The Use of Complementary and Integrative Medicine in Combination With Pharmacological Antiemetics to Address Chemotherapy-Induced Nausea and Vomiting in Pediatric Oncology: A Scoping Review.

Background: Chemotherapy is a common treatment in childhood cancer but causes significant side effects, among the most notable being nausea and vomiting, known as chemotherapy-induced nausea and vomiting (CINV). Pharmacological antiemetics and complementary and integrative medicine (CIM) have been studied separately to manage CINV, but a gap exists in understanding their use together. We aimed to investigate the potential multimodal effects of CIM and pharmacological antiemetics on CINV in pediatric oncology patients undergoing chemotherapy. Method: Systematic searches were conducted in four databases to identify studies evaluating the efficacy of CIM in combination with pharmacological antiemetics in patients ages 0-21 with cancer undergoing chemotherapy. Relevant data were extracted from each study and evaluated. Results: Eighteen sources examining CIM therapies in three distinct categories (herbal, physical, and psychological) were identified. Three of four herbal interventions yielded significant results, all of which implemented oral ginger. Physical interventions included manual and wristband acupressure, auricular acupuncture, and needle and laser acupuncture. Significant results were found in only four of these 10 studies. Among psychological interventions, two of four yielded significant results. Discussion: There is no clear evidence of benefit from CIM therapies in addition to pharmacological antiemetics to better control CINV. However, this review provides support and direction for future research to examine potential effects. Complementary therapies generally have little potential for harm, are relatively low cost, and low burden. Therefore, if there is a perceived benefit for patients and families, complementary and integrative therapies should be considered.

Uptake and outcomes of supervised exercise therapy for peripheral artery disease: The importance of vascular medicine specialists at a large midwestern health care system during the first 5 years of CMS reimbursement.

BACKGROUND: Supervised exercise therapy (SET) is the cornerstone of medical therapy for symptomatic peripheral artery disease (PAD). Despite the efficacy of SET, initial reports following the 2017 Centers for Medicare and Medicaid Services (CMS) reimbursement decision indicate low SET uptake, referral, and completion. Vascular medicine specialists are key to the success of such programs. We examined rates of SET referral, completion, and outcomes in a health system with a robust SET program during the first 5 years of CMS reimbursement. METHODS: A retrospective chart review of patients with PAD referred to SET between October 1, 2017 and December 31, 2022 was conducted. Patient demographic and medical characteristics, SET indication, referring provider specialty, SET participation (e.g., exercise modality, number of sessions, treadmill prescription), and outcomes were abstracted. Descriptive statistics, t-tests, and multiple linear regression were used to examine the sample, evaluate outcomes, and explore outcomes by relevant covariates (i.e., age, sex, referring provider specialty). RESULTS: Of 5320 patients with PAD, N = 773 were referred to SET; N = 415 enrolled and were included in the present study. Vascular medicine and vascular surgery specialists were the two primary sources of referrals (30.6% and 51.6%, respectively). A total of 207 patients (49.9%) completed SET. Statistically significant and clinically meaningful improvements were observed in all outcomes. CONCLUSION: SET referral and completion rates are low in the 5 years following CMS reimbursement, despite the advocacy of vascular medicine specialists. SET is effective in improving patient functional capacity and quality of life. Additional efforts are needed to increase both SET availability and referrals as part of comprehensive treatment of PAD.

Obesity dominates early effects on cardiac structure and arterial stiffness in people with type 2 diabetes.

OBJECTIVE: Type 2 diabetes (T2D) and obesity are global epidemics leading to excess cardiovascular disease (CVD). This study investigates standard and novel cardiac MRI parameters to detect subclinical cardiac and central vascular dysfunction in inactive people with and without T2D. METHODS: Physically inactive age and BMI-similar premenopausal women and men with ( n  = 22) and without [ n  = 34, controls with overweight/obesity (CWO)] uncomplicated T2D were compared to an age-similar and sex-similar reference control cohort ( n  = 20). Left ventricular (LV) structure, function, and aortic stiffness were assessed by MRI. Global arterial pulse wave velocity (PWV) was assessed using carotid-to-femoral applanation tonometry. Regional PWV was measured via 2D phase-contrast MRI and 4D flow MRI. RESULTS: Global arterial PWV did not differ between CWO and T2D. 2D PC-MRI PWV in the ascending aorta was higher in people with T2D compared with CWOs ( P  < 0.01). 4D flow PWV in the thoracic aorta was higher in CWO ( P  < 0.01), and T2D ( P  < 0.001) compared with RC. End-diastolic volume, end-systolic volume, stroke volume, and cardiac output were lower in CWO and T2D groups compared with reference control. CONCLUSION: Subclinical changes in arterial stiffening and cardiac remodeling in inactive CWO and T2D compared with reference control support obesity and/or physical inactivity as determinants of incipient CVD complications in uncomplicated T2D. Future studies should determine the mechanistic causes of the CVD complications in greater detail in order to create therapeutic targets. CLINICAL TRIAL REGISTRATION: Cardiovascular Mechanisms of Exercise Intolerance in Diabetes and the Role of Sex (NCT03419195).

Study Design, Rationale, and Methodology for Promote Weight Loss in Patients With Peripheral Artery Disease Who Also Have Obesity: The PROVE Trial.

Background Overweight and obesity are associated with adverse functional outcomes in people with peripheral artery disease (PAD). The effects of weight loss in people with overweight/obesity and PAD are unknown. Methods The PROVE (Promote Weight Loss in Obese PAD Patients to Prevent Mobility Loss) Trial is a multicentered randomized clinical trial with the primary aim of testing whether a behavioral intervention designed to help participants with PAD lose weight and walk for exercise improves 6-minute walk distance at 12-month follow-up, compared with walking exercise alone. A total of 212 participants with PAD and body mass index ≥25 kg/m2 will be randomized. Interventions are delivered using a Group Mediated Cognitive Behavioral intervention model, a smartphone application, and individual telephone coaching. The primary outcome is 12-month change in 6-minute walk distance. Secondary outcomes include total minutes of walking exercise/wk at 12-month follow-up and 12-month change in accelerometer-measured physical activity, the Walking Impairment Questionnaire distance score, and the Patient-Reported Outcomes Measurement Information System mobility questionnaire. Tertiary outcomes include 12-month changes in perceived exertional effort at the end of the 6-minute walk, diet quality, and the Short Physical Performance Battery. Exploratory outcomes include changes in gastrocnemius muscle biopsy measures of mitochondrial cytochrome C oxidase activity, mitochondrial biogenesis, capillary density, and inflammatory markers. Conclusions The PROVE randomized clinical trial will evaluate the effects of exercise with an intervention of coaching and a smartphone application designed to achieve weight loss, compared with exercise alone, on walking performance in people with PAD and overweight/obesity. Results will inform optimal treatment for the growing number of patients with PAD who have overweight/obesity. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04228978.

Development and Initial Validation of a Measure to Assess Self-Efficacy to Reduce Sedentary Behavior.

INTRODUCTION: The purpose of this study was to assess the reliability and construct validity of a measure designed to evaluate self-efficacy to reduce sedentary behavior (SB). METHODS: Initial instrument development was based on semistructured interviews and in-depth review of existing measures of self-efficacy for physical activity (PA). Items were drafted by the study authors and reviewed by SB experts. Participants recruited via Amazon Mechanical Turk completed the pool of items and the Exercise Confidence Survey and provided self-reported PA, SB, and demographic information. The sample was divided into two random halves, and exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were performed on each half, respectively. Internal consistency reliability (Cronbach's alpha) was calculated for the final scale. Initial criterion validity was examined in relation to self-reported SB and PA. Analyses were conducted in SAS 9.4 and Mplus 8.3. RESULTS: Data were collected from N = 818 adults (47.6% women, mean (standard deviation) age, 37.8 (10.6)). EFA results strongly supported a one-factor scale. Items with low factor loadings (<0.65) were dropped from the scale; 10 items were retained. CFA demonstrated that the 10-item measure fit the data well, but one item had a low factor loading. A final scale with nine items was retained, with good fit to the data ( χ2 (27) = 90.79, P < 0.0001, comparative fit statistic = 0.97, root mean square error of approximation = 0.08 [90% confidence interval, 0.06-0.09], standardized root mean square residual = 0.03), and all items had high factor loadings (>0.70). Internal consistency reliability was high ( α = 0.91). Self-efficacy to reduce SB was significantly and positively correlated with exercise confidence ( r = 0.32-0.38, P < 0.0001). CONCLUSIONS: We developed a nine-item measure of self-efficacy to reduce SB that demonstrates strong initial psychometric properties. Although related to exercise self-efficacy, self-efficacy to reduce SB represents a distinct construct.

Risk Factors for Tube Feeding at Discharge in Infants Undergoing Neonatal Surgery for Congenital Heart Disease: A Systematic Review.

Approximately 30-50% of infants undergoing neonatal surgery for congenital heart disease (CHD) cannot meet oral feeding goals by discharge and require feeding tube support at home. Feeding tubes are associated with increased readmission rates and consequent hospital, payer, and family costs, and are a burden for family caregivers. Identification of modifiable risk factors for oral feeding problems could support targeted care for at-risk infants. Therefore, the aim of this systematic review is to determine risk factors for tube feeding at discharge in infants undergoing neonatal surgery for CHD. Following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, a search was conducted using MEDLINE, CINAHL, and Cochrane Database of Systematic Reviews. Studies published before 2010 were excluded. The search resulted in 607 records, of which 18 were included. Studies were primarily retrospective cohort designs and results were often inconsistent. Study quality was assessed using the Joanna Briggs Critical Appraisal Tools. As a group, the studies exhibited substantial risk for bias. Based on the findings, infants who struggle with feeding preoperatively, experience increased nil per os duration and/or low oral feeding volume postoperatively, experience increased duration of mechanical ventilation, or have vocal cord dysfunction may be at risk for tube feeding at hospital discharge. Factors warranting further examination include cardiac physiology (e.g., aortic arch obstruction) and the relationship between neurodevelopment and oral feeding. Clinicians should use caution in assuming risk for an individual and prioritize early implementation of interventions that facilitate oral feeding development.

Use of Cannabidiol in the Management of Insomnia: A Systematic Review.

Background: Cannabidiol (CBD), one of the major cannabinoids derived from the cannabis plant, is available over the counter. CBD is often used by patients for the management of insomnia, yet research supporting CBDs effectiveness as a treatment for insomnia is inadequate. Objective: The objective of this review was to critically evaluate the literature regarding the therapeutic benefits of CBD in the management of insomnia. Methods: A comprehensive search of the following databases from inception to December 29, 2021, was conducted: Ovid MEDLINE® and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus. The search included randomized controlled trials, nonrandomized experimental studies, cross-sectional studies, cohort studies, case series, and case reports. Risk of bias was assessed with the Agency for Healthcare Research and Quality design-specific recommended criteria. Results: Thirty-four studies were eligible for inclusion. All studies reported improvement in the insomnia symptoms of at least a portion of their participants. Of the 34 studies, 19 studies used CBD predominant therapy and 21 studies used nearly equal ratios of CBD to Δ9-tetrahydrocannabinol (THC). Of the studies that performed hypothesis testing, 4 of 7 studies with a CBD predominant arm and 12 of 16 studies with a nearly equal ratio of CBD to THC arm reported significant improvement in insomnia outcomes. However, only 2 of the 34 studies focused on patients with insomnia, of which 1 study was a case report. Additionally, several studies used nonvalidated subjective measures, and most studies failed to include objective measures for symptom assessment. Conclusions: The results of our systematic review suggest that CBD alone or with equal quantities of THC may be beneficial in alleviating the symptoms of insomnia. Nevertheless, future research assessing CBDs effectiveness in population of patients specifically with insomnia utilizing validated subjective and objective measures is necessary before definitive inferences can be made.

Sex Differences in Physical Activity Among Individuals With Type 2 Diabetes Across the Life Span: A Systematic Review and Meta-analysis.

BACKGROUND: Physical activity (PA) is a cornerstone of type 2 diabetes mellitus (T2DM) treatment. Sex differences in PA behavior or barriers/facilitators to PA among individuals with T2DM are unclear. PURPOSE: To summarize the evidence related to sex differences in participation in PA and barriers/facilitators to PA among individuals with T2DM across the life span. DATA SOURCES: Systematic searches (CRD42021254246) were conducted with Ovid MEDLINE, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine Database (AMED), APA PsychInfo, and SPORTDiscus. STUDY SELECTION: We included studies with assessment of PA, sedentary behaviors (SB), or barriers/facilitators to PA among individuals with T2DM by sex or gender. DATA EXTRACTION: Participant characteristics, meeting PA guidelines, participation in PA and SB, and barriers/facilitators to PA were extracted by two independent reviewers. DATA SYNTHESIS: A total of 53 articles (65,344 participants) were included in the systematic review and 21 articles in the meta-analysis. Sex differences were not observed in meeting of PA guidelines among adolescents (odds ratio 0.70 [95% CI 0.31, 1.59]), but males were more likely than females to meet PA guidelines among adults (1.65 [1.36, 2.01]) and older adults (1.63 [1.27, 2.09]). Males performed more moderate-to-vigorous PA (MVPA) than females across all age-groups. Common barriers to PA were lack of time (men) and lack of social support and motivation (women). LIMITATIONS: Limitations include heterogeneity of measures used to assess PA and lack of stratification of data by sex. CONCLUSIONS: Sex differences in meeting PA guidelines were not observed among adolescents but were apparent among adults and older adults with T2DM. Females consistently engaged in less MVPA than males across the life span.

Predictive Bidirectional Relations Between Pain, Fatigue, and Dyscognition in Fibromyalgia.

Fibromyalgia (FM) is a common and disabling disorder characterized by chronic widespread pain, fatigue, and dyscognition. Previous studies have shown strong positive correlations between pain, fatigue, and dyscognition. However, bidirectional relationships, particularly with dyscognition modeled as a predictor, have rarely been established. The purpose of this study was to examine the bidirectional, predictive nature of the relationships between these FM symptoms. Pain, fatigue, and dyscognition were measured via the Brief Pain Inventory, Multidimensional Fatigue Inventory, and Multiple Ability Self-Report Questionnaire at baseline and a 2-year follow-up in a large sample of 450 well-characterized female patients with FM. Relationships between FM symptoms were evaluated using a cross-lagged, longitudinal model. Dyscognition, pain, and fatigue were positively correlated at both baseline and follow-up (rs .13 -.53, Ps<.01). Dyscognition at baseline was predictive of dyscognition (B=.76, ß=.75, P<.001), pain, (B=.01, ß=.09, P=.033) and fatigue (B=.05, ß=.08, P=.050) at follow-up. Pain at baseline was predictive of pain (B=.59, ß=.59, P<.001), dyscognition (B=.88, ß=.07, P=.022), and fatigue (B=.85, ß=.11, P=.004) at follow-up. Fatigue at baseline was only associated with fatigue (B=.61, ß=.60, P<.001) at follow-up. Dyscognition is predictive of future pain and fatigue in patients with FM. Continued work should examine dyscognition as a clinical predictor of future severity of core symptoms such as pain and fatigue.

Single-leg exercise training augments in vivo skeletal muscle oxidative flux and vascular content and function in adults with type 2 diabetes.

KEY POINTS: People with type 2 diabetes (T2D) have impaired skeletal muscle oxidative flux due to limited oxygen delivery. In the current study, this impairment in oxidative flux in people with T2D was abrogated with a single-leg exercise training protocol. Additionally, single-leg exercise training increased skeletal muscle CD31 content, calf blood flow and state 4 mitochondrial respiration in all participants. ABSTRACT: Cardiorespiratory fitness is impaired in type 2 diabetes (T2D), conferring significant cardiovascular risk in this population; interventions are needed. Previously, we reported that a T2D-associated decrement in skeletal muscle oxidative flux is ameliorated with acute use of supplemental oxygen, suggesting that skeletal muscle oxygenation is rate-limiting to in vivo mitochondrial oxidative flux during exercise in T2D. We hypothesized that single-leg exercise training (SLET) would improve the T2D-specific impairment in in vivo mitochondrial oxidative flux during exercise. Adults with (n = 19) and without T2D (n = 22) with similar body mass indexes and levels of physical activity participated in two weeks of SLET. Following SLET, in vivo oxidative flux measured by 31 P-MRS increased in participants with T2D, but not people without T2D, measured by the increase in initial phosphocreatine synthesis (P = 0.0455 for the group × exercise interaction) and maximum rate of oxidative ATP synthesis (P = 0.0286 for the interaction). Additionally, oxidative phosphorylation increased in all participants with SLET (P = 0.0209). After SLET, there was no effect of supplemental oxygen on any of the in vivo oxidative flux measurements in either group (P > 0.02), consistent with resolution of the T2D-associated oxygen limitation previously observed at baseline in subjects with T2D. State 4 mitochondrial respiration also improved in muscle fibres ex vivo. Skeletal muscle vasculature content and calf blood flow increased in all participants with SLET (P < 0.0040); oxygen extraction in the calf increased only in T2D (P = 0.0461). SLET resolves the T2D-associated impairment of skeletal muscle in vivo mitochondrial oxidative flux potentially through improved effective blood flow/oxygen delivery.

Statin Therapy and Symptom Burden in Patients With Fibromyalgia: A Prospective Questionnaire Study.

OBJECTIVE: To evaluate the association between statin use and symptom severity, tender point count, fatigue, cognition, mood, and sleep issues in patients with fibromyalgia (FM). METHODS: Between May 2012 and November 2013, 668 patients with FM were surveyed. Patients were stratified into statin users and statin nonusers. Primary outcome was FM symptom severity (FIQ-R questionnaire) and tender point count. Secondary outcomes included fatigue (MFI-20), cognitive dysfunction (MASQ), anxiety (GAD-7), depression (PHQ-9), and sleep issues (SPI-II). Regression analysis assessed for differences in these clinical outcomes between statin users and statin nonusers and adjusted for age, sex, body mass index, ethnicity, tobacco use, opioid use, and neuropathic medication use. RESULTS: Of the FM patients, 79 (11.8%) were statin users, whereas 589 (88.2%) reported no current statin use. Compared with the control cohort, statin users were older (55.0±11.3 years vs 46.2±12.9 years; P<.001) and had a higher body mass index (33.0±7.0 kg/m2 vs 29.8±7.7 kg/m2; P=.001). Adjusted linear regression revealed no association between statin use and symptom severity (total FIQ-R scores, 57.7±18.3 vs 59.0±18.1; adjusted ß coefficient, -0.4; 95% CI, -4.8 to 4.1; P=.871). There was also no association between statin use and tender point count (14.8±4.1 vs 14.5±4.2; adjusted ß coefficient, 0.2; 95% CI, -0.8 to 1.2; P=.732). Secondary outcome analysis revealed no difference between statin users and statin nonusers in metrics measuring fatigue, cognition, anxiety, depression, and sleep problems. CONCLUSION: Administration of statin therapy for at least 1 month is not a risk factor for worse symptom burden in patients with FM. Statin therapy should be offered to dyslipidemic FM patients with an appropriate medical indication to optimize their cardiovascular health.

Acute effects of sedentary breaks on vascular health in adults at risk for type 2 diabetes: A systematic review.

The aim of this systematic review was to evaluate the available evidence regarding the acute effects of interrupting/breaking up prolonged sedentary behavior (SB) on vascular health among individuals at elevated risk for type 2 diabetes (T2D). Searches of MEDLINE, Embase, Web of Science, and Cochrane Library databases were conducted on April 7, 2020. Included studies: (1) examined the effect of breaking up prolonged SB in adults with or at elevated risk for T2D and (2) assessed a vascular health outcome, such as blood pressure (BP), flow-mediated dilation (FMD), pulse-wave velocity, or endothelin-1. A total of 20 articles (17 unique studies) were included. Only three studies reported adequate statistical power for the specified vascular outcome. The available evidence suggests that light and moderate intensity activity breaks are effective in acutely lowering BP when compared to prolonged sitting. The small number of studies that included FMD or other vascular outcomes prohibits conclusions regarding the impact of SB breaks on these outcomes. Few studies evaluating the impact of breaking up SB among adults at risk for T2D have included and been adequately powered to examine vascular outcomes, but our preliminary finding, that certain SB breaks improve BP, provides proof-of-concept for this line of inquiry. Future studies should examine both the acute and chronic vascular effects of breaking up SB among individuals most vulnerable to the effects of SB (e.g. older adults, those with T2D), as these individuals are both highly sedentary and at greatest risk of poor health outcomes. PROSPERO ID: CRD42020183423.