Exploring Genetic Testing for Rare Disorders of Obesity: Experience and Perspectives of Pediatric Weight Management Providers.

Background: This study describes experiences and perspectives of pediatric weight management (PWM) providers on the implementation of genetic testing for rare causes of obesity. Methods: Purposive and snowball sampling recruited PWM providers via email to complete a 23-question survey with multiple choice and open-ended questions. Analyses include descriptive statistics, Fisher's exact test, one-way ANOVA with Tukey's post hoc test, and qualitative analysis. Results: Of the 55 respondents, 80% reported ordering genetic testing. Respondents were primarily physicians (82.8%) in practice for 11-20 years (42%), identified as female (80%), White (76.4%), and non-Hispanic (92.7%) and provided PWM care 1-4 half day sessions per week. Frequently reported patient characteristics that prompted testing did not vary by provider years of experience (YOE). These included obesity onset before age 6, hyperphagia, dysmorphic facies, and developmental delays. The number of patient characteristics that prompted testing varied by YOE (p = 0.03); respondents with 6-10 YOE indicated more patient characteristics than respondents with >20 YOE (mean 10.3 vs. mean 6.2). The reported primary benefit of testing was health information for patients/families; the primary drawback was the high number of indeterminate tests. Ethical concerns expressed were fear of increasing weight stigma, discrimination, and impact on insurance coverage. Respondents (42%) desired training and guidance on interpreting results and counseling patients and families. Conclusions: Most PWM providers reported genetic testing as an option for patient management. Provider training in genetics/genomics and research into provider and family attitudes on the genetics of obesity and the value of genetic testing are next steps to consider.

Parenting styles and dimensions in parents of children with developmental disabilities.

Parenting influences child development. There is limited research, however, related to parenting children who have developmental disabilities. The aims of this study were to: (1) describe the parenting styles and dimensions of parents of children with developmental disabilities and (2) assess differences in parenting styles and dimensions among parents of children with autism spectrum disorder (ASD), Down syndrome (DS), and spina bifida (SB). Secondary data analysis was conducted from a nationwide cross-sectional study of 496 parents of children aged 5-16 years with ASD (n = 180), DS (n = 156), or SB (n = 160). Parent scores indicated high use of the authoritative parenting style and associated parenting dimensions, mid-to-low use of the permissive parenting style, and low use of the authoritarian parenting style and associated dimensions. Variation in parenting styles and dimensions among parents was primarily related to the child's diagnosis and family income. An unanticipated but positive finding was that parents with lower family incomes had significantly higher scores for the authoritative parenting style. Results from this study can inform future research that might inform clinical practice.

Photobiomodulation at 830 nm Reduced Nitrite Production by Peripheral Blood Mononuclear Cells Isolated from Multiple Sclerosis Subjects.

Background: Multiple sclerosis (MS) is a neurodegenerative condition characterized by high concentration of nitric oxide leading to the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), a condition known as nitrosative stress. ROS and RNS produce the inhibition of the mitochondrial electron transport chain leading to mitochondrial dysfunction, reduction of adenosine triphosphate, and death of neurons, producing severe and irreversible damage in the central nervous system of people with MS (PwMS). Current drug treatments for MS focus on the regulation of immune response in acute stages of disease, but they do not regulate nitrosative stress which is present in the acute and chronic stages of disease. Previously, our laboratory showed that photobiomodulation (PBM) on experimental autoimmune encephalomyelitis mice, the animal model of MS, reduced clinical severity of disease, gene expression of inducible nitric oxide synthase (iNOS), and the levels of nitrite in in vivo and in vitro experiments. Objective: We evaluated the effect of PBM on the regulation of nitrosative stress in PwMS. Methods: PBM was applied on peripheral blood mononuclear cells (PBMCs) obtained from PwMS to evaluate PBM on the regulation of nitrate as a marker of nitrosative stress. Results: PBM at 830 nm (10 J/cm2 at 72 h) reduced the levels of nitrite and this reduction was in relationship with the increase of interleukin-10 and the reduction of interferon-γ produced by the PBMCs regardless of the severity of disease present in the participants. Conclusions: PBM at 830 nm can potentially be used to reduce nitrosative stress at any point of disease in PwMS.

The Impact of Stand-Biased Desks on Afterschool Physical Activity Behaviors of Elementary School Children.

The purpose of this secondary analysis was to assess whether students' use of stand-biased desks during the school day influenced physical activity (PA) and sedentary behaviors (SB) during the afterschool period. By using a crossover design consisting of two 9-week intervention periods, 99 participants from grades 3, 4, and 6 were randomly assigned by their teacher to either a traditional (Group 1; sit−stand) or stand-biased (Group 2; stand−sit) desk in the classroom. The desk type then switched between intervention periods. Afterschool PA and SB were measured by accelerometry at baseline (fall) and following both intervention periods at post I (winter) and post II (spring). Independent sample t-tests and mixed-effects modeling were applied at a significance value of p < 0.05 to detect differences between groups. No significant differences in afterschool SB, light-intensity PA (LPA), or moderate- to vigorous-intensity PA (MVPA) were found between groups. There were also no significant two- or three-way interaction effects detected between desk assignment, time, and afterschool SB, LPA, or MVPA. Stand-biased desks in the classroom were not detrimental to children's afterschool PA and SB.

Stand-Biased Desks Impact on Cognition in Elementary Students Using a Within-Classroom Crossover Design.

Background: There is emerging literature that standing desk interventions may help to improve cognitive performance in school-aged children. The current study examines how desks that promote standing affect cognition over the course of a school year in third, fourth, and sixth graders. Methods: Nighty-nine students between the ages of 8 and 12 (M = 10.23; 58% Male) were assigned to either stand-biased desks or traditional sitting desks. A within-classroom design was used with students switching desks after 9 weeks. Cognitive assessments and teacher behavioral ratings were administered at baseline and readministered before students switched desks and at the conclusion of the study. Results: There were no significant effects on cognition or behavioral ratings from standing-biased desk intervention. Grade significantly moderated the relationship between stand-biased desks and cognition in that third graders showed increased cognitive control (p = 0.02, f2 = 0.06). Further, sex moderated the relationship in that females at stand-biased desks showed increased cognitive control (p = 0.03, f2 = 0.04). Conclusions: These results suggest that stand-biased desks impact cognition depending on grade and sex, indicating a complex relationship that should be teased out further in future research. Stand-biased desks showed moderate improvements in cognition and no deleterious effects, suggesting that they may be a helpful classroom intervention for children in elementary school.

Photobiomodulation Modulates Interleukin-10 and Interferon Gamma Production by Mononuclear Cells from Healthy Donors and Persons with Multiple Sclerosis.

Background: Photobiomodulation (PBM) therapy was previously shown to reduce the clinical severity of disease and modulated pro- and anti-inflammatory cytokines in an animal model of multiple sclerosis (MS). Objective: Previous observations were extended to determine the effect of PBM therapy on peripheral blood mononuclear cells and CD4+ T cells isolated from persons with MS (PwMS) and healthy donors. Methods: Using an in vitro cell culture system, isolated cells were activated and treated with red or near-infrared light wavelengths to determine the effect of PBM on the production of interferon gamma and interleukin-10 (IL-10). Results: PBM modulated cytokine production in MS subjects and healthy donors in a dose- and wavelength-dependent manner, with MS subjects and healthy donors responding differently to administered light. In addition, disease severity affected the response of immune cells, for instance, 670 nm increased IL-10 production associated with increased disease severity. Conclusions: The data show that PBM therapy has the potential to modulate pro- and anti-inflammatory cytokines in PwMS over the course of disease. Further experiments applying PBM treatment directly on patients should be carried out with extreme caution to avoid severe imbalance in the immune response.

Objective Physical Activity Levels, Sedentary Time, and Muscle Mass, Strength, and Function: Impact on Physical and Mental Health-Related Quality of Life in Older Adults.

Limited physical activity, sedentary behavior, and reduction in muscle mass, strength, and function are accompanied by negative outcomes. The relationship between these factors and physical and mental health-related quality of life (HRQoL) has yet to be elucidated in continuing care retirement community (CCRC) residents. The current study investigated the relationships among physical activity, sedentary behavior, and muscle mass, strength, and function to physical and mental HRQoL. A sample of 105 CCRC residents participated in this cross-sectional correlational study. Findings demonstrated that low physical activity and muscle function were significantly associated with low physical HRQoL and explained 38% of the variance in physical HRQoL. Handgrip strength was significantly associated with low mental HRQoL and explained 8% of the variance in mental HRQoL. Older adults living in CCRCs may benefit from interventions targeting physical activity and the distinct muscle components of sarcopenia that have the potential to improve physical and mental HRQoL. [Research in Gerontological Nursing, 15(3), 131-139.].

Self-management processes, sedentary behavior, physical activity and dietary self-management behaviors: impact on muscle outcomes in continuing care retirement community residents.

BACKGROUND: Despite the known benefits of non-sedentary behavior, physical activity, and protein and caloric intake to health and muscle mass, strength, and function, many older adults do not meet physical activity and dietary recommendations. A better understanding of the factors associated with sedentary behavior, physical activity and dietary self-management behaviors, and muscle outcomes (muscle mass, strength, and function) is needed, particularly among continuing care retirement community residents. The objective of this study was to examine the factors associated with sedentary behavior, physical activity and dietary self-management behaviors, and muscle outcomes among continuing care retirement community residents. It also aimed to determine whether sedentary behavior and physical activity and dietary self-management behaviors mediate the relationships between self-efficacy, goal congruence, aging expectations, social support, and muscle outcomes. METHODS: A sample of 105 continuing care retirement community residents (age > 70 years) participated in this correlational, cross-sectional study. Questionnaires on pain, self-efficacy, goal congruence, aging expectation, social support, and daily protein and caloric intake were administered. Physical activity and sedentary behavior (ActiGraph wGT3X-BT), muscle mass (ImpediMed SFB7), muscle strength (Jamar Smart Digital Hand Dynamometer), and muscle function (Short Physical Performance Battery) were measured. Multiple regression, logistic regression, and mediation analyses were performed. RESULTS: Low goal congruence predicted engagement in sedentary behavior and light physical activity. Higher levels of self-efficacy and social support were associated with increased likelihoods of achieving greater moderate physical activity and meeting daily recommendations for caloric intake, respectively. Self-efficacy and goal congruence predicted muscle function and strength. Moreover, sedentary behavior and achieving greater moderate physical activity were found to partially but significantly mediate the relationship between self-efficacy and muscle function. CONCLUSION: Future research should evaluate whether attempts to reduce sedentary behavior and promote physical activity and dietary self-management behaviors and muscle outcomes are more successful when modifications to the self-management process factors are also targeted.

Validation of Wearable Camera Still Images to Assess Posture in Free-Living Conditions.

PURPOSE: To assess the convergent validity of body worn wearable camera (WC) still-images (IMGs) for determining posture compared with activPAL (AP) classifications. METHODS: Participants (n=16, mean age 46.7±23.8yrs, 9F) wore an Autographer WC above the xyphoid process and an AP during three, 2hr free-living visits. IMGs were captured on average 8.47 seconds apart and were annotated with output consisting of events, transitory states, unknown and gaps. Events were annotations that matched AP classifications (sit, stand and move) consisting of at least 3 IMGs, transitory states were posture annotations fewer than 3 IMGs, unknown were IMGs that could not be accurately classified, and gaps were time between annotations. For analyses, annotation and AP output were converted to one-sec epochs and matched second-by-second. Total and average length of visits and events are reported in minutes. Bias and 95% CIs for event posture times from IMGs to AP posture times were calculated to determine accuracy and precision. Confusion matrices using total AP posture times were computed to determine misclassification. RESULTS: 43 visits were analyzed with a total visit and event time of 5027.73 and 4237.23 minutes and average visit and event lengths being 116.92 and 98.54 minutes, respectively. Bias was not statistically significant for sitting but significant for standing and movement (0.84, -6.87 and 6.04 minutes). From confusion matrices, IMGs correctly classified sitting, standing and movement 85.69%, 54.87%, and 69.41% of total AP time, respectively. CONCLUSION: WC IMGs provide a good estimation of overall sitting time but underestimate standing and overestimate movement time. Future work is warranted to improve posture classifications and examine IMG accuracy and precision in assessing activity type behaviors.

Accelerometer Calibration: The Importance of Considering Functionality.

PURPOSE: To compare the accuracy and precision of a hip-worn accelerometer to predict energy cost during structured activities across motor performance and disease conditions. METHODS: 118 adults self-identifying as healthy (n = 44) and those with arthritis (n = 23), multiple sclerosis (n = 18), Parkinson's disease (n = 17), and stroke (n =18) underwent measures of motor performance and were categorized into groups: Group 1, usual; Group 2, moderate impairment; and Group 3, severe impairment. The participants completed structured activities while wearing an accelerometer and a portable metabolic measurement system. Accelerometer-predicted energy cost (metabolic equivalent of tasks [METs]) were compared with measured METs and evaluated across functional impairment and disease conditions. Statistical significance was assessed using linear mixed effect models and Bayesian information criteria to assess model fit. RESULTS: All activities' accelerometer counts per minute (CPM) were 29.5-72.6% less for those with disease compared with those who were healthy. The predicted MET bias was similar across disease, -0.49 (-0.71, -0.27) for arthritis, -0.38 (-0.53, -0.22) for healthy, -0.44 (-0.68, -0.20) for MS, -0.34 (-0.58, -0.09) for Parkinson's, and -0.30 (-0.54, -0.06) for stroke. For functional impairment, there was a graded reduction in CPM for all activities: Group 1, 1,215 CPM (1,129, 1,301); Group 2, 789 CPM (695, 884); and Group 3, 343 CPM (220, 466). The predicted MET bias revealed similar results across the Group 1, -0.37 METs (-0.52, -0.23); Group 2, -0.44 METs (-0.60, -0.28); and Group 3, -0.33 METs (-0.55, -0.13). The Bayesian information criteria showed a better model fit for functional impairment compared with disease condition. CONCLUSION: Using functionality to improve accelerometer calibration could decrease variability and warrants further exploration to improve accelerometer prediction of physical activity.

Examining the effects of multiple chronic conditions on cognitive decline and potential moderators among older Koreans: Findings from the Korean Longitudinal Study of Ageing 2006-2016.

BACKGROUND: More than half of older Koreans have two or more chronic conditions, known as multiple chronic conditions (MCC). Successful self-management (e.g., diet control, exercise, taking medications) is critical to prevent worsening of condition or acquisition of additional chronic conditions. This study investigated the effects of MCC on cognitive decline and risk factors in each chronic condition group over a 10-year period. METHODS: Six waves (2006-2016) of the Korean Longitudinal Study of Ageing were used, featuring 2,198 older adults who were cognitively healthy at baseline. MCC were categorized into three groups: no chronic condition (n=831), one chronic condition (n=813), and two or more chronic conditions (n=554). Linear mixed-effects model analyses were conducted using SAS 9.4. RESULTS: Individuals with MCC showed greater cognitive decline than those with no or one chronic condition. Different factors were associated with cognition in each group. Among those with no chronic condition, age, income, education, and functional limitation were associated with cognitive decline. Among those with one chronic condition, age, marital status, working status, self-rated health, and arthritis were associated with cognitive decline. Among those with two or more chronic conditions, age, income, marital status, and living arrangement were associated with cognitive decline. Listed factors have p-values less than .05. CONCLUSIONS: Findings indicate MCC is significantly related with cognitive decline. Risk factors for cognitive decline differed across three chronic condition groups. Self-management programs that target each group can be a promising strategy to mitigate cognitive decline among older Koreans.

Attentiveness and Fidgeting While Using a Stand-Biased Desk in Elementary School Children.

Standing desks are a viable option to decrease sedentary time in the classroom. However, it is important that standing desks are not detrimental to classroom behavior or learning. The purpose of this study was to evaluate the impact of stand-biased desks on fidgeting and attentiveness. Ninety-seven students in grades 3, 4, and 6 (ages 8-12 years) volunteered to participate in this study. The intervention employed a within-classroom crossover design, with teacher-determined allocation for seating within each classroom and included the replacement of one-half of the traditional sitting desks with stand-biased desks. Direct observation of student's attentive and fidgeting behaviors occurred at three assessment periods, at baseline when all students were in a sitting desk condition and at the end of each nine-week intervention. Stand-biased desks did not influence fidgeting behavior, but did have an impact on attentive behavior. Students that were less attentive at baseline had a 40-80% increase incidence rate in non-attentive behavior while in the traditional desk as compared to the stand-biased desk after the intervention. While fidgeting and non-attentive episodes (p = 0.034) were significantly related, the type of desk did not significantly moderate this relationship (p = 0.810). Standing desks can be incorporated into the classroom without negatively influencing classroom behavior.

Acceptance and Feasibility of Seated Elliptical Pedaling to Replace Sedentary Behavior in Older Adults.

The purpose of this study was to explore the feasibility and acceptability of a seated pedaling device to reduce sedentary behavior (SB) in the homes of older adults. METHODS: Each participant (N = 20) was outfitted with an activity monitor and seated pedaling device in the home for 7 days and randomly assigned to one of four light-intensity pedaling groups (15, 30, 45, and 60 min/day). RESULTS: There was 100% adherence in all groups and significant group differences in the minutes pedaled per day (p < .001), with no significant difference in the total pedaling days completed (p = .241). The 15-, 30-, 45-, and 60-min groups experienced a 4.0%, 5.4%, 10.6%, and 11.3% reduction in SB on the days pedaled, respectively. CONCLUSION: Clinically relevant reductions in SB time were achievable in this 1-week trial. Long-term adherence and the impact of replacing SB with seated light activities on geriatric-relevant health outcomes should be investigated.

US data on children and youth caregivers in amyotrophic lateral sclerosis.

OBJECTIVE: An estimated 1.4 million young caregivers (<19 years of age) in the United States provide care to ill family members yet remain hidden from state and national caregiving programs and services, including amyotrophic lateral sclerosis (ALS) caregiving services. Given the intensive care needs and acuity of ALS, appreciation of the young caregiver experience within the family context may have a significant impact on patient and family quality of life. This article seeks to identify family and youth caregiver characteristics and perceptions of care through interviews with 38 youth caregivers and their families with ALS. METHODS: Online adult surveys and follow-up youth interviews were conducted with families with ALS across the United States in this cross-sectional study. Participants were accessed through chapters of the ALS Association. Both thematic content analysis and descriptive statistics were used. RESULTS: Youth caregivers (n = 38) ranged in age from 8 to 18 years and spent an average of 5 h/d providing care for an average of 12 tasks. Persons with ALS relied on youth primarily due to cost and identified complex feelings about relying on youth caregivers, including feeling like a failure, guilty, but proud. CONCLUSION: Youth are intricately involved in all areas of caregiving in ALS. They are isolated and have little training or guidance in care, yet they are able to identify ways to manage their care burden. Results provide clear implications for health care professionals in designing best care and support practices for persons with ALS and their young caregivers.

Identification of Latent Classes of Motor Performance in a Heterogenous Population of Adults.

OBJECTIVE: To determine classes of motor performance based on community deployable motor impairment and functional tests in a heterogeneous adult population. DESIGN: Sixteen tests of limb-specific and whole-body measures of motor impairment and function were obtained. Linear regression analysis was used to dichotomize performance on each test as falling within or outside the age- and sex-predicted values. Latent class analysis was used to determine 3 classes of motor performance. The chi-square test of association and the Fisher exact test were used for categorical variables, and analysis of variance and the Kruskal-Wallis test were used for continuous variables to evaluate the relationship between demographic characteristics and latent classes. SETTING: General community. PARTICIPANTS: Individuals (N=118; 50 men) participated in the study. Quota sampling was used to recruit individuals who self-identified as healthy (n=44) or currently living with a preexisting chronic health condition, including arthritis (n=19), multiple sclerosis (n=18), Parkinson disease (n=17), stroke (n=18), or low functioning (n=2). INTERVENTION: Not applicable. MAIN OUTCOME MEASURE: Latent classes of motor performance. RESULTS: Across the entire sample, 3 latent classes of motor performance were determined that clustered individuals with motor performance falling: (1) within predicted values on most of the tests (expected class), (2) outside predicted values on some of the tests (moderate class), and (3) outside predicted values on most of the tests (severe class).The ability to distinguish between the respective classes based on the percent chance of falling outside predicted values was achieved using the following community deployable motor performance tests: 10-meter walk test (22%, 80%, and 100%), 6-minute walk test (14.5%, 37.5%, and 100%), grooved pegboard test (23%, 38%, and 100%), and modified physical performance test (3%, 54%, and 96%). CONCLUSIONS: In this heterogeneous group of adults, we found 3 distinct classes of motor performance, with the sample clustering into an expected test score group, a moderate test score deficiency group, and a severed test score deficiency group. Based on the motor performance tests, we established that community deployable, easily administered testing could accurately predict the established clusters of motor performance.

Do Stand-Biased Desks in the Classroom Change School-Time Activity and Sedentary Behavior?

The purpose of this study was to determine the effect of stand-biased desks on the physical activity and sedentary behavior of third, fourth and sixth grade students across the school year. Methods: This within classroom crossover design study used teacher-determined allocation for seating within each classroom. Half of the students used a stand-biased desk and half used a sitting desk. Five-day hip-worn accelerometer assessments were completed at baseline and at the end of each nine-week intervention period. A mixed effects model was used to determine the differences in the percentage of time spent active and sedentary. Results: A total of 22, 36 and 41 students in 3rd, 4th and 6th grades, respectively, completed this study (57.1% male, 79.3% White). Regardless of the desk type, students became more sedentary (p < 0.001) and less active (p < 0.001) in the classroom as the school year progressed. After controlling for baseline activity, there was a significant interaction between the type of desk and time (p = 0.029). Students who spent a higher percentage of their classroom time sedentary engaged in less sedentary behavior when using a stand-biased desk compared to the traditional desk. Conclusion: The standing desk intervention was effective in mitigating the increase in sedentary behavior for those who started the school year more sedentary.

Pattern Analysis of Sedentary Behavior Change after a Walking Intervention.

OBJECTIVES: We examined the pattern of change in sedentary behavior (SB) resulting from a physical activity (PA) intervention in older adults, and the influence of sex on changes in SB. METHODS: One hundred twenty (N = 120) inactive older adults from 2 12-week step/day-target interventions were included in this pooled reanalysis. Participants were randomly assigned to an intervention (STEP) or control group (CON). A Hip-worn accelerometer (Actigraph) was used to assess SB and PA. RESULTS: Significant decreases in SB (-25 minutes) were largely accounted for by the increase in moderate- to vigorous-intensity PA (MVPA; +17.3 minutes). More broadly, data showed that for every 1% increase in proportion of time spent in MVPA, SB decreased by 1.21%. Results of the pattern analysis showed significant pre-post decreases in the number of daily sedentary bouts lasting 10, 20, and 30 minutes and the number of sit-to-stand transitions in the STEP group. Males tended to decrease time spent in longer bouts and females tended to decrease the number of sit-to-stand transitions to achieve lower SB. CONCLUSIONS: Decreases in SB were accomplished through reductions in shorter bouts of SB and likely through a variety of small changes that differed between individual participants and sexes.

Isotemporal Substitution of Sedentary Behavior and Physical Activity on Function.

The amount of time spent in sedentary behaviors (SB) progressively increases with age, while reducing time spent in light-intensity physical activity (LPA) and moderate- to vigorous-intensity physical activity (MVPA). These trajectories in PA and SB are linked to accelerated reductions in physical functioning. PURPOSE: This study aimed to examine the association of substituting SB time with LPA and MVPA on physical function in older adults. METHODS: Ninety-one older adults (mean age, 70.7 ± 10.2 yr) wore a hip-mounted accelerometer to measure SB, LPA, and MVPA time. Measures of physical function included a 400-m walk test (400W), the usual gait speed (UGS), the five times sit-to-stand (5xSTS) test, and the short physical performance battery (SPPB). Isotemporal substitution regression modeling was performed to assess the relationship of replacing the amount of time spent in one activity for another. RESULTS: Replacing 30 min·d of SB with LPA was associated with a significant improvement in 400W (P = 0.0497), whereas MVPA resulted in a significant improvement (P < 0.01) in 400W, UGS, 5xSTS, and SPPB. Replacing 60 min·d of SB with 10 min·d of MVPA and 50 min·d of LPA was associated with significant improvements in the 400W, UGS, and 5xSTS (P < 0.05). Meanwhile, as little as 5 min·d of MVPA and 55 min·d of LPA were linked to a 78% increased odds of scoring with good function in the SPPB (P = 0.0247). CONCLUSION: Replacing SB with LPA was linked to a significant improvement in the 400W, but not the other brief functional measures. Mixed doses of LPA and MVPA may add flexibility to interventions targeting reductions of SB in older adults for clinically relevant improvements in physical function.

Population Analysis of Adverse Events in Different Age Groups Using Big Clinical Trials Data.

BACKGROUND: Understanding adverse event patterns in clinical studies across populations is important for patient safety and protection in clinical trials as well as for developing appropriate drug therapies, procedures, and treatment plans. OBJECTIVES: The objective of our study was to conduct a data-driven population-based analysis to estimate the incidence, diversity, and association patterns of adverse events by age of the clinical trials patients and participants. METHODS: Two aspects of adverse event patterns were measured: (1) the adverse event incidence rate in each of the patient age groups and (2) the diversity of adverse events defined as distinct types of adverse events categorized by organ system. Statistical analysis was done on the summarized clinical trial data. The incident rate and diversity level in each of the age groups were compared with the lowest group (reference group) using t tests. Cohort data was obtained from ClinicalTrials.gov, and 186,339 clinical studies were analyzed; data were extracted from the 17,853 clinical trials that reported clinical outcomes. The total number of clinical trial participants was 6,808,619, and total number of participants affected by adverse events in these trials was 1,840,432. The trial participants were divided into eight different age groups to support cross-age group comparison. RESULTS: In general, children and older patients are more susceptible to adverse events in clinical trial studies. Using the lowest incidence age group as the reference group (20-29 years), the incidence rate of the 0-9 years-old group was 31.41%, approximately 1.51 times higher (P=.04) than the young adult group (20-29 years) at 20.76%. The second-highest group is the 50-59 years-old group with an incidence rate of 30.09%, significantly higher (P<.001) when compared with the lowest incidence in the 20-29 years-old group. The adverse event diversity also increased with increase in patient age. Clinical studies that recruited older patients (older than 40 years) were more likely to observe a diverse range of adverse events (P<.001). Adverse event diversity increased at an average rate of 77% for each age group (older than 30 years) until reaching the 60-69 years-old group, which had a diversity level of 54.7 different types of adverse events per trial arm. The 70-100 years-old group showed the highest diversity level of 55.5 events per trial arm, which is approximately 3.44 times more than the 20-29 years-old group (P<.001). We also observe that adverse events display strong age-related patterns among different categories. CONCLUSION: The results show that there is a significant adverse event variance at the population level between different age groups in clinical trials. The data suggest that age-associated adverse events should be considered in planning, monitoring, and regulating clinical trials.

Muscle activation and energy expenditure of sedentary behavior alternatives in young and old adults.

The physiological mechanisms that underlie the metabolic benefits of breaking up sedentary behavior (SB) have yet to be determined. The purpose of this study is to compare energy expenditure (EE) and muscle activation (MA) responses to sitting and four SB alternatives in younger and older adults. Twenty-two adults, grouped by age (21-35 and 62-76 years), completed five randomly ordered 20 min tasks: (1) continuous sitting (Sit), (2) sitting on a stability ball (Ball), (3) continuous standing (Stand), (4) sitting interrupted by walking (S/W), and (5) sitting interrupted by standing (S/S). Muscle activation of two upper (trapezius and erector spinae) and two lower (rectus femoris and medial gastrocnemius) body muscles and total body EE were measured continuously. A linear mixed model using gender and age as a covariate with Bonferroni adjustment were used to determine significant differences between tasks. Collectively, S/W produced significantly higher MA and EE compared with Sit (p < 0.001). Stand and Ball provided significantly greater EE, but not MA, compared to Sit (p < 0.05), while S/S did not significantly change EE or MA compared to Sit. There were no net EE differences when comparing age groups across the tasks. Upper body MA was not consistent in both age groups across tasks. Specifically, during S/W the upper body MA of older adults (9.7 ± 1.5% MVC) was double that of young adults (4.8 ± 0.7% MVC, p = 0.006). Lower body MA responded similarly to all tasks in both age groups. Disrupting sitting with walking produced the largest increase in EE and MA compared to other SB alternatives in both age groups. These results are important considering the wide use of SB alternatives by researchers and public health practitioners.