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Purpose: The magnitude of cardiorespiratory fitness (CRF) impairment during anticancer treatment and CRF response to aerobic exercise training (AT) are highly variable. The aim of this ancillary analysis was to leverage machine learning approaches to identify patients at high risk of impaired CRF and poor CRF response to AT., Methods: We evaluated heterogeneity in CRF among 64 women with metastatic breast cancer randomly assigned to 12 weeks of highly structured AT (n = 33) or control (n = 31). Unsupervised hierarchical cluster analyses were used to identify representative variables from multidimensional prerandomization (baseline) data, and to categorize patients into mutually exclusive subgroups (ie, phenogroups). Logistic and linear regression evaluated the association between phenogroups and impaired CRF (ie, ≤16 mL O 2 ·kg -1 ·min -1 ) and CRF response., Results: Baseline CRF ranged from 10.2 to 38.8 mL O 2 ·kg -1 ·min -1 ; CRF response ranged from -15.7 to 4.1 mL O 2 ·kg -1 ·min -1 . Of the n = 120 candidate baseline variables, n = 32 representative variables were identified. Patients were categorized into two phenogroups. Compared with phenogroup 1 (n = 27), phenogroup 2 (n = 37) contained a higher number of patients with none or >three lines of previous anticancer therapy for metastatic disease and had lower resting left ventricular systolic and diastolic function, cardiac output reserve, hematocrit, lymphocyte count, patient-reported outcomes, and CRF ( P < .05) at baseline. Among patients allocated to AT (phenogroup 1, n = 12; 44%; phenogroup 2, n = 21; 57%), CRF response (-1.94 ± 3.80 mL O 2 ·kg -1 ·min -1 v 0.70 ± 2.22 mL O 2 ·kg -1 ·min -1 ) was blunted in phenogroup 2 compared with phenogroup 1., Conclusion: Phenotypic clustering identified two subgroups with unique baseline characteristics and CRF outcomes. The identification of CRF phenogroups could help improve cardiovascular risk stratification and guide investigation of targeted exercise interventions among patients with cancer.

Background: Research on cardiorespiratory fitness (CRF) in relation to physical activity (PA) and fatigue after stroke is limited. Increased knowledge of interrelationships between these factors can help optimize rehabilitation strategies and improve health-outcomes., Objectives: We aimed to: 1) evaluate CRF, PA, and fatigue, 2) characterize patients with impaired versus non-impaired CRF, and 3) examine associations of CRF with PA and fatigue, three months after first-ever ischemic stroke., Methods: In this cross-sectional study CRF was measured as peak oxygen uptake (VO 2peak ) by cardiopulmonary exercise testing. PA was measured using accelerometers. Fatigue was assessed with the 7-item Fatigue Severity Scale (FSS)., Results: The sample (n=74, mean age 64±13 years, 36% women) had a mean VO 2peak of 27.0±8.7 (86% of predicted). Fifty-one percent met the World Health Organization's recommendation of ≥150 min of moderate PA/week. Mean steps-per-day was 9316±4424 (113% of predicted). Thirty-five percent of the sample had moderate-to-high fatigue (FSS≥4), mean FSS score was 3.2±1.8.  Patients with impaired CRF (VO 2peak <80% of predicted) had higher body-fat-percent (p<0.01), less moderate-to-vigorous PA (MVPA) (p<0.01) and a trend toward higher fatigue (p=0.053) compared to the non-impaired. Backward regression analysis showed that higher CRF was associated with more MVPA (unstandardized beta [95% CI]: 0.38 [0.15, 0.63], p=0.002) and less fatigue (unstandardized beta [95% CI]: -3.9 [-6.4, -1.6], p=0.004)., Conclusions: Stroke patients had lower CRF compared to reference values. Impaired CRF was mainly related to overweight. Higher CRF was associated with more MVPA and less fatigue. Exercise after stroke may be especially beneficial for patients with impaired CRF.

Objective: Offspring of parents with schizophrenia spectrum disorders (SSD) have an increased risk of neurodevelopmental disturbances. However, the ability to provide very early interventions to support these children and their families requires profound knowledge regarding characteristic features of both the parents and their offspring. Information on this subject is currently sparse. The aim of the present study is to investigate clinical and sociodemographic variables in offspring in the age range of 0-3 years of mothers diagnosed with SSD., Methods: The study is descriptive with a cross-sectional design and includes parent-child dyads consisting of mothers diagnosed with SSD (ICD-10: F20-29) and their offspring aged 0-3 years, who were referred for examination and intervention at the infant and toddler psychiatric units, at the Mental Health Services, Capital Region, Copenhagen University Hospitals in two locations (Bispebjerg and Glostrup). Clinical and sociodemographic data were extracted from the Copenhagen "Infant Psychiatric Database" and processed by descriptive analysis., Results: Out of 95 parent-child dyads considered for the study population, 85 were included. 27.8% of the mothers had psychiatric comorbidities, and 18.9% of the fathers had a psychiatric diagnosis at the time of investigation. Of the children, 89.7% were born full term (≥37th week) and most of them had a birth weight of ≥2500 g (81.8%). Of the mothers, 50% had experienced pregnancy complications of varying severity. Birth complications were seen in 62.9% of the dyads. Psychopathology was identified in 50% of the children at age 0-3 years, and 62.2% of the parent-child dyads appeared to have an affected relationship., Conclusion: Results show widespread psychopathology in offspring aged 0-3 years of mothers with SSD. Moreover, several psychosocial stressors, clinical parental features, and relational disturbances are identified. These results contribute to a better understanding and identification of early risk markers of long-term psychopathology in this infant patient group, and hence serve as potential targets for early interventions., (© 2023 The Authors. Acta Psychiatrica Scandinavica published by John Wiley & Sons Ltd.)

Blood volume (BV) is an important clinical parameter and is usually reported per kg of body mass (BM). When fat mass is elevated, this underestimates BV/BM. One aim was to study if differences in BV/BM related to sex, age, and fitness would decrease if normalized to lean body mass (LBM). The analysis included 263 women and 319 men (age: 10-93 years, body mass index: 14-41 kg/m 2 ) and 107 athletes who underwent assessment of BV and hemoglobin mass (Hb mass ), body composition, and cardiorespiratory fitness. BV/BM was 25% lower (70.3 ± 11.3 and 80.3 ± 10.8 mL/kg BM ) in women than men, respectively, whereas BV/LBM was 6% higher in women (110.9 ± 12.5 and 105.3 ± 11.2 mL/kg LBM ). Hb mass /BM was 34% lower (8.9 ± 1.4 and 11.5 ± 11.2 g/kg BM ) in women than in men, respectively, but only 6% lower (14.0 ± 1.5 and 14.9 ± 1.5 g/kg LBM )/LBM. Age did not affect BV. Athlete's BV/BM was 17.2% higher than non-athletes, but decreased to only 2.5% when normalized to LBM. Of the variables analyzed, LBM was the strongest predictor for BV (R 2  = .72, p < .001) and Hb mass (R 2  = .81, p < .001). These data may only be valid for BV/Hb mass when assessed by CO re-breathing. Hb mass /LBM could be considered a valuable clinical matrix in medical care aiming to normalize blood homeostasis., (© 2023 The Authors. American Journal of Hematology published by Wiley Periodicals LLC.)

Aims: To objectively study cardiorespiratory fitness (CRF) and physical activity (PA) and to evaluate limiting factors of exercise intolerance associated with poor CRF after severe pre-eclampsia., Methods: In this single-centre, cross-sectional study, CRF was measured as peak oxygen uptake (VO 2peak ) during a cardiopulmonary exercise test (CPET) on a treadmill in women 7 years after severe pre-eclampsia. Ninety-six patients and 65 controls were eligible to participate. Cardiac output (CO) was measured by impedance cardiography. PA was measured using accelerometers., Results: In 62 patients and 35 controls (mean age 40 ± 3 years), the VO 2peak (in mL·kg-1·min-1) values were 31.4 ± 7.2 and 39.1 ± 5.4, respectively (p<0.01). In the patients, the COpeak was (9.6 L·min-1), 16% lower compared to controls (p<0.01). Twelve patients (19%) had a cardiac limitation to CPET. Twenty-three (37%) patients and one (3%) control were classed as unfit, with no cardiopulmonary limitations. The patients demonstrated 25% lower PA level (in counts per minute; p<0.01) and 14% more time being sedentary (p<0.01), compared with the controls. Twenty-one patients (34%) compared with four (17%) controls did not meet the World Health Organization's recommendations for PA (p=0.02). Body mass index and PA level accounted for 65% of the variability in VO 2peak ., Conclusion: Significantly lower CRF and PA levels were found in patients on long-term follow-up after severe pre-eclampsia. CPET identified cardiovascular limitations in one third of patients. One third appeared unfit, with adiposity and lower PA levels. These findings highlight the need for clinical follow-up and exercise interventions after severe pre-eclampsia.

Background: It has been hypothesized that post-stroke fatigue (PSF) is associated with reduced physical activity (PA) and impaired physical fitness (fitness). Understanding associations between PSF and PA, and/or fitness could help guide the development of targeted exercise interventions to treat PSF., Aims: Our systematic review and meta-analysis aimed to investigate PSF's associations with PA and fitness., Summary of Review: Following a registered protocol, we included studies with cross-sectional or prospective observational designs, published in English or a Scandinavian language, which reported an association of PSF with PA and/or fitness in adult stroke survivors. We searched MEDLINE, Embase, AMED, CINAHL, PsycINFO, ClinicalTrials.gov, and World Health Organization's International Clinical Trials Registry Platform from inception to November 30, 2022. Risk of bias was assessed using Quality in Prognosis Studies. Thirty-two unique studies (total n = 4721 participants, 55% male), and three study protocols were included. We used random-effects meta-analysis to pool data for PA and fitness outcomes, and vote-counting of direction of association to synthesize data that could not be meta-analyzed. We found moderate-certainty evidence of a weak association between higher PSF and impaired fitness (meta r  = -0.24; 95% confidence interval (CI) = -0.33, -0.15; n = 905, 7 studies), and very low-certainty evidence of no association between PSF and PA (meta r  = -0.09; 95% CI = -0.34, 0.161; n = 430, 3 studies). Vote-counting showed a higher proportion of studies with associations between higher PSF and impaired fitness (pˆ = 0.83; 95% CI = 0.44, 0.97; p = 0.22, n = 298, 6 studies), and with associations between higher PSF and lower PA (pˆ = 0.75; 95% CI = 0.51, 0.90; p = 0.08, n = 2566, 16 studies). Very low- to moderate-certainty evidence reflects small study sample sizes, high risk of bias, and inconsistent results., Conclusions: The meta-analysis showed moderate-certainty evidence of an association between higher PSF and impaired fitness. These results indicate that fitness might protect against PSF. Larger prospective studies and randomized controlled trials evaluating the effect of exercise on PSF are needed to confirm these findings., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Cancer therapy-related cardiotoxicity is a major cause of cardiovascular morbidity in childhood cancer survivors. The aims of this study were to investigate systolic myocardial function and its association to cardiorespiratory fitness in pediatric childhood cancer survivors., Methods: In this sub-study of the international study "Physical Activity and fitness in Childhood Cancer Survivors" (PACCS), echocardiographic measures of left ventricular global longitudinal strain (LV-GLS) and right ventricular longitudinal strain (RV-LS) were measured in 128 childhood cancer survivors aged 9-18 years and in 23 age- and sex-matched controls. Cardiorespiratory fitness was measured as peak oxygen consumption achieved on treadmill and correlated to myocardial function., Results: Mean LV-GLS was reduced in the childhood cancer survivors compared to the controls, -19.7% [95% confidence interval (CI) -20.1% to -19.3%] vs. -21.3% (95% CI: -22.2% to -20.3%) ( p  = 0.004), however, mainly within normal range. Only 13% of the childhood cancer survivors had reduced LV longitudinal strain z -score. Mean RV-LS was similar in the childhood cancer survivors and the controls, -23.2% (95% CI: -23.7% to -22.6%) vs. -23.3% (95% CI: -24.6% to -22.0%) ( p  = 0.8). In the childhood cancer survivors, lower myocardial function was associated with lower peak oxygen consumption [correlation coefficient ( r ) = -0.3 for LV-GLS]. Higher doses of anthracyclines ( r  = 0.5 for LV-GLS and 0.2 for RV-LS) and increasing time after treatment ( r  = 0.3 for LV-GLS and 0.2 for RV-LS) were associated with lower myocardial function., Conclusions: Left ventricular function, but not right ventricular function, was reduced in pediatric childhood cancer survivors compared to controls, and a lower left ventricular myocardial function was associated with lower peak oxygen consumption. Furthermore, higher anthracycline doses and increasing time after treatment were associated with lower myocardial function, implying that long-term follow-up is important in this population at risk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Engan, Diab, Brun, Raastad, Torsvik, Omdal, Ghavidel, Greve, Ruud, Edvardsen and Leirgul.)

Background: Anthracycline-based chemotherapy has been mainstay of adjuvant breast cancer therapy for decades. Although effective, anthracyclines place long-term breast cancer survivors at risk of late effects, such as reduced cardiorespiratory fitness and increased risk of cardiovascular disease. Previous research has shown beneficial effects of exercise training on cardiorespiratory fitness, but the effects of exercise on limiting factors for cardiorespiratory fitness, cardiovascular risk factors, and patient-reported outcomes in long-term survivors are less clear. Whether previous exposure to breast cancer therapy modulates the effects of exercise is also unknown., Objective: The primary aim of the CAUSE (Cardiovascular Survivors Exercise) trial is to examine the effect of aerobic exercise on cardiorespiratory fitness in anthracycline-treated long-term breast cancer survivors. Secondary aims are to examine effects of exercise training on limiting factors for cardiorespiratory fitness, cardiovascular risk factors, and patient-reported outcomes, and to compare baseline values and effects of exercise training between similar-aged women with and those without prior breast cancer. A third aim is to examine the 24-month postintervention effects of aerobic exercise on primary and secondary outcomes., Methods: The CAUSE trial is a 2-armed randomized controlled trial, where 140 long-term breast cancer survivors, 8-12 years post diagnosis, are assigned to a 5-month nonlinear aerobic exercise program with 3 weekly sessions or to standard care. Seventy similar-aged women with no history of cancer will undergo the same exercise program. Cardiorespiratory fitness measured as peak oxygen consumption (VO 2peak ), limiting factors for VO 2peak (eg, cardiac function, pulmonary function, hemoglobin mass, blood volume, and skeletal muscle characteristics), cardiovascular risk factors (eg, hypertension, diabetes, dyslipidemia, obesity, physical activity level, and smoking status), and patient-reported outcomes (eg, body image, fatigue, mental health, and health-related quality of life) will be assessed at baseline, post intervention, and 24 months post intervention., Results: A total of 209 patients were included from October 2020 to August 2022, and postintervention assessments were completed in January 2023. The 24-month follow-up will be completed in February 2025., Conclusions: The findings from the CAUSE trial will provide novel scientific understanding of the potential benefits of exercise training in long-term breast cancer survivors., Trial Registration: ClinicalTrials.gov NCT04307407; https://clinicaltrials.gov/ct2/show/NCT04307407., International Registered Report Identifier (irrid): DERR1-10.2196/45244., (©Tormod Skogstad Nilsen, Mali Sæter, Sebastian Imre Sarvari, Kristin Valborg Reinertsen, Sara Hassing Johansen, Elisabeth Rustad Edvardsen, Jostein Hallén, Elisabeth Edvardsen, May Grydeland, Cecilie Essholt Kiserud, Hanne Cathrine Lie, Paul André Solberg, Torbjørn Wisløff, Adam Philip Sharples, Truls Raastad, Kristina Hermann Haugaa, Lene Thorsen. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 15.03.2023.)

Background: Childhood cancer survivors (CCS) are at risk of polyneuropathy due to chemotherapy, but studies in young survivors are scarce and diagnosis is challenging. We aimed to study the presence of polyneuropathy and the possible effect of cumulative doses of chemotherapeutic agents in a representative group of adolescent survivors., Methods: CCS aged nine to 18 years and age- and sex-matched controls were recruited from the cross-sectional Physical Activity and Fitness among Childhood Cancer Survivors (PACCS) study. CCS with various cancer diagnoses who had ended cancer treatment one year or more before study were included. Polyneuropathy was evaluated clinically and with nerve conduction studies (NCSs) in three motor and five sensory nerves. We used mixed-effects linear regression models to compare CCS and controls, and investigate possible associations between cumulative chemotherapy doses and NCS amplitudes., Results: A total of 127 CCS and 87 controls were included, with 14% CCS having probable or confirmed polyneuropathy. NCS amplitudes were lower in survivors compared with controls in all nerves. The largest mean difference was 3.47 μV (95% confidence interval [CI], 2.18 to 4.75) in the tibial plantar medial sensory and 1.91 mV (95% CI, 0.78 to 3.04) in the tibial motor nerve. The cumulative dose of platinum derivatives was associated with lower tibial motor nerve amplitude (-0.20; 95% CI, -0.35 to -0.04 mV for 100 mg/m 2 dose increase) but not in other nerves. We found no significant associations between vinca alkaloids cumulative dose and amplitudes., Conclusions: CCS without clinical signs or symptoms of polyneuropathy may have subtle nerve affection. The clinical long-term impact of this novel observation should be evaluated in larger, longitudinal studies., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Genetic introgression of farmed salmon into wild populations can damage the genetic integrity of wild stocks and is therefore considered as an environmental threat. One possible solution is to induce sterility in farmed salmon. We have searched for proteins potentially essential for germline survival in Atlantic salmon. One of these is the argonaute protein Piwil1, known to be required for germ cell survival. To examine Piwil1 function in salmon, we induced indels in the N domain by CRISPR-Cas9. The encoded domain is present in all vertebrate Piwi proteins and has been linked to Tdrd1 protein interaction and PAZ lobe structure. The F0 founder generation of piwil1 crispant males and females displayed a mosaic pattern of piwil1 mutations, exhibiting highly mutated alleles (53%-97%) in their fin gDNA samples. In general, piwil1 crispants carried germ cells, went through puberty and became fertile, although a transient and partial germ cell loss and delays during the spermatogenic process were observed in many male crispants, suggesting that Piwil1 functions during salmon spermatogenesis. By crossing highly mutated F0 founders, we produced F1 fish with a mixture of: loss-of-function alleles ( - ); functional in frame mutated alleles ( + ) and wt alleles ( + ). In F1, all piwil1 -/- fish lacked germ cells, while piwil1 +/+ siblings showed normal ovaries and testes. Yet, most juvenile F1 piwil1 +/ - males and females displayed an intermediate phenotype with a higher somatic/germ cell ratio without an increase in germ cell apoptosis, suggestive of a gene dose effect on the number of germ cells and/or insufficient replacement of lost germ cells in heterozygous fish. Interestingly, the two longest in-frame indels in the N domain also ensured germ cell loss. Hence, the loss of 4-6 aa in this region Phe130 - Ser136 may result in crucial changes of the protein structure, potentially affecting piRNA binding of the PAZ lobe, and/or affecting the binding of Piwil1 interacting proteins such as Tdrd protein, with critical consequences for the survival of primordial germ cells. In conclusion, we show that loss of piwil1 leads to loss of germ cells in salmon and that part of the N domain of Piwil1 is crucial for its function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 F. L, K. O, E, L, R. B, B, P. G, T. J, R. W and A.)

Background: Estimated peak oxygen consumption (Vo 2 peak) is widely used in oncology; however, estimated Vo 2 peak equations were developed in noncancer settings., Objectives: The aim of this study was to evaluate the validity of estimated Vo 2 peak in women with primary breast cancer and to develop oncology-specific estimated Vo 2 peak equations., Methods: Vo 2 peak was directly measured (TrueOne 2400, Parvo Medics) during 380 cardiopulmonary exercise tests in women previously treated for breast cancer (mean age: 59 ± 10 years; 3.1 ± 1.2 years post-therapy). The American College of Sports Medicine (ACSM), the Fitness Registry and the Importance of Exercise National Database (FRIEND), and heart failure (HF)-FRIEND equations were used to estimate Vo 2 peak. New equations were developed using patient and peak (Onc peak ) or submaximal (Onc sub ) exercise test characteristics., Results: The median differences between measured and estimated Vo 2 peak were 7.0 mL O 2 ·kg -1 ·min -1 , 3.9 mL O 2 ·kg -1 ·min -1 , and -0.2 mL O 2 ·kg -1 ·min -1 for ACSM, FRIEND, and HF-FRIEND, respectively. The number of estimated Vo 2 peak values within ±3.5 mL O 2 ·kg -1 ·min -1 of the measured values was 70 (18%), 164 (43%), and 306 (81%) for ACSM, FRIEND, and HF-FRIEND, respectively. The Onc peak and Onc Sub models included body mass index, age, a history of chemotherapy or radiation, the peak measured heart rate, and the treadmill grade and/or speed. The median differences between measured and estimated Vo 2 peak were 0.02 mL O 2 ·kg -1 ·min -1 (Onc peak ) and -0.2 mL O 2 ·kg -1 ·min -1 (Onc sub ). Eighty-six percent (n = 325) and 76% (n = 283) estimated Vo 2 peak values were within ±3.5 mL O 2 ·kg -1 ·min -1 of the measured Vo 2 peak values for Onc peak and Onc sub , respectively., Conclusions: HF-FRIEND or oncology-specific equations could be applied to estimate Vo 2 peak in patients previously treated for breast cancer in settings where cardiopulmonary exercise tests are not available. (Trial Comparing the Effects of Linear Versus Nonlinear Aerobic Training in Women With Operable Breast Cancer [EXCITE]; NCT01186367., Competing Interests: This study was supported by a research grant from the National Cancer Institute (R01-CA142566) awarded to Dr Jones and grants from AKTIV Against Cancer and the Memorial Sloan Kettering Cancer Center Support Grant/Core Grant (P30 CA008748). Dr Jones has stock ownership in Pacylex, Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

The role of dysfunction of the single ventricle in Fontan failure is incompletely understood. We aimed to evaluate hemodynamic responses to preload increase in Fontan circulation, to determine whether circulatory limitations in different locations identified by experimental preload increase are associated with cardiorespiratory fitness (CRF), and to assess the impact of left versus right ventricular morphology. In 38 consecutive patients (median age = 16.6 years, 16 females), heart catheterization was supplemented with a rapid 5-mL/kg body weight volume expansion. Central venous pressure (CVP), ventricular end-diastolic pressure (VEDP), and peak systolic pressure were averaged for 15‒30 s, 45‒120 s, and 4‒6 min (steady state), respectively. CRF was assessed by peak oxygen consumption (VO 2peak ) and ventilatory threshold (VT). Median CVP increased from 13 mmHg at baseline to 14.5 mmHg (p < 0.001) at steady state. CVP increased by more than 20% in eight patients. Median VEDP increased from 10 mmHg at baseline to 11.5 mmHg (p < 0.001). Ten patients had elevated VEDP at steady state, and in 21, VEDP increased more than 20%. The transpulmonary pressure difference (CVP‒VEDP) and CVP were consistently higher in patients with right ventricular morphology across repeated measurements. CVP at any stage was associated with VO 2peak and VT. VEDP after volume expansion was associated with VT. Preload challenge demonstrates the limitations beyond baseline measurements. Elevation of both CVP and VEDP are associated with impaired CRF. Transpulmonary flow limitation was more pronounced in right ventricular morphology. Ventricular dysfunction may contribute to functional impairment after Fontan operation in young adulthood.ClinicalTrials.gov identifier NCT02378857., (© 2021. The Author(s).)

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., (©Hanne C Lie, Sigmund Anderssen, Corina Silvia Rueegg, Truls Raastad, May Grydeland, Lene Thorsen, Trine Stensrud, Elisabeth Edvardsen, Marie Hamilton Larsen, Ingrid Kristin Torsvik, Lars Peder Bovim, Miriam Götte, Päivi Maria Lähteenmäki, Susi Kriemler, Hanne Bækgaard Larsen, Martin Kaj Fridh, Kristin Ørstavik, Henrik Brun, Iren Matthews, Else Hornset, Ellen Ruud. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 08.03.2022.)

Background: Poor cardiorespiratory fitness (CRF) is a cardinal feature of post-treatment primary lung cancer. The most effective exercise therapy regimen to improve CRF has not been determined., Methods: In this parallel-group factorial randomized controlled trial, lung cancer survivors with poor CRF (below age-sex sedentary values) were randomly allocated to receive 48 consecutive supervised sessions thrice weekly of (i) aerobic training (AT)-cycle ergometry at 55% to >95% of peak oxygen consumption (VO 2 peak); (ii) resistance training (RT)-lower and upper extremity exercises at 50-85% of maximal strength; (iii) combination training (CT)-AT plus RT; or (iv) stretching attention control (AC) for 16 weeks. The primary endpoint was change in CRF (VO 2 peak, mL O 2 ·kg -1 ·min -1 ). Secondary endpoints were body composition, muscle strength, patient-reported outcomes, tolerability (relative dose intensity of exercise), and safety. Analysis of covariance determined change in primary and secondary endpoints from baseline to post-intervention (Week 17) with adjustment for baseline values of the endpoint and other relevant clinical covariates., Results: Ninety patients (65 ± 9 years; 66% female) were randomized (AT, n = 24; RT, n = 23; CT, n = 20; and AC, n = 23) of the planned n = 160. No serious adverse events were observed. For the overall cohort, the lost-to-follow-up rate was 10%. Mean attendance was ≥75% in all groups. In intention-to-treat analysis, VO 2 peak increased 1.1 mL O 2 ·kg -1 ·min -1 [95% confidence interval (CI): 0.0, 2.2, P = 0.04] and 1.4 mL O 2 ·kg -1 ·min -1 (95% CI: 0.2, 2.5, P = 0.02) in AT and CT, respectively, compared with AC. There was no difference in VO 2 peak change between RT and AC (-0.1 mL O 2 ·kg -1 ·min -1 , 95% CI: -1.2, 1.0, P = 0.88). Favourable improvements in maximal strength and body composition were observed in RT and CT groups compared with AT and AC groups (Ps < 0.05). No between-group changes were observed for any patient-reported outcomes. Relative dose intensity of exercise was lower in RT and CT compared with AT (Ps < 0.05)., Conclusions: In the context of a smaller than planned sample size, AT and CT significantly improved VO 2 peak in lung cancer survivors; however, the tolerability-to-benefit ratio was superior for AT and hence may be the preferred modality to target impaired CRF in post-treatment lung cancer survivors., (© 2021 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background: Loss of bone mineral and skeletal muscle mass is common after lung transplantation (LTx), and physical activity (PA) may prevent further deterioration. We aimed to assess the effects of 20-week high-intensity training (HIT) on body composition, bone health, and PA in LTx recipients, 6-60 months after surgery., Methods: In a randomized controlled trial, 51 LTx recipients underwent Dual-energy X-ray absorptiometry (DXA), and PA level and sedentary time were objectively recorded by accelerometers for seven consecutive days. Of these, 39 participants completed the study, including 19 participants in the HIT group and 20 participants in the standard care group., Results: Following the intervention, ANCOVA models revealed a nonsignificant between-group difference for change in lean body mass (LBM) and bone mineral density (BMD) of the lumbar spine of 0.4% (95% CI = -3.2, 1.5) (p = .464) and 1.0% (95% CI=-1.3, 3.4) (p = .373), respectively. Trabecular bone score (TBS) of the lumbar spine (L1-L4), however, increased by 2.2 ± 5.0% in the exercise group and decreased by -1.6 ± 5.9% in the control group, giving a between-group difference of 3.8% (95% CI=0.1, 7.5) (p = .043). There were no between-group differences in PA or sedentary time., Conclusion: High-intensity training after LTx improved TBS significantly, but not PA, LBM or BMD., (© 2021 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Purpose: Survivors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at risk for cardiopulmonary adverse events. Data on long-term effects on cardiorespiratory fitness are limited. To address the gap in knowledge, we aimed to determine peak oxygen uptake (V̇O 2 peak) and identify associations between cardiorespiratory fitness and clinical characteristics, self-reported physical activity, cardiac, and pulmonary function., Methods: In a nationwide, single-center cross-sectional study, 90 survivors [aged median (range) 35 (17-54) years, 56% females] were examined, 17 (6-26) years after allo-HSCT. Myeloablative conditioning comprised busulfan/cyclophosphamide or cyclophosphamide only. Methods included pulmonary function tests, echocardiography, and cardiopulmonary exercise test., Results: Chronic graft-versus-host disease (cGVHD) was found in 31% of the subjects, of whom 40% had bronchiolitis obliterans syndrome (BOS). Seventy-one percent of the survivors did not meet WHO recommendations for physical activity and 42% were overweight. Reduced gas diffusion (DL CO ) and systolic ventricular dysfunction (LVEF) were found in 44% and 31%, respectively. For the group, mean (95% CI), V̇O 2 peak was 36.4 (34.7-38.0) mL/min/kg [89 (85-93)% of predicted]. V̇O 2 peak was low at 43%. Cardiopulmonary factors and deconditioning were equally common limitations for exercise. In a multiple linear regression model, low V̇O 2 peak was associated with low DL CO , low LVEF, BOS, overweight, and inactivity., Conclusion: Half of the survivors had reduced cardiorespiratory fitness median 17 years after allo-HSCT. Cardiopulmonary factors and deconditioning were equally common limitations to exercise. We encourage long-term cardiopulmonary monitoring of allo-HSCT survivors and targeted advice on modifiable lifestyle factors.

The randomized "Testicular cancer and Aerobic and Strength Training trial" (TAST-trial) aimed to evaluate the effect of high-intensity interval training (HIIT) on cardiorespiratory fitness during cisplatin-based chemotherapy (CBCT) for testicular cancer (TC). Here, we report on an unexpected high number of thromboembolic (TE) events among patients randomized to the intervention arm, and on a review of the literature on TE events in TC patients undergoing CBCT. Patients aged 18 to 60 years with a diagnosis of metastatic germ cell TC, planned for 3 to 4 CBCT cycles, were randomized to a 9 to 12 weeks exercise intervention, or to a single lifestyle counseling session. The exercise intervention included two weekly HIIT sessions, each with 2 to 4 intervals of 2 to 4 minutes at 85% to 95% of peak heart rate. The study was prematurely discontinued after inclusion of 19 of the planned 94 patients, with nine patients randomized to the intervention arm and 10 to the control arm. Three patients in the intervention arm developed TE complications; two with pulmonary embolism and one with myocardial infarction. All three patients had clinical stage IIA TC. No TE complications were observed among patients in the control arm. Our observations indicate that high-intensity aerobic training during CBCT might increase the risk of TE events in TC patients, leading to premature closure of the TAST-trial., (© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Peak oxygen uptake (VO 2peak ) remains low after lung transplantation (LTx). We evaluated the effect of high-intensity interval training (HIIT) on VO 2peak , muscular strength, health-related quality of life (HRQOL), pulmonary function, and physical function after LTx., Methods: In this randomized controlled trial, 54 participants were enrolled from 6 to 60 months after LTx. The HIIT group (n = 25) followed a supervised HIIT program, consisting of endurance and strength trainings 3 times a week for 20 weeks. The control group (n = 29) received usual care. The primary outcome was a change in VO 2peak measured by cardiopulmonary exercise testing. The secondary outcomes were changes in 1-repetition maximum (1RM) for arm press and leg press, HRQOL (36-Item Short-Form Health Survey [SF-36]), pulmonary function (forced expiratory volume in 1 sec, diffusing capacity of the lungs for carbon monoxide), and physical function (1RM in handgrip, 15-sec stair run, and 30-sec chair stand)., Results: A total of 46 participants completed the study, including 23 of 25 in the intervention group. For the primary outcome, the intention-to-treat analysis revealed a non-significant between-group difference for change in VO 2peak of 0.7 ml/(kg.min) (95% CI = ‒0.3, 1.8) (p = 0.17). The between-group differences for 1RM arm press and leg press and mental aspect of SF-36 were 4.9 kg (95% CI = ‒0.1, 9.9) (p = 0.05), 11.6 kg (95% CI = 0.1, 23.0) (p < 0.05), and 5.7 kg (95% CI = 0.9, 10.4) (p = 0.02), respectively. There were no between-group differences in pulmonary function or physical function. When excluding participants with an attendance of <70% (n = 16), the between-group difference for VO 2peak was 1.2 ml/(kg.min) (95% CI = 0.1, 2.4) (p = 0.032)., Conclusions: HIIT improved muscular strength and HRQOL but did not improve VO 2peak more than usual care after LTx. However, with acceptable adherence, HIIT appears to have beneficial effects on VO 2peak ., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate changes in pulmonary function and feasibility of portable continuous laryngoscopy during maximal uphill running., Methods: Healthy volunteers participated in an uphill race. Forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC) were obtained before and 5 and 10 min after finishing the race. Capillary blood lactate concentration ([BLa - ]) and Borg score for perceived exertion were registered immediately after the race. One participant wore a portable video-laryngoscope during the race, and the video was assessed for technical performance., Results: Twenty adult subjects participated with a mean (SD) age of 40.2 (9.7) years. Mean (SD) race duration and post-exercise [BLa - ] was 13.9 (2.3) min and 10.7 (2.1) mmol/L, respectively, and the median (range) Borg score for perceived exertion was 9 (5-10). Mean percentage change (95% CI) 5 and 10 min post-exercise in FEV 1 were 6.9 (3.7 to 10.2) % and 5.9 (2.7 to 9.0) %, respectively, and in FVC 5.2 (2.3 to 8.1) % and 4.7 (1.6 to 7.9) %, respectively. The recorded video of the larynx was of good quality., Conclusions: Maximal aerobic field exercise induced bronchodilatation in the majority of the healthy non-asthmatic participants. It is feasible to perform continuous video-laryngoscopy during heavy uphill exercise., Competing Interests: Competing interests: EE received salary from GlaxoSmithKline with no potential conflicts of interest with respect to the research, authorship and/or publication of this article. The other authors have no conflicts of interest relevant to this article to disclose., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Objectives: (1) To describe the cardiorespiratory fitness (CRF) in an adult cystic fibrosis population related to sex and age, (2) to evaluate the cause of low CRF and (3) to study the association between peak oxygen uptake (VO 2 peak) and forced expiratory volume in 1 s (FEV 1 )., Methods: A total of 204 cardiopulmonary treadmill exercise tests (CPETs) performed by 116 patients were included. VO 2 peak, gas exchange, heart rate, oxygen saturation and ventilatory variables were measured.A low CRF was defined as a VO 2 peak <80% of predicted, ventilatory limitation was defined as a breathing reserve <15%, exercise hypoxaemia was defined as an oxygen saturation <88% and ventilation-perfusion mismatch was defined as a minute ventilation/ventilatory equivalent for carbon dioxide slope ≥34. In patients who had performed three or more CPETs, the annual change in FEV 1 and VO 2 peak were calculated using linear regression., Results: The VO 2 peak was 40.6±11.5 and 35.2±8.9 mL kg -1 min -1 , which was 87±23 and 93±20 in percentage of predicted for men and women, respectively. VO 2 peak was moderately affected by age, for men (r=-0.36, p<0.001) and women (r=-0.53, p<0.001), respectively. In 45 of 101 tests where CRF was low, no cardiorespiratory limiting factors were identified. The correlation coefficient between VO 2 peak and FEV 1 was r=0.64 (p<0.001). In participants with a low CRF, FEV 1 ranged from 20% to 112% of predicted., Conclusions: The correlation between VO 2 peak and FEV 1 was moderate. The majority of the tests resulted in a VO 2 peak within normal limits. Interestingly, 44% of the tests with a low VO 2 peak could be explained by deconditioning. Thus, exercise therapy may be beneficial for these patients., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The original article [1] contains errors in Tables 1 and 3: Table 1 erroneously mentions use of a treadmill which should instead state 'bicycle', and Table 3 has a minor typesetting mistake.

Background: Low cardiorespiratory fitness and inactivity are common after lung transplantation (LTx). The causes of exercise intolerance are incompletely understood., Objectives: The aim of this study was to objectively assess cardiorespiratory fitness and physical activity, evaluate causes of exercise intolerance, and explore clinical factors associated with cardiorespiratory fitness after bilateral LTx (BLTx)., Materials and Methods: Peak oxygen uptake (V∙O2peak) and exercise-limiting factors were evaluated by a treadmill cardiopulmonary exercise test (CPET) 6-60 months after BLTx. Physical activity was measured with accelerometers, and results were compared with Norwegian normative data and the World Health Organization's (WHO) recommendations for physical activity., Results: In 54 included BLTx recipients (mean age 50 ± 15 years, 50% females), V∙O2peak (mL × kg-1 × min-1) was 21.8 ± 7.7 for men and 22.4 ± 6.2 for women, corresponding to 57 ± 17 and 70 ± 12% of predicted, respectively. Three patients (6%) met criteria for normal V∙O2peak. Deconditioning limited V∙O2peak in 22 patients (41%), while ventilatory limitation and abnormal gas exchange were observed in 14 (26%) and 20 (37%) patients, respectively (some had more than 1 finding). Forty-three patients (86%) did not meet the WHO physical activity recommendations. There was a moderate correlation between V∙O2peak and physical activity (r = 0.642, p < 0.01). Body mass index, physical activity, forced expiratory volume after 1 second, sex, and hemoglobin together accounted for 73% of the variability in V∙O2peak., Conclusions: Low cardiorespiratory fitness was observed in the majority of BLTx recipients. Both deconditioning and cardiopulmonary limitations were common findings. Nearly 90% were classified as being inactive according to physical activity recommendations. CPET appears to identify a deconditioned subgroup of BLTx recipients for whom exercise training may be especially beneficial., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Objective: To perform a comprehensive evaluation of and identify correlates for physical fitness in consecutive patients with juvenile idiopathic arthritis (JIA) who have been diagnosed in the era of biologics and to compare the results with those obtained in healthy controls., Methods: The study cohort included 60 patients with JIA (50 girls) ages 10-16 years and 60 age- and sex-matched controls. The JIA group included 30 patients with persistent oligoarticular JIA and 30 patients with extended oligoarticular or polyarticular disease. Measures of physical fitness included cardiorespiratory fitness (CRF) by peak oxygen uptake (Vo 2peak ) during a continuous graded treadmill exercise test, muscle strength by isokinetic and isometric knee and hand grip evaluations, and bone mineral density (BMD) and body composition by dual-energy x-ray absorptiometry. Physical activity was assessed by accelerometry., Results: Forty-two percent of the patients were being treated with biologic drugs. Patients with JIA demonstrated lower muscle strength and total body BMD compared to controls, but there were no differences in CRF and body composition. Physical fitness was comparable between the persistent oligoarticular and extended oligoarticular/polyarticular-JIA groups. In patients with JIA, we identified associations between higher vigorous physical activity and higher CRF and muscle strength, but did not find any association between physical fitness and disease variables., Conclusion: In this cohort of patients with JIA, we found suboptimal muscle strength and BMD compared to controls, but no differences in CRF and body composition. Vigorous physical activities appeared important for optimizing muscle strength and CRF in patients with JIA; the importance of such activities should be highlighted in patient education., (© 2018, American College of Rheumatology.)

Objectives: Patients with end-stage renal disease (ESRD) undergoing haemodialysis (HD) have significantly reduced cardiorespiratory fitness and health-related quality of life (HRQoL). Our hypothesis was that high-intensity interval training (HIIT) is a feasible and safe form of exercise during HD and that HIIT would elicit greater change in cardiorespiratory fitness and HRQoL compared with moderate-intensity continuous training (MICT)., Methods: Twenty patients were randomised to either HIIT (n=6), MICT (n=8) (two times a week within 22 weeks) or usual care (n=6). Feasibility was assessed by session attendance and adherence to exercise intensity. Safety was assessed by adverse event reporting. Efficacy was determined from change in peak oxygen uptake (VO 2peak ), 6 min walk distance and a HRQoL questionnaire (the COOP-WONCA chart)., Results: Eleven patients (55%) completed premeasurements and postmeasurements. The main reason for drop-out was due to kidney transplant during follow-up. The patients completed the same number of sessions in each group and adhered to the target heart rates after habituation. There were no adverse events. In the HIIT group, two of the three patients increased VO 2peak by 46% and 53%, respectively. Three of the five patients in the MICT group increased their VO 2peak by 6%, 18% and 36%, respectively., Conclusions: This pilot study demonstrated that HIIT is a feasible and safe exercise model for intradialytic exercise in patients undergoing HD. There might be a considerable potential of intradialytic HIIT in patients undergoing HD. Further studies with larger sample sizes are needed to determine if HIIT is an optimal approach in patients with ESRD undergoing HD., Trial Registration Number: NCT01728415., Competing Interests: Competing interests: EE received salary from GlaxoSmithKline with no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Knowledge of the effect of marine protein hydrolysate (MPH) supplementation to promote recovery after high intensity performance training is scarce. The aim of this study was to examine the effect of MPH supplementation to whey protein (WP) and carbohydrate (CHO): (CHO-WP-MPH), on short-term recovery following high intensity performance, compared to an isoenergetic and isonitrogenous supplement of WP and CHO: (CHO-WP), in male cyclists., Methods: This was a double-blinded crossover study divided into three phases. Fourteen healthy men participated. In phase I, an incremental bicycle exercise test was performed for establishment of intensities used in phase II and III. In phase II (9-16 days after phase 1), the participants performed first one high intensity performance cycling session, followed by nutrition supplementation (CHO-WP-MPH or CHO-WP) and 4 hours of recovery, before a subsequent high intensity performance cycling session. Phase III (1 week after phase II), was similar to phase II except for the nutrition supplementation, where the participants received the opposite supplementation compared to phase II. Primary outcome was difference in time to exhaustion between the cycling sessions, after nutrition supplementations containing MPH or without MPH. Secondary outcomes were differences in heart rate (HR), respiratory exchange ratio (RER), blood lactate concentration and glucose., Results: The mean age of the participants was 45.6 years (range 40-58). The maximal oxygen uptake (mean ± SD) measured at baseline was 54.7 ± 4.1 ml∙min - 1 ∙kg - 1 . There were no significant differences between the two nutrition supplementations measured by time to exhaustion at the cycling sessions (mean diff  = 0.85 min, p = 0.156, 95% confidence interval (CI), - 0.37, 2.06), HR (mean diff  = 0.8 beats pr.min, p = 0.331, 95% CI, - 0.9, 2.5), RER (mean diff  = - 0.05, p = 0.361, 95% CI -0.07 - 0.17), blood lactate concentration (mean diff  = - 0.24, p = 0.511, 95% CI, - 1.00, 0.53) and glucose (mean diff  = 0.23, p = 0.094, 95% CI, - 0.05, 0.51)., Conclusions: A protein supplement with MPH showed no effects on short-term recovery in middle-aged healthy male cyclists compared to a protein supplement without MPH., Trial Registration: The study was registered 02.05.2017 at ClinicalTrials.gov (Protein Supplements to Cyclists, NCT03136133 , https://clinicaltrials.gov/ct2/show/NCT03136133?cond=marine+peptides&rank=1 .

The purpose of this pilot study was to describe and explore a group-based multifaceted intervention for patients with fatigue after acquired brain injury (ABI). We hypothesised that post-intervention changes would result in reduced fatigue, in addition to improved emotional health, sleep and attentional control. Eight subjects with traumatic brain injury (n = 3) and cerebrovascular insults (n = 5) were included. Inclusion was based upon the presence of fatigue complaints. The participants received 36 hours of intervention. Changes related to fatigue, emotional health and sleep was assessed with self-rating measures. Additionally, a neuropsychological test (Conners' Continuous Performance Test II) was included as a measure of attentional control. All subjects were assessed at baseline, post-intervention, and at 3 and 9 months follow-up. Findings indicated reduced fatigue levels (post-intervention and 3 months follow-up), anxiety (9 months follow-up), and daytime sleepiness (3 and 9 months follow-up). Pilot results suggest that multifaceted group-based interventions may have the potential to alleviate symptoms of fatigue, anxiety and sleepiness after ABI. At an individual level, a low load of psychological distress, insomnia symptoms, dysexecutive symptoms, in addition to a strong sense of self-efficacy, may be central in order to reduce levels of fatigue.

Background: Poor cardiorespiratory fitness is previously reported in patients with juvenile idiopathic arthritis (JIA) measured both by maximal and submaximal exercise tests, but a submaximal exercise test with acceptable measurement properties is currently lacking for both clinical and research purposes in this patient population. The objectives of this study were to evaluate the measurement properties and performance of a submaximal treadmill test in patients with JIA, and to compare the results with those obtained in controls., Methods: Fifty-nine patients (50 girls), aged 10-16 years, with oligo- (n = 30) and polyarticular (n = 29) JIA, and 59 age- and sex-matched controls performed an eight-minute submaximal treadmill test for estimating peak oxygen uptake (VO 2peak ) followed by a maximal treadmill test measuring VO 2peak directly. During the submaximal treadmill test, the study participants walked with no inclination at a speed between 3.2-7.2 km/h for four minutes, and then continued to walk at the same speed for four minutes with five % inclination. VO 2peak was directly measured during a continuous graded exercise test on treadmill until exhaustion. Thirty-seven patients participated in the evaluation of the reliability. Criterion validity and reliability were evaluated with interclass correlation coefficient (ICC); measurement errors by Bland-Altman plot, standard error of measurement and smallest detectable change., Results: In patients with JIA, the ICC (95% CI) for criterion validity was acceptable at group level 0.71 (0.51, 0.82), but not at individual level. The test-retest reliability and inter-rater reliability were acceptable at individual (0.84 (0.71, 0.91) and 0.92 (0.83, 0.96), respectively) and group levels (0.91 (0.83, 0.96) and 0.96 (0.91, 0.98), respectively). The measurement errors (for test-retest reliability/inter-rater reliability) were large. Bland-Altman plots showed no systematic differences, but a large variability for both the validity and reliability. The performance of and estimated VO 2peak from the submaximal test were not associated with disease variables and were comparable between patients and controls., Conclusion: The submaximal treadmill test is valid for use in patients with JIA on group level, but not on individual level. The reliability is acceptable. Due to large measurement errors, the submaximal treadmill test is not optimal for use in daily clinical practice to estimate VO 2peak in individual patients.

Objectives: To evaluate the association between cardiorespiratory fitness (CRF), lung cancer incidence and cancer mortality in men., Design: Prospective cohort study., Methods: Maximal exercise testing was performed in 4920 men (59.2±11.4years) free from malignancy at baseline. Multivariate Cox hazard models adjusted for established cancer risk factors including smoking were analyzed for lung cancer incidence and cancer mortality among those who were diagnosed with lung cancer. Population attributable risks (PAR) of low CRF (<5 METs) were determined., Results: During 12.7±7.5years follow-up, 105 (2.1%) participants were diagnosed with lung cancer and 83 (79%) of those died from cancer after 3.6±4.6 years from diagnosis. CRF was inversely and independently associated with cancer outcomes. A 1-MET increase and categories of moderate and high CRF were associated with 10%, 47% and 65% reduction in lung cancer incidence (p=0.002), and 13%, 58% and 76% reduction in cancer mortality (p=0.002), respectively. Also, individuals who were diagnosed with lung cancer and were at moderate or high CRF categories at baseline exhibited longer survival time (p<0.001). The PARs% for lung cancer incidence and cancer mortality were 8.7% and 18.5%, respectively., Conclusions: Higher CRF is associated with lower lung cancer incidence in men. Among individuals who were diagnosed with lung cancer, higher CRF was associated with reduced cancer mortality and longer survival time. These results support the protective benefits of higher CRF in the prevention of lung cancer outcomes. Eliminating low CRF as a risk factor would potentially prevent considerable lung cancer morbidity and mortality., (Copyright © 2018 Sports Medicine Australia. All rights reserved.)

Objectives: To compare cardiorespiratory fitness (CRF) expressed as maximal oxygen uptake (VO2max) between patients with long-term JDM and controls and between patients with active and inactive disease, as well as to explore exercise limiting factors and associations between CRF and disease variables., Methods: JDM patients (n = 45) and age- and gender-matched controls (n = 45) performed a cardiopulmonary exercise test (CPET) on a treadmill until exhaustion. Physical activity was measured by accelerometers. Disease activity, damage and muscle strength/function were assessed by validated tools. Clinically inactive disease was defined according to PRINTO criteria., Results: The mean disease duration was 20.8 (s.d. 11.9) years and 29/45 (64%) patients had inactive disease. A low VO2max was found in 27% of patients vs 4% of controls (P = 0.006). The mean VO2max and maximal ventilation (VEmax) were lower in patients with active and inactive disease compared with controls. Patients with active disease also had lower maximal voluntary ventilation (MVV) compared with controls and lower VEmax and MVV compared with those with inactive disease. Patients with inactive disease had lower physical activity levels compared with controls. VO2max correlated negatively with disease damage in patients with inactive disease and positively with muscle strength/function in patients with active disease., Conclusion: CRF was lower in JDM patients, both with active and inactive disease, compared with controls after a mean 20 years disease duration. Cardiopulmonary exercise test results suggested different limiting factors contributing to the reduced CRF according to disease activity, including deconditioning in inactive disease and reduced ventilatory capacity in active disease. Further research is needed to verify this., (© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: Maximal heart rate (HR) is commonly defined as the highest HR obtained during a progressive exercise test to exhaustion. Maximal HR is considered one of the criteria to assess maximum exertion in exercise tests, and is broadly used when prescribing exercise intensity. The aim of the present study was to compare peak HR measurements during maximal treadmill running and active play in obese children and adolescents., Design: Comparison of peak heart rate during active play vs. maximal treadmill running in 39 (7⁻17 years old, 18 males) obese children and adolescents., Methods: Heart rate was recorded during intensive active play sessions, as well as during a progressive running test on a treadmill until exhaustion. HR, respiratory exchange ratio (RER), and oxygen uptake were continuously measured during the test. The criteria for having reached maximal effort was a subjective assessment by the technician that the participants had reached his or her maximal effort, and a RER above 1.00 or reporting perceived exertion (RPE) above 17 using the Borg-RPE 6⁻20 -Scale., Results: Thirty-four children had a RER ≥1.00, and 37 reported a RPE ≥ 17. Thirty-two children fulfilled both criteria. During active play, peak HR was significantly ( p < 0.0001) increased (4%) (mean and 95% confidence intervals; 204 (201, 207) beats/min), compared to during maximal treadmill running (196 (194, 199) beats/min), respectively., Conclusion: The results of the present study indicate that peak heart rate measurements during progressive running to exhaustion in obese children and adolescents cannot necessarily be determined as maximal heart rate.

Purpose: This study's purpose was to examine whether established risk categories of waist circumference (WC)-normal, high risk, and very high health risk-reflected significant differences in cardiorespiratory fitness (CRF) and physical activity (PA) level., Methods: CRF was directly measured as maximal oxygen uptake during a progressive graded treadmill test to exhaustion in 722 individuals (349 women) aged 20-85 years. WC was measured between the lower rib and the iliac crest. Objectively measured PA was assessed using an accelerometer., Results: Men in the normal risk group (WC < 94 cm) had a 31% higher CRF and 43% higher level of moderate-to-vigorous PA than men in the very high risk group (with a WC > 102 cm). Corresponding numbers for women within normal (WC < 80 cm) and very high risk group (WC > 88 cm) were 25% and 18% ( p  < 0.05). There was a high negative correlation between CRF and WC in men ( r  = -0.68), and a moderate correlation for women ( r  = -0.49; p  < 0.001). For each cm increase in WC, CRF was reduced by 0.48 and 0.27 mL/kg/min in men and women, respectively ( p  < 0.001)., Conclusion: The recommended WC thresholds for abdominal obesity reflected significant differences in CRF for both men and women, and could serve as a useful instrument for estimating health-related differences in CRF.

Background: Survivors of childhood acute lymphoblastic leukemia (ALL) are at risk of late treatment-related side-effects. Data regarding prevalence and risk factors for impairments in pulmonary function and cardiorespiratory fitness are limited, and reported findings are inconsistent and inconclusive., Material and Methods: In a cross-sectional study, 116 ALL survivors (median 5 years at diagnosis, 29 years at follow-up, 53% females) were examined, median 23 years after treatment with chemotherapy only. Individual cumulative doses of cytostatic agents were calculated. Methods included blood tests, echocardiography, pulmonary function tests and cardiorespiratory exercise test., Results: Females had lower % predicted gas diffusing capacity (DLCO) than males (mean [SD] 84 [13] versus 97 [14], p < .001). Impairment in DLCO was found in 34% females versus 7% males, p < .001. In a multiple linear regression model, female gender, body mass index (BMI) and smoking were risk factors for reduced % predicted DLCO, with a borderline significant effect of left ventricular ejection fraction (LVEF). Impaired cardiorespiratory fitness was found in 42% of the survivors, with a borderline increased risk in females, p = .06. Smoking and BMI were risk factors for reduced % predicted VO 2 peak. Subjects exposed to anthracyclines had lower LVEF% and % predicted VO 2 peak than those not exposed, (mean [SD] 56.2 [4.3] versus 59.2 [5.2], p = .01 and 86.9 [18.4] versus 92.8 [18.4], p = .03, respectively)., Conclusions: Impairments in pulmonary function and cardiorespiratory fitness are common in very long-term survivors of childhood ALL. Risk factors are female gender, BMI and smoking. In order to preserve pulmonary function and cardiorespiratory fitness, we suggest increased attention and targeted advice on modifiable lifestyle factors such as smoking, inactivity and overweight.

Background: Given the risk of developing acute and long-term adverse effects in patients receiving cisplatin-based chemotherapy for testicular cancer (TC), risk-reducing interventions, such as physical activity (PA), may be relevant. Limited knowledge is available on the challenges met when conducting PA intervention trials in patients with TC during and shortly after chemotherapy. The aims of the present feasibility study are therefore to determine patient recruitment, compliance and adherence to a PA intervention., Results: Patients with metastatic TC referred to cisplatin-based chemotherapy were eligible. They followed an individual low-threshold PA intervention, including counseling from a personal coach during and 3 months after chemotherapy. Outcomes were recruitment rate, compliance rate and adherence to the intervention including preferences for type of PA and barriers for PA. During 8 months 12 of 18 eligible patients were invited, all consented, but three dropped out. Walking and low intensity activities were preferred and nausea and feeling unwell were the most often reported barriers towards PA., Discussion: In order to achieve adequate recruitment, compliance and complete data in future PA intervention trials, close cooperation with treating physicians, individual PA plans and availability of personalized coaching are required. Trial registration NCT01749774, November 2012, ClinicalTrials.gov.

Background: Air travel may imply a health hazard for patients with cystic fibrosis (CF) due to hypobaric environment in the aircraft cabin. The objective was to identify pre-flight variables, which might predict severe hypoxaemia in adult CF patients during air travel., Methods: Thirty adult CF-patients underwent pre-flight evaluation with spirometry, arterial oxygen tension (PaO 2 ), pulse oximetry (SpO 2 ) and cardiopulmonary exercise testing (CPET) at sea level (SL). The results were related to the PaO 2 obtained during a hypoxia-altitude simulation test (HAST) in which a cabin altitude of 2438 m (8000 ft) was simulated by breathing 15.1% oxygen., Results: Four patients fulfilled the criteria for supplemental oxygen during air travel (PaO 2 HAST  < 6.6 kPa). While walking slowly during HAST, another eleven patients dropped below PaO 2 HAST 6.6 kPa. Variables obtained during CPET (PaO 2 CPET , SpO 2 CPET , minute ventilation/carbon dioxide output, maximal oxygen uptake) showed the strongest correlation to PaO 2 HAST ., Conclusions: Exercise testing might be of value for predicting in-flight hypoxaemia and thus the need for supplemental oxygen during air travel in CF patients. Trial registration The study is retrospectively listed in the ClinicalTrials.gov Protocol Registration System: NCT01569880 (date; 30/3/2012).

Objective: To evaluate the effect of regular exercise on maternal arterial blood pressure (BP) at rest and during uphill walking, in healthy former inactive pregnant women., Methods: A single-blind, single-center, randomized controlled trial including 61 out of 105 healthy, inactive nulliparous pregnant women, initially enrolled in a controlled trial studying the effect of 12 weeks of aerobic exercise (60 min 2/week) on maternal weight gain. Primary outcome was the mean adjusted difference in change in resting systolic and diastolic BP from baseline to after intervention. Secondary outcome was the mean adjusted difference in change in systolic BP during uphill treadmill walking at critical power. Measurements were performed prior to the intervention (gestation week 17.6 ± 4.2) and after the intervention (gestation week 36.5 ± 0.9)., Results: At baseline, resting systolic and diastolic BP was 115/66 ± 12/7 and 115/67 ± 10/9 mmHg in the exercise (n = 35) and control group (n = 26), respectively. After the intervention, resting systolic BP was 112 ± 8 mmHg in the exercise group and 119 ± 14 mmHg in the control group, giving a between-group difference of 7.5 mmHg (95% CI 1.5 to 12.6, p = 0.013). Diastolic BP was 71 ± 9 and 76 ± 8 mmHg, with a between-group difference of 3.9 mmHg (95% CI -0.07 to 7.8, p = 0.054). During uphill treadmill walking at critical power, the between-group difference in systolic and diastolic BP was 5.9 mmHg (95% CI -4.4 to 16.1, p = 0.254) and 5.5 mmHg (95% CI -0.2 to 11.1, p = 0.059), respectively., Conclusions: Aerobic exercise reduced resting systolic BP in healthy former inactive pregnant women.

Aim: To evaluate the effect of lung cancer surgery on cardiorespiratory fitness (CRF), and to assess the agreement between the predicted postoperative (ppo) V̇O 2peak and actually measured postoperative peak oxygen uptake (V̇O 2peak )., Methods: Before and 4-6 weeks after lung cancer surgery, 70 patients (35 women) underwent measurements of pulmonary function and CRF via a cardiopulmonary exercise test. In addition, the 23 non-exercising patients underwent measurements after 6 months. The ppo V̇O 2peak calculated from the number of functional segments removed was compared with the actually measured postoperative values of V̇O 2peak for accuracy and precision., Results: After surgery, the V̇O 2peak decreased from 23.9±5.8 to 19.2±5.5 mL/kg/min (-19.6±15.7%) (p<0.001). The breathing reserve increased by 5% (p=0.001); the oxygen saturation remained unchanged (p=0.30); the oxygen pulse decreased by -1.9 mL/beat (p<0.001); the haemoglobin concentration decreased by 0.7 g/dL (p=0.001). The oxygen pulse was the strongest predictor for change in V̇O 2peak ; adjusted linear squared: r 2 =0.77. Six months after surgery, the V̇O 2peak remained unchanged (-3±15%, p=0.27). The ppo V̇O 2peak (mL/kg/min) was 18.6±5.4, and the actually measured V̇O 2peak was 19.2±5.5 (p=0.24). However, the limits of agreement were large (CI -7.4 to 8.2). The segment method miscalculated the ppo V̇O 2peak by more than ±10 and ±20% in 54% and 25% of the patients, respectively., Conclusions: The reduction in V̇O 2peak and lack of improvement 6 months after lung cancer surgery cannot be explained by the loss of functional lung tissue. Predicting postoperative V̇O 2peak based on the amount of lung tissue removed is not recommendable due to poor precision., Trial Registration Number: NCT01748981.

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world's oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits.