with severe, progressive TAO unresponsive to CS. METHODS Electronic medical record review of consecutive patients receiving RTX during the previous 18 months. Responses to therapy were graded using standard clinical assessment and flow cytometric analysis of peripheral lymphocytes. MAIN OUTCOME MEASURES Clinical activity score (CAS), proptosis, strabismus, treatment side effects, and quantification of regulatory T cells. RESULTS Six patients were studied. Systemic CS failed to alter clinical activity in all patients (mean CAS+/-standard deviation, 5.3+/-1.0 before vs. 5.5+/-0.8 during therapy for 7.5+/-6.4 months; P = 1.0). However, after RTX treatment, CAS improved from 5.5+/-0.8 to 1.3+/-0.5 at 2 months after treatment (P<0.03) and remained quiescent in all patients (CAS, 0.7+/-0.8; P<0.0001) at a mean follow-up of 6.2+/-4.5 months. Vision improved bilaterally in all 4 patients with dysthyroid optic neuropathy (DON). None of the 6 patients experienced disease relapse after RTX infusion, and proptosis remained stable (Hertel measurement, 24+/-3.7 mm before therapy and 23.6+/-3.7 mm after therapy; P = 0.17). The abundance of T regulatory cells, assessed in 1 patient, increased within 1 week of RTX and remained elevated at 18 months of follow-up. CONCLUSIONS In progressive, CS-resistant TAO, rapid and sustained resolution of orbital inflammation and DON followed treatment with RTX. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Development of Criteria for Evaluating Clinical Response in Thyroid Eye Disease Using a Modified Delphi Technique

OBJECTIVE To identify components of a provisional clinical response index for thyroid eye disease using a modified Delphi technique. METHODS The International Thyroid Eye Disease Society conducted a structured, 3-round Delphi exercise establishing consensus for a core set of measures for clinical trials in thyroid eye disease. The steering committee discussed the results in a face-to-face meeting (nominal group technique) and evaluated each criterion with respect to its feasibility, reliability, redundancy, and validity. Redundant measures were consolidated or excluded. RESULTS Criteria were parsed into 11 domains for the Delphi surveys. Eighty-four respondents participated in the Delphi 1 survey, providing 220 unique items. Ninety-two members (100% of the respondents from Delphi 1 plus 8 new participants) responded in Delphi 2 and rated the same 220 items. Sixty-four members (76% of participants) rated 153 criteria in Delphi 3 (67 criteria were excluded because of redundancy). Criteria with a mean greater than 6 (1 = least appropriate to 9 = most appropriate) were further evaluated by the nominal group technique and provisional core measures were chosen. CONCLUSIONS Using a Delphi exercise, we developed provisional core measures for assessing disease activity and severity in clinical trials of therapies for thyroid eye disease. These measures will be iteratively refined for use in multicenter clinical trials.

A Three-Dimensional Construct of the Aging Eyebrow: The Illusion of Volume Loss

BACKGROUND The eyebrows and eyebrow fat pads, key structures in upper facial aesthetics, are particularly vulnerable to age-related changes. OBJECTIVES In this study, the authors compare the impact of aging on the eyebrows and eyebrow fat pad volume in men and women through three-dimensional (3D) volumetric analysis. METHODS Electronic medical records of patients seen at the Jules Stein Eye Institute in the Division of Orbital and Ophthalmic Plastic Surgery between 2005 and 2010 were reviewed. Patients were included if they had undergone investigative imaging of the orbit for unilateral pathology. Computed tomography (CT) scans of patients with Graves disease diagnosis, extensive orbital trauma, and/or previous eyebrow surgery were excluded. A total of 52 CT scans (24 men and 28 women) were retained for analysis. A 3D reconstruction software was used to analyze the scans and calculate volumes of the retroorbicularis oculi fat (ROOF), galeal fat (ROOF and subcutaneous fat), and soft tissue muscles. RESULTS Galeal and brow fat volumes showed a significant positive trend toward enlargement in women (P values of .01 and .05, respectively). Although men showed a tendency toward fat enlargement with age, this was not statistically significant. Soft tissue-muscle volume decreased significantly in aging women (9.32 mm(3)/y) (P = .02). Data indicated that soft tissue volume in men tended to increase with age (3.92 mm(3)/y) but not significantly (P = .36). Neither total volume nor brow thickness appeared to change significantly in women (P = .56, P = .73). In men, total volume and brow thickness showed weak evidence of increasing with age (P = .12, P = .22). Linear regressions of Hertel measurements with and without sex interaction showed no statistically significant trend between the amount of proptosis and the galeal or brow fat. CONCLUSIONS Although overall eyebrow volume does not change with age, the relative contribution of fat and soft tissue to the total volume does seem to change. This pattern also differs between males and females. As women age, the fat volume increases and the soft tissue volume decreases. In men, the shift from soft tissue volume to fat volume is less pronounced. Although many clinicians have been drawn to the concept of fat volume deflation as a key element of facial aging, this study does not support this perspective in the eyebrow fat pad. An increasingly refined understanding of the dynamics of facial aging is mandatory for clinical diagnosis and will likely provide the framework from which to develop more innovative treatment options.

A Cognitive Behavioral Therapy–Based Text Messaging Intervention Versus Medical Management for HIV-Infected Substance Users: Study Protocol for a Pilot Randomized Trial

Background Evidence-based psychosocial interventions for addictions and related conditions such as cognitive behavioral therapy (CBT) are underutilized. Obstacles to implementation of CBT in clinical settings include limited availability of quality training, supervision, and certification in CBT for clinicians; high rates of clinician turnover and high caseloads; and limited qualifications of the workforce to facilitate CBT expertise. Objective Mobile phone–based delivery of CBT, if demonstrated to be feasible and effective, could be transformative in broadening its application and improving the quality of addiction treatment. No experimental interventions that deliver CBT targeting both drug use and medication adherence using text messaging have been previously reported; as such, the objective of this study is to develop and test an SMS-based treatment program for HIV-positive adults with comorbid substance use disorders. Methods With user input, we developed a 12-week CBT-based text messaging intervention (TXT-CBT) targeting antiretroviral (ART) adherence, risk behaviors, and drug use in a population of HIV-infected substance users. Results The intervention has been developed and is presently being tested in a pilot randomized clinical trial. Results will be reported later this year. Conclusions This investigation will yield valuable knowledge about the utility of a cost-effective, readily deployable text messaging behavioral intervention for HIV-infected drug users.

Barriers to initiation of extended release naltrexone among HIV-infected adults with alcohol use disorders

Alcohol consumption is a major risk factor for the acquisition of HIV/AIDS and is associated with greater disease burden and mortality among those who become HIV-infected. Of the extant pharmacological treatments for alcohol use disorders, naltrexone is recognized as one of the most efficacious, producing robust reductions in alcohol craving and use. Given that treatment with oral naltrexone has been limited by problems with adherence, which are particularly prevalent among individuals with multiple chronic, co-occurring conditions, long-acting formulations may be a promising approach for HIV-infected substance users. However, little is known about the barriers to initiation of extended-release naltrexone (XR-NTX) treatment among alcohol users living with HIV. In this report we present and discuss the content analysis of open-ended survey questions, as well as lessons learned, with regards to barriers to initiation and maintenance of XR-NTX treatment collected as part of an RCT evaluating a cognitive behavioral text messaging intervention for HIV-infected adults with alcohol use disorders. Barriers to initiation and maintenance of XR-NTX pharmacotherapy among HIV+ individuals with alcohol use disorders seem to fall in one of two categories: [1] barriers that are amenable to change, which include distance and transportation issues, fear of injections, and belief that alcohol use does not warrant pharmacotherapy, and [2] barriers that are not amenable to change, such as the potential interaction of XR-NTX with another medication regimen.

Eyebrow tissue expansion: an underappreciated entity in thyroid-associated orbitopathy.

OBJECTIVES To report photographic evidence of eyebrow tissue expansion in patients with thyroid-associated orbitopathy (TAO) and to demonstrate consistency in grading through the use of standardized photographs. METHODS A retrospective cohort study of patients referred for evaluation of TAO in an orbitofacial tertiary care center between January 1, 2000, and December 31, 2010. A grading key was produced with representative views of each of 4 grades (0 [no expansion] to 3 [severe expansion]), corresponding to increasing severity of eyebrow tissue expansion. Photographs of each study patient, including both premorbid and morbid photographs, were retrieved from an electronic medical record system and graded by 6 independent, masked observers using this 4-point system. RESULTS Seventy-five patients with TAO were identified for inclusion. The average grade was 0.3 for premorbid eyes and 1.1 for morbid eyes. Intraclass correlation coefficients for the premorbid photographs were 0.705 and 0.632 for the right and left eyes, respectively. Intraclass correlation coefficients for the morbid photographs were 0.921 and 0.916 for the right and left eyes, respectively. CONCLUSIONS Eyebrow tissue expansion is a common manifestation in TAO. Comparison of premorbid and morbid photographs is a useful means to identify and characterize the extent of brow involvement. The use of a grading key improves the consistency of identifying and grading eyebrow tissue expansion. Recognition of the eyebrow tissue as distinct anatomically in TAO may be crucial to rehabilitation of these patients, which may entail multiple surgical procedures.

Changes in Stress Reactivity among Stimulant Dependent Adults AfterTreatment with Mindfulness Based Relapse Prevention: Results from a PilotRandomized Clinical Trial

Background: In light of recent evidence suggesting the presence of stress processing deficits in stimulant users, coupled with laboratory studies demonstrating an association between stress reactivity and relapse to stimulant use, interventions that target stress-induced craving and stress reactivity may reduce relapse risk in this population. Objective: This study examines changes in stress reactivity among adults with stimulant use disorders (N=22) in response to an 8 week Mindfulness Based Relapse Prevention (MBRP) intervention. Methods: Study participants were enrolled in a in a pilot randomized clinical trial, evaluating the efficacy of MBRP, relative to a health education control condition (HE). At baseline and treatment-end, biological and subjective responses to a laboratory psychosocial stress task (i.e., the Trier Social Stress Task) were measured. Results: MBRP participants evidenced significantly lower levels of salivary cortisol in response to the posttreatment laboratory stress provocation, relative to those in the HE condition. Likewise, HE participants evidenced disproportionately greater increases in subjective stress, anxiety and stimulant cravings in response to the posttreatment stress provocation, relative to those who received MBRP. Conclusion: Results of this pilot investigation suggest that MBRP effectively attenuates stress reactivity among adults with stimulant use disorders. This approach may have utility as an adjunct to comprehensive programs treating stimulant addiction. Future research evaluating the impact of changes in stress reactivity on post-treatment relapse to stimulant use and the long-term effects of MBRP on stress reactivity is warranted.