Effect of a 1-year physical activity intervention on quality of life, fatigue, and distress in adult childhood cancer survivors-A randomized controlled trial (SURfit).

INTRODUCTION: Childhood cancer survivors (CCS) are at risk of experiencing lower quality-of-life, fatigue, and depression. Few randomized controlled trials have studied the effect of physical activity (PA) on these in adult long-term CCS. This study investigated the effect of a 1-year individualized PA intervention on health-related quality-of-life (HRQOL), fatigue, and distress symptoms in adult CCS. METHODS: The SURfit trial randomized 151 CCS ≥16 years old, <16 at diagnosis and ≥5 years since diagnosis, identified through the Swiss Childhood Cancer Registry. Intervention participants received personalized PA counselling to increase intense PA by ≥2.5 h/week for 1 year. Controls maintained usual PA levels. The authors assessed physical- and mental-HRQOL, fatigue, and distress symptoms at baseline, 3, 6, and 12 months. T-scores were calculated using representative normative populations (mean = 50, standard deviation = 10). Generalized linear mixed-effects models with intention-to-treat (ITT, primary), and three per-protocol allocations were used. RESULTS: At 12 months, ITT (-3.56 larger decrease, 95% confidence interval -5.69 to -1.43, p = .001) and two per-protocol analyses found significantly lower fatigue. Physical-HRQOL improved significantly in two per-protocol analyses at 12 months. No other effects were found. CONCLUSION: SURfit showed that increased intense PA over 1 year improved fatigue in adult CCS. Survivors should be recommended PA to reduce the burden of late-effects.

Physical Activity Among Adolescent Cancer Survivors: The PACCS Study.

OBJECTIVES: Physical activity (PA) may modify risks of late effects after cancer. We aimed to examine levels of PA and sedentary time (ST) in a large, international sample of adolescent childhood cancer survivors in relation to sociodemographic and cancer-related factors and compare levels of PA and ST to reference cohorts. METHODS: Survivors from any cancer diagnosis who had completed cancer treatment ≥1 year ago, aged 9 to 16 years, were eligible for the multicenter Physical Activity in Childhood Cancer Survivors study. PA and ST were measured by ActiGraph GT3X+ accelerometers. We performed linear regression analyses to assess factors associated with moderate-to-vigorous PA (MVPA) and ST, and compared marginal means of total PA, MVPA, and ST in 432 survivors to sex- and age-stratified references (2-year intervals) using immediate t-tests for aggregated data. RESULTS: Among survivors, 34% fulfilled the World Health Organization's PA recommendation of ≥60 min of daily MVPA on average and their ST was 8.7 hours per day. Being female, older, overweight, a survivor of central nervous system tumor, or having experienced relapse were associated with lower MVPA and/or higher ST. Generally, male survivors spent less time in MVPA compared with references, whereas female survivors had similar levels. Both male and female survivors had higher ST than references in nearly all age groups. CONCLUSIONS: The low PA and high ST in this large sample of adolescent childhood cancer survivors is worrisome. Combined, our results call for targeted interventions addressing both PA and ST in follow-up care after childhood cancer.

Effect of a 1-year physical activity intervention on cardiovascular health in long-term childhood cancer survivors-a randomised controlled trial (SURfit).

BACKGROUND: This randomised controlled trial (RCT) assessed the effect of a 1-year, partially supervised, physical activity (PA) intervention on a cardiovascular disease (CVD) risk score in adult survivors of childhood cancer. METHODS: We included childhood cancer survivors ≥16 y at enrolment, <16 y at diagnosis and ≥5 y in remission. The intervention group was asked to perform an additional ≥2.5 h of intense physical activity/week, controls continued exercise as usual; assessments were performed at baseline, 6 months (T6) and 12 months (T12). The primary endpoint was change in a CVD risk score (average z-score of waist circumference, blood pressure, fasting glucose, inverted high-density lipoprotein cholesterol, triglycerides, and inverted cardiorespiratory fitness) from baseline to T12. We performed intention-to-treat (ITT, primary) and 3 per protocol analyses. RESULTS: We randomised 151 survivors (44% females, 30.4 ± 8.6 years). We found a significant and robust reduction of the CVD risk score in the intervention compared to the control group at T6 and T12 across all analyses; with a difference in the reduction of the CVD risk z-score of -0.18 (95% confidence interval -0.29 to -0.06, P = 0.003) at T12 in favour of the intervention group (ITT analysis). CONCLUSIONS: This RCT showed that a long-term PA intervention can reduce CVD risk in long-term survivors of childhood cancer. TRIAL REGISTRATION: Clinicaltrials.gov: NCT02730767.

Adherence and contamination in a 1-year physical activity program in childhood cancer survivors: A report from the SURfit study.

PURPOSE: Meeting intervention requirements is crucial in behavioral trials. We examined patterns and predictors of physical activity (PA) adherence and contamination in a 1-year individualized randomized controlled PA behavioral intervention in childhood cancer survivors (CCS). METHODS: CCS aged ≥16 at enrolment, <16 at diagnosis, and ≥5 years in remission were identified from the Swiss Childhood Cancer Registry. We asked participants randomized to the intervention group to perform an additional ≥2.5 h of intense PA/week and controls to continue as usual. Adherence to the intervention was assessed by online diary (adherent if ≥2/3 of individual PA goal reached) and contamination for the control group by pre- and post-questionnaire including PA levels (contaminated if >60 min increase/week in PA). Predictors of adherence/contamination including quality of life (36-Item Short Form Survey) were assessed by questionnaire. We used logistic (control group) and mixed logistic regression models (exercise group) to estimate predictors of study adherence and contamination. RESULTS: One hundred and forty-four survivors (30.4 ± 8.7 years old, 43% females) were included. Adherence was 48% (35/73) in the intervention group, while 17% (12/71) of controls contaminated group allocation. Predictors for PA adherence were female sex (OR 2.35, p = 0.03), higher physical (OR 1.34, p = 0.01) and mental quality of life (OR 1.37, p = 0.001), and week into the intervention (OR 0.98, p < 0.001). Clear differences in PA behavior of adherent and non-adherent participants were seen from week four. No significant predictors for contamination were found for controls. CONCLUSION: Adherence to PA behavior interventions remain challenging in both groups. Further long-term trials should consider intense motivational support within the first month, more detailed data collection for the control group, adjustments to power calculations and other study designs to minimize non-adherence and contamination.

Respiratory morbidity in preschool and school-age children born very preterm and its association with parents' health-related quality of life and family functioning.

The purpose of this study is to describe the prevalence and severity of respiratory symptoms in children born very preterm and to assess their association with parents' health-related quality of life (HRQoL) and family functioning. We conducted a cross-sectional study and recruited children born less than 32 weeks' gestation between January 2006 and December 2019, in the greater Zurich area, Switzerland. Between May and December 2021, parents were invited to complete an online survey for their preterm child and for a control term born (≥ 37 weeks' gestation) sibling aged 1 to 18 years. We used a validated questionnaire to assess respiratory symptoms and the Pediatrics Quality of Life Family Impact Module (PedsQL FIM) to assess parents' HRQoL and family functioning. The survey was completed for 616 very preterm children (99 with bronchopulmonary dysplasia (BPD)) and 180 controls. Girls made up 45% (46% in controls) of the sample, and 63% (60% in controls) of participants were aged 6 to 18 years (school-age). Very preterm children reported a higher risk of respiratory symptoms than controls, especially preschoolers and those with moderate-to-severe BPD. Parents of children with "mild" and "moderate-severe" respiratory symptoms had on average -3.9 (95%CI: -6.6 to -1.1) and -8.2 (-11.2 to -5.2) lower PedsQL FIM total score, respectively, than parents of children with no symptoms. The same pattern was observed after stratifying by age categories.  Conclusions: Our study suggests that respiratory morbidity in very preterm children has a negative impact on parents' HRQoL and family functioning, even beyond the first years of life. What is Known: • The burden of respiratory morbidity associated with very premature birth is high and last far beyond the neonatal period. • Respiratory morbidity contributes to lower health-related quality of life (HRQoL) in parents of very preterm children in early infancy. What is New: • Respiratory morbidity in very preterm children has a negative impact on parents' HRQoL and family functioning beyond the first years of life. • Parents of very preterm children with moderate and severe respiratory symptoms are the ones who report lower scores, both for preschool and school-age children.

Cystic fibrosis related diabetes is not associated with maximal aerobic exercise capacity in cystic fibrosis: a cross-sectional analysis of an international multicenter trial.

BACKGROUND: Previous studies have reported differences in aerobic exercise capacity, expressed as peak oxygen uptake (VO2peak), between people with and without cystic fibrosis (CF) related diabetes (CFRD). However, none of the studies controlled for the potential influence of physical activity on VO2peak. We investigated associations between CFRD and VO2peak following rigorous control for confounders including objectively measured physical activity. METHODS: Baseline data from the international multicenter trial ACTIVATE-CF with participants ≥12 years performing up to 4 h per week of vigorous physical activity were used for this project. Multivariable models were computed to study associations between CFRD and VO2peak (mL.min-1) adjusting for a set of pre-defined covariates: age, sex, weight, forced expiratory volume in 1 s (FEV1), breathing reserve index, Pseudomonas aeruginosa infection, and physical activity (aerobic step counts from pedometry). Variables were selected based on their potential confounding effect on the association between VO2peak and CFRD. RESULTS: Among 117 randomized individuals, 103 (52% female) had a maximal exercise test and were included in the analysis. Participants with (n = 19) and without (n = 84) CFRD did not differ in FEV1, physical activity, nutritional status, and other clinical characteristics. There were also no differences in VO2peak (mL.min-1 or mL.kg-1.min-1 or% predicted). In the final multivariable model, all pre-defined covariates were significant predictors of VO2peak (mL.min-1), however CFRD [coefficient 82.1, 95% CI -69.5 to 233.8, p = 0.28] was not. CONCLUSIONS: This study suggests no meaningful differences in VO2peak between people with and without CFRD given comparable levels of physical activity.

Effect of a physical activity intervention on lower body bone health in childhood cancer survivors: A randomized controlled trial (SURfit).

It remains controversial whether physical activity promotes bone health in childhood cancer survivors (CCS). We aimed to assess the effect of a one-year general exercise intervention on lower body bone parameters of CCS. CCS ≥16 years at enrollment, <16 years at diagnosis and ≥5 years in remission were identified from the national Childhood Cancer Registry. Participants randomized to the intervention group were asked to perform an additional ≥2.5 hours of intense physical activity/week, controls continued exercise as usual. Bone health was assessed as a secondary trial endpoint at baseline and after 12-months. We measured tibia bone mineral density (BMD) and morphology by peripheral quantitative computed tomography and lumbar spine, hip and femoral neck BMD by dual-energy x-ray absorptiometry. We performed intention-to-treat, per protocol, and an explorative subgroup analyses looking at low BMD using multiple linear regressions. One hundred fifty-one survivors (44% females, 7.5 ± 4.9 years at diagnosis, 30.4 ± 8.6 years at baseline) were included. Intention-to-treat analysis revealed no differences in changes between the intervention and control group. Per protocol analyses showed evidence for an improvement in femoral neck and trabecular BMD between 1.5% and 1.8% more in participants being compliant with the exercise program. Trabecular BMD increased 2.8% more in survivors of the intervention group with BMD z-score ≤-1 compared to those starting at z-score >-1. A nonstandardized personalized exercise programs might not be specific enough to promote bone health in CCS, although those compliant and those most in need may benefit. Future trials should include bone stimulating exercise programs targeting risk groups with reduced bone health and motivational features to maximize compliance.

The relationship of parenting style and eating behavior in preschool children.

BACKGROUND: Eating behavior represents individual appetitive traits which are related to the individual's regulation of food intake. Eating behavior develops at an early age. There is some evidence that parenting styles might impact on the child's eating behavior. The aim of this study was to investigate the relationship of different dimensions of positive and negative parenting styles with the child's eating behavior at a critical age period of the child's early development. METHODS: Parents of 511 preschool children (aged 2-6 years) completed the Children Eating Behavior Questionnaire and the Alabama Parenting Questionnaire. RESULTS: Analyses revealed that different dimensions of negative parenting styles were associated with eating behavior of the child. In details, inconsistent parenting showed a consistent association with eating behavior of a child (i.e. higher emotional eating, higher food responsiveness, higher food fussiness, higher satiety responsiveness and more enjoyment of food), whereas corporal punishment was associated with more emotional overeating and more food responsiveness but less satiety responsiveness. Further, powerful implementation was related to higher food responsiveness and less enjoyment of food and low monitoring was associated with higher emotional overeating and more slowness in eating. There was no such consistent association of positive parenting and eating behavior. CONCLUSIONS: More negative parenting styles were associated with eating behavior which is more often related to potential weight problems in a long term, whereas positive parenting did not show such a consistent relationship with eating behavior. Negative parenting should be in the focus of prevention and treatment of eating behavior problems in young children. TRIAL REGISTRATION: ISRCTN41045021 (06/05/2014).

Device-measured physical activity and cardiovascular disease risk in adolescent childhood cancer survivors. A physical activity in childhood cancer survivors (PACCS) study.

Objectives: We aimed to compare cardiovascular disease (CVD) risk factors in childhood cancer survivors (CCS) with age- and sex-stratified reference material and examine the association between physical activity (PA) intensities and CVD risk factors in CCS. Materials and methods: Within the cross-sectional, multicenter Physical Activity in Childhood Cancer Survivors (PACCS) study, we collected data on CVD risk factors [VO2-peak (mL⋅kg-1⋅min-1), body mass index (BMI, kg/m2), systolic blood pressure (SBP, mmHg), and total-cholesterol/HDL-cholesterol (Total/HDL)] among CCS aged 9-18 years. CVD risk factors were compared to references with immediate t-tests. We transformed CVD risk factors into z-scores based on international references and generated an individual CVD risk score: [inverse ZVO2-peak + Z BMI + Z SBP + Z Total/HDL )/4]. Multivariable mixed linear regression models were used to analyze the associations between device-measured PA intensities and CVD risk factors. Results: We included 157 CCS aged on average 13.4 years at inclusion and 8.2 years from diagnosis. Male CCS had lower VO2-peak compared to references (45.4 vs. 49.4 mL⋅kg-1⋅min-1, P = 0.001), higher diastolic BP (67 vs. 63 mmHg, P < 0.001), lower HDL (1.35 vs. 1.44 mmol/L, P = 0.012), as well as a tendency to higher CVD risk score (z-score=0.14 vs. 0.00, P = .075). Female CCS' CVD risk factors were comparable to references. Vigorous-intensity PA (VPA) was associated with CVD risk factors. A 10-min increase in VPA was associated with higher VO2-peak (ß = 4.9, 95% CI, 2.1-7.7), lower Total/HDL (ß = -0.3, 95% CI, -0.6 to -0.1) and a lower CVD risk score (ß = -0.4, 95% CI, -0.6 to -0.2). Conclusion: Male adolescent CCS had less favorable values of CVD risk factors compared to references. VPA in adolescent CCS is associated with clinically meaningful favorable values of CVD risk factors.

Physical activity and exercise training in cystic fibrosis.

BACKGROUND: Physical activity (including exercise) may form an important part of regular care for people with cystic fibrosis (CF). This is an update of a previously published review. OBJECTIVES: To assess the effects of physical activity interventions on exercise capacity by peak oxygen uptake, lung function by forced expiratory volume in one second (FEV1), health-related quality of life (HRQoL) and further important patient-relevant outcomes in people with cystic fibrosis (CF). SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register which comprises references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. The most recent search was on 3 March 2022. We also searched two ongoing trials registers: clinicaltrials.gov, most recently on 4 March 2022; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), most recently on 16 March 2022.  SELECTION CRITERIA: We included all randomised controlled trials (RCTs) and quasi-RCTs comparing physical activity interventions of any type and a minimum intervention duration of two weeks with conventional care (no physical activity intervention) in people with CF. DATA COLLECTION AND ANALYSIS: Two review authors independently selected RCTs for inclusion, assessed methodological quality and extracted data. We assessed the certainty of the evidence using GRADE.  MAIN RESULTS: We included 24 parallel RCTs (875 participants). The number of participants in the studies ranged from nine to 117, with a wide range of disease severity. The studies' age demographics varied: in two studies, all participants were adults; in 13 studies, participants were 18 years and younger; in one study, participants were 15 years and older; in one study, participants were 12 years and older; and seven studies included all age ranges. The active training programme lasted up to and including six months in 14 studies, and longer than six months in the remaining 10 studies. Of the 24 included studies, seven implemented a follow-up period (when supervision was withdrawn, but participants were still allowed to exercise) ranging from one to 12 months. Studies employed differing levels of supervision: in 12 studies, training was supervised; in 11 studies, it was partially supervised; and in one study, training was unsupervised. The quality of the included studies varied widely. This Cochrane Review shows that, in studies with an active training programme lasting over six months in people with CF, physical activity probably has a positive effect on exercise capacity when compared to no physical activity (usual care) (mean difference (MD) 1.60, 95% confidence interval (CI) 0.16 to 3.05; 6 RCTs, 348 participants; moderate-certainty evidence). The magnitude of improvement in exercise capacity is interpreted as small, although study results were heterogeneous. Physical activity interventions may have no effect on lung function (forced expiratory volume in one second (FEV1) % predicted) (MD 2.41, 95% CI ‒0.49 to 5.31; 6 RCTs, 367 participants), HRQoL physical functioning (MD 2.19, 95% CI ‒3.42 to 7.80; 4 RCTs, 247 participants) and HRQoL respiratory domain (MD ‒0.05, 95% CI ‒3.61 to 3.51; 4 RCTs, 251 participants) at six months and longer (low-certainty evidence). One study (117 participants) reported no differences between the physical activity and control groups in the number of participants experiencing a pulmonary exacerbation by six months (incidence rate ratio 1.28, 95% CI 0.85 to 1.94) or in the time to first exacerbation over 12 months (hazard ratio 1.34, 95% CI 0.65 to 2.80) (both high-certainty evidence); and no effects of physical activity on diabetic control (after 1 hour: MD ‒0.04 mmol/L, 95% CI ‒1.11 to 1.03; 67 participants; after 2 hours: MD ‒0.44 mmol/L, 95% CI ‒1.43 to 0.55; 81 participants; moderate-certainty evidence). We found no difference between groups in the number of adverse events over six months (odds ratio 6.22, 95% CI 0.72 to 53.40; 2 RCTs, 156 participants; low-certainty evidence). For other time points (up to and including six months and during a follow-up period with no active intervention), the effects of physical activity versus control were similar to those reported for the outcomes above. However, only three out of seven studies adding a follow-up period with no active intervention (ranging between one and 12 months) reported on the primary outcomes of changes in exercise capacity and lung function, and one on HRQoL. These data must be interpreted with caution. Altogether, given the heterogeneity of effects across studies, the wide variation in study quality and lack of information on clinically meaningful changes for several outcome measures, we consider the overall certainty of evidence on the effects of physical activity interventions on exercise capacity, lung function and HRQoL to be low to moderate. AUTHORS' CONCLUSIONS: Physical activity interventions for six months and longer likely improve exercise capacity when compared to no training (moderate-certainty evidence). Current evidence shows little or no effect on lung function and HRQoL (low-certainty evidence). Over recent decades, physical activity has gained increasing interest and is already part of multidisciplinary care offered to most people with CF. Adverse effects of physical activity appear rare and there is no reason to actively discourage regular physical activity and exercise. The benefits of including physical activity in an individual's regular care may be influenced by the type and duration of the activity programme as well as individual preferences for and barriers to physical activity. Further high-quality and sufficiently-sized studies are needed to comprehensively assess the benefits of physical activity and exercise in people with CF, particularly in the new era of CF medicine.

Effects of acetazolamide on pulmonary artery pressure and prevention of high-altitude pulmonary edema after rapid active ascent to 4,559 m.

Acetazolamide prevents acute mountain sickness (AMS) by inhibition of carbonic anhydrase. Since it also reduces acute hypoxic pulmonary vasoconstriction (HPV), it may also prevent high-altitude pulmonary edema (HAPE) by lowering pulmonary artery pressure. We tested this hypothesis in a randomized, placebo-controlled, double-blind study. Thirteen healthy, nonacclimatized lowlanders with a history of HAPE ascended (<22 h) from 1,130 to 4,559 m with one overnight stay at 3,611 m. Medications were started 48 h before ascent (acetazolamide: n = 7, 250 mg 3 times/day; placebo: n = 6, 3 times/day). HAPE was diagnosed by chest radiography and pulmonary artery pressure by measurement of right ventricular to atrial pressure gradient (RVPG) by transthoracic echocardiography. AMS was evaluated with the Lake Louise Score (LLS) and AMS-C score. The incidence of HAPE was 43% versus 67% (acetazolamide vs. placebo, P = 0.39). Ascent to altitude increased RVPG from 20 ± 5 to 43 ± 10 mmHg (P < 0.001) without a group difference (P = 0.68). Arterial Po2 fell to 36 ± 9 mmHg (P < 0.001) and was 8.5 mmHg higher with acetazolamide at high altitude (P = 0.025). At high altitude, the LLS and AMS-C score remained lower in those taking acetazolamide (both P < 0.05). Although acetazolamide reduced HAPE incidence by 35%, this effect was not statistically significant, and was considerably less than reductions of about 70%-100% with prophylactic dexamethasone, tadalafil, and nifedipine performed with the same ascent profile at the same location. We could not demonstrate a reduction in RVPG compared with placebo treatment despite reductions in AMS severity and better arterial oxygenation. Limited by small sample size, our data do not support recommending acetazolamide for the prevention of HAPE in mountaineers ascending rapidly to over 4,500 m.NEW & NOTEWORTHY This randomized, placebo-controlled, double-blind study is the first to investigate whether acetazolamide, which reduces acute mountain sickness (AMS), inhibits short-term hypoxic pulmonary vasoconstriction, and also prevents high-altitude pulmonary edema (HAPE) in a fast-climbing ascent to 4,559 m. We found no statistically significant reduction in HAPE incidence or differences in hypoxic pulmonary artery pressures compared with placebo despite reductions in AMS and greater ventilation-induced arterial oxygenation. Our data do not support recommending acetazolamide for HAPE prevention.

The Physical Activity and Fitness in Childhood Cancer Survivors (PACCS) Study: Protocol for an International Mixed Methods Study.

BACKGROUND: Survivors of childhood cancer represent a growing population with a long life expectancy but high risks of treatment-induced morbidity and premature mortality. Regular physical activity (PA) may improve their long-term health; however, high-quality empirical knowledge is sparse. OBJECTIVE: The Physical Activity and Fitness in Childhood Cancer Survivors (PACCS) study comprises 4 work packages (WPs) aiming for the objective determination of PA and self-reported health behavior, fatigue, and quality of life (WP 1); physical fitness determination (WP 2); the evaluation of barriers to and facilitators of PA (WP 1 and 3); and the feasibility testing of an intervention to increase PA and physical fitness (WP 4). METHODS: The PACCS study will use a mixed methods design, combining patient-reported outcome measures and objective clinical and physiological assessments with qualitative data gathering methods. A total of 500 survivors of childhood cancer aged 9 to 18 years with ≥1 year after treatment completion will be recruited in follow-up care clinics in Norway, Denmark, Finland, Germany, and Switzerland. All participants will participate in WP 1, of which approximately 150, 40, and 30 will be recruited to WP 2, WP3, and WP 4, respectively. The reference material for WP 1 is available from existing studies, whereas WP 2 will recruit healthy controls. PA levels will be measured using ActiGraph accelerometers and self-reports. Validated questionnaires will be used to assess health behaviors, fatigue, and quality of life. Physical fitness will be measured by a cardiopulmonary exercise test, isometric muscle strength tests, and muscle power and endurance tests. Limiting factors will be identified via neurological, pulmonary, and cardiac evaluations and the assessment of body composition and muscle size. Semistructured, qualitative interviews, analyzed using systematic text condensation, will identify the perceived barriers to and facilitators of PA for survivors of childhood cancer. In WP 4, we will evaluate the feasibility of a 6-month personalized PA intervention with the involvement of local structures. RESULTS: Ethical approvals have been secured at all participating sites (Norwegian Regional Committee for Medical Research Ethics [2016/953 and 2018/739]; the Oslo University Hospital Data Protection Officer; equivalent institutions in Finland, Denmark [file H-19032270], Germany, and Switzerland [Ethics Committee of Northwestern and Central Switzerland, project ID: 2019-00410]). Data collection for WP 1 to 3 is complete. This will be completed by July 2022 for WP 4. Several publications are already in preparation, and 2 have been published. CONCLUSIONS: The PACCS study will generate high-quality knowledge that will contribute to the development of an evidence-based PA intervention for young survivors of childhood cancer to improve their long-term care and health. We will identify physiological, psychological, and social barriers to PA that can be targeted in interventions with immediate benefits for young survivors of childhood cancer in need of rehabilitation. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/35838.

Effects of a Partially Supervised Conditioning Program in Cystic Fibrosis: An International Multicenter, Randomized Controlled Trial (ACTIVATE-CF).

Rationale: The long-term effects of vigorous physical activity (PA) on lung function in cystic fibrosis are unclear. Objectives: To evaluate effects of a 12-month partially supervised PA intervention using motivational feedback. Methods: In a parallel-arm multicenter randomized controlled trial (ACTIVATE-CF), relatively inactive patients aged at least 12 years were randomly assigned (1:1 ratio) to an intervention group or control group. The intervention group consented to add 3 hours of vigorous PA per week, whereas the control group was asked not to change their PA behavior. Primary endpoint was change in percent predicted FEV1 (ΔFEV1) at 6 months. Secondary endpoints included PA, exercise capacity, exercise motives, time to first exacerbation and exacerbation rates, quality of life, anxiety, depression, stress, and blood glucose control. Data were analyzed using mixed linear models. Measurements and Main Results: A total of 117 patients (40% of target sample size) were randomized to an intervention (n = 60) or control group (n = 57). After 6 months, ΔFEV1 was significantly higher in the control group compared with the intervention group (2.70% predicted [95% confidence interval, 0.13-5.26]; P = 0.04). The intervention group reported increased vigorous PA compared with the control group at each study visit, had higher exercise capacity at 6 and 12 months, and higher PA at 12 months. No effects were seen in other secondary outcomes. Conclusions: ACTIVATE-CF increased vigorous PA and exercise capacity, with effects carried over for the subsequent 6 months, but resulted in better FEV1 in the control group.

Children's moderate-to-vigorous physical activity on weekdays versus weekend days: a multi-country analysis.

PURPOSE: The Structured Days Hypothesis (SDH) posits that children's behaviors associated with obesity - such as physical activity - are more favorable on days that contain more 'structure' (i.e., a pre-planned, segmented, and adult-supervised environment) such as school weekdays, compared to days with less structure, such as weekend days. The purpose of this study was to compare children's moderate-to-vigorous physical activity (MVPA) levels on weekdays versus weekend days using a large, multi-country, accelerometer-measured physical activity dataset. METHODS: Data were received from the International Children's Accelerometer Database (ICAD) July 2019. The ICAD inclusion criteria for a valid day of wear, only non-intervention data (e.g., baseline intervention data), children with at least 1 weekday and 1 weekend day, and ICAD studies with data collected exclusively during school months, were included for analyses. Mixed effects models accounting for the nested nature of the data (i.e., days within children) assessed MVPA minutes per day (min/day MVPA) differences between weekdays and weekend days by region/country, adjusted for age, sex, and total wear time. Separate meta-analytical models explored differences by age and country/region for sex and child weight-status. RESULTS/FINDINGS: Valid data from 15 studies representing 5794 children (61% female, 10.7 ± 2.1 yrs., 24% with overweight/obesity) and 35,263 days of valid accelerometer data from 5 distinct countries/regions were used. Boys and girls accumulated 12.6 min/day (95% CI: 9.0, 16.2) and 9.4 min/day (95% CI: 7.2, 11.6) more MVPA on weekdays versus weekend days, respectively. Children from mainland Europe had the largest differences (17.1 min/day more MVPA on weekdays versus weekend days, 95% CI: 15.3, 19.0) compared to the other countries/regions. Children who were classified as overweight/obese or normal weight/underweight accumulated 9.5 min/day (95% CI: 6.9, 12.2) and 10.9 min/day (95% CI: 8.3, 13.5) of additional MVPA on weekdays versus weekend days, respectively. CONCLUSIONS: Children from multiple countries/regions accumulated significantly more MVPA on weekdays versus weekend days during school months. This finding aligns with the SDH and warrants future intervention studies to prioritize less-structured days, such as weekend days, and to consider providing opportunities for all children to access additional opportunities to be active.

Physical fitness and modifiable cardiovascular disease risk factors in survivors of childhood cancer: A report from the SURfit study.

BACKGROUND: Childhood cancer survivors are at risk for cardiovascular disease (CVD) because of intensive cancer therapies often accompanied by an unhealthy lifestyle. This study was aimed at 1) describing modifiable CVD risk factors in survivors and 2) investigating the association between different aspects of physical fitness and CVD risk factors. METHODS: The authors analyzed cross-sectional data from ≥5-year survivors who were 16 years old or younger at their cancer diagnosis and 16 years old or older at the time of the study. Single CVD risk factors (waist circumference, blood pressure, fasting glucose, inverse high-density lipoprotein, and triglycerides), a composite CVD risk score (combined z scores of all CVD risk factors), and metabolic syndrome were evaluated. Physical fitness measures included cardiopulmonary exercise testing (CPET), a handgrip test, and a 1-minute sit-to-stand test (STS). Multivariable logistic regression was used for the association between fitness measures and CVD risk factors, with adjustments made for demographic factors and cancer therapy. RESULTS: This study included 163 survivors with a median age at diagnosis of 7 years and a median age at the time of the study of 28 years. Among those survivors, 27% had a high waist circumference, 32% had high blood pressure, 19% had high triglycerides, 20% had an increased composite CVD risk score, and 10% had metabolic syndrome. A better performance during CPET, handgrip testing, and STS was associated with a lower probability of having a high waist circumference, high triglycerides, and metabolic syndrome. CONCLUSIONS: Better aerobic fitness (CPET) and, to a lesser extent, handgrip and STS were associated with fewer CVD risk factors. Further investigations are warranted to investigate which fitness measures should preferably be used to screen survivors to promote physical activity in those with impaired test performance. LAY SUMMARY: This study investigated the relationship between physical fitness of adult childhood cancer survivors and their risk factors for cardiovascular disease. Cardiovascular risk factors such as high blood pressure, a high waist circumference, and high blood lipids were frequently found in childhood cancer survivors. Survivors with better physical fitness (measured by a cycling test or simple strength and endurance tests) had a lower chance of having cardiovascular risk factors. This suggests that childhood cancer survivors could benefit from physical activity and general fitness by increasing their physical fitness and possibly decreasing their risk of cardiovascular disease.

Variations in accelerometry measured physical activity and sedentary time across Europe - harmonized analyses of 47,497 children and adolescents.

BACKGROUND: Levels of physical activity and variation in physical activity and sedentary time by place and person in European children and adolescents are largely unknown. The objective of the study was to assess the variations in objectively measured physical activity and sedentary time in children and adolescents across Europe. METHODS: Six databases were systematically searched to identify pan-European and national data sets on physical activity and sedentary time assessed by the same accelerometer in children (2 to 9.9 years) and adolescents (≥10 to 18 years). We harmonized individual-level data by reprocessing hip-worn raw accelerometer data files from 30 different studies conducted between 1997 and 2014, representing 47,497 individuals (2-18 years) from 18 different European countries. RESULTS: Overall, a maximum of 29% (95% CI: 25, 33) of children and 29% (95% CI: 25, 32) of adolescents were categorized as sufficiently physically active. We observed substantial country- and region-specific differences in physical activity and sedentary time, with lower physical activity levels and prevalence estimates in Southern European countries. Boys were more active and less sedentary in all age-categories. The onset of age-related lowering or leveling-off of physical activity and increase in sedentary time seems to become apparent at around 6 to 7 years of age. CONCLUSIONS: Two third of European children and adolescents are not sufficiently active. Our findings suggest substantial gender-, country- and region-specific differences in physical activity. These results should encourage policymakers, governments, and local and national stakeholders to take action to facilitate an increase in the physical activity levels of young people across Europe.

High impact physical activity and bone health of lower extremities in childhood cancer survivors: A cross-sectional study of SURfit.

Childhood cancer survivors (CCS) are at risk of reduced bone health and premature osteoporosis. As physical activity with high impact loading (IL-PA) is known to promote bone health, we compared bone densitometry and microstructure between groups of CCS who performed different amounts of physical activities in their daily life. We used baseline data of a single-center PA trial including 161 CCS from the Swiss Childhood Cancer Registry, aged <16 at diagnosis, ≥16 at study and ≥5 years since diagnosis. Lower body bone health was assessed with peripheral quantitative computed tomography (pQCT) and dual-energy X-ray absorptiometry (DXA). Daily IL-PA (duration in activities >2 g acceleration and numbers of vertical impacts/hr >2 g) was captured using hip-worn accelerometers (1-3 weeks). For both IL-PA approaches, we formed low, middle and high activity groups based on tertiles. Bone health of the high and middle active groups was compared to the low active group. 63% of CCS had indication of at least one bone mineral density z-score ≤ -1 measured by pQCT or DXA. The high IL-PA group performing 2.8 min/day or 19.1 impact peaks/hr > 2 g (median) showed about 3-13% better microstructural and densitometric bone health as compared to the low IL-PA group with 0.38 min/day or 0.85 peaks/hr > 2 g. Just a few minutes and repetitions of high IL-PA as easily modifiable lifestyle factor may be sufficient to improve bone health in adult CCS. Future longitudinal research is needed to better understand pattern and dosage of minimal impact loading needed to strengthen bone in growing and adult CCS.

Correction to: A closer look at the relationship among accelerometer-based physical activity metrics: ICAD pooled data.

Following publication of the original article [1], the author reported that the name of the collaborator group was missing from the author group.

A closer look at the relationship among accelerometer-based physical activity metrics: ICAD pooled data.

BACKGROUND: Accelerometers are widely used to assess child physical activity (PA) levels. Using the accelerometer data, several PA metrics can be estimated. Knowledge about the relationships between these different metrics can improve our understanding of children's PA behavioral patterns. It also has significant implications for comparing PA metrics across studies and fitting a statistical model to examine their health effects. The aim of this study was to examine the relationships among the metrics derived from accelerometers in children. METHODS: Accelerometer data from 24,316 children aged 5 to 18 years were extracted from the International Children's Accelerometer Database (ICAD) 2.0. Correlation coefficients between wear time, sedentary behavior (SB), light-intensity PA (LPA), moderate-intensity PA (MPA), vigorous-intensity PA (VPA), moderate- and vigorous-intensity PA (MVPA), and total activity counts (TAC) were calculated. RESULTS: TAC was approximately 22X103 counts higher (p < 0.01) with longer wear time (13 to 18 h/day) as compared to shorter wear time (8 to < 13 h/day), while MVPA was similar across the wear time categories. MVPA was very highly correlated with TAC (r = .91; 99% CI = .91 to .91). Wear time-adjusted correlation between SB and LPA was also very high (r = -.96; 99% CI = -.96, - 95). VPA was moderately correlated with MPA (r = .58; 99% CI = .57, .59). CONCLUSIONS: TAC is mostly explained by MVPA, while it could be more dependent on wear time, compared to MVPA. MVPA appears to be comparable across different wear durations and studies when wear time is ≥8 h/day. Due to the moderate to high correlation between some PA metrics, potential collinearity should be addressed when including multiple PA metrics together in statistical modeling.

Cardiopulmonary Exercise Testing Provides Additional Prognostic Information in Cystic Fibrosis.

RATIONALE: The prognostic value of cardiopulmonary exercise testing (CPET) for survival in cystic fibrosis (CF) in the context of current clinical management, when controlling for other known prognostic factors, is unclear. OBJECTIVES: To determine the prognostic value of CPET-derived measures beyond peak oxygen uptake ( V. o2peak) following rigorous adjustment for other predictors. METHODS: Data from 10 CF centers in Australia, Europe, and North America were collected retrospectively. A total of 510 patients completed a cycle CPET between January 2000 and December 2007, of which 433 fulfilled the criteria for a maximal effort. Time to death/lung transplantation was analyzed using Cox proportional hazards regression. In addition, phenotyping using hierarchical Ward clustering was performed to characterize high-risk subgroups. MEASUREMENTS AND MAIN RESULTS: Cox regression showed, even after adjustment for sex, FEV1% predicted, body mass index (z-score), age at CPET, Pseudomonas aeruginosa status, and CF-related diabetes as covariates in the model, that V. o2peak in % predicted (hazard ratio [HR], 0.964; 95% confidence interval [CI], 0.944-0.986), peak work rate (% predicted; HR, 0.969; 95% CI, 0.951-0.988), ventilatory equivalent for oxygen (HR, 1.085; 95% CI, 1.041-1.132), and carbon dioxide (HR, 1.060; 95% CI, 1.007-1.115) (all P < 0.05) were significant predictors of death or lung transplantation at 10-year follow-up. Phenotyping revealed that CPET-derived measures were important for clustering. We identified a high-risk cluster characterized by poor lung function, nutritional status, and exercise capacity. CONCLUSIONS: CPET provides additional prognostic information to established predictors of death/lung transplantation in CF. High-risk patients may especially benefit from regular monitoring of exercise capacity and exercise counseling.