Benson-Henry Institute

Importance: Personalized treatment choices would increase the effectiveness of internet-based cognitive behavioral therapy (iCBT) for depression to the extent that patients differ in interventions that better suit them. Objective: To provide personalized estimates of short-term and long-term relative efficacy of guided and unguided iCBT for depression using patient-level information. Data Sources: We searched PubMed, Embase, PsycInfo, and Cochrane Library to identify randomized clinical trials (RCTs) published up to January 1, 2019. Study Selection: Eligible RCTs were those comparing guided or unguided iCBT against each other or against any control intervention in individuals with depression. Available individual patient data (IPD) was collected from all eligible studies. Depression symptom severity was assessed after treatment, 6 months, and 12 months after randomization. Data Extraction and Synthesis: We conducted a systematic review and IPD network meta-analysis and estimated relative treatment effect sizes across different patient characteristics through IPD network meta-regression. Main Outcomes and Measures: Patient Health Questionnaire-9 (PHQ-9) scores. Results: Of 42 eligible RCTs, 39 studies comprising 9751 participants with depression contributed IPD to the IPD network meta-analysis, of which 8107 IPD were synthesized. Overall, both guided and unguided iCBT were associated with more effectiveness as measured by PHQ-9 scores than control treatments over the short term and the long term. Guided iCBT was associated with more effectiveness than unguided iCBT (mean difference [MD] in posttreatment PHQ-9 scores, -0.8; 95% CI, -1.4 to -0.2), but we found no evidence of a difference at 6 or 12 months following randomization. Baseline depression was found to be the most important modifier of the relative association for efficacy of guided vs unguided iCBT. Differences between unguided and guided iCBT in people with baseline symptoms of subthreshold depression (PHQ-9 scores 5-9) were small, while guided iCBT was associated with overall better outcomes in patients with baseline PHQ-9 greater than 9. Conclusions and Relevance: In this network meta-analysis with IPD, guided iCBT was associated with more effectiveness than unguided iCBT for individuals with depression, benefits were more substantial in individuals with moderate to severe depression. Unguided iCBT was associated with similar effectiveness among individuals with symptoms of mild/subthreshold depression. Personalized treatment selection is entirely possible and necessary to ensure the best allocation of treatment resources for depression.

Over the past 24 years, the authors have implanted >870 massive frozen cadaveric allografts mostly for the treatment of defects created by the resection of a bone tumor. Most of the grafts were obtained from the authors' institutional bone bank. The results show that only stage and type of graft affected outcome predictably. Specifically, grafts for a Stage 2 or Stage 3 tumor had a poorer outcome than those for Stages 0 and 1. The results for allograft arthrodeses were considerably poorer than osteoarticular, intercalary, and allograft plus prosthesis. The other major factors in results were complications--recurrence, infection, fracture, and nonunion--with the former 2 having a profound negative effect on outcome. After the first year of susceptibility to infection (10%) and the third year of increased risk of fracture (19%), the grafts become stable, and approximately 75% are retained by patients and are considered to be successful for >20 years after implantation. Osteoarthritis becomes a problem at approximately 6 years for osteoarticular grafts, and so far, 16% of the patients with distal femoral, proximal tibial, or proximal femoral grafts have required total joint replacements. Although the current results are adequate, they are imperfect, and research should be directed at improving the results.

Stress has significant adverse effects on health and is a risk factor for many illnesses. Neurobiological studies have implicated the amygdala as a brain structure crucial in stress responses. Whereas hyperactive amygdala function is often observed during stress conditions, cross-sectional reports of differences in gray matter structure have been less consistent. We conducted a longitudinal MRI study to investigate the relationship between changes in perceived stress with changes in amygdala gray matter density following a stress-reduction intervention. Stressed but otherwise healthy individuals (N = 26) participated in an 8-week mindfulness-based stress reduction intervention. Perceived stress was rated on the perceived stress scale (PSS) and anatomical MR images were acquired pre- and post-intervention. PSS change was used as the predictive regressor for changes in gray matter density within the bilateral amygdalae. Following the intervention, participants reported significantly reduced perceived stress. Reductions in perceived stress correlated positively with decreases in right basolateral amygdala gray matter density. Whereas prior studies found gray matter modifications resulting from acquisition of abstract information, motor and language skills, this study demonstrates that neuroplastic changes are associated with improvements in a psychological state variable.

BACKGROUND: Mindfulness-based therapies are being used in a wide range of common chronic conditions in both treatment and prevention despite lack of consensus about their effectiveness in different patient categories. OBJECTIVE: To systematically review the evidence of effectiveness MBSR and MBCT in different patient categories. METHODS: A systematic review and meta-analysis of systematic reviews of RCTs, using the standardized MBSR or MBCT programs. We used PRISMA guidelines to assess the quality of the included reviews and performed a random effects meta-analysis with main outcome measure Cohen's d. All types of participants were considered. RESULTS: The search produced 187 reviews: 23 were included, covering 115 unique RCTs and 8,683 unique individuals with various conditions. Compared to wait list control and compared to treatment as usual, MBSR and MBCT significantly improved depressive symptoms (d=0.37; 95%CI 0.28 to 0.45, based on 5 reviews, N=2814), anxiety (d=0.49; 95%CI 0.37 to 0.61, based on 4 reviews, N=2525), stress (d=0.51; 95%CI 0.36 to 0.67, based on 2 reviews, N=1570), quality of life (d=0.39; 95%CI 0.08 to 0.70, based on 2 reviews, N=511) and physical functioning (d=0.27; 95%CI 0.12 to 0.42, based on 3 reviews, N=1015). Limitations include heterogeneity within patient categories, risk of publication bias and limited long-term follow-up in several studies. CONCLUSION: The evidence supports the use of MBSR and MBCT to alleviate symptoms, both mental and physical, in the adjunct treatment of cancer, cardiovascular disease, chronic pain, depression, anxiety disorders and in prevention in healthy adults and children.

BACKGROUND: Burnout is characterized by physical and emotional exhaustion from long-term exposure to emotionally demanding work. Burnout affects interpersonal skills, job performance, career satisfaction, and psychological health. However, little is known about the burden of burnout among healthcare providers in sub-Saharan Africa. METHODS: Relevant articles were identified through a systematic review of PubMed, Web of Science (Thomson Reuters), and PsycINFO (EBSCO). Studies were selected for inclusion if they examined a quantitative measure of burnout among healthcare providers in sub-Saharan Africa. RESULTS: A total of 65 articles met our inclusion criteria for this systematic review. Previous studies have examined burnout in sub-Saharan Africa among physicians (N = 12 articles), nurses (N = 26), combined populations of healthcare providers (N = 18), midwives (N = 2), and medical or nursing students (N = 7). The majority of studies assessed burnout using the Maslach Burnout Inventory. The highest levels of burnout were reported among nurses, although all healthcare providers showed high burnout. Burnout among healthcare providers is associated with their work environments, interpersonal and professional conflicts, emotional distress, and low social support. CONCLUSIONS: Available studies on this topic are limited by several methodological challenges. More rigorously designed epidemiologic studies of burnout among healthcare providers are warranted. Health infrastructure improvements will eventually be essential, though difficult to achieve, in under-resourced settings. Programs aimed at raising awareness and coping with burnout symptoms through stress management and resilience enhancement trainings are also needed.

The relaxation response (RR) is the counterpart of the stress response. Millennia-old practices evoking the RR include meditation, yoga and repetitive prayer. Although RR elicitation is an effective therapeutic intervention that counteracts the adverse clinical effects of stress in disorders including hypertension, anxiety, insomnia and aging, the underlying molecular mechanisms that explain these clinical benefits remain undetermined. To assess rapid time-dependent (temporal) genomic changes during one session of RR practice among healthy practitioners with years of RR practice and also in novices before and after 8 weeks of RR training, we measured the transcriptome in peripheral blood prior to, immediately after, and 15 minutes after listening to an RR-eliciting or a health education CD. Both short-term and long-term practitioners evoked significant temporal gene expression changes with greater significance in the latter as compared to novices. RR practice enhanced expression of genes associated with energy metabolism, mitochondrial function, insulin secretion and telomere maintenance, and reduced expression of genes linked to inflammatory response and stress-related pathways. Interactive network analyses of RR-affected pathways identified mitochondrial ATP synthase and insulin (INS) as top upregulated critical molecules (focus hubs) and NF-κB pathway genes as top downregulated focus hubs. Our results for the first time indicate that RR elicitation, particularly after long-term practice, may evoke its downstream health benefits by improving mitochondrial energy production and utilization and thus promoting mitochondrial resiliency through upregulation of ATPase and insulin function. Mitochondrial resiliency might also be promoted by RR-induced downregulation of NF-κB-associated upstream and downstream targets that mitigates stress.

Background: The aims of this study were to (1) estimate the prevalence of clinical depression and posttraumatic stress disorder (PTSD) one to two months (Time 1) and five to eight months (Time 2) after musculoskeletal trauma and (2) determine the cross-sectional and longitudinal relationship of psychological variables (depression, PTSD, catastrophic thinking, and pain anxiety) at Time 1 to musculoskeletal disability and pain intensity at Time 1 and Time 2, after accounting for injury characteristics and demographic variables. Methods: Patients with one or more fractures that had been treated operatively completed measures of depression, PTSD, pain anxiety, catastrophic thinking, musculoskeletal disability (the Short Musculoskeletal Function Assessment [SMFA]), and pain (the Numerical Rating Scale) at rest and during activity at Time 1 (152 patients) and at Time 2 (136 patients). Additional explanatory variables included injury severity, use of opioid pain medication at Time 1, and multiple or single injuries. Results: The screening criteria for an estimated diagnosis of clinical depression were met by thirty-five of the 152 patients at Time 1, and twenty-nine of the 136 patients at Time 2. Screening criteria for an estimated diagnosis of PTSD were met by forty-three of the 152 patients at Time 1 and twenty-five of the 136 patients at Time 2. Cross-sectional hierarchical linear regression models that included multiple injuries, scores of the Abbreviated Injury Scale, and self-reported opioid use explained between 24% and 29% of the variance in pain and disability, respectively, at Time 1. After the addition of psychological variables, the model explained between 49% and 55% of the variance. Catastrophic thinking (as measured with use of the Pain Catastrophizing Scale) at Time 1 was the sole significant predictor of pain at rest, pain during activity, and disability (as measured with use of the SMFA) at Time 2. Conclusions: We found that psychological factors that are responsive to cognitive behavioral therapy—catastrophic thinking, in particular—are strongly associated with pain intensity and disability in patients recovering from musculoskeletal trauma. Level of Evidence: Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence. Peer Review: This article was reviewed by the Editor-in-Chief and one Deputy Editor, and it underwent blinded review by two or more outside experts. It was also reviewed by an expert in methodology and statistics. The Deputy Editor reviewed each revision of the article, and it underwent a final review by the Editor-in-Chief prior to publication. Final corrections and clarifications occurred during one or more exchanges between the author(s) and copyeditors.

BACKGROUND: Mind-body practices that elicit the relaxation response (RR) have been used worldwide for millennia to prevent and treat disease. The RR is characterized by decreased oxygen consumption, increased exhaled nitric oxide, and reduced psychological distress. It is believed to be the counterpart of the stress response that exhibits a distinct pattern of physiology and transcriptional profile. We hypothesized that RR elicitation results in characteristic gene expression changes that can be used to measure physiological responses elicited by the RR in an unbiased fashion. METHODS/PRINCIPAL FINDINGS: We assessed whole blood transcriptional profiles in 19 healthy, long-term practitioners of daily RR practice (group M), 19 healthy controls (group N(1)), and 20 N(1) individuals who completed 8 weeks of RR training (group N(2)). 2209 genes were differentially expressed in group M relative to group N(1) (p<0.05) and 1561 genes in group N(2) compared to group N(1) (p<0.05). Importantly, 433 (p<10(-10)) of 2209 and 1561 differentially expressed genes were shared among long-term (M) and short-term practitioners (N(2)). Gene ontology and gene set enrichment analyses revealed significant alterations in cellular metabolism, oxidative phosphorylation, generation of reactive oxygen species and response to oxidative stress in long-term and short-term practitioners of daily RR practice that may counteract cellular damage related to chronic psychological stress. A significant number of genes and pathways were confirmed in an independent validation set containing 5 N(1) controls, 5 N(2) short-term and 6 M long-term practitioners. CONCLUSIONS/SIGNIFICANCE: This study provides the first compelling evidence that the RR elicits specific gene expression changes in short-term and long-term practitioners. Our results suggest consistent and constitutive changes in gene expression resulting from RR may relate to long term physiological effects. Our study may stimulate new investigations into applying transcriptional profiling for accurately measuring RR and stress related responses in multiple disease settings.

BACKGROUND: Burnout is a syndrome characterized by emotional exhaustion, increased depersonalization, and a diminished sense of personal accomplishment due to chronic emotional stress at work. Burnout impacts job satisfaction, job performance, vulnerability to illnesses, and interpersonal relationships. There is a gap in the systematic data on the burden of burnout among healthcare professionals from different sectors of healthcare in Middle Eastern countries. Our objective was to examine the burden of burnout among healthcare providers in the Middle East, how it was assessed, which sectors were included, and what interventions have been used. METHODS: Articles were found through a systematic review of search results including PubMed, Web of Science (Thomson Reuters), and PsycINFO (EBSCO) using search terms reflecting burnout in Middle Eastern countries among populations of healthcare providers. Studies were included if they examined a quantitative measure of burnout among healthcare providers in the Middle East. RESULTS: There were 138 articles that met our inclusion criteria for this systematic review. Studies focused on burnout in the Middle East among physicians (N = 54 articles), nurses (N = 55), combined populations of healthcare workers (N = 22), and medical students (N = 7). The Maslach Burnout Inventory was the most common tool to measure burnout. Burnout is common among physicians, nurses, and other healthcare professionals, with prevalence estimates predominantly ranging between 40 and 60%. Burnout among healthcare providers in the Middle East is associated with characteristics of their work environments, exposure to violence and terror, and emotional distress and low social support. CONCLUSIONS: Burnout is highly prevalent among healthcare providers across countries in the Middle East. Previous studies examining burnout in this region have limitations in their methodology. More thoroughly developed epidemiologic studies of burnout are necessary. Health system strengthening is needed in a region that has endured years of ongoing conflict, and there is an urgency to design and implement programs that tackle burnout among health professionals.

Naturally occurring human genetic variants that are predicted to inactivate protein-coding genes provide an in vivo model of human gene inactivation that complements knockout studies in cells and model organisms. Here we report three key findings regarding the assessment of candidate drug targets using human loss-of-function variants. First, even essential genes, in which loss-of-function variants are not tolerated, can be highly successful as targets of inhibitory drugs. Second, in most genes, loss-of-function variants are sufficiently rare that genotype-based ascertainment of homozygous or compound heterozygous 'knockout' humans will await sample sizes that are approximately 1,000 times those presently available, unless recruitment focuses on consanguineous individuals. Third, automated variant annotation and filtering are powerful, but manual curation remains crucial for removing artefacts, and is a prerequisite for recall-by-genotype efforts. Our results provide a roadmap for human knockout studies and should guide the interpretation of loss-of-function variants in drug development.

OBJECTIVE: To determine whether individuals with situs inversus totalis (SI), a condition in which there is a mirror-image reversal of asymmetric visceral organs, have alterations in brain asymmetries. BACKGROUND: The human brain is asymmetric in structure and function. Although correlations between anatomic asymmetries and functional lateralization in human brain have been demonstrated, it has been difficult to further analyze them. Characterization of asymmetries of brain structure and function in SI might advance the understanding of these relationships. METHODS: Using anatomic and functional MRI techniques, we analyzed asymmetries in the brains of three individuals with SI. RESULTS: Two major anatomic asymmetries of the cerebral hemispheres, the frontal and occipital petalia, were reversed in individuals with SI. In contrast, SI subjects had left cerebral hemisphere language dominance on functional MRI analysis as well as strong right-handedness. CONCLUSION: These observations suggest that the developmental factors determining anatomic asymmetry of the cerebral petalia and viscera are distinct from those producing the functional lateralization of language.

The management of depression and other negative psychological states in cardiac patients has been a focus of multiple treatment trials, though such trials have not led to substantial improvements in cardiac outcomes. In contrast, there has been minimal focus on interventions to increase positive psychological states in cardiac patients, despite the fact that optimism and other positive states have been associated with superior cardiovascular outcomes. Our objective was to develop an 8-week, phone-based positive psychology intervention for patients hospitalized with acute cardiac disease (acute coronary syndrome or decompensated heart failure). Such an intervention would consist of positive psychology exercises adapted for this specific population, and it would need to be feasible for practitioners and patients in real-world settings. By adapting exercises that were previously validated in healthy individuals, we were able to generate a positive psychology telemedicine intervention for cardiac patients that focused on optimism, kindness, and gratitude. In addition, we successfully created a companion treatment manual for subjects to enhance the educational aspects of the intervention and facilitate completion of exercises. Finally, we successfully performed a small pilot trial of this intervention, and found that the positive psychology intervention appeared to be feasible and well-accepted in a cohort of patients with acute cardiac illness. Future studies should further develop this promising intervention and examine its impact on psychological and medical outcomes in this vulnerable population of cardiac patients.

#### Summary points Generalized anxiety disorder (GAD) is relatively common, with lifetime prevalence rates of 4-7%. It is a disorder of chronic uncontrollable worry, compounded by physiological symptoms such as disturbed sleep, muscle tension, and difficulty concentrating. The disorder is associated with seriously impaired social and occupational functioning, comorbidity with other disorders, and increased risk for suicide.1 GAD can go undiagnosed because of a focus on physical symptoms and because of the stigma of mental illness. However, the disorder can be treated. This article reviews current knowledge about the diagnosis and treatment of GAD, including pharmacotherapy and psychosocial therapies. #### Sources and selection criteria We based this review on articles found by searching PubMed and the Cochrane Database of Systematic Reviews using the terms “generalized anxiety disorder” and “generalised anxiety disorder”. Our search was limited to English language articles published between 2005 and 2012. Meta-analyses, reviews, and randomised controlled trials were prioritized. GAD is characterized by excessive worry and symptoms of physiological arousal such as restlessness, insomnia, and muscle tension (box). To meet Diagnostic and Statistical Manual of Mental Disorders , fourth edition (DSM-IV) criteria for the disorder, the patient must have excessive and difficult to control anxiety about several different events or activities.2 For example, anxiety confined to concern about personal safety would not qualify (but should elicit inquiries about symptoms of post-traumatic stress disorder or agoraphobia, for example). In addition to worry, patients must have at least three of the six physiological arousal symptoms listed in the box. …

BACKGROUND: Very little is known about herbal and dietary supplement disclosure in adults with chronic medical conditions, especially on a national level. OBJECTIVE: To examine herbal and dietary supplement disclosure to conventional health care providers by adults with chronic medical conditions. DESIGN: Data on herbal and dietary supplement use (N = 5456 users) in the previous year were used from the 2002 National Health Interview Survey. Bi-variable analyses compared characteristics between herbal and dietary supplement disclosers and nondisclosers. Multivariable logistic regression identified independent correlates of herbal and dietary supplement disclosure. RESULTS: Overall, only 33% of herbal and dietary supplement users reported disclosing use of herbal and dietary supplements to their conventional health care provider. Among herbal and dietary supplement users with chronic conditions, less than 51% disclosed use to their conventional health care provider. Hispanic (adjusted odds ratio and 95% confidence interval = 0.70 [0.52, 0.94]) and Asian American (adjusted odds ratio and 95% confidence interval = 0.54 [0.33, 0.89]) adults were much less likely than non-Hispanic white Americans to disclose herbal and dietary supplement use. Having less than a high school education (adjusted odds ratio and 95% confidence interval = 0.61 [0.45, 0.82]) and not having insurance (adjusted odds ratio and 95% confidence interval = 0.77 [0.59, 1.00]) were associated with being less likely to disclose herbal and dietary supplement use. CONCLUSION: Herbal and dietary supplement disclosure rates are low, even among adults with chronic conditions. These findings raise concerns about the safety of herbal and dietary supplements in combination with allopathic care. Future studies should focus on educating physicians about crosscultural care as well as eliciting information about herbal and dietary supplement use.

We are excited to present the abstracts of the keynote speakers, parallel sessions and oral and poster presentations of the World Congress on

OBJECTIVES: The study objectives were to develop and objectively assess the therapeutic effect of a novel movement-based complementary and alternative medicine approach for children with an autism-spectrum disorder (ASD). DESIGN: A within-subject analysis comparing pre- to post-treatment scores on two standard measures of childhood behavioral problems was used. SETTINGS AND LOCATION: The intervention and data analysis occurred at a tertiary care, medical school teaching hospital. SUBJECTS: Twenty-four (24) children aged 3-16 years with a diagnosis of an ASD comprised the study group. INTERVENTION: The efficacy of an 8-week multimodal yoga, dance, and music therapy program based on the relaxation response (RR) was developed and examined. OUTCOME MEASURES: The study outcome was measured using The Behavioral Assessment System for Children, Second Edition (BASC-2) and the Aberrant Behavioral Checklist (ABC). RESULTS: Robust changes were found on the BASC-2, primarily for 5-12-year-old children. Unexpectedly, the post-treatment scores on the Atypicality scale of the BASC-2, which measures some of the core features of autism, changed significantly (p=0.003). CONCLUSIONS: A movement-based, modified RR program, involving yoga and dance, showed efficacy in treating behavioral and some core features of autism, particularly for latency-age children.

BACKGROUND: Poor psychological and physical resilience in response to stress drives a great deal of health care utilization. Mind-body interventions can reduce stress and build resiliency. The rationale for this study is therefore to estimate the effect of mind-body interventions on healthcare utilization. OBJECTIVE: Estimate the effect of mind body training, specifically, the Relaxation Response Resiliency Program (3RP) on healthcare utilization. DESIGN: Retrospective controlled cohort observational study. SETTING: Major US Academic Health Network. SAMPLE: All patients receiving 3RP at the MGH Benson-Henry Institute from 1/12/2006 to 7/1/2014 (n = 4452), controls (n = 13149) followed for a median of 4.2 years (.85-8.4 yrs). MEASUREMENTS: Utilization as measured by billable encounters/year (be/yr) stratified by encounter type: clinical, imaging, laboratory and procedural, by class of chief complaint: e.g., Cardiovascular, and by site of care delivery, e.g., Emergency Department. Subgroup analysis by propensity score matched pre-intervention utilization rate. RESULTS: At one year, total utilization for the intervention group decreased by 43% [53.5 to 30.5 be/yr] (p <0.0001). Clinical encounters decreased by 41.9% [40 to 23.2 be/yr], imaging by 50.3% [11.5 to 5.7 be/yr], lab encounters by 43.5% [9.8 to 5.6], and procedures by 21.4% [2.2 to 1.7 be/yr], all p < 0.01. The intervention group's Emergency department (ED) visits decreased from 3.6 to 1.7/year (p<0.0001) and Hospital and Urgent care visits converged with the controls. Subgroup analysis (identically matched initial utilization rates-Intervention group: high utilizing controls) showed the intervention group significantly reduced utilization relative to the control group by: 18.3% across all functional categories, 24.7% across all site categories and 25.3% across all clinical categories. CONCLUSION: Mind body interventions such as 3RP have the potential to substantially reduce healthcare utilization at relatively low cost and thus can serve as key components in any population health and health care delivery system.

The role of excessive or persistent stress as a major contributor to morbidity and mortality is well recognized. Meditation and other mind–body practices are increasingly popular for their perceived physical and mental health benefits and stress relief.

Importance: Persistent smoking may cause adverse outcomes among patients with cancer. Many cancer centers have not fully implemented evidence-based tobacco treatment into routine care. Objective: To determine the effectiveness of sustained telephone counseling and medication (intensive treatment) compared with shorter-term telephone counseling and medication advice (standard treatment) to assist patients recently diagnosed with cancer to quit smoking. Design, Setting, and Participants: This unblinded randomized clinical trial was conducted at Massachusetts General Hospital/Dana-Farber/Harvard Cancer Center and Memorial Sloan Kettering Cancer Center. Adults who had smoked 1 cigarette or more within 30 days, spoke English or Spanish, and had recently diagnosed breast, gastrointestinal, genitourinary, gynecological, head and neck, lung, lymphoma, or melanoma cancers were eligible. Enrollment occurred between November 2013 and July 2017; assessments were completed by the end of February 2018. Interventions: Participants randomized to the intensive treatment (n = 153) and the standard treatment (n = 150) received 4 weekly telephone counseling sessions and medication advice. The intensive treatment group also received 4 biweekly and 3 monthly telephone counseling sessions and choice of Food and Drug Administration-approved cessation medication (nicotine replacement therapy, bupropion, or varenicline). Main Outcome and Measures: The primary outcome was biochemically confirmed 7-day point prevalence tobacco abstinence at 6-month follow-up. Secondary outcomes were treatment utilization rates. Results: Among 303 patients who were randomized (mean age, 58.3 years; 170 women [56.1%]), 221 (78.1%) completed the trial. Six-month biochemically confirmed quit rates were 34.5% (n = 51 in the intensive treatment group) vs 21.5% (n = 29 in the standard treatment group) (difference, 13.0% [95% CI, 3.0%-23.3%]; odds ratio, 1.92 [95% CI, 1.13-3.27]; P < .02). The median number of counseling sessions completed was 8 (interquartile range, 4-11) in the intensive treatment group. A total of 97 intensive treatment participants (77.0%) vs 68 standard treatment participants (59.1%) reported cessation medication use (difference, 17.9% [95% CI, 6.3%-29.5%]; odds ratio, 2.31 [95% CI, 1.32-4.04]; P = .003). The most common adverse events in the intensive treatment and standard treatment groups, respectively, were nausea (n = 13 and n = 6), rash (n = 4 and n = 1), hiccups (n = 4 and n = 1), mouth irritation (n = 4 and n = 0), difficulty sleeping (n = 3 and n = 2), and vivid dreams (n = 3 and n = 2). Conclusions and Relevance: Among smokers recently diagnosed with cancer in 2 National Cancer Institute-designated Comprehensive Cancer Centers, sustained counseling and provision of free cessation medication compared with 4-week counseling and medication advice resulted in higher 6-month biochemically confirmed quit rates. However, the generalizability of the study findings is uncertain and requires further research. Trial Registration: ClinicalTrials.gov Identifier: NCT01871506.

Isolated systolic hypertension is common in the elderly, but decreasing systolic blood pressure (SBP) without lowering diastolic blood pressure (DBP) remains a therapeutic challenge. Although stress management training, in particular eliciting the relaxation response, reduces essential hypertension its efficacy in treating isolated systolic hypertension has not been evaluated. We conducted a double-blind, randomized trial comparing 8 weeks of stress management, specifically relaxation response training (61 patients), versus lifestyle modification (control, 61 patients). Inclusion criteria were >or=55 years, SBP 140-159 mm Hg, DBP <90 mm Hg, and at least two antihypertensive medications. The primary outcome measure was change in SBP after 8 weeks. Patients who achieved SBP <140 mm Hg and >or=5 mm Hg reduction in SBP were eligible for 8 additional weeks of training with supervised medication elimination. SBP decreased 9.4 (standard deviation [SD] 11.4) and 8.8 (SD 13.0) mm Hg in relaxation response and control groups, respectively (both ps <0.0001) without group difference (p=0.75). DBP decreased 1.5 (SD 6.2) and 2.4 (SD 6.9) mm Hg (p=0.05 and 0.01, respectively) without group difference (p=0.48). Forty-four (44) in the relaxation response group and 36 in the control group were eligible for supervised antihypertensive medication elimination. After controlling for differences in characteristics at the start of medication elimination, patients in the relaxation response group were more likely to successfully eliminate an antihypertensive medication (odds ratio 4.3, 95% confidence interval 1.2-15.9, p=0.03). Although both groups had similar reductions in SBP, significantly more participants in the relaxation response group eliminated an antihypertensive medication while maintaining adequate blood pressure control.