Attenuation of Anxiety-Potentiated Startle After Treatment With Escitalopram or Mindfulness Meditation in Anxiety Disorders.

BACKGROUND: Biological markers for anxiety disorders may further understanding of disorder pathophysiology and suggest potential targeted treatments. The fear-potentiated startle (FPS) (a measure of startle to predictable threat) and anxiety-potentiated startle (APS) (startle to unpredictable threat) laboratory paradigm has been used to detect physiological differences in individuals with anxiety disorders compared with nonanxious control individuals, and in pharmacological challenge studies in healthy adults. However, little is known about how startle may change with treatment for anxiety disorders, and no data are available regarding alterations due to mindfulness meditation training. METHODS: Ninety-three individuals with anxiety disorders and 66 healthy individuals completed 2 sessions of the neutral, predictable, and unpredictable threat task, which employs a startle probe and the threat of shock to assess moment-by-moment fear and anxiety. Between the two testing sessions, patients received randomized 8-week treatment with either escitalopram or mindfulness-based stress reduction. RESULTS: APS, but not FPS, was higher in participants with anxiety disorders compared with healthy control individuals at baseline. Further, there was a significantly greater decrease in APS for both treatment groups compared with the control group, with the patient groups showing reductions bringing them into the range of control individuals at the end of the treatment. CONCLUSIONS: Both anxiety treatments (escitalopram and mindfulness-based stress reduction) reduced startle potentiation during unpredictable (APS) but not predictable (FPS) threat. These findings further validate APS as a biological correlate of pathological anxiety and provide physiological evidence for the impact of mindfulness-based stress reduction on anxiety disorders, suggesting that there may be comparable effects of the two treatments on anxiety neurocircuitry.

Mindfulness-Based Stress Reduction vs Escitalopram for the Treatment of Adults With Anxiety Disorders: A Randomized Clinical Trial.

Importance: Anxiety disorders are common, highly distressing, and impairing conditions. Effective treatments exist, but many patients do not access or respond to them. Mindfulness-based interventions, such as mindfulness-based stress reduction (MBSR) are popular and can decrease anxiety, but it is unknown how they compare to standard first-line treatments. Objective: To determine whether MBSR is noninferior to escitalopram, a commonly used first-line psychopharmacological treatment for anxiety disorders. Design, Setting, and Participants: This randomized clinical trial (Treatments for Anxiety: Meditation and Escitalopram [TAME]) included a noninferiority design with a prespecified noninferiority margin. Patients were recruited between June 2018 and February 2020. The outcome assessments were performed by blinded clinical interviewer at baseline, week 8 end point, and follow-up visits at 12 and 24 weeks. Of 430 individuals assessed for inclusion, 276 adults with a diagnosed anxiety disorder from 3 urban academic medical centers in the US were recruited for the trial, and 208 completed the trial. Interventions: Participants were 1:1 randomized to 8 weeks of the weekly MBSR course or the antidepressant escitalopram, flexibly dosed from 10 to 20 mg. Main Outcomes and Measures: The primary outcome measure was anxiety levels as assessed with the Clinical Global Impression of Severity scale (CGI-S), with a predetermined noninferiority margin of -0.495 points. Results: The primary noninferiority sample consisted of 208 patients (102 in MBSR and 106 in escitalopram), with a mean (SD) age of 33 (13) years; 156 participants (75%) were female; 32 participants (15%) were African American, 41 (20%) were Asian, 18 (9%) were Hispanic/Latino, 122 (59%) were White, and 13 (6%) were of another race or ethnicity (including Native American or Alaska Native, more than one race, or other, consolidated owing to low numbers). Baseline mean (SD) CGI-S score was 4.44 (0.79) for the MBSR group and 4.51 (0.78) for the escitalopram group in the per-protocol sample and 4.49 (0.77) vs 4.54 (0.83), respectively, in the randomized sample. At end point, the mean (SD) CGI-S score was reduced by 1.35 (1.06) for MBSR and 1.43 (1.17) for escitalopram. The difference between groups was -0.07 (0.16; 95% CI, -0.38 to 0.23; P = .65), where the lower bound of the interval fell within the predefined noninferiority margin of -0.495, indicating noninferiority of MBSR compared with escitalopram. Secondary intent-to-treat analyses using imputed data also showed the noninferiority of MBSR compared with escitalopram based on the improvement in CGI-S score. Of patients who started treatment, 10 (8%) dropped out of the escitalopram group and none from the MBSR group due to adverse events. At least 1 study-related adverse event occurred for 110 participants randomized to escitalopram (78.6%) and 21 participants randomized to MBSR (15.4%). Conclusions and Relevance: The results from this randomized clinical trial comparing a standardized evidence-based mindfulness-based intervention with pharmacotherapy for the treatment of anxiety disorders found that MBSR was noninferior to escitalopram. Trial Registration: ClinicalTrials.gov Identifier: NCT03522844.

Virtual reality for management of cancer pain: Study rationale and design.

BACKGROUND: Patients with cancer commonly experience acute and/or chronic moderate to severe pain related to disease, treatment, or both. While pain management strategies typically focus on drug therapies, non-pharmacological interventions may prove beneficial without risk of significant clinical side effects or contraindications. One novel strategy, virtual reality, has been shown to improve pain control in addition to usual pharmacological interventions. METHODS: This is a prospective, two-armed, single center randomized controlled study of a virtual reality intervention in 128 hospitalized subjects with cancer reporting pain rated at least 4/10 compared to an active control intervention, two-dimensional guided imagery. The primary outcome is change in self-reported pain score. Secondary end points include changes in self-reported distress, quality of life, and satisfaction with pain management. We will also explore patient preferences for distraction therapy content and themes through quantitative analysis of survey data, semi-structured interviews, and a collaging exercise. CONCLUSION: This randomized controlled study aims to provide empiric data to support application and expansion of novel technologies such as virtual reality to augment usual pharmacological pain management strategies in hospitalized patients with cancer.

Virtual reality for pain management in advanced heart failure: A randomized controlled study.

BACKGROUND: Hospitalized patients with advanced heart failure often experience acute and/or chronic pain. While virtual reality has been extensively studied across a wide range of clinical settings, no studies have yet evaluated potential impact on pain management on this patient population. AIM: To investigate the impact of a virtual reality experience on self-reported pain, quality-of-life, general distress, and satisfaction compared to a two-dimensional guided imagery active control. DESIGN: Single-center prospective randomized controlled study. The primary outcome was the difference in pre- versus post-intervention self-reported pain scores on a numerical rating scale from 0 to 10. Secondary outcomes included changes in quality-of-life scores, general distress, and satisfaction with the intervention. SETTING/PARTICIPANTS: Between October 2018 and March 2020, 88 participants hospitalized with advanced heart failure were recruited from an urban tertiary academic medical center. RESULTS: Participants experienced significant improvement in pain score after either 10 minutes of virtual reality (change from pre- to post -2.9 ± 2.6, p < 0.0001) or 10 minutes of guided imagery (change from pre- to post -1.3 ± 1.8, p = 0.0001); the virtual reality arm experienced a 1.5 unit comparatively greater reduction in pain score compared to guided imagery (p = 0.0011). Total quality-of-life and general distress scores did not significantly change for either arm. Seventy-eight participants (89%) responded that they would be willing to use the assigned intervention again. CONCLUSION: Virtual reality may be an effective nonpharmacologic adjuvant pain management intervention in hospitalized patients with heart failure. TRIAL REGISTRATION: ClinicalTrials.gov database (NCT04572425).

Biotin Interference in Assays for Thyroid Hormones, Thyrotropin and Thyroglobulin.

Background: Biotin has been reported to interfere with several commonly used laboratory assays resulting in misleading values and possible erroneous diagnosis and treatment. This report describes a prospective study of possible biotin interference in thyroid-related laboratory assays, with a comparison of different commonly used assay platforms. Materials and Methods: Thirteen adult subjects (mean age 45 ± 13 years old) were administered biotin 10 mg/day for eight days. Blood specimens were collected at three time points on day 1 and on day 8 (baseline, two, and five hours after biotin ingestion). Thyrotropin (TSH), free triiodothyronine (fT3), free thyroxine (fT4), total triiodothyronine (TT3), total thyroxine (TT4), thyroxine binding globulin (TBG), and thyroglobulin (Tg) levels were analyzed with four different platforms: Abbott Architect, Roche Cobas 6000, Siemens IMMULITE 2000, and liquid chromatography with tandem mass spectrometry (LC-MS/MS). TSH, fT3, fT4, TT3, and TT4 were measured with Abbott Architect and Roche Cobas 6000. fT3, fT4, TT3, and TT4 were also measured by LC-MS/MS. Tg was measured by Siemens IMMULITE 2000. TBG was assessed with Siemens IMMULITE 2000. Results: Significant changes in TSH, fT4, and TT3 measurements were observed after biotin exposure when the Roche Cobas 6000 platform was used. Biotin intake resulted in a falsely lower Tg level when measurements were performed with Siemens IMMULITE 2000. At the time points examined, maximal biotin interference was observed two hours after biotin exposure both on day 1 and day 8. Conclusions: A daily dose of 10 mg was shown to interfere with specific assays for TSH, fT4, TT3, and Tg. Physicians must be aware of the potential risk of erroneous test results in subjects taking biotin supplements. Altered test results for TSH and Tg can be particularly problematic in patients requiring careful titration of levothyroxine therapy such as those with thyroid cancer.

Rationale, design, and methods of a two-site randomized controlled trial: Comparative effectiveness of two treatments for posttraumatic stress disorder in veterans.

PTSD is associated with serious problems in interpersonal functioning, including higher rates of marital conflict and divorce, disrupted relationships with family and friends, estrangement from others and social isolation. Cognitive behavioral and trauma focused treatments are effective for treating PTSD symptoms, but a substantial proportion of individuals, particularly veterans, with PTSD, do not engage, complete, or fully respond to these treatments, and the effects of these treatments on interpersonal functioning are unknown. There is a critical need for alternative treatments with established efficacy, and for treatments that directly address problems in relationship functioning. Interpersonal Psychotherapy for PTSD (IPT-PTSD) is a promising candidate for such a treatment. This paper describes the rationale, design, and methods of the first randomized controlled equivalence trial comparing IPT-PTSD with a first-line gold standard treatment for PTSD (Prolonged Exposure; PE) in the treatment of PTSD in veterans. Both treatments include up to 12 weekly individual sessions. Assessments were conducted at baseline, following sessions four and eight, end of treatment, and 3 and 6 months post-treatment. Primary hypotheses are that IPT-PTSD will be statistically equivalent to PE in reducing the severity of PTSD symptoms, and superior to PE in improving interpersonal functioning. Secondary hypotheses propose that IPT will be superior to PE in improving overall social adjustment and quality of life, and in reducing suicidal ideation. Findings from this study have the potential to improve treatment options for veterans struggling with PTSD and interpersonal problems.

Treatment for anxiety: Mindfulness meditation versus escitalopram (TAME): Design of a randomized, controlled non-inferiority trial.

Anxiety disorders (generalized anxiety disorder, social anxiety disorder, panic disorder, and agoraphobia) are common, distressing, and impairing. While pharmacotherapy and psychotherapy are first-line treatment strategies for anxiety disorders, many patients are reluctant to take psychiatric medication, and many prefer to avoid any kind of mental health treatment due to stigma or distrust of traditional medical care. We present the trial protocol for the first study comparing first-line medication treatment with Mindfulness-Based Stress Reduction (MBSR), a popular mindfulness meditation training program, for the treatment of anxiety disorders. We will use a non-inferiority, comparative effectiveness trial design, in which individuals with diagnosed anxiety disorders will be randomized to either pharmacotherapy with escitalopram or MBSR for 8 weeks of treatment. Treatment outcome will be based on gold standard symptom severity measures assessed by trained independent evaluators blind to treatment allocation. Secondary outcomes will include key symptom and function measures, as well as tolerability and satisfaction with treatment. Findings will provide crucial information to inform decision making about the relative benefits of MBSR versus a first line medication for anxiety disorders by patients, medical care providers, healthcare insurers and other stakeholders.

Virtual reality for pain management in patients with heart failure: Study rationale and design.

BACKGROUND: Patients with advanced heart failure commonly experience acute and/or chronic moderate to severe pain related to disease, treatment, or both. While pain management strategies typically focus on drug therapies, non-pharmacological interventions may prove beneficial without risk of significant clinical side effects or contraindications. One novel strategy, virtual reality, has been shown to improve pain control in addition to usual pharmacological interventions. METHODS: This is a prospective, two-armed, single center randomized controlled pilot study of a virtual reality intervention in 128 hospitalized subjects with ACC/AHA stage C or stage D heart failure who self-report pain rated 4/10 or greater compared to an active control, two-dimensional guided imagery. The primary outcome is change in self-reported pain score measured by the Brief Pain Inventory (Short Form). Secondary end points include changes in self-reported distress, quality of life, and satisfaction with pain management. CONCLUSION: This randomized controlled study aims to provide empiric data to support application and expansion of novel technologies such as virtual reality to augment usual pharmacological pain management strategies in hospitalized patients with heart failure.

Effects of mindfulness meditation on occupational functioning and health care utilization in individuals with anxiety.

OBJECTIVES: To examine the effect of mindfulness meditation on occupational functioning in individuals with Generalized anxiety disorder (GAD). METHODS: Fifty-seven individuals with GAD (mean (SD) age=39 (13); 56% women) participated in an 8-week clinical trial in which they were randomized to mindfulness-based stress reduction (MBSR) or an attention control class. In this secondary analysis, absenteeism, entire workdays missed, partial workdays missed, and healthcare utilization patterns were assessed before and after treatment. RESULTS: Compared to the attention control class, participation in MBSR was associated with a significantly greater decrease in partial work days missed for adults with GAD (t=2.734, df=51, p=0.009). Interestingly, a dose effect was observed during the 24-week post-treatment follow-up period: among MBSR participants, greater home mindfulness meditation practice was associated with less work loss and with fewer mental health professional visits. CONCLUSION: Mindfulness meditation training may improve occupational functioning and decrease healthcare utilization in adults with GAD.

Phase 2 clinical trial of sunitinib as adjunctive treatment in patients with advanced differentiated thyroid cancer.

OBJECTIVE: Our objective was to evaluate the efficacy and safety of sunitinib following at least one course of radioactive iodine treatment in patients with advanced differentiated thyroid cancer (DTC). The study endpoints included best response rate (including best objective response rate) and progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, measurement of serum thyroglobulin (Tg), and toxicity evaluation. DESIGN AND METHODS: This was a single center, nonrandomized, open-label, phase 2 clinical trial. In total, 23 patients were enrolled and were treated with a starting daily, oral dose of 37.5  mg sunitinib. Patients were evaluated with imaging, laboratory tests, and physical examination periodically per protocol. RESULTS: The mean best response was a decrease of 17.2% (S.D. 22.8) in tumor sum from baseline. Six (26%) patients achieved a partial response (PR), and 13 (57%) had stable disease (SD) for a clinical benefit rate (PR+SD) of 83%. The overall median PFS was 241 days (interquartile limits, 114-518). No statistically significant difference was observed between the medians of the baseline and post-treatment Tg values (P=0.24). The most common adverse events included grades 1 and 2 decreases in blood cell counts (especially leukocytes), diarrhea, fatigue, hand-foot skin reaction, nausea, musculoskeletal pain, and hypertension. CONCLUSIONS: These data demonstrate that sunitinib exhibits significant anti-tumor activity in patients with advanced DTC. Since sunitinib was relatively well-tolerated, there is the potential for clinical benefit in these patients, and further investigation of this agent is warranted.

Safety of Bifidobacterium animalis subsp. lactis (B. lactis) strain BB-12-supplemented yogurt in healthy adults on antibiotics: a phase I safety study.

Probiotics are live microorganisms that, when administered in sufficient doses, provide health benefits on the host. The United States Food and Drug Administration (FDA) requires phase I safety studies for probiotics when the intended use of the product is as a drug. The purpose of the study was to determine the safety of Bifidobacterium animalis subsp lactis (B. lactis) strain BB-12 (BB-12)-supplemented yogurt when consumed by a generally healthy group of adults who were prescribed a 10-day course of antibiotics for a respiratory infection. Secondary aims were to assess the ability of BB-12 to affect the expression of whole blood immune markers associated with cell activation and inflammatory response. A phase I, double-blinded, randomized controlled study was conducted in compliance with FDA guidelines for an Investigational New Drug (IND). Forty participants were randomly assigned to consume 4 ounces of either BB-12 -supplemented yogurt or non-supplemented control yogurt daily for 10 d. The primary outcome was to assess safety and tolerability, assessed by the number of reported adverse events. A total of 165 non-serious adverse events were reported, with no differences between the control and BB-12 groups. When compared to the control group, B lactis fecal levels were modestly higher in the BB-12-supplemented group. In a small subset of patients, changes in whole blood expression of genes associated with regulation and activation of immune cells were detected in the BB-12-supplemented group. BB-12-supplemented yogurt is safe and well tolerated when consumed by healthy adults concurrently taking antibiotics. This study will form the basis for future randomized clinical trials investigating the potential immunomodulatory effects of BB-12-supplemented yogurt in a variety of disease states.