High-intensity training in patients with lacunar stroke: A one-year follow-up.

OBJECTIVES: Physical inactivity is a major risk factor for stroke. It is a challenge for patients to initiate and adhere to regular exercise post-stroke. Early initiation of home-based high-intensity interval training (HIIT) may engage patients in physical activity, improve cardiorespiratory fitness, and reduce risk of recurrent stroke. MATERIALS AND METHODS: Post-intervention follow-up of patients with lacunar stroke, randomized to three-months HIIT including weekly motivational calls, or usual care. At follow-up (six- and 12-months post-stroke), we investigated changes in cardiorespiratory fitness, physical activity, fatigue, depression, mental well-being, stress, cognition, cardiovascular function, and recurrent stroke. RESULTS: We included 71 patients of whom 59 patients (mean age: 63.9 ± 8.8 years) completed six- and 12-month follow-up. No change was detected in cardiorespiratory fitness between groups from baseline to 12-months follow-up. At six months, vigorous-intensity activity (median hours/week [interquartile range]) was maintained in the intervention group (baseline, 0[0;2]; post-intervention, 2[0;3]; six-month, 2[0;4]) and increased in the usual care group (baseline, 0[0;1]; post-intervention, 1[0;2]; six-month, 1[0;3]), with no difference between groups. Vigorous-intensity activity declined to baseline levels at 12-months in both groups. Secondary outcomes improved from baseline to 12-months with no significant differences between groups. Similar rate of recurrent stroke (n=3) occurred in each group with a three-month delay in the intervention group. CONCLUSIONS: Early initiated HIIT did not increase long-term cardiorespiratory fitness, but increased time spent doing vigorous-intensity activities post-stroke. Decline to baseline activity level at 12 months warrants identification of motivators to initiate and sustain physical activity post-stroke.

Factors influencing functioning after volar locking plate fixation of distal radius fractures: a scoping review of 148 studies.

BACKGROUND AND PURPOSE: A better understanding of factors that influence functioning may improve the identification of patients with distal radius fractures (DRFs) who need hand therapy. The purpose of this scoping review was to provide a comprehensive overview of factors that have been evaluated for their influence on hand functioning following volar plate fixation of DRFs. MATERIAL AND METHODS: 6 databases were searched from 2005 to 2021 for publications regarding surgical treatment for a DRF with a volar locking plate. Included studies evaluated demographic, perioperative, and postoperative factors within the 6 weeks post-surgery for their influence on functioning at least 3 months post-surgery. Functioning was assessed with patient-reported outcome measures. The factors were categorized into themes and mapped to the International Classification of Functioning, Disability and Health (ICF). RESULTS: 148 studies were included. 708 factors were categorized into 39 themes (e.g. pain) and mapped to the ICF components. The themes were primarily mapped to "body functions and structures" (n = 26) and rarely to "activities and participation" (n = 5). Fracture type (n = 40), age (n = 38), and sex (n = 22) were the most frequently evaluated factors. CONCLUSION: This scoping review identified an extensive number of factors evaluated within 6 weeks after surgery for their influence on functioning at least 3 months after volar plate fixation of a DRF and the existing research has primarily evaluated factors related to "body functions and structures," with limited focus on factors related to "activities and participation."

Effects of a 12-Week Multimodal Exercise Intervention Among Older Patients with Advanced Cancer: Results from a Randomized Controlled Trial.

BACKGROUND: Older patients with cancer are at risk of physical decline and impaired quality of life during oncological treatment. Exercise training has the potential to reduce these challenges. The study aim was to investigate the feasibility and effect of a multimodal exercise intervention in older patients with advanced cancer (stages III/IV). PATIENTS AND METHODS: Eighty-four older adults (≥65 years) with advanced pancreatic, biliary tract, or non-small cell lung cancer who received systemic oncological treatment were randomized 1:1 to an intervention group or a control group. The intervention was a 12-week multimodal exercise-based program including supervised exercise twice weekly followed by a protein supplement, a home-based walking program, and nurse-led support and counseling. The primary endpoint was change in physical function (30-second chair stand test) at 13 weeks. RESULTS: Median age of the participants was 72 years (interquartile range [IQR] 68-75). Median adherence to the exercise sessions was 69% (IQR 21-88) and 75% (IQR 33-100) for the walking program. At 13 weeks, there was a significant difference in change scores of 2.4 repetitions in the chair stand test, favoring the intervention group (p < .0001). Furthermore, significant beneficial effects were seen for physical endurance (6-minute walk test), hand grip strength, physical activity, symptom burden, symptoms of depression and anxiety, global health status (quality of life), and lean body mass. No effects were seen for dose intensity, hospitalizations, or survival. CONCLUSION: A 12-week multimodal exercise intervention with targeted support proved effective in improving physical function in older patients with advanced cancer during oncological treatment.

High Intensity Aerobic exercise training and Immune cell Mobilization in patients with lung cancer (HI AIM)-a randomized controlled trial.

BACKGROUND: The increasing role of exercise training in cancer care is built on evidence that exercise can reduce side effects of treatment, improve physical functioning and quality of life. We and others have shown in mouse tumor models, that exercise leads to an adrenalin-mediated increased influx of T and NK cells into the tumor, altering the tumor microenvironment (TME) and leading to reduced tumor growth. These data suggest that exercise could improve immune responses against cancer cells by increase immune cell infiltration to the tumor and potentially having an impact on disease progression. Additionally, there are data to suggest that infiltration of T and NK cells into the TME is correlates with response to immune checkpoint inhibitors in patients. We have therefore initiated the clinical trial HI AIM, to investigate if high intensity exercise can mobilize and increase infiltration of immune cells in the TME in patients with lung cancer. METHODS: HI AIM (NCT04263467) is a randomized controlled trial (70 patients, 1:1) for patients with non-small cell lung cancer. Patients in the treatment arm, receive an exercise-intervention consisting of supervised and group-based exercise training, comprising primarily intermediate to high intensity interval training three times per week over 6 weeks. All patients will also receive standard oncological treatments; checkpoint inhibitors, checkpoint inhibitors combined with chemotherapy or oncological surveillance. Blood samples and biopsies (ultrasound guided), harvested before, during and after the 6-week training program, will form basis for immunological measurements of an array of immune cells and markers. Primary outcome is circulating NK cells. Secondary outcome is other circulating immune cells, infiltration of immune cells in tumor, inflammatory markers, aerobic capacity measured by VO2 max test, physical activity levels and quality of life measured by questionnaires, and clinical outcomes. DISCUSSION: To our knowledge, HI AIM is the first project to combine supervised and monitored exercise in patients with lung cancer, with rigorous analyses of immune and cancer cell markers over the course of the trial. Data from the trial can potentially support exercise as a tool to mobilize cells of the immune system, which in turn could potentiate the effect of immunotherapy. TRIAL REGISTRATION: The study was prospectively registered at ClinicalTrials.gov on February 10th 2020, ID: NCT04263467. https://clinicaltrials.gov/ct2/show/NCT04263467.

Physical activity after colorectal cancer surgery-a cross sectional study of patients with a long-term stoma.

PURPOSE: Physical activity is recommended to cancer survivors by the World Health Organisation (WHO) and is associated with improved survival after colorectal cancer. It remains unclear whether having a stoma is a barrier for an active lifestyle. We examined the level of physical activity and explored factors impacting physical activity in survivors with a stoma. METHODS: A total of 1265 (65%) patients in the Danish Stoma Database completed a multidimensional survey. Physical activity of moderate- and vigorous-intensity was assessed using two validated questions. Based on WHO guidelines, physical activity was categorised into 'Meeting' or 'Not Meeting' recommendations. Multivariate regression analysis, adjusting for potential confounders, provided odds ratio (OR) and 95% confidence intervals (CI) for factors' association with'Not Meeting' guideline recommendations. RESULTS: In total, 571 patients with colorectal cancer reported on physical activity at a median of 4.3 years (interquartile range 3.1-5.8) after stoma surgery. Two hundred ninety-three patients (51%) were 'Meeting recommendations' and 63% of them were 'Highly active'. Two hundred seventy-eight were 'Not meeting' recommendations (49%). Of the factors analysed, patients without support garment were more likely (OR 1.72 [95% CI 1.16; 2.54] not to meet guideline recommendations. We found no association between stoma type, surgical procedure, parastomal bulging and 'problematic stoma' and level of physical activity, respectively. CONCLUSION: In this large sample of survivors with a stoma half of patients met or exceeded guideline recommendations. Of patients not meeting recommendations some could potentially meet the recommendations by modest increases in either moderate or vigorous activity.

Impact of a Parastomal Bulge on Quality of Life - A Cross-sectional Study of Patients From the Danish Stoma Database.

OBJECTIVE: To investigate stoma specific and generic HRQoL in patients with and without a parastomal bulge. BACKGROUND: Most patients have to live with their stoma complicated by a parastomal bulge. How this affects quality of life remains unclear. METHODS: Patients in the Danish Stoma Database completed the Short-form 36 health survey and the stoma-QOL questionnaire. Linear regression analysis, adjusted for potential confounding factors, provided mean and mean score differences and 95% confidence intervals for each HRQoL scale and item. Cohens d provided estimates of effect size. RESULTS: A total of 1265 patients (65%) completed the questionnaire 4.4 (interquartile range 3.1-6.0) years after stoma surgery. Of these, 693 (55%) patients with a parastomal bulge had significantly impaired (P < 0.01) HRQoL across all stoma specific and generic health domains compared to patients without a parastomal bulge. In patients with a benign diagnosis or an ileostomy, a parastomal bulge impacted significantly on Social Functioning and Mental Health resulting in a worse Mental Component Summary. A large bulge >10 cm impaired HRQoL (P < 0.01) across all stoma specific and generic domains. The impact on HRQoL was independent of time with the bulge. CONCLUSIONS: A novel finding in this large, unselected sample from high-quality regional registries was that parastomal bulging was associated with substantial and sustained impairment of HRQoL.

Reliability of graded cycling test with talk test and 30-s chair-stand test in men with prostate cancer on androgen deprivation therapy.

PURPOSE: To investigate the absolute and relative reliability of the "graded cycling test with talk test" (GCT-TT) and the "30-second chair-stand test" (30s-CST) in men with prostate cancer receiving androgen deprivation therapy (ADT). METHODS: Men with prostate cancer on ADT were included in this test-retest study. GCT-TT and 30s-CST were performed twice with 1 hour between test sessions. All tests were conducted by two experienced physiotherapists and all patients were familiar with the tests. Only intra-tester reliability was investigated as the test and retest of each participant were performed by the same physiotherapist. Intraclass correlation coefficient (ICC2.1), standard error of measurement (SEM and SEM95), and smallest real difference (SRD) were calculated. RESULTS: Sixty men were included with a mean age of 70.8 ± 6.6 (mean ± SD) years. All performed 30s-CST twice without any problems. Two participants were excluded from the analysis of the GCT-TT results. Relative reliability for 30s-CST (ICC2.1) was 0.97 [95% CI: 0.94-0.98] with low measurement error: SEM95, 1.9 repetitions, and SRD, 2.6 repetitions. The corresponding results for GCT-TT were ICC2.1, 0.90 [95% CI: 0.84-0.94]; SEM95, 19.9 W; and SRD, 28.2 W. CONCLUSIONS: The reliability of 30s-CST and GCT-TT is substantial for men with prostate cancer receiving ADT. Overall, an average 30s-CST improvement of 1.9 repetitions on a group level and three repetitions for individual patients are considered real improvements. A GCT-TT improvement exceeding 19.9 W represents a real improvement for a group of patients. Individual patients need to improve two steps (30 W).

Geriatric assessment and intervention in older vulnerable patients undergoing surgery for colorectal cancer: a protocol for a randomised controlled trial (GEPOC trial).

BACKGROUND: The incidence of colorectal cancer (CRC) increases with age. Older patients are a heterogeneous group ranging from fit to frail with various comorbidities. Frail older patients with CRC are at increased risk of negative outcomes and functional decline after cancer surgery compared to younger and fit older patients. Maintenance of independence after treatment is rarely investigated in clinical trials despite older patients value it as high as survival. Comprehensive geriatric assessment (CGA) is an evaluation of an older persons' medical, psychosocial, and functional capabilities to develop an overall plan for treatment and follow-up. The beneficial effect of CGA is well documented in the fields of medicine and orthopaedic surgery, but evidence is lacking in cancer surgery. We aim to investigate the effect of CGA on physical performance in older frail patients undergoing surgery for CRC. METHODS: GEPOC is a single centre randomised controlled trial including older patients (≥65 years) undergoing surgical resection for primary CRC. Frail patients (≤14/17 points using the G8 screening tool) will be randomised 1:1 to geriatric intervention and exercise (n = 50) or standard of care along (n = 50) with their standard surgical procedure. Intervention includes preoperative CGA, perioperative geriatric in-ward review and postoperative follow-up. All patients in the intervention group will participate in a pre- and postoperative resistance exercise programme (twice/week, 2 + 12 weeks). Primary endpoint is change in 30-s chair stand test. Assessment of primary endpoint will be performed by physiotherapists blinded to patient allocation. Secondary endpoints: changes in health related quality of life, physical strength and capacity (handgrip strength, gait speed and 6 min walking test), patient perceived quality of recovery, complications to surgery, body composition (Dual-energy X-ray absorptiometry and bioelectric impedance), serum biomarkers, readmission, length of stay and survival. DISCUSSION: This ongoing trial will provide valuable knowledge on whether preoperative CGA and postoperative geriatric follow-up and intervention including an exercise program can counteract physical decline and improve quality of life in frail CRC patients undergoing surgery. TRIAL REGISTRATION: Prospectively registered at Clinicaltrials.gov NCT03719573 (October 2018).

Clinical management of acute low back pain in elite and subelite rowers: a Delphi study of experienced and expert clinicians.

OBJECTIVES: Rowing-related low back pain (LBP) is common but published management research is lacking. This study aims to establish assessment and management behaviours and beliefs of experienced and expert clinicians when elite and subelite rowers present with an acute episode of LBP; second, to investigate how management differs for developing and masters rowers. This original research is intended to be used to develop rowing-related LBP management guidelines. METHODS: A three-round Delphi survey was used. Experienced clinicians participated in an internet-based survey (round 1), answering open-ended questions about assessment and management of rowing-related LBP. Statements were generated from the survey for expert clinicians to rate (round 2) and rerate (round 3). Consensus was gained when agreement reached a mean of 7 out of 10 and disagreement was 2 SD or less. RESULTS: Thirty-one experienced clinicians participated in round 1. Thirteen of 20 invited expert clinicians responded to round 2 (response rate 65%) and 12 of the 13 participated in round 3 (response rate 92%).One hundred and fifty-three of 215 statements (71%) relating to the management of LBP in elite and subelite rowers acquired consensus status. Four of six statements (67%) concerning developing rowers and two of four (50%) concerning masters rowers gained consensus. CONCLUSION: In the absence of established evidence, these consensus-derived statements are imperative to inform the development of guidelines for the assessment and management of rowing-related LBP. Findings broadly reflect adult LBP guidelines with specific differences. Future research is needed to strengthen specific recommendations and develop best practice guidelines in this athletic population.

The relationship between rowing-related low back pain and rowing biomechanics: a systematic review.

BACKGROUND: Low back pain (LBP) is common in rowers. Understanding rowing biomechanics may help facilitate prevention and improve rehabilitation. OBJECTIVES: To define the kinematics and muscle activity of rowers and to compare with rowers with current or LBP history. DESIGN: Systematic review. DATA SOURCES: EMBASE, MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Web of Science and Scopus from inception to December 2019. Grey literature was searched. STUDY ELIGIBILITY CRITERIA: Experimental and non-experimental designs. METHODS: Primary outcomes were kinematics and muscle activity. Modified Quality Index (QI) checklist was used. RESULTS: 22 studies were included (429 participants). Modified QI score had a mean of 16.7/28 points (range: 15-21). Thirteen studies investigated kinematics and nine investigated muscle activity. Rowers without LBP ('healthy') have distinct kinematics (neutral or anterior pelvic rotation at the catch, greater hip range of motion, flatter low back spinal position at the finish) and muscle activity (trunk extensor dominant with less flexor activity). Rowers with LBP had relatively greater posterior pelvic rotation at the catch, greater hip extension at the finish and less efficient trunk muscle activity. In both groups fatigue results in increased lumbar spine flexion at the catch, which is greater on the ergometer. There is insufficient evidence to recommend one ergometer type (fixed vs dynamic) over the other to avoid LBP. Trunk asymmetries are not associated with LBP in rowers. CONCLUSION: Improving clinicians' and coaches' understanding of safe and effective rowing biomechanics, particularly of the spine, pelvis and hips may be an important strategy in reducing incidence and burden of LBP.

Treating low back pain in athletes: a systematic review with meta-analysis.

OBJECTIVE: To summarise the evidence for non-pharmacological management of low back pain (LBP) in athletes, a common problem in sport that can negatively impact performance and contribute to early retirement. DATA SOURCES: Five databases (EMBASE, Medline, CINAHL, Web of Science, Scopus) were searched from inception to September 2020. The main outcomes of interest were pain, disability and return to sport (RTS). RESULTS: Among 1629 references, 14 randomised controlled trials (RCTs) involving 541 athletes were included. The trials had biases across multiple domains including performance, attrition and reporting. Treatments included exercise, biomechanical modifications and manual therapy. There were no trials evaluating the efficacy of surgery or injections. Exercise was the most frequently investigated treatment; no RTS data were reported for any exercise intervention. There was a reduction in pain and disability reported after all treatments. CONCLUSIONS: While several treatments for LBP in athletes improved pain and function, it was unclear what the most effective treatments were, and for whom. Exercise approaches generally reduced pain and improved function in athletes with LBP, but the effect on RTS is unknown. No conclusions regarding the value of manual therapy (massage, spinal manipulation) or biomechanical modifications alone could be drawn because of insufficient evidence. High-quality RCTs are urgently needed to determine the effect of commonly used interventions in treating LBP in athletes.

2021 consensus statement for preventing and managing low back pain in elite and subelite adult rowers.

PURPOSE: To synthesise evidence on low back pain (LBP) in adult rowers and to create a consensus statement to inform clinical practice. METHODS: There were four synthesis steps that informed the consensus statement. In step one, seven expert clinicians and researchers established the scope of the consensus statement and conducted a survey of experienced and expert clinicians to explore current practice. In step two, working groups examined current evidence relating to key scope questions and summarised key issues. In step three, we synthesised evidence for each group and used a modified Delphi process to aid in the creation of the overall consensus statements. Finally, in step four, we combined information from step three with the findings of the clinician survey (and with athlete and coach input) to produce recommendations for clinical practice. RESULTS: The scope of the consensus statement included epidemiology; biomechanics; management; the athlete's voice and clinical expertise. Prevention and management of LBP in rowers should include education on risk factors, rowing biomechanics and training load. If treatment is needed, non-invasive management, including early unloading from aggravating activities, effective pain control and exercise therapy should be considered. Fitness should be maintained with load management and progression to full training and competition. The role of surgery is unclear. Management should be athlete focused and a culture of openness within the team encouraged. CONCLUSION: Recommendations are based on current evidence and consensus and aligned with international LBP guidelines in non-athletic populations, but with advice aimed specifically at rowers. We recommend that research in relation to all aspects of prevention and management of LBP in rowers be intensified.

Prevalence and risk factors for back pain in sports: a systematic review with meta-analysis.

OBJECTIVES: We aimed to determine the prevalence of low back pain (LBP) in sport, and what risk factors were associated with LBP in athletes. DESIGN: Systematic review with meta-analysis. DATA SOURCES: Literature searches from database inception to June 2019 in Medline, Embase, Cumulated Index to Nursing and Allied Health Literature (CINAHL), Web of Science and Scopus, supplemented by grey literature searching. ELIGIBILITY CRITERIA: Studies evaluating prevalence of LBP in adult athletes across all sports. RESULTS: Eighty-six studies were included (30 732, range 20-5958, participants), of which 45 were of 'high' quality. Definitions of LBP varied widely, and in 17 studies, no definition was provided. High-quality studies were pooled and the mean point prevalence across six studies was 42%; range 18%-80% (95% CI 27% to 58%, I2=97%). Lifetime prevalence across 13 studies was 63%; range 36%-88% (95% CI 51% to 74%, I2=99%). Twelve-month LBP prevalence from 22 studies was 51%; range 12%-94% (95% CI 41% to 61%, I2=98%). Comparison across sports was limited by participant numbers, study quality and methodologies, and varying LBP definitions. Risk factors for LBP included history of a previous episode with a pooled OR of 3.5; range 1.6-4.0 (95% CI 1.9 to 6.4). Statistically significant associations were reported for high training volume, periods of load increase and years of exposure to the sport. CONCLUSION: LBP in sport is common but estimates vary. Current evidence is insufficient to identify which sports are at highest risk. A previous episode of LBP, high training volume, periods of load increase and years of exposure are common risk factors.

Protein supplementation combined with low-intensity resistance training in geriatric medical patients during and after hospitalisation: a randomised, double-blind, multicentre trial.

Sarcopenia (loss of muscle mass/strength) burdens many older adults - hospitalised older adults being particularly vulnerable. Treating the condition, protein supplementation (PrS) and resistance training (RT) may act synergistically. Therefore, this block-randomised, double-blind, multicentre intervention study, recruiting geriatric patients > 70 years from three medical departments, investigated the effect of PrS combined with RT during hospitalisation and 12 weeks after discharge. Participants were randomly allocated (1:1) to receive PrS (totally 27·5 g whey protein/d, about 2000 kJ/d) or isoenergetic placebo-products (< 1·5 g protein/d) divided into two servings per d to supplement the habitual diet. Both groups were engaged in a standardised, progressive low-intensity RT programme for the lower extremities (hospital: supervised daily/after discharge: self-training 4×/week). From April 2016 to September 2017, 2351 patients were screened, 462 were eligible, and 165 included. Fourteen were excluded and ten dropped out, leaving 141 participants in the intention-to-treat analysis. The average total protein intake during hospitalisation/after discharge was 1·0 (interquartile range (IQR) 0·8, 1·3)/1·1 (IQR 0·9, 1·3) g/kg per d (protein-group) and 0·6 (IQR 0·5, 0·8)/0·9 (IQR 0·6, 1·0) g/kg per d (placebo group). Both groups improved significantly for the primary and secondary endpoints of muscle mass/strength, functional measurements and quality of life, but no additional effect of PrS was seen for the primary endpoint (30-s chair stand test, repetitions, median changes from baseline: (standard test: 0 (IQR 0, 5) (protein group) v. 2 (IQR 0, 6) (placebo group) and modified test: 2 (IQR 0, 5) (protein group) v. 2 (IQR -1, 5) (placebo group)) or any secondary endpoints (Mann-Whitney U tests, P > 0·05). In conclusion, PrS increasing the total protein intake by 0·4 and 0·2 g/kg per d during hospitalisation and after discharge, respectively, does not seem to increase the adaptive response to low-intensity RT in geriatric medical patients.

Self-Reported Physical Activity and Cardiovascular Disease Risk Factors in Patients with Lacunar Stroke.

BACKGROUND: Physical inactivity is a major modifiable risk factor for stroke. The aim was to explore if stroke patients admitted with lacunar stroke adhere to the international recommendations on physical activity prestroke (≥150 minutes of moderate-intensity activity, or ≥75 minutes of vigorous-intensity activity, or an equivalent combination). Further, to assess association between prestroke physical activity and cardiovascular disease (CVD) risk factors. METHODS: A cross-sectional study, including patients with lacunar stroke according to the Trial of Org 10172 in Acute Stroke Treatment criteria. Data collected included prestroke physical activity using the self-reported Physical Activity Scale. Cardiorespiratory fitness was estimated as the power output from the Graded Cycling Test with Talk Test and sociodemographic factors including age, sex, education, and CVD risk factors including pre-existing diabetes, history of hypertension, body mass index, and lipids were assessed. RESULTS: We included 19 women and 52 men (mean age 64 years). Overall, 79% of the recruited patients adhered to the physical activity recommendations prestroke, but only 35% did vigorous-intensity activity. Prestroke physical activity was associated with a history of hypertension. CONCLUSIONS: A high proportion of the lacunar stroke patients reported to adhere to the recommendations on physical activity prestroke; however, only one third engaged in vigorous-intensity activity. Studies are warranted to investigate if vigorous-intensity activity is effective as secondary prevention in patients with a lacunar stroke.

Engaging the older cancer patient; Patient Activation through Counseling, Exercise and Mobilization - Pancreatic, Biliary tract and Lung cancer (PACE-Mobil-PBL) - study protocol of a randomized controlled trial.

BACKGROUND: Several intervention studies have demonstrated that exercise training has beneficial effects among cancer patients. However, older cancer patients are underrepresented in clinical trials, and only few exercise-based studies have focused specifically on older patients with cancer. In particular, research investigating the effects of exercise training among older patients with advanced cancer is lacking. The purpose of the current study is to investigate the effect of a 12-week multimodal and exercise-based intervention among older patients (≥65 years) with advanced pancreatic, biliary tract or lung cancer, who are treated with first-line palliative chemotherapy, immunotherapy or targeted therapy. METHODS: PACE-Mobil-PBL is a two-armed randomized controlled trial. Participants will be randomized 1:1 to an intervention group (N = 50) or a control group (N = 50). Participants in the intervention group will receive standard oncological treatment and a 12-week multimodal intervention, comprised of: (I) supervised exercise training, twice weekly in the hospital setting, (II) home-based walking with step counts and goal-setting, (III) supportive and motivational nurse-led counseling, and (IV) protein supplement after each supervised training session. Participants in the control group will receive standard oncological treatment. The primary outcome is physical function measured by the 30-s chair stand test. Secondary outcomes include measures of feasibility, activity level, physical capacity and strength, symptom burden, quality of life, toxicity to treatment, dose reductions, inflammatory biomarkers, body weight and composition, hospitalizations and survival. Assessments will be conducted at baseline, and after 6, 12 and 16 weeks. DISCUSSION: The current study is one of the first to investigate the effect of an exercise-based intervention specifically targeting older patients with advanced cancer. PACE-Mobil-PBL supports the development of health promoting guidelines for older patients with cancer, and the study results will provide new and valuable knowledge in this understudied field. TRIAL REGISTRATION: The study was prospectively registered at ClinicalTrials.gov on January 26, 2018 (ID: NCT03411200 ).

Progressive resistance training in head and neck cancer patients during concomitant chemoradiotherapy -- design of the DAHANCA 31 randomized trial.

BACKGROUND: Head and neck cancer patients undergoing concomitant chemoradiotherapy (CCRT) frequently experience loss of muscle mass and reduced functional performance. Positive effects of exercise training are reported for many cancer types but biological mechanisms need further elucidation. This randomized study investigates whether progressive resistance training (PRT) may attenuate loss of muscle mass and functional performance. Furthermore, biochemical markers and muscle biopsies will be investigated trying to link biological mechanisms to training effects. METHODS: At the Departments of Oncology at Herlev and Aarhus University Hospitals, patients with stage III/IV squamous cell carcinoma of the head and neck, scheduled for CCRT are randomized 1:1 to either a 12-week PRT program or control group, both with 1 year follow-up. Planned enrollment is 72 patients, and stratification variables are study site, sex, p16-status, and body mass index. Primary endpoint is difference in change in lean body mass (LBM) after 12 weeks of PRT, assessed by dual-energy X-ray absorptiometry (DXA). The hypothesis is that 12 weeks of PRT can attenuate the loss of LBM by at least 25%. Secondary endpoints include training adherence, changes in body composition, muscle strength, functional performance, weight, adverse events, dietary intake, self-reported physical activity, quality of life, labor market affiliation, blood biochemistry, plasma cytokine concentrations, NK-cell frequency in blood, sarcomeric protein content in muscles, as well as muscle fiber type and fiber size in muscle biopsies. Muscle biopsies are optional. DISCUSSION: This randomized study investigates the impact of a 12-week progressive resistance training program on lean body mass and several other physiological endpoints, as well as impact on adverse events and quality of life. Furthermore, a translational approach is integrated with extensive biological sampling and exploration into cytokines and mechanisms involved. The current paper discusses decisions and methods behind exercise in head and neck cancer patients undergoing concomitant chemoradiotherapy. TRIAL REGISTRATION: Approved by the Regional Ethics Committee for the Capital Region of Denmark (protocol id: H-15003725) and registered retrospectively at ClinicalTrials.gov ( NCT02557529 ) September 11th 2015.

Living with a parastomal bulge - patients' experiences of symptoms.

AIMS AND OBJECTIVES: To investigate experienced symptoms of parastomal bulging in relation to an ileostomy or colostomy. BACKGROUND: Parastomal bulging is a common complication of stoma formation that can affect patients' physical, psychological and social function. Symptom burdens reported by health professionals vary from asymptomatic to high symptom load; however, patients' experiences of symptoms are lacking. DESIGN AND METHOD: A qualitative design with focus group interviews was chosen for data collection. Twenty patients participated in five semi-structured interviews. Analysis was performed using a phenomenological-hermeneutic approach. FINDINGS: The bulge caused different unfamiliar bodily sensations that interacted with patients' everyday lives. Some but not all of these sensations were modifiable. As the bulge and the ostomy changed size and shape, patients had to adjust and readjust stoma care continuously. The physical change called for patients' awareness and posed a threat to patients' control of the ostomy and challenged stoma self-care. The bulge caused a bodily asymmetry that deformed the patients' bodies in a way that exceeded the perceived alteration already caused by the stoma. To cover the physical disfigurement, new clothing solutions, garment wear and creativity were essential in everyday life. Patients gradually adapted to the bulge over time. Easy access to professional help was crucial in order to find the best appliance and garment solution in relation to the bulge. CONCLUSIONS: Various symptoms related to the parastomal bulge affected patients' everyday lives in different ways and underpinned that an individualised approach is important when addressing patients' problems and complaints. Research into nonsurgical treatments and patient perspectives is limited and highly warranted to improve clinical outcome. RELEVANCE TO CLINICAL PRACTICE: The ever-changing bulge posed a threat to patients' control of the ostomy and required specific care from the stoma therapist. Needs-based access to counselling, advice and supplementary materials is important.

"Graded Cycling Test with Talk Test" Is a Reliable Test to Monitor Cardiovascular Fitness in Patients with Minor Stroke.

BACKGROUND: Physical exercise is generally recommended as part of life style changes post stroke. Monitoring cardiovascular effects may help motivate patients for further exercise, and can be an instrument to assess intervention effects in clinical trials. In 1 of 4 stroke patients, the heart rate variability may challenge currently used cardiovascular monitoring. The Graded Cycling Test with Talk Test is a submaximal exercise test independent of heart rate variability, shown reliable for patients with cardiac disease. METHODS: Patients diagnosed with lacunar stroke according to TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria performed an incremental exercise test on a stationary bicycle with a 15 W (watt) increase in workload every minute. Toward the end of each incremental step, the patients recited a standardized text passage and subsequently were asked: "Are you still able to speak comfortably?" The test was stopped when the patients were no longer able to speak comfortably. Two consecutive tests were performed separated by 1 hour rest. RESULTS: Sixty patients completed the study. The intraclass correlation coefficient (ICC2.1) was as follows: .97 [95% CI: .95-.98] with only a minor measurement error: 12.9 W for groups of patients (standard error of measurement, SEM95) and 18.3 W for individual patients (smallest real difference). CONCLUSION: The "Graded Cycling Test with Talk Test" is feasible and reliable for monitoring exercise effects in patients with lacunar stroke. The high ICC2.1 and small measurement error suggest it to be a valuable outcome measurement in clinical practice.

Approaches to Design an Efficient, Predictable Global Post-approval Change Management System that Facilitates Continual Improvement and Drug Product Availability.

The complexity and inter-connectedness of operating in a global world for drug product supply has become an undeniable reality, further underscored by the COVID-19 pandemic. For Post-Approval Changes (PACs) that are an inevitable part of a product's commercial life, the impact of the growing global regulatory complexity and related drug shortages has brought the Global PAC Management System to an inflection point in particular for companies that have their products marketed in many countries.This paper illustrates through data analyzed for the first time from 145,000 + PACs for 156 countries, collected by 18 global pharma companies over a 3-year period (2019-2021), how severe the problem of global regulatory complexity is. Only PACs requiring national regulatory agency (NRA) approval prior to implementation were included in the data set. 1 of the 156 country NRAs approved all submitted PACs within a period of 6 months. The 6-month timeline was chosen because it is the recommended review timeline for major changes in the WHO guidance for vaccines and biotherapeutic products. 10 out of the 156 (6%) countries had no more than 10% of the PACs reviewed and approved in > 6 months. In 33 (22%) countries more than half of the PACs took > 6 months for approval. It is rare that the same PAC is approved globally within 6 months as individual NRAs take from a few months to years (in some cases > 5 years) for their review.The global PAC management complexity has steadily grown over the past 20 years. Attempts thus far to solve this problem have not made any meaningful difference. Senior leaders and decision-makers across the interdependent components of the complex Global PAC Management System (industry and regulators) must come together and collaboratively manage the problem holistically with the objective of ensuring global drug product availability instead of continuing with distinct stakeholder or country-focused solutions, which can tend to worsen the problem.In this paper, the Chief Quality Officers (CQOs) from 18 of the largest innovator pharma companies (see Acknowledgements) are speaking with One-Voice-of-Quality for PACs (1VQ for PACs Initiative). They are recommending a set of 8 approaches to activate a holistic transformation of the Global PAC Management System. This article presents their view on the problem of global regulatory complexity for managing PACs, it's impact on continual improvement and the risk to drug product supply, as well as approaches that can help alleviate the problem.