Study protocol for a non-inferiority randomised controlled trial of SKY breathing meditation versus cognitive processing therapy for PTSD among veterans

Introduction Post-traumatic stress disorder (PTSD) is a debilitating, highly prevalent condition. Current clinical practice guidelines recommend trauma-focused psychotherapy (eg, cognitive processing therapy; CPT) as the first-line treatment for PTSD. However, while these treatments show clinically meaningful symptom improvement, the majority of those who begin treatment retain a diagnosis of PTSD post-treatment. Perhaps for this reason, many individuals with PTSD have sought more holistic, mind–body, complementary and integrative health (CIH) interventions. However, there remains a paucity of high-quality, active controlled efficacy studies of CIH interventions for PTSD, which precludes their formal recommendation. Methods and analyses We present the protocol for an ongoing non-inferiority parallel group randomised controlled trial (RCT) comparing the efficacy of a breathing meditation intervention (Sudarshan Kriya Yoga [SKY]) to a recommended evidence-based psychotherapy (CPT) for PTSD among veterans. Assessors are blinded to treatment group. The primary outcome measure is the PTSD Checklist-Civilian Version and a combination of clinical, self-report, experimental and physiological outcome measures assess treatment-related changes across each of the four PTSD symptom clusters (re-experiencing, avoidance, negative cognitions or mood and hyperarousal/reactivity). Once the RCT is completed, analyses will use both an intent-to-treat (using the ‘last observation carried forward’ for missing data) and a per-protocol or ‘treatment completers’ procedure, which is the most rigorous approach to non-inferiority designs. Ethics and dissemination To the best of our knowledge, this is this first non-inferiority RCT of SKY versus CPT for PTSD among veterans. The protocol is approved by the Stanford University Institutional Review Board. All participants provided written informed consent prior to participation. Results from this RCT will inform future studies including larger multi-site efficacy RCTs of SKY for PTSD and other mental health conditions, as well as exploration of cost-effectiveness and evaluation of implementation issues. Results will also inform evidence-based formal recommendations regarding CIH interventions for PTSD

Emotion dysregulation and heart rate variability improve in US veterans undergoing treatment for posttraumatic stress disorder: Secondary exploratory analyses from a randomised controlled trial

Background Emotion regulation (ER) is a key process underlying posttraumatic stress disorder (PTSD), yet, little is known about how ER changes with PTSD treatment. Understanding these effects may shed light on treatment processes. Methods We recently completed a non-inferiority design randomised controlled trial demonstrating that a breathing-based yoga practice (Sudarshan kriya yoga; SKY) was not clinically inferior to cognitive processing therapy (CPT) across symptoms of PTSD, depression, or negative affect. Here, in secondary exploratory analyses (intent-to-treat N = 85; per protocol N = 59), we examined whether self-reported ER (Difficulties in Emotion Regulation Scale; DERS) and physiological ER (heart rate variability; HRV) improved with treatment for clinically significant PTSD symptoms among US Veterans. Results DERS-Total and all six subscales improved with small-to-moderate effect sizes (d = .24–.66) following CPT or SKY, with no differences between treatment groups. Following SKY (but not CPT), HR max–min (average difference between maximum and minimum beats per minute), LF/HF (low-to-high frequency) ratio, and normalised HF-HRV (high frequency power) improved (moved towards a healthier profile; d = .42–.55). Conclusions To our knowledge, this is the first study to demonstrate that a breathing-based yoga (SKY) improved both voluntary/intentional and automatic/physiological ER. In contrast, trauma-focused therapy (CPT) only reliably improved self-reported ER. Findings have implications for PTSD treatment and interventions for emotional disorders more broadly. Trial registration Secondary analyses of ClinicalTrials.gov NCT02366403

Randomised clinical non-inferiority trial of breathing-based meditation and cognitive processing therapy for symptoms of post-traumatic stress disorder in military veterans

Objective Test whether Sudarshan Kriya Yoga (SKY) was non-inferior to cognitive processing therapy (CPT) for treating symptoms of post-traumatic stress disorder (PTSD) among veterans via a parallel randomised controlled non-inferiority trial. Setting Outpatient Veterans Affairs healthcare centre. Participants 85 veterans (75 men, 61% white, mean age 56.9) with symptoms of PTSD participated between October 2015 and March 2020: 59 participants completed the study. Interventions SKY emphasises breathing routines and was delivered in group format in a 15-hour workshop followed by two 1-hour sessions per week for 5 weeks. CPT is an individual psychotherapy which emphasises shifting cognitive appraisals and was delivered in two 1-hour sessions per week for 6 weeks. Measures The primary outcome measure was the PTSD Checklist-Civilian Version (PCL-C). The secondary measures were the Beck Depression Inventory-II (BDI-II) and Positive and Negative Affect Scale (PANAS). Results Mean PCL-C at baseline was 56.5 (±12.6). Intent-to-treat analyses showed that PCL-C scores were reduced at 6 weeks (end of treatment) relative to baseline (SKY, −5.6, d=0.41, n=41: CPT, −6.8, d=0.58, n=44). The between-treatment difference in change scores was within the non-inferiority margin of 10 points (−1.2, 95% CI −5.7 to 3.3), suggesting SKY was not inferior to CPT. SKY was also non-inferior at 1-month (CPT–SKY: −2.1, 95% CI −6.9 to 2.8) and 1-year (CPT–SKY: −1.8, 95% CI −6.6 to 2.9) assessments. SKY was also non-inferior to CPT on the BDI-II and PANAS at end of treatment and 1 month, but SKY was inferior to CPT on both BDI-II and PANAS at 1 year. Dropout rates were similar (SKY, 27%, CPT, 34%: OR=1.36, 95% CI 0.51 to 3.62, p=0.54). Conclusions SKY may be non-inferior to CPT for treating symptoms of PTSD and merits further consideration as a treatment for PTSD

Linking NHS data for pediatric pharmacovigilance: Results of a Delphi survey

Background: Adverse drug events are a major cause of patient safety incidents. Current systems of pharmacovigilance under-report adverse drug reactions (ADRs), especially in children, leading to delays in their identification. This is of particular concern, as children especially have an increased vulnerability toADRs. Objectives: The objective was to seek consensus among healthcare professionals (HCPs) about barriers and facilitators to the linkage of routinely collected health data for pediatric pharmacovigilance in Scotland. Methods: A Delphi survey was conducted with a random sample of HCPs including nurses, pharmacists and doctors, working in primary or secondary care, in Scotland. Participants were identified from sampling frames of the target professionals such as an NHS workforce list for general practitioners and recruited by postal invitation. A total of 819 HCPs were invited to take part. Those agreeing to participate were given the option of completing the questionnaires online or as hard copy. Reminders were sent twice at a fortnightly interval. Questions content included description of professional role as well as testing for the willingness to support the proposed project and was informed by the Theoretical Domains Framework of Behavior Change (TDF) and earlier qualitative work. Three Delphi rounds were administered, including a first round for item generation. Results: 121 of those invited agreed to take part (15%). The first round of the Delphi study included 21 open questions and generated over a 1000 individual statements from 61 participants that returned the questionnaires (50.4%). These were rationalized to 149 items for the second round in which participants rated their views on the importance (or not) of each item on a 9-point Likert scale (strongly disagree - strongly agree). After the third round, there was consensus on items that focused on professional standards, and practical requirements, overall there was support for data linkage and a multi-professional approach. Conclusions: It would be acceptable to stakeholders to introduce a data linkage system for pharmacovigilance as long as identified concerns are addressed. Concerns included adherence to current professional, legal and ethical standards, as well resolving practical issues

Heterogeneity in blood pressure transitions over the life course: Age-specific emergence of racial/ethnic and sex disparities in the United States

Importance: Many studies have assessed racial/ethnic and sex disparities in the prevalence of elevated blood pressure (BP) from childhood to adulthood, yet few have examined differences in age-specific transitions between categories of BP over the life course in contemporary, multiracial/multiethnic populations. Objective: To estimate age, racial/ethnic, and sex-specific annual net transition probabilities between categories of BP using Markov modeling of cross-sectional data from the National Health and Nutrition Examination Survey. Design, Setting, and Participants: National probability sample (National Health and Nutrition Examination Survey in 2007-2008, 2009-2010, and 2011-2012) of 17 747 African American, white American, and Mexican American participants aged 8 to 80 years. The data were analyzed from September 2014 to November 2015. Main Outcomes and Measures: Age-specific American Heart Association-defined BP categories. Results: Three National Health and Nutrition Examination Survey cross-sectional samples were used to characterize the ages at which self-reported African American (n = 4973), white American (n = 8886), and Mexican American (n = 3888) populations transitioned between ideal BP, prehypertension, and hypertension across the life course. At age 8 years, disparities in the prevalence of ideal BP were observed, with the prevalence being lower among boys (86.6%-88.8%) compared with girls (93.0%-96.3%). From ages 8 to 30 years, annual net transition probabilities from ideal to prehypertension among male individuals were more than 2 times the net transition probabilities of their female counterparts. The largest net transition probabilities for ages 8 to 30 years occurred in African American young men, among whom a net 2.9% (95% CI, 2.3%-3.4%) of those with ideal BP transitioned to prehypertension 1 year later. Mexican American young women aged 8 to 30 years experienced the lowest ideal to prehypertension net transition probabilities (0.6%; 95% CI, 0.3%-0.8%). After age 40 years, ideal to prehypertension net transition probabilities stabilized or decreased (range, 3.0%-4.5%) for men, whereas net transition probabilities for women increased rapidly (range, 2.6%-13.0%). Mexican American women exhibited the largest ideal to prehypertension net transition probabilities after age 60 years. The largest prehypertension to hypertension net transition probabilities occurred at young ages in boys of white race/ethnicity and African Americans, approximately age 8 years and age 25 years, respectively, while net transition probabilities for white women and Mexican Americans increased over the life course. Conclusions and Relevance: Heterogeneity in net transition probabilities from ideal BP emerge during childhood, with associated rapid declines in ideal BP observed in boys and African Americans, thus introducing disparities. Primordial prevention beginning in childhood and into early adulthood is necessary to preempt the development of prehypertension and hypertension, as well as associated racial/ethnic and sex disparities

Erratum: Author Correction: Transitions from Ideal to Intermediate Cholesterol Levels may vary by Cholesterol Metric (Scientific reports (2018) 8 1 (2782))

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper

Transitions from Ideal to Intermediate Cholesterol Levels may vary by Cholesterol Metric

To examine the ability of total cholesterol (TC), a low-density lipoprotein cholesterol (LDL-C) proxy widely used in public health initiatives, to capture important population-level shifts away from ideal and intermediate LDL-C throughout adulthood. We estimated age (≥20 years)-, race/ethnic (Caucasian, African American, and Hispanic/Latino)-, and sex- specific net transition probabilities between ideal, intermediate, and poor TC and LDL-C using National Health and Nutrition Examination Survey (2007–2014; N = 13,584) and Hispanic Community Health Study/Study of Latinos (2008–2011; N = 15,612) data in 2016 and validated and calibrated novel Markov-type models designed for cross-sectional data. At age 20, >80% of participants had ideal TC, whereas the race/ethnic- and sex-specific prevalence of ideal LDL-C ranged from 39.2%-59.6%. Net transition estimates suggested that the largest one-year net shifts away from ideal and intermediate LDL-C occurred approximately two decades earlier than peak net population shifts away from ideal and intermediate TC. Public health and clinical initiatives focused on monitoring TC in middle-adulthood may miss important shifts away from ideal and intermediate LDL-C, potentially increasing the duration, perhaps by decades, that large segments of the population are exposed to suboptimal LDL-C

Observation of a Narrow Resonance of Mass 2.46 GeV/c^2 Decaying to D_s^*+ pi^0 and Confirmation of the D_sJ^* (2317) State

Using 13.5 inverse fb of e+e- annihilation data collected with the CLEO II detector we have observed a narrow resonance in the Ds*+pi0 final state, with a mass near 2.46 GeV. The search for such a state was motivated by the recent discovery by the BaBar Collaboration of a narrow state at 2.32 GeV, the DsJ*(2317)+ that decays to Ds+pi0. Reconstructing the Ds+pi0 and Ds*+pi0 final states in CLEO data, we observe peaks in both of the corresponding reconstructed mass difference distributions, dM(Dspi0)=M(Dspi0)-M(Ds) and dM(Ds*pi0)=M(Ds*pi0)-M(Ds*), both of them at values near 350 MeV. We interpret these peaks as signatures of two distinct states, the DsJ*(2317)+ plus a new state, designated as the DsJ(2463)+. Because of the similar dM values, each of these states represents a source of background for the other if photons are lost, ignored or added. A quantitative accounting of these reflections confirms that both states exist. We have measured the mean mass differences = 350.0 +/- 1.2 [stat] +/- 1.0 [syst] MeV for the DsJ*(2317) state, and = 351.2 +/- 1.7 [stat] +/- 1.0 [syst] MeV for the new DsJ(2463)+ state. We have also searched, but find no evidence, for decays of the two states via the channels Ds*+gamma, Ds+gamma, and Ds+pi+pi-. The observations of the two states at 2.32 and 2.46 GeV, in the Ds+pi0 and Ds*+pi0 decay channels respectively, are consistent with their interpretations as (c anti-strange) mesons with orbital angular momentum L=1, and spin-parities of 0+ and 1+.Comment: 16 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, version to be published in Physical Review D; minor modifications and fixes to typographical errors, plus an added section on production properties. The main results are unchanged; they supersede those reported in hep-ex/030501

Measurement of the Charge Asymmetry in B→K∗(892)±π∓B\to K^* (892)^{\pm}\pi^{\mp}

We report on a search for a CP-violating asymmetry in the charmless hadronic decay B -> K*(892)+- pi-+, using 9.12 fb^-1 of integrated luminosity produced at \sqrt{s}=10.58 GeV and collected with the CLEO detector. We find A_{CP}(B -> K*(892)+- pi-+) = 0.26+0.33-0.34(stat.)+0.10-0.08(syst.), giving an allowed interval of [-0.31,0.78] at the 90% confidence level.Comment: 7 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PR

Study of the q^2-Dependence of B --> pi ell nu and B --> rho(omega)ell nu Decay and Extraction of |V_ub|

We report on determinations of |Vub| resulting from studies of the branching fraction and q^2 distributions in exclusive semileptonic B decays that proceed via the b->u transition. Our data set consists of the 9.7x10^6 BBbar meson pairs collected at the Y(4S) resonance with the CLEO II detector. We measure B(B0 -> pi- l+ nu) = (1.33 +- 0.18 +- 0.11 +- 0.01 +- 0.07)x10^{-4} and B(B0 -> rho- l+ nu) = (2.17 +- 0.34 +0.47/-0.54 +- 0.41 +- 0.01)x10^{-4}, where the errors are statistical, experimental systematic, systematic due to residual form-factor uncertainties in the signal, and systematic due to residual form-factor uncertainties in the cross-feed modes, respectively. We also find B(B+ -> eta l+ nu) = (0.84 +- 0.31 +- 0.16 +- 0.09)x10^{-4}, consistent with what is expected from the B -> pi l nu mode and quark model symmetries. We extract |Vub| using Light-Cone Sum Rules (LCSR) for 0<= q^2<16 GeV^2 and Lattice QCD (LQCD) for 16 GeV^2 <= q^2 < q^2_max. Combining both intervals yields |Vub| = (3.24 +- 0.22 +- 0.13 +0.55/-0.39 +- 0.09)x10^{-3}$ for pi l nu, and |Vub| = (3.00 +- 0.21 +0.29/-0.35 +0.49/-0.38 +-0.28)x10^{-3} for rho l nu, where the errors are statistical, experimental systematic, theoretical, and signal form-factor shape, respectively. Our combined value from both decay modes is |Vub| = (3.17 +- 0.17 +0.16/-0.17 +0.53/-0.39 +-0.03)x10^{-3}.Comment: 45 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PR