Publications

STUDY OBJECTIVES: Heart rate variability (HRV) measures provide valuable insights into physiology; however, gaps remain in understanding circadian patterns in heart rate dynamics. We aimed to explore day-night differences in heart rate dynamics in patients with chronic cardiopulmonary disease compared with healthy controls.

METHODS: Using 24-hour heart rate data from patients with chronic obstructive pulmonary disease (COPD) and/or heart failure (n = 16) and healthy adult controls (older group: ≥50 years, n = 42; younger group: 20-49 years, n = 136), we compared day-night differences in conventional time and frequency domain HRV indices and a multiscale-entropy-based complexity index (CI1-20) of HRV among the 3 groups.

RESULTS: Twenty-four-hour HRV showed significant day-night differences (marked with "△") among younger healthy (mean age: 34.5 years), older healthy (mean age: 61.6 years), and cardiopulmonary patients (mean age: 68.4 years), including change in percentage of adjacent intervals that differ > 50 ms (△pNN50), high frequency (△HF), normalized low frequency (△nLF), ratio (△LF/HF), and △CI1-20. Among these, △LF/HF (2.13 ± 2.35 vs 1.1 ± 2.47 vs -0.35 ± 1.25; P < .001) and △CI1-20 (0.15 ± 0.24 vs 0.02 ± 0.28 vs -0.21 ± 0.27; P < .001) were significant in each pairwise comparison following analysis of variance tests. Average CI1-20 was highest in younger healthy individuals and lowest in cardiopulmonary patients (1.37 ± 0.12 vs 1.01 ± 0.27; P < .001). Younger healthy patients showed a heart rate complexity dipping pattern (night < day), older healthy patients showed nondipping, and cardiopulmonary patients showed reverse dipping (night > day).

CONCLUSIONS: As measures of 24-hour variability, traditional and complexity-based metrics of HRV exhibit large day-night differences in healthy individuals; these differences are blunted, or even reversed, in individuals with cardiopulmonary pathology. Measures of diurnal dynamics may be useful indices of reduced adaptive capacity in patients with cardiopulmonary conditions.

CITATION: Ma Y, Chang M-C, Litrownik D, Wayne PM, Yeh GY. Day-night patterns in heart rate variability and complexity: differences with age and cardiopulmonary disease. J Clin Sleep Med. 2023;19(5):873-882.

College-aged individuals with anxiety are vulnerable to developing persistent concussion symptoms, yet evidence-based treatments for this population are limited. Understanding these individuals' perspectives is critical for developing effective interventions. We conducted qualitative interviews with 17 college-aged individuals (18-24 years old) with a recent (≤10 weeks) concussion and at least mild anxiety (≥5 on the GAD-7 questionnaire) to understand the life impact of their concussion. We identified 5 themes: (1) disruption to daily activities (e.g., reduced participation in hobbies and physical activity); (2) disruption to relationships (e.g., reduced social engagement, feeling dismissed by others, stigma, and interpersonal friction); (3) disruptions in school/work (e.g., challenges participating due to light sensitivity, cognitive or sleep disturbance, and related emotional distress); (4) changes in view of the self (e.g., feeling "unlike oneself", duller, or more irritable), and (5) finding "silver linings" after the injury (e.g., increased motivation). Concussions impact the lives of college-aged individuals with co-occurring anxiety in a broad range of domains, many of which remain largely neglected in standard concussion clinical assessment and treatment. Assessing and addressing these issues has the potential to limit the negative impact of concussion, promote recovery, and potentially help prevent persistent concussion symptoms in this at-risk population.

BACKGROUND: Multisite musculoskeletal pain is highly prevalent among older adults yet undertreated. Studies support the promise of Tai Chi for managing pain and lowering fall risk. Since the COVID-19 pandemic, effective alternatives to classroom-based exercise programming are warranted.

AIMS: To recruit 100 racially diverse older adults with multisite pain and increased fall risk, who are interested in participating in a future Tai Chi clinical trial, and to evaluate the feasibility and acceptability of a short-term, remotely delivered home-based Tai Chi program.

METHODS: A random sample of adults aged 65 years or older living in diverse Boston neighborhoods were sent mailed invitations to participate in a telephone screening survey. Eligible adults were invited to join a 4-week Tai Chi program offered online via Zoom. Primary outcomes were class attendance, experience, and program safety.

RESULTS: Among 334 survey respondents, 105 were eligible for the intervention. Average age of eligible participants was 74 years, 75% were women, and 62% were Black. We assigned 32 participants to 4 Tai Chi or 2 light exercise groups conducted via Zoom; of these, 24 (75%) completed the program and 79% attended ≥6 of 8 classes. There were no adverse events reported. Two-thirds reported it was very easy to join the online classes and 88%, very easy to see the instructor.

CONCLUSION: Mailed invitations were effective for recruiting a racially diverse sample. Remote exercise programming delivered online via live Zoom sessions is safe and feasible for diverse older adults who have multisite pain and risk of falls.

Background: Methods of conservative management for breast cancer-related lymphedema (BCRL) are burdensome in terms of time, cost, and convenience. In addition, many patients are not candidates for surgical treatment. Preliminary results have demonstrated possible beneficial effects of acupuncture for patients with BCRL. In this small pilot study, we examined the safety and feasibility of an acupuncture randomized control trial (RCT) in this patient cohort, utilizing a battery of standardized clinical and patient-centered outcome measures. Methods and Results: Patients with BCRL were randomized 2:1 to the acupuncture (n = 10) or the control (n = 4) group. Patients received acupuncture to the unaffected extremity biweekly for 6 weeks. Feasibility was defined as enrollment ≥80%, completion of ≥9 of 12 acupuncture sessions per person, and ≥75% completion of three of three measurement visits. To inform a future adequately powered RCT, we describe within-group changes in patient-centered outcomes, including circumferential measurements, bioimpedance spectroscopy, perometry, cytokine levels, and patient quality of life. Adverse events were systematically tracked. Fourteen patients completed the study. Of those who received acupuncture (n = 10), 8 completed all 12 acupuncture sessions, and 2 patients completed 11 sessions. Ninety-three percent of all participants completed all three measurement visits. There was no consistent improvement in arm volumes. Inflammatory marker levels had inconclusive fluctuations among both groups. All patients receiving acupuncture demonstrated an improvement in their functional quality-of-life score. No severe adverse events occurred. Conclusions: A randomized controlled study of acupuncture for BCRL is feasible. The acupuncture intervention is acceptable in this population, without safety concerns in a small sample and warrants further investigation.

Chronic musculoskeletal pain is prevalent and undertreated in older adults. In particular, multisite pain is associated with serious functional consequences and falls and appears to be a novel geriatric syndrome. The causes of multisite pain are often multifactorial, and emerging evidence supports a complex pathway whereby multisite pain leads to cognitive problems, mobility decline, fear of falling, falls, and reduced participation in life roles. A few pharmacologic approaches are safe and effective for older adults with chronic multisite pain and evidence for effectiveness of non-pharmacologic treatments for this common condition is very limited. Compared to light physical exercise, mind-body exercise may prove to be more beneficial for older adults living with chronic pain. Tai Chi, as a movement-based mind-body exercise, can relieve pain symptoms, improve cognition and physical function, and lower risk for falls in older adults. However, little is known about the potential benefits of Tai Chi for older adults with multisite pain syndrome. Future large-scale randomized-controlled trials are needed to investigate the effectiveness of Tai Chi in alleviating pain and lowering fall risk in older adults with multisite pain, and the biological mechanisms that underlie its potential benefits to chronic pain, physical and cognitive functions, and falls in this at-risk population.

BACKGROUND: For cancer survivors, there is a paucity of fear of recurrence (FOR) interventions that integrate empirically supported mind-body and psychological skills for managing FOR and are delivered in scalable formats.

OBJECTIVE: To adapt an evidence-based resiliency intervention to address FOR among cancer survivors.

METHODS: A multidisciplinary team of researchers, clinicians, and patient stakeholders followed an iterative intervention adaptation process (ORBIT). In Step 1, we sought to define key FOR management skills through a literature review and feedback from stakeholders. In Step 2, we integrated findings into a treatment manual and refined procedures for in-person delivery to groups of cancer survivors, defined as adults who had completed primary cancer treatment for non-metastatic cancer. In Step 3, we conducted a single arm trial to assess initial acceptability and change in FOR severity with 23 cancer survivors (N=4 intervention groups). In Step 4, we conducted additional qualitative interviews with 28 cancer survivors (N=6 focus groups stratified by FOR severity, N=15 individual interviews) to define adaptive and maladaptive strategies for coping with FOR and to identify preferences for delivery. In Step 5, we refined the treatment manual and procedures for testing in a future pilot randomized feasibility trial.

RESULTS: We identified critical feedback using a combination of qualitative and quantitative methods. The single arm trial suggested preliminary feasibility and sustained reductions in FOR severity, yet need for refinement (i.e., eligibility, delivery modality), prompting additional qualitative interviews for further targeting. The resulting intervention (IN FOCUS) is comprised of virtual, synchronous, group-delivered sessions that offer an integrated approach to FOR management by teaching cognitive-behavioral techniques, meditation, relaxation training, adaptive health behaviors, and positive psychology skills. Sessions are targeted by applying skills to FOR and associated healthcare engagement.

CONCLUSIONS: IN FOCUS is a targeted intervention for teaching mind-body resiliency skills to groups of cancer survivors with elevated FOR. Next steps are testing feasibility in a pilot randomized trial.

OBJECTIVE: To conduct a systematic review evaluating the impact of stretching on inflammation and its resolution using in vivo rodent models. Findings are evaluated for their potential to inform the design of clinical yoga studies to assess the impact of yogic stretching on inflammation and health.

METHODS: Studies were identified using four databases. Eligible publications included English original peer-reviewed articles between 1900-May 2020. Studies included those investigating the effect of different stretching techniques administered to a whole rodent model and evaluating at least one inflammatory outcome. Studies stretching the musculoskeletal and integumentary systems were considered. Two reviewers removed duplicates, screened abstracts, conducted full-text reviews, and assessed methodological quality.

RESULTS: Of 766 studies identified, 25 were included for synthesis. Seven (28%) studies had a high risk of bias in 3 out of 10 criteria. Experimental stretching protocols resulted in a continuum of inflammatory responses with therapeutic and injurious effects, which varied with a combination of three stretching parameters–duration, frequency, and intensity. Relative to injurious stretching, therapeutic stretching featured longer-term stretching protocols. Evidence of pro- and mixed-inflammatory effects of stretching was found in 16 muscle studies. Evidence of pro-, anti-, and mixed-inflammatory effects was found in nine longer-term stretching studies of the integumentary system.

CONCLUSION: Despite the overall high quality of these summarized studies, evaluation of stretching protocols paralleling yogic stretching is limited. Both injurious and therapeutic stretching induce aspects of inflammatory responses that varied among the different stretching protocols. Inflammatory markers, such as cytokines, are potential outcomes to consider in clinical yoga studies. Future translational research evaluating therapeutic benefits should consider in vitro studies, active vs. passive stretching, shorter-term vs. longer-term interventions, systemic vs. local effects of stretching, animal models resembling human anatomy, control and estimation of non-specific stresses, development of in vivo self-stretching paradigms targeting myofascial tissues, and in vivo models accounting for gross musculoskeletal posture.

Chronic musculoskeletal pain is prevalent, challenging to treat, and often disabling. Evidence supports the role of psychological factors in pain-related outcomes, and it is now accepted that rehabilitation should combine physical and psychological approaches (ie, psychologically informed practice). This Perspective articulates a vision for technology-enhanced psychologically informed practice for chronic musculoskeletal pain, highlights relevant research evidence, discusses how technology can circumvent implementation barriers, and proposes directions for future research.

BACKGROUND: There is a knowledge gap in the physiological effects of short-term yoga exercise interventions.

OBJECTIVE: To evaluate the feasibility of a randomized controlled trial (RCT) assessing the acute effects of a yoga exercise protocol practiced at 2 intensities (high or moderate) on temporal responses of a battery of systemic circulatory cytokines in healthy yoga-naïve adults.

METHODS: This study was a three-arm, pre-post pilot-RCT employing a single bout of yoga exercise intervention. Groups were high-intensity yoga (HY, n = 10), moderate-intensity yoga (MY, n = 10), and a sedentary, no-intervention control group (CON, n = 10). Blood samples were collected at baseline and post-intervention at 6 timepoints (0-, 30-, 60-, 120-, 180-minutes, and 24-hours post-intervention) and were processed with a pre-defined inflammatory panel of 13 cytokines. Heart rate (HR) was assessed with a Polar H10® device. The PROMIS Pain intensity Questionnaire was used to assess body soreness.

RESULTS: We demonstrate feasibility of recruitment, randomization, and retention of participants based upon predetermined metrics, including: proportion of eligible to enrolled participants (55%); recruitment period (11-months); participant retention (97%); completion rate for questionnaires (99%); completion of physiological measures (98%); and adherence to the yoga exercise protocol (88%). Cytokine levels over time were heterogeneous within and between groups. Responses of a subset of cytokines were positively correlated with 1 another in high- and moderate-intensity yoga exercise groups but not in the control group. Median values for HR were 91 (IQR: 71-95) in the HY, 95 (IQR: 88-100) in the MY, and 73 (IQR: 72-75) in the CON. Pre-post changes in body soreness after the yoga exercise intervention were most evident in the HY group.

CONCLUSION: Along with observed trends in select cytokines, findings encourage a more definitive trial aimed at understanding the short-term effects of yoga exercise on inflammatory immune markers and pain in sedentary healthy adults. Clinicaltrials.gov ID# NCT04444102.