Amit Sood

Stress Management and Resilience Training Among Department of Medicine Faculty: A Pilot Randomized Clinical Trial

BackgroundPhysician distress is common and related to numerous factors involving physicians’ personal and professional lives. The present study was designed to assess the effect of a Stress Management and Resiliency Training (SMART) program for increasing resiliency and quality of life, and decreasing stress and anxiety among Department of Medicine (DOM) physicians at a tertiary care medical center.ParticipantsForty DOM physicians were randomized in a wait-list controlled clinical trial to either the SMART intervention or a wait-list control group for 8 weeks. The intervention involved a single 90 min one-on-one training in the SMART program. Primary outcome measures assessed at baseline and week 8 included the Connor Davidson Resilience Scale (CDRS), Perceived Stress Scale (PSS), Smith Anxiety Scale (SAS) and Linear Analog Self Assessment Scale (LASA).ResultsThirty-two physicians completed the study. A statistically significant improvement in resiliency, perceived stress, anxiety, and overall quality of life at 8 weeks was observed in the study arm compared to the wait-list control arm: CDRS: mean ± SD change from baseline +9.8 ± 9.6 vs. -0.8 ± 8.2, t(30) = 3.18, p = 0.003; PSS: -5.4 ± 8.1 vs. +2.2 ± 6.1, t(30) = -2.76, p = 0.010; SAS: -11.8 ± 12.3 vs.+ 2.9 ± 8.9, t(30) = -3.62, p = 0.001; and LASA: +0.4 ± 1.4 vs. -0.6 ± 1.0, t(30) = 2.29, p = 0.029.ConclusionsA brief training to enhance resilience and decrease stress among physicians using the SMART program was feasible. Further, the intervention provided statistically significant improvement in resilience, stress, anxiety, and overall quality of life. In the future, larger clinical trials with longer follow-up and possibly wider dissemination of this intervention are warranted.

Efficacy of Antioxidant Supplementation in Reducing Primary Cancer Incidence and Mortality : Systematic Review and Meta-analysis

OBJECTIVE To estimate the association between antioxidant use and primary cancer incidence and mortality and to evaluate these effects across specific antioxidant compounds, target organs, and participant subgroups. METHODS Multiple electronic databases (MEDLINE, Cochrane Controlled Clinical Trials Register, EMBASE, Science Citation Index) were searched from their dates of inception until August 2005 to identify eligible randomized clinical trials. Random effects meta-analyses estimated pooled relative risks (RRs) and 95% confidence intervals (CIs) that described the effect of antioxidants vs placebo on cancer incidence and cancer mortality. RESULTS Twelve eligible trials, 9 of high methodological quality, were identified (total subject population, 104,196). Antioxidant supplementation did not significantly reduce total cancer incidence (RR, 0.99; 95% CI, 0.94-1.04) or mortality (RR, 1.03; 95% CI, 0.92-1.15) or any site-specific cancer incidence. Beta carotene supplementation was associated with an increase in the incidence of cancer among smokers (RR, 1.10; 95% CI, 1.03-1.10) and with a trend toward increased cancer mortality (RR, 1.16; 95% CI, 0.98-1.37). Selenium supplementation was associated with reduced cancer incidence in men (RR, 0.77; 95% CI, 0.64-0.92) but not in women (RR, 1.00; 95% CI, 0.89-1.13, value for interaction, P< .001) and with reduced cancer mortality (RR, 0.78; 95% CI, 0.65-0.94). Vitamin E supplementation had no apparent effect on overall cancer incidence (RR, 0.99; 95% CI, 0.94-1.04) or cancer mortality (RR, 1.04; 95% CI, 0.97-1.12). CONCLUSION Beta carotene supplementation appeared to increase cancer incidence and cancer mortality among smokers, whereas vitamin E supplementation had no effect. Selenium supplementation might have anticarcinogenic effects in men and thus requires further research.

Wisconsin Ginseng (Panax quinquefolius) to Improve Cancer-Related Fatigue: A Randomized, Double-Blind Trial, N07C2

BACKGROUND Safe, effective interventions to improve cancer-related fatigue (CRF) are needed because it remains a prevalent, distressing, and activity-limiting symptom. Based on pilot data, a phase III trial was developed to evaluate the efficacy of American ginseng on CRF. METHODS A multisite, double-blind trial randomized fatigued cancer survivors to 2000mg of American ginseng vs a placebo for 8 weeks. The primary endpoint was the general subscale of the Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-SF) at 4 weeks. Changes from baseline at 4 and 8 weeks were evaluated between arms by a two-sided, two-sample t test. Toxicities were evaluated by self-report and the National Cancer Institutes Common Terminology Criteria for Adverse Events (CTCAE) provider grading. RESULTS Three hundred sixty-four participants were enrolled from 40 institutions. Changes from baseline in the general subscale of the MFSI-SF were 14.4 (standard deviation [SD] = 27.1) in the ginseng arm vs 8.2 (SD = 24.8) in the placebo arm at 4 weeks (P = .07). A statistically significant difference was seen at 8 weeks with a change score of 20 (SD = 27) for the ginseng group and 10.3 (SD = 26.1) for the placebo group (P = .003). Greater benefit was reported in patients receiving active cancer treatment vs those who had completed treatment. Toxicities per self-report and CTCAE grading did not differ statistically significantly between arms. CONCLUSIONS Data support the benefit of American ginseng, 2000mg daily, on CRF over an 8-week period. There were no discernible toxicities associated with the treatment. Studies to increase knowledge to guide the role of ginseng to improve CRF are needed.

Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Long-Acting Methylphenidate for Cancer-Related Fatigue: North Central Cancer Treatment Group NCCTG-N05C7 Trial

PURPOSE Fatigue is one of the most common symptoms experienced by patients with cancer. This trial was developed to evaluate the efficacy of long-acting methylphenidate for improving cancer-related fatigue and to assess its toxicities. PATIENTS AND METHODS Adults with cancer were randomly assigned in a double-blinded manner to receive methylphenidate (target dose, 54 mg/d) or placebo for 4 weeks. The Brief Fatigue Inventory was the primary outcome measure, while secondary outcome measures included a Symptom Experience Diary (SED), the Short Form-36 (SF-36) Vitality Subscale, a linear analog self-assessment, the Pittsburgh Sleep Quality Index, and the Subject Global Impression of Change. RESULTS In total, 148 patients were enrolled. Using an area under the serum concentration-time curve analysis, there was no evidence that methylphenidate, as compared with placebo, improved the primary end point of cancer-related fatigue in this patient population (P = .35). Comparisons of secondary end points, including clinically significant changes in quality-of-life variables and cancer-related fatigue change from baseline, were similarly negative. However, a subset analysis suggested that patients with more severe fatigue and/or with more advanced disease did have some fatigue improvement with methylphenidate (eg, in patients with stage III or IV disease, the mean improvement in usual fatigue was 19.7 with methylphenidate v 2.1 with placebo; P = .02). There was a significant difference in self-reported toxicities (SED), with increased levels of nervousness and appetite loss in the methylphenidate arm. CONCLUSION This clinical trial was unable to support the primary prestudy hypothesis that the chosen long-acting methylphenidate product would decrease cancer-related fatigue.

Stress Management and Resilience Training (SMART) Program to Decrease Stress and Enhance Resilience Among Breast Cancer Survivors: A Pilot Randomized Clinical Trial

UNLABELLED This randomized controlled trial assessed the effect of a SMART (Stress Management and Resiliency Training) program among 25 women diagnosed with breast cancer. Resilience, perceived stress, anxiety, and quality of life improved at 12 weeks in the active but not the control arm. A brief training in the SMART program can enhance resilience and quality of life and decrease stress and anxiety. INTRODUCTION Patients with breast cancer experience stress and anxiety related to their diagnosis, with resulting lower quality of life. The purpose of this study was to assess the effect of a SMART (Stress Management and Resiliency Training) program for increasing resiliency and for decreasing stress and anxiety among mentors who themselves were previously diagnosed with breast cancer. MATERIALS AND METHODS The program consisted of two 90-minute group training sessions, a brief individual session, and 3 follow-up telephone calls. Twenty-four mentors at Mayo Clinic in Rochester, Minnesota, were randomized in a single-blind, wait-list controlled clinical trial to either the SMART intervention or a control group for 12 weeks. Primary outcome measures assessed at baseline and at week 12 included the Connor Davidson Resilience Scale, Perceived Stress Scale, Smith Anxiety Scale, and Linear Analog Self Assessment Scale. RESULTS Twenty patients completed the study. A statistically significant improvement in resilience, perceived stress, anxiety, and overall quality of life at 12 weeks, compared with baseline was observed in the study arm. No significant difference in any of these measures was noted in the control group. CONCLUSION This study demonstrates that a brief, predominantly group-based resilience training intervention is feasible in patients with previous breast cancer; also, it may be efficacious.

The efficacy of resiliency training programs: a systematic review and meta-analysis of randomized trials.

Importance Poor mental health places a burden on individuals and populations. Resilient persons are able to adapt to life’s challenges and maintain high quality of life and function. Finding effective strategies to bolster resilience in individuals and populations is of interest to many stakeholders. Objectives To synthesize the evidence for resiliency training programs in improving mental health and capacity in 1) diverse adult populations and 2) persons with chronic diseases. Data Sources Electronic databases, clinical trial registries, and bibliographies. We also contacted study authors and field experts. Study Selection Randomized trials assessing the efficacy of any program intended to enhance resilience in adults and published after 1990. No restrictions were made based on outcome measured or comparator used. Data Extraction and Synthesis Reviewers worked independently and in duplicate to extract study characteristics and data. These were confirmed with authors. We conducted a random effects meta-analysis on available data and tested for interaction in planned subgroups. Main Outcomes The standardized mean difference (SMD) effect of resiliency training programs on 1) resilience/hardiness, 2) quality of life/well-being, 3) self-efficacy/activation, 4) depression, 5) stress, and 6) anxiety. Results We found 25 small trials at moderate to high risk of bias. Interventions varied in format and theoretical approach. Random effects meta-analysis showed a moderate effect of generalized stress-directed programs on enhancing resilience [pooled SMD 0.37 (95% CI 0.18, 0.57) p = .0002; I2 = 41%] within 3 months of follow up. Improvement in other outcomes was favorable to the interventions and reached statistical significance after removing two studies at high risk of bias. Trauma-induced stress-directed programs significantly improved stress [−0.53 (−1.04, −0.03) p = .03; I2 = 73%] and depression [−0.51 (−0.92, −0.10) p = .04; I2 = 61%]. Conclusions We found evidence warranting low confidence that resiliency training programs have a small to moderate effect at improving resilience and other mental health outcomes. Further study is needed to better define the resilience construct and to design interventions specific to it. Registration Number PROSPERO #CRD42014007185

Varenicline and bupropion sustained-release combination therapy for smoking cessation

INTRODUCTION Varenicline and bupropion sustained release (SR) are both safe and effective for the treatment of tobacco dependence and have different mechanisms of action. Combination pharmacotherapy with these agents may increase long-term smoking abstinence rates above what is observed with single-agent therapy. METHODS We enrolled cigarettes smokers in an open-label, one-arm, Phase II clinical trial to obtain preliminary data on the potential effectiveness and safety of combination therapy with varenicline and bupropion SR for the treatment of tobacco dependence. Eligible subjects received varenicline titrated to 1.0 mg by mouth twice daily and bupropion SR titrated to 150 mg by mouth twice daily for a total of 12 weeks along with behavioral therapy. Self-reported smoking abstinence was biochemically confirmed with expired carbon monoxide. A total of 38 smokers with a mean age of 49.1 years (SD = 12.4) who smoked an average of 19.9 cigarettes/day (SD = 7.8) for 30 years (SD = 12.3) were enrolled. RESULTS Seven-day point-prevalent smoking abstinence rates were 71% (95% CI = 54%-85%) at 3 months and 58% (95% CI = 41%-74%) at 6 months. Mean weight change during the medication phase among smoking-abstinent subjects was 1.6 kg (SD = 2.4). For both medications, 74% of subjects took at least 90% of the prescribed doses. The most common side effects were sleep disturbance (26%) and nausea (24%). No increase in depressive symptoms was observed, and no subjects reported suicidal ideation. DISCUSSION Combination therapy with varenicline and bupropion SR may be effective for increasing smoking abstinence rates above that observed with monotherapy.

A critical review of complementary therapies for cancer-related fatigue.

Purpose: To review the available literature on the use of complementary and alternative medicine (CAM) treatments for cancer-related fatigue with an aim to develop directions for future research. Methods: PubMed, EMBASE, CINAHL, PsycINFO, and SPORTDiscus were searched for relevant studies. Original clinical trials reporting on the use of CAM treatments for cancer-related fatigue were abstracted and critically reviewed. Results: CAM interventions tested for cancer-related fatigue include acupuncture, aromatherapy, adenosine triphosphate infusions, energy conservation and activity management, healing touch, hypnosis, lectinstandardized mistletoe extract, levocarnitine, massage, mindfulness-based stress reduction, polarity therapy, relaxation, sleep promotion, support group, and Tibetan yoga. Several of these interventions seem promising in initial studies. Conclusion: Currently, insufficient data exist to recommend any specific CAM modality for cancer-related fatigue. Therefore, potentially effective CAM interventions ready for further study in large, randomized clinical trials (eg, acupuncture, massage, levocarnitine, and the use of mistletoe) should be pursued. Other interventions should be tested in well-designed feasibility and phase II trials.

Efficacy and Safety of Varenicline for Smoking Cessation

Effective treatment of nicotine addiction is essential for reducing the substantial current and predicted morbidity and mortality associated with tobacco smoking. Despite the availability of effective treatments for smoking cessation, such as nicotine replacement therapy and bupropion sustained-release (SR), abstinence rates remain less than optimal. Varenicline is the first in a new class of agents for smoking cessation, the alpha(4)beta(2) nicotinic acetylcholine receptor (nAChR) partial agonists. Nicotine addiction is mediated by stimulation of central alpha(4)beta(2) nAChRs by nicotine, which causes the release of dopamine, ultimately leading to the pleasurable effects of smoking. As a nAChR partial agonist, varenicline attenuates the craving and withdrawal symptoms that occur with abstinence from nicotine and also reduces the rewarding effects of nicotine obtained from smoking in patients who lapse. Thus, varenicline offers a new therapeutic option for the treatment of nicotine addiction. Clinical trials have demonstrated superior efficacy of this agent over placebo and bupropion-SR for achieving abstinence from smoking, and varenicline has also been shown to significantly delay smoking relapse. As the newest agent approved for smoking cessation, the mechanism of action, efficacy, and safety of varenicline.

Use of methylphenidate in patients with cancer

Cancer and its treatment are often associated with symptoms such as depression, somnolence, cognitive abnormalities, and fatigue. Methylphenidate, a stimulant medication, is commonly used to treat these symptoms. Several small pilot and a few adequately powered studies have assessed the safety and efficacy of methylphenidate in patients with cancer. Overall, the studies so far suggest that methylphenidate is well-tolerated in patients with cancer. Further, the studies have provided initial evidence of efficacy of this agent in patients with cancer. The present article reviews the evidence base behind the use of methylphenidate in these patients.