Effects of physical exercise during adjuvant chemotherapy for breast cancer on long-term tested and perceived cognition: results of a pragmatic follow-up study.

PURPOSE: Cancer-related cognitive impairment (CRCI) following chemotherapy is commonly reported in breast cancer survivors, even years after treatment. Data from preclinical studies suggest that exercise during chemotherapy may prevent or diminish cognitive problems; however, clinical data are scarce. METHODS: This is a pragmatic follow-up study of two original randomized trials, which compares breast cancer patients randomized to exercise during chemotherapy to non-exercise controls 8.5 years post-treatment. Cognitive outcomes include an online neuropsychological test battery and self-reported cognitive complaints. Cognitive performance was compared to normative data and expressed as age-adjusted z-scores. RESULTS: A total of 143 patients participated in the online cognitive testing. Overall, cognitive performance was mildly impaired on some, but not all, cognitive domains, with no significant differences between groups. Clinically relevant cognitive impairment was present in 25% to 40% of all participants, regardless of study group. We observed no statistically significant effect of exercise, or being physically active during chemotherapy, on long-term cognitive performance or self-reported cognition, except for the task reaction time, which favored the control group (ß = -2.04, 95% confidence interval: -38.48; -2.38). We observed no significant association between self-reported higher physical activity levels during chemotherapy or at follow-up and better cognitive outcomes. CONCLUSION: In this pragmatic follow-up study, exercising and being overall more physically active during or after adjuvant chemotherapy for breast cancer was not associated with better tested or self-reported cognitive functioning, on average, 8.5 years after treatment. Future prospective studies are needed to document the complex relationship between exercise and CRCI in cancer survivors.

Maximal cardiopulmonary exercise testing in laryngectomised patients using different heat and moisture exchangers - feasibility and exercise responses.

OBJECTIVE: After laryngectomy, the breathing resistance of heat and moisture exchangers may limit exercise capacity. Breathing gas analysis during cardiopulmonary exercise testing is not possible using regular masks. This study tested the feasibility of cardiopulmonary exercise testing with a heat and moisture exchanger in situ, using an in-house designed connector. Additionally, we explored the effect of different heat and moisture exchanger resistances on exercise capacity in this group. METHODS: Ten participants underwent two cardiopulmonary exercise tests using their daily life heat and moisture exchanger (0.3 hPa or 0.6 hPa) and one specifically developed for activity (0.15 hPa). Heat and moisture exchanger order was randomised and blinded. RESULTS: All participants completed both tests. No (serious) adverse events occurred. Only four subjects reached a respiratory exchange ratio of more than 1.1 in at least one test. Maximum exercise levels using heat and moisture exchangers with different resistances did not differ. CONCLUSION: Cardiopulmonary exercise testing in laryngectomees with a heat and moisture exchanger is feasible; however, the protocol does not seem appropriate to reach this group's maximal exercise capacity. Lowering heat and moisture exchanger resistance does not increase exercise capacity in this sample.

Effects of exercise during chemotherapy for breast cancer on long-term cardiovascular toxicity.

OBJECTIVE: Animal data suggest that exercise during chemotherapy is cardioprotective, but clinical evidence to support this is limited. This study evaluated the effect of exercise during chemotherapy for breast cancer on long-term cardiovascular toxicity. METHODS: This is a follow-up study of two previously performed randomised trials in patients with breast cancer allocated to exercise during chemotherapy or non-exercise controls. Cardiac imaging parameters, including T1 mapping (native T1, extracellular volume fraction (ECV)), left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS), cardiorespiratory fitness, and physical activity levels, were acquired 8.5 years post-treatment. RESULTS: In total, 185 breast cancer survivors were included (mean age 58.9±7.8 years), of whom 99% and 18% were treated with anthracyclines and trastuzumab, respectively. ECV and Native T1 were 25.3%±2.5% and 1026±51 ms in the control group, and 24.6%±2.8% and 1007±44 ms in the exercise group, respectively. LVEF was borderline normal in both groups, with an LVEF<50% prevalence of 22.5% (n=40/178) in all participants. Compared with control, native T1 was statistically significantly lower in the exercise group (ß=-20.16, 95% CI -35.35 to -4.97). We found no effect of exercise on ECV (ß=-0.69, 95% CI -1.62 to 0.25), LVEF (ß=-1.36, 95% CI -3.45 to 0.73) or GLS (ß=0.31, 95% CI -0.76 to 1.37). Higher self-reported physical activity levels during chemotherapy were significantly associated with better native T1 and ECV. CONCLUSIONS: In long-term breast cancer survivors, exercise and being more physically active during chemotherapy were associated with better structural but not functional cardiac parameters. The high prevalence of cardiac dysfunction calls for additional research on cardioprotective measures, including alternative exercise regimens. TRIAL REGISTRATION NUMBER: NTR7247.

An overview of innovative living arrangements within long-term care and their characteristics: a scoping review.

BACKGROUND: Within long-term care, a culture change (e.g. focus on increasing autonomy in everyday life) is leading to the development of innovative living arrangements for older adults. Insight into characteristics of innovative living arrangements, which are described as an alternative to regular nursing homes, is lacking. This review aims to provide an overview of innovative living arrangements and to describe their defining characteristics. METHODS: A scoping review was performed following the framework of Arksey and O'Malley. The preferred reporting items for systematic reviews and meta-analyses with extension, for scoping reviews (PRISMA-ScR) was also followed. The databases PubMed, PsycInfo, CINAHL, and Web of Science were searched. Articles, published between 2012 and 2023 were included when they presented an innovative living arrangement as an alternative to regular nursing homes. A thematic analysis was performed, describing the physical, social, and organizational environment of the innovative living arrangements. RESULTS: Fifty-six articles were identified describing seven types of distinct innovative living arrangements: small-scale living, the green house model, shared housing arrangements, green care farms, dementia villages, group homes, intergenerational living, and an 'other' category. The themes included supporting autonomy and creating a small-scale and/or homelike environment, which were emphasized in most innovative living arrangements. Other themes, such as involvement of the community, focus on nature, integration of work tasks, and involvement of family members, were emphasized in a subsection of the described living arrangements. Twenty-eight articles reported on the effects of the innovative living environment on residents, family members, or staff members. Most articles (N = 22) studied resident-related outcomes, focusing mainly on quality of life and aspects of daily life. CONCLUSION: More insight into the mechanisms of the social and organizational environments is needed, which may lead to greater transparency and homogeneity regarding the description of living arrangements. This review shows that more knowledge is needed about the potential key elements of innovative living arrangements, especially related to their social and organizational environment. This may provide a better guide for developers within long-term care.

Exercise testing and training in frail older adults with an orthopedic impairment participating in a geriatric rehabilitation program: an international Delphi study.

BACKGROUND: Little is known about exercise testing and training in orthopedic geriatric rehabilitation. This study aims to obtain expert-consensus-based recommendations on this matter. METHODS: Using an online Delphi study we aimed to reach international expert consensus on statements related to testing and training of endurance capacity and muscle strength. Participants needed to have relevant research or clinical expertise. Statements were evaluated and explanatory comments could be provided. After each round anonymous results were presented to participants. Statements could be adjusted or new ones could be formulated if necessary. Consensus was defined as > 75% of participants agreeing. RESULTS: Thirty experts completed the first round. Twenty-eight (93%) the second and 25 (83%) completed the third round. The majority of experts were physical therapists. Consensus was reached on a total of 34 statements. The statements and comments reflected the need for a pragmatic and tailored approach in this population both for testing and training. For example, for testing endurance capacity, a 6 Minute walk test was promoted and for testing muscle strength, performance in a functional activity was suggested. Ratings of perceived exertion were promoted for monitoring intensity of endurance and muscle strength training in patients without cognitive impairment. CONCLUSION: In orthopedic GR, endurance and muscle strength testing should be pragmatic and is preferably performed in functional activities. For endurance training existing guidelines of the American College of Sports Medicine can be strived for but adapted as needed and for muscle strength training only lower intensities are agreed upon.

The quality of geriatric rehabilitation from the patients' perspective: a scoping review.

BACKGROUND: the efficacy and outcomes of geriatric rehabilitation (GR) have previously been investigated. However, a systematic synthesis of the aspects that are important to patients regarding the quality of GR does not exist. OBJECTIVE: the aim of this scoping review was to systematically synthesise the patients' perspective on the quality of GR. METHODS: we followed the Scoping Review framework and gathered literature including a qualitative study design from multiple databases. The inclusion criteria were: a qualitative study design; a geriatric population; that patients had participated in a geriatric rehabilitation programme and that geriatric rehabilitation was assessed by the patient. The results sections of the included studies were analysed using a thematic analysis approach. RESULTS: twenty articles were included in this review. The main themes identified were: (i) the need for information about the rehabilitation process, (ii) the need for telling one's story, (iii) the need for support (physical, psychological, social and how to cope with limitations), (iv) the need for shared decision-making and autonomy, (v) the need for a stimulating rehabilitation environment and (vi) the need for rehabilitation at home. CONCLUSION: in this study, we identified the aspects that determine the quality of rehabilitation from the patient's perspective, which may lead to a more holistic perspective on the quality of GR.

EffectiveNess of a multimodal preHAbilitation program in patieNts with bladder canCEr undergoing radical cystectomy: protocol of the ENHANCE multicentre randomised controlled trial.

INTRODUCTION: Radical cystectomy (RC) is the standard treatment for patients with non-metastatic muscle-invasive bladder cancer, as well as for patients with therapy refractory high-risk non-muscle invasive bladder cancer. However, 50-65% of patients undergoing RC experience perioperative complications. The risk, severity and impact of these complications is associated with a patient's preoperative cardiorespiratory fitness, nutritional and smoking status and presence of anxiety and depression. There is emerging evidence supporting multimodal prehabilitation as a strategy to reduce the risk of complications and improve functional recovery after major cancer surgery. However, for bladder cancer the evidence is still limited. The aim of this study is to investigate the superiority of a multimodal prehabilitation programme versus standard-of-care in terms of reducing perioperative complications in patients with bladder cancer undergoing RC. METHODS AND ANALYSIS: This multicentre, open label, prospective, randomised controlled trial, will include 154 patients with bladder cancer undergoing RC. Patients are recruited from eight hospitals in The Netherlands and will be randomly (1:1) allocated to the intervention group receiving a structured multimodal prehabilitation programme of approximately 3-6 weeks, or to the control group receiving standard-of-care. The primary outcome is the proportion of patients who develop one or more grade ≥2 complications (according to the Clavien-Dindo classification) within 90 days of surgery. Secondary outcomes include cardiorespiratory fitness, length of hospital stay, health-related quality of life, tumour tissue biomarkers of hypoxia, immune cell infiltration and cost-effectiveness. Data collection will take place at baseline, before surgery and 4 and 12 weeks after surgery. ETHICS AND DISSEMINATION: Ethical approval for this study was granted by the Medical Ethics Committee NedMec (Amsterdam, The Netherlands) under reference number 22-595/NL78792.031.22. Results of the study will be published in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05480735.

Effect of a multifaceted antibiotic stewardship intervention to improve antibiotic prescribing for suspected urinary tract infections in frail older adults (ImpresU): pragmatic cluster randomised controlled trial in four European countries.

OBJECTIVE: To evaluate whether antibiotic prescribing for suspected urinary tract infections in frail older adults can be reduced through a multifaceted antibiotic stewardship intervention. DESIGN: Pragmatic, parallel, cluster randomised controlled trial, with a five month baseline period and a seven month follow-up period. SETTING: 38 clusters consisting of one or more general practices (n=43) and older adult care organisations (n=43) in Poland, the Netherlands, Norway, and Sweden, from September 2019 to June 2021. PARTICIPANTS: 1041 frail older adults aged 70 or older (Poland 325, the Netherlands 233, Norway 276, Sweden 207), contributing 411 person years to the follow-up period. INTERVENTION: Healthcare professionals received a multifaceted antibiotic stewardship intervention consisting of a decision tool for appropriate antibiotic use, supported by a toolbox with educational materials. A participatory-action-research approach was used for implementation, with sessions for education, evaluation, and local tailoring of the intervention. The control group provided care as usual. MAIN OUTCOME MEASURES: The primary outcome was the number of antibiotic prescriptions for suspected urinary tract infections per person year. Secondary outcomes included the incidence of complications, all cause hospital referrals, all cause hospital admissions, all cause mortality within 21 days after suspected urinary tract infections, and all cause mortality. RESULTS: The numbers of antibiotic prescriptions for suspected urinary tract infections in the follow-up period were 54 prescriptions in 202 person years (0.27 per person year) in the intervention group and 121 prescriptions in 209 person years (0.58 per person year) in the usual care group. Participants in the intervention group had a lower rate of receiving an antibiotic prescription for a suspected urinary tract infection compared with participants in the usual care group, with a rate ratio of 0.42 (95% confidence interval 0.26 to 0.68). No differences between intervention and control group were observed in the incidence of complications (<0.01 v 0.05 per person year), hospital referrals (<0.01 v 0.05), admissions to hospital (0.01 v 0.05), and mortality (0 v 0.01) within 21 days after suspected urinary tract infections, nor in all cause mortality (0.26 v 0.26). CONCLUSIONS: Implementation of a multifaceted antibiotic stewardship intervention safely reduced antibiotic prescribing for suspected urinary tract infections in frail older adults. TRIAL REGISTRATION: ClinicalTrials.gov NCT03970356.

Methenamine hippurate to prevent recurrent urinary tract infections in older women: protocol for a randomised, placebo-controlled trial (ImpresU).

INTRODUCTION: Methenamine hippurate is a urinary antiseptic used as preventive treatment for recurrent urinary tract infections (UTIs) in some Scandinavian countries. However, the scientific evidence for the preventive effect and safety for longer-term use is limited. The aim of this study is to assess whether methenamine hippurate can reduce the incidence of UTIs in older women with recurrent UTIs. METHODS AND ANALYSIS: The ImpresU consortium is a collaboration between Norway, Sweden, Poland and the Netherlands. The study is a randomised, controlled, triple-blind phase IV clinical trial. Women ≥70 years with recurrent UTIs are screened for eligibility in a general practice setting. We aim to include 400 women in total, with 100 recruited from each collaborating country. The participants are randomised to treatment with methenamine hippurate 1 g or placebo tablets two times per day for a treatment period of 6 months, followed by a drug-free follow-up period of 6 months. The primary outcome is number of antibiotic treatments for UTIs during the treatment period. The secondary outcomes include number of antibiotic treatments for UTIs during the follow-up period and self-reported symptom of severity and duration of UTI episodes. Differences in complications between the treatment groups are measured as safety outcomes. We also aim to investigate whether strain characteristics or phylogenetic subgroups of Escherichia coli present in the urine culture at inclusion have a modifying effect on the outcomes. ETHICS AND DISSEMINATION: Ethical approvals are obtained in all participating countries. The results will be communicated in peer-reviewed journals and at scientific conferences. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT04077580); EudraCT: 2018-002235-15.

Physical Activity and Cardiac Function in Long-Term Breast Cancer Survivors: A Cross-Sectional Study.

Background: Higher levels of physical activity are associated with a lower risk of cardiovascular disease in the general population. Whether the same holds for women who underwent treatment for breast cancer is unclear. Objectives: The aim of this study was to evaluate the association between physical activity in a typical week in the past 12 months and cardiac dysfunction in breast cancer survivors. Methods: We used data from a cohort of breast cancer survivors who were treated at ages 40 to 50 years (N = 559). The association between physical activity and global longitudinal strain (GLS) and left ventricular ejection fraction (LVEF) was evaluated using both linear and modified Poisson regression analyses adjusted for relevant confounders. Results: In total, 559 breast cancer survivors were included, with median age of 55.5 years and a median time since treatment of 10.2 years. GLS was less favorable in inactive survivors (-17.1%) than in moderately inactive (-18.4%), moderately active (-18.2%), and active survivors (-18.5%), with an adjusted significant difference for active versus inactive survivors (ß = -1.31; 95% CI: -2.55 to -0.06)). Moderately active (n = 57/130) and active survivors (n = 87/124) had significantly lower risks of abnormal GLS (defined as >-18%) compared with inactive survivors (n = 17/26) (RR: 0.65 [95% CI: 0.45-0.94] and RR: 0.61 [95% CI: 0.43-0.87], respectively). LVEF, in normal ranges in all activity categories, was not associated with physical activity. Conclusions: In long-term breast cancer survivors, higher physical activity levels were associated with improved GLS but not LVEF, with the relatively largest benefit for doing any activity versus none. This finding suggests that increasing physical activity may contribute to cardiovascular health benefits, especially in inactive survivors.

Decisions on antibiotic prescribing for suspected urinary tract infections in frail older adults: a qualitative study in four European countries.

BACKGROUND: a suspected urinary tract infection (UTI) is the most common reason to prescribe antibiotics in a frail older patient. Frequently, antibiotics are prescribed unnecessarily. To increase appropriate antibiotic use for UTIs through antibiotic stewardship interventions, we need to thoroughly understand the factors that contribute to these prescribing decisions. OBJECTIVES: (1) to obtain insight into factors contributing to antibiotic prescribing for suspected UTIs in frail older adults. (2) To develop an overarching model integrating these factors to guide the development of antibiotic stewardship interventions for UTIs in frail older adults. METHODS: we conducted an exploratory qualitative study with 61 semi-structured interviews in older adult care settings in Poland, the Netherlands, Norway and Sweden. We interviewed physicians, nursing staff, patients and informal caregivers. RESULTS: participants described a chain of decisions by patients, caregivers and/or nursing staff preceding the ultimate decision to prescribe antibiotics by the physician. We identified five themes of influence: (1) the clinical situation and its complexity within the frail older patient, (2) diagnostic factors, such as asymptomatic bacteriuria, (3) knowledge (gaps) and attitude, (4) communication: interprofessional, and with patients and relatives and (5) context and organisation of care, including factors such as availability of antibiotics (over the counter), antibiotic stewardship efforts and factors concerning out-of-hours care. CONCLUSIONS: decision-making on suspected UTIs in frail older adults is a complex, multifactorial process. Due to the diverse international setting and stakeholder variety, we were able to provide a comprehensive overview of factors to guide the development of antibiotic stewardship interventions.

Construct Validity of the Steep Ramp Test for Assessing Cardiorespiratory Fitness in Patients With Breast Cancer and the Effect of Chemotherapy-Related Symptom Burden.

OBJECTIVE: To investigate the construct validity of the Steep Ramp Test (SRT) by longitudinally comparing the correlation between maximum short exercise capacity of the SRT and direct measurements of peak oxygen consumption (Vo2peak) during or shortly after treatment in patients with breast cancer and the potential effect of chemotherapy-induced symptom burden. DESIGN: Cross-sectional. SETTING: Multicenter. PARTICIPANTS: We used data from 2 studies that included women with breast cancer treated with chemotherapy, resulting in 274 observations. A total of 161 patients (N=161) performed the cardiopulmonary exercise test and the SRT in 2 test sessions on different time points around chemotherapy treatment. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Fatigue was assessed with the Multidimensional Fatigue Inventory, and nausea and vomiting and pain by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. The longitudinal correlation between the maximum short exercise capacity and Vo2peak was investigated using a linear mixed model. Interaction terms were added to the model to investigate whether the correlation varied by symptom burden. RESULTS: We found a statistically significant moderate correlation between Vo2peak and maximum short exercise capacity (0.61; 95% confidence interval, 0.51-0.70; P<.01) over time. This correlation was slightly attenuated (-0.07; 95% confidence interval, -0.13 to 0.00; P=.04) in patients with chemotherapy-related nausea and vomiting, indicating smaller correlations of Vo2peak with the maximum short exercise capacity with increasing symptom burden. Pain and fatigue did not significantly modify the correlation. CONCLUSIONS: The SRT can only be used as a proxy for changes in aerobic capacity with great caution and with attention for the level of nausea and vomiting.

Physical Fitness and Chemotherapy Tolerance in Patients with Early-Stage Breast Cancer.

INTRODUCTION: An optimal relative dose intensity (RDI) of adjuvant chemotherapy is associated with better survival in patients with breast cancer. Little is known about the role of physical fitness in attaining an adequate RDI in patients with early-stage breast cancer. We investigated the association between pretreatment physical fitness and RDI in this population. METHODS: We pooled individual patient data from two randomized exercise trials that studied exercise programs in early breast cancer: the Physical Exercise During Adjuvant Chemotherapy Effectiveness Study (n = 230) and the Physical Activity during Chemotherapy Treatment (n = 204) study. Logistic regression models were used to evaluate the association between pretreatment fitness and achieving an optimal RDI (≥85%). In addition, we added an interaction term to the model to explore the potential moderating effect of participating in an exercise program. RESULTS: Data were available for 419 patients (mean age at diagnosis, 50.0 ± 8.6 yr). In the total sample, lower pretreatment physical fitness was associated with significantly lower odds of achieving ≥85% RDI: age-adjusted odds ratio (OR) of 0.66 (95% confidence interval (CI), 0.46-0.94). In patients allocated to the supervised exercise intervention during chemotherapy (n = 173), the association between pretreatment physical fitness and RDI was almost completely mitigated (OR, 0.95 (95% CI, 0.54-1.56)), whereas it was more pronounced in patients who received care as usual (n = 172; OR, 0.31 (95% CI, 0.13-0.63); Pinteraction = 0.022). CONCLUSIONS: Early-stage breast cancer patients with relatively lower levels of pretreatment physical fitness have lower odds of achieving an optimal dose of chemotherapy. Given that physical fitness is modifiable and our results suggest that following a moderate-to-high intensity exercise training during chemotherapy could improve treatment completion, clinicians should not refrain from referring patients to supportive exercise programs because of low fitness.

Multifaceted antibiotic stewardship intervention using a participatory-action-research approach to improve antibiotic prescribing for urinary tract infections in frail elderly (ImpresU): study protocol for a European qualitative study followed by a pragmatic cluster randomised controlled trial.

INTRODUCTION: Almost 60% of antibiotics in frail elderly are prescribed for alleged urinary tract infections (UTIs). A substantial part of this comprises prescriptions in case of non-specific symptoms or asymptomatic bacteriuria, for which the latest guidelines promote restrictiveness with antibiotics. We aim to reduce inappropriate antibiotic use for UTIs through an antibiotic stewardship intervention (ASI) that encourages to prescribe according to these guidelines. To develop an effective ASI, we first need a better understanding of the complex decision-making process concerning suspected UTIs in frail elderly. Moreover, the implementation approach requires tailoring to the heterogeneous elderly care setting. METHODS AND ANALYSIS: First, we conduct a qualitative study to explore factors contributing to antibiotic prescribing for UTIs in frail elderly, using semi-structured interviews with general practitioners, nursing staff, patients and informal caregivers. Next, we perform a pragmatic cluster randomised controlled trial in elderly care organisations. A multifaceted ASI is implemented in the intervention group; the control group receives care as usual. The ASI is centred around a decision tool that promotes restrictive antibiotic use, supported by a toolbox with educational materials. For the implementation, we use a modified participatory-action-research approach, guided by the results of the qualitative study. The primary outcome is the number of antibiotic prescriptions for suspected UTIs. We aim to recruit 34 clusters with in total 680 frail elderly residents ≥70 years. Data collection takes place during a 5-month baseline period and a 7-month follow-up period. Finally, we perform a process evaluation. The study has been delayed for 6 months due to COVID-19 and is expected to end in July 2021. ETHICS AND DISSEMINATION: Ethical approvals and/or waivers were obtained from the ethical committees in Poland, the Netherlands, Norway and Sweden. The results will be disseminated through publication in peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: NCT03970356.

Characteristics of Participants and Nonparticipants in a Blended Internet-Based Physical Activity Trial for Breast and Prostate Cancer Survivors: Cross-sectional Study.

BACKGROUND: As the number of cancer survivors is increasing, it is important to be able to offer exercise and physical activity (PA)-promoting interventions that are both effective and reasonably accessible. Internet-based interventions are typically less expensive and more accessible alternatives to on-site supervised interventions. Currently, little is known about the characteristics of nonparticipants in PA promotion trials in the cancer survivorship setting, both in general and specifically in trials using internet-supported interventions. OBJECTIVE: This study aims to gain insight into the characteristics associated with nonparticipation in a blended internet-based supported intervention trial to promote PA. METHODS: Breast and prostate cancer survivors, 3-36 months after primary curative treatment, were invited to participate in the PABLO trial; this trial compared an internet-based intervention to enhance PA levels, with or without additional support from a physical therapist, to usual care. Participants and nonparticipants were asked to complete a comprehensive questionnaire assessing sociodemographics, fatigue, and health-related quality of life. Baseline data for participants and nonparticipants were compared using the independent Student t test and chi-square test. RESULTS: The inclusion rate in the trial was 11.03% (137/1242). Of the nonparticipants, 13.95% (154/1104) completed the questionnaire. Participants were more highly educated (P=.04), had a paid job less often (P=.03), and were on sick leave more often (P=.03). They reported less PA per week, both moderate (P=.03) and vigorous (P<.01), before diagnosis and during leisure time (P<.01, effect size [ES]=0.44). They reported a significantly lower stage of change (P≤.01), lower self-efficacy (P<.01, ES=0.61), perceived barriers to PA (P<.01, ES=0.54), and more general fatigue (P<.01, ES=0.60). Participants reported lower health-related quality of life for most domains (ES ranging from 0.34 for mental health to 0.48 for social functioning). No significant differences were found for other sociodemographics, mood state, or attitudes toward or perceived social support for PA. CONCLUSIONS: The participants who self-selected for trial participation reported lower PA levels before diagnosis and a stronger need for support compared with nonparticipants. The trial thus included those patients who might benefit the most from internet-based supportive PA interventions. TRIAL REGISTRATION: Netherlands trial register NTR6911; https://www.trialregister.nl/trial/6733.

Efficacy of Physical Exercise to Offset Anthracycline-Induced Cardiotoxicity: A Systematic Review and Meta-Analysis of Clinical and Preclinical Studies.

Background Physical exercise is an intervention that might protect against doxorubicin-induced cardiotoxicity. In this meta-analysis and systematic review, we aimed to estimate the effect of exercise on doxorubicin-induced cardiotoxicity and to evaluate mechanisms underlying exercise-mediated cardioprotection using (pre)clinical evidence. Methods and Results We conducted a systematic search in PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Cochrane's and Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk-of-bias tools were used to assess the validity of human and animal studies, respectively. Cardiotoxicity outcomes reported by ≥3 studies were pooled and structured around the type of exercise intervention. Forty articles were included, of which 3 were clinical studies. Overall, in humans (sample sizes ranging from 24 to 61), results were indicative of exercise-mediated cardioprotection, yet they were not sufficient to establish whether physical exercise protects against doxorubicin-induced cardiotoxicity. In animal studies (n=37), a pooled analysis demonstrated that forced exercise interventions significantly mitigated in vivo and ex vivo doxorubicin-induced cardiotoxicity compared with nonexercised controls. Similar yet slightly smaller effects were found for voluntary exercise interventions. We identified oxidative stress and related pathways, and less doxorubicin accumulation as mechanisms underlying exercise-induced cardioprotection, of which the latter could act as an overarching mechanism. Conclusions Animal studies indicate that various exercise interventions can protect against doxorubicin-induced cardiotoxicity in rodents. Less doxorubicin accumulation in cardiac tissue could be a key underlying mechanism. Given the preclinical evidence and limited availability of clinical data, larger and methodologically rigorous clinical studies are needed to clarify the role of physical exercise in preventing cardiotoxicity in patients with cancer. Registration URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42019118218.

Expiratory Muscle Strength Training in patients After Total Laryngectomy; A Feasibility Pilot Study.

OBJECTIVES: Expiratory muscle strength training (EMST) is a threshold based device-driven treatment for improving expiratory pressure. EMST proved to be effective in different patient groups to improve cough function. To date, EMST has not been tested in the total laryngectomy population (TL). METHODS: This prospective, randomized case-series study examined feasibility, safety, and compliance of EMST in a group of TL participants and its effects on pulmonary function, physical exertion, fatigue, and vocal functioning. Ten TL participants were included in the study to perform a 4 till 8 weeks of EMST. Objective and subjective outcome measures included manometry, spirometry, cardio pulmonary exercise testing (CPET), voice recordings, and patient reported outcome measures. Group means were reported and estimates of the effect are shown with a 95% confidence interval, using single sample t-tests. RESULTS: Nine participants completed the full study protocol. Compliance to the training program was high. All were able to perform the training, although it requires adjustments of the device and skills of the participants. Maximum expiratory pressure (MEP) and vocal functioning in loudness improved over time. After EMST no changes were seen in other objective and subjective outcomes. CONCLUSIONS: EMST appears to be feasible and safe after total laryngectomy. MEP improved over time but no improvement in the clinically relevant outcome measures were seen in this sample of relatively fit participants. Further investigation of the training in a larger group of participants who report specifically pulmonary complaints is recommended to investigate if the increase in MEP results in clinical benefits. LEVEL OF EVIDENCE: 4.

GERiatric Screening in the treatment of elderly patients with Ovarian Carcinoma (GERSOC): study protocol for a pragmatic, cluster randomised controlled trial.

BACKGROUND: Approximately 40% of the newly diagnosed patients with advanced ovarian cancer are aged 70 years or older. Standard treatment for advanced disease consists of cytoreductive surgery and combination chemotherapy. In older patients, standard treatment is often withheld or prematurely stopped due to suspected frailty. It remains challenging to distinguish fit elderly patients who can endure standard therapy from frail patients who may benefit from an adapted treatment strategy. As a comprehensive geriatric assessment (CGA) can contribute to the identification of frail patients and improve tailored therapy in this population, screening tests were developed to select those who may benefit from a CGA. However, the use of these geriatric screening tests has rarely been compared with usual clinical care. The GERSOC-trial will evaluate whether geriatric screening in elderly patients with advanced-stage ovarian cancer improves treatment completion and quality of life. METHODS: This pragmatic, cluster randomised controlled trial will be conducted at a minimum of 20 hospitals in the Netherlands. Hospitals are randomly assigned to geriatric screening care (in which a geriatric screening comprised of the G8 questionnaire and the Timed Up and Go test is performed), or care as usual (in which current usual care is continued). A total of 320 patients aged ≥ 70 years with primary, advanced-stage ovarian carcinoma will be included. Patients considered fit on geriatric screening will receive standard treatment; patients who are considered unfit will be referred to a geriatrician for analysis and treatment advice. The primary outcome is the percentage difference in completed standard and adapted therapies between the two study arms. Secondary outcomes include quality of life, cost-effectiveness and survival. DISCUSSION: This trial aims to gather evidence for the use of geriatric screening in treatment decision-making in elderly patients with advanced ovarian cancer. If proven feasible, beneficial and cost-effective, geriatric screening may be implemented in routine clinical practice. TRIAL REGISTRATION: Netherlands Trial Registry, ID: NL6745. Registered on 2 August 2017.

Education Needs of Dutch Physical Therapists for the Treatment of Patients With Advanced Cancer: A Mixed Methods Study.

BACKGROUND: The survival rates for patients with advanced cancer have increased over time. Many patients experience symptoms and functional limitations that impair activities of daily living and limit quality of life. A number of these health problems are amenable to physical therapist treatment. However, physical therapists caring for patients with advanced cancer require special training and skills. OBJECTIVE: The study aimed to assess the educational needs and clinical uncertainties of Dutch physical therapists in relation to treatment of patients with advanced cancer. DESIGN: This was a mixed methods study. METHODS: A survey and 2 focus groups were conducted among physical therapists working in primary care who had previously received at least basic oncology training. RESULTS: A total of 162 physical therapists completed the survey. The most frequently reported educational needs were related to effective interprofessional collaboration (61.7%), knowledge of medical treatment (49.4%), and current evidence on physical therapist interventions in this population (49.4%). In the focus groups, physical therapists (n = 17) voiced uncertainties about treating patients with bone metastases, setting realistic goals, when and how to end a treatment episode, interprofessional collaboration, finding and using evidence, and using clinimetrics. CONCLUSION: These results support the need for specific education programs for physical therapists working with advanced cancer patients to increase the availability of high-quality oncology rehabilitation for this population.