Safety, Feasibility, and Acceptability of a Multisite Individualized Exercise Intervention for People with Multiple Myeloma.

INTRODUCTION: High rates of disease- and treatment-related symptoms, such as bone lesions, in people with multiple myeloma (MM) create uncertainty on the safety and feasibility of exercise. This study determined the safety, feasibility, and acceptability of an individualized exercise medicine program for people with MM at any disease stage. METHODS: A multisite, randomized waitlist-controlled trial was conducted of an individualized, high-intensity aerobic, resistance, and impact-loading exercise program. The exercise sessions were supervised twice weekly by accredited exercise physiologists, with one additional unsupervised session per week, for 12 wk. Safety was determined by number of adverse and serious adverse events. Feasibility outcome measures were study eligibility, recruitment, adherence, and attrition. Acceptability was determined by qualitative interviews and subjective levels of enjoyment. RESULTS: Of 203 people with MM screened, 88% were eligible, with 34% accepting participation (60 people) and 20% attrition for the between-group analysis, meeting a priori criteria (≥25% and <25%, respectively). No adverse or serious adverse events attributed to testing and/or exercise training were reported. Attendance at supervised exercise sessions was 98%, with 45% completion of the home-based exercise sessions. Adherence rates were 35%, 63%, and 34% for the aerobic, resistance, and impact-loading protocols, with 55%, 80%, and 37% of participants meeting a priori criteria (75% of protocol). Acceptability of the exercise program was high (mean, 82%; 95% confidence interval, 78%-87%) and highly supported by qualitative responses. CONCLUSIONS: An individualized, high-intensity aerobic, resistance, and impact-loading exercise medicine program is safe and acceptable, and feasible by some measures for people with MM. Adherence to the prescribed exercise protocols was limited by comorbidities and disease symptoms. Strategies to improve unsupervised exercise completion are warranted in this population.

Safety, Feasibility, and Efficacy of Exercise Interventions for People With Multiple Myeloma: A Systematic Review.

Bone lesions and other disease- and treatment-related side effects commonly experienced by people with multiple myeloma (MM) may impede their ability to exercise. This systematic review evaluated the safety, feasibility, and efficacy of exercise program participation on the physiological and/or psychological health of people with MM. Literature searches were conducted through five electronic databases and appraised using the Delphi list of criteria. Controlled trials that assessed the safety and feasibility of an exercise intervention and its effects on disease- or treatment-related symptoms in people with MM were included. Seven studies of varying quality involving 563 participants were included. All studies concluded that exercise was safe, reporting zero serious and 4 adverse events attributable to exercise testing or training. Attendance ranged from 58% to 96%, however no study reported adherence to the exercise prescription. Compared to a control group, exercise did not appear to affect fatigue, depression, anxiety, body composition, quality of life, or sleep. Isolated studies identified between-group differences favoring exercise in lower limb strength (+8.4 kg, 95% CI 0.5, 16.3, P= .04), peak oxygen uptake (+1.2 mL/kg/min, 95% CI 0.3, 3.7, P= .02), physical activity (+6.5MET-hs/wk, P< .001), stem cell collection attempts (1.1 ± 0.2 vs. 1.5 ± 0.9, P< .01), and red blood cell (1.8 ± 2.2 vs. 2.4 ± 2.6, P< .05) and platelet transfusions (2.3 ± 1.6 vs. 3.5 ± 3.4, P < .05) during transplantation. Exercise interventions appear safe and well attended by people with MM. The lack of improvements in disease- and treatment-related symptoms requires further exploration to determine whether exercise is a sufficient stimulus to elicit benefits in this unique population.

An Individualized Exercise Intervention for People with Multiple Myeloma-Study Protocol of a Randomized Waitlist-Controlled Trial.

People with multiple myeloma (MM) are second only to people with lung cancer for the poorest reported health-related quality of life (HRQoL) of all cancer types. Whether exercise can improve HRQoL in MM, where bone pain and lesions are common, requires investigation. This trial aims to evaluate the efficacy of an exercise intervention compared with control on HRQoL in people with MM. Following baseline testing, people with MM (n = 60) will be randomized to an exercise (EX) or waitlist control (WT) group. EX will complete 12-weeks of supervised (24 sessions) and unsupervised (12 sessions) individualized, modular multimodal exercise training. From weeks 12-52, EX continue unsupervised training thrice weekly, with one optional supervised group-based session weekly from weeks 12-24. The WT will be asked to maintain their current activity levels for the first 12-weeks, before completing the same protocol as EX for the following 52 weeks. Primary (patient-reported HRQoL) and secondary (bone health and pain, fatigue, cardiorespiratory fitness, muscle strength, body composition, disease response, and blood biomarkers) outcomes will be assessed at baseline, 12-, 24- and 52-weeks. Adverse events, attendance, and adherence will be recorded and cost-effectiveness analysis performed. The findings will inform whether exercise should be included as part of standard myeloma care to improve the health of this unique population.

Promoting exercise for patients with multiple myeloma: attitudes and practices of clinical haematologists.

PURPOSE: To explore the attitudes and practices of clinical haematologists towards promoting physical activity (PA) and exercise for patients with multiple myeloma (MM). METHODS: Using a quantitative cross-sectional survey, clinical haematologists reported on the perceived benefits and acceptability of PA and exercise and frequency, confidence and barriers to providing exercise advice. RESULTS: Clinical haematologists (n=34; 68% response rate), who cumulatively treated ~340 patients with MM each week, completed the survey. Almost all (97%) agreed that PA was important, with benefits for quality of life, activities of daily living, mental health and fatigue. Whilst 88% discussed PA at least occasionally with their patients, approximately two-thirds were not confident advising specific exercises (68%) or identifying PA resources (62%). Despite this, 44% never referred patients to exercise professionals, with 18% only doing so if the patient asked. Over half did not recommend exercise when patients had spine fractures or were physically unwell. No differences were observed in individual factors (age, gender, practice type and own PA participation) and promotion of PA. CONCLUSIONS: Clinical haematologists perceive PA as important, but lack confidence on what exercise/s to recommend and if exercise is appropriate for specific disease complications. They tend to not refer patients to exercise professionals. IMPLICATIONS FOR CANCER SURVIVORS: Patients with MM often suffer from symptoms and toxicities that may be alleviated through PA. However, PA participation rates are low. Support for clinical haematologists for when and how to discuss exercise, and clearer referral pathways to exercise professionals may improve PA uptake and hence ensure access to optimal care, thereby improving patient outcomes.

Physical Activity in People with Multiple Myeloma: Associated Factors and Exercise Program Preferences.

People with multiple myeloma (MM) often experience disease symptoms and treatment toxicities that can be alleviated through physical activity (PA). However, the majority of people with MM are insufficiently active. This study explored PA among people with MM, including differences by treatment stage, symptoms and demographics, and programming preferences. Overall, 126 people with MM (77% response rate) completed the survey. Pre-diagnosis, 25.4% were sufficiently active, with 12.0% remaining active after treatment. Respondents who were physically active pre-diagnosis were 46.7 times (95% confidence intervals CI: 2.03, 1072.1) more likely to meet PA guidelines following an MM diagnosis compared to people not meeting guidelines pre-diagnosis. Experiencing MM symptoms and receiving PA advice from healthcare professionals were not associated with meeting PA guidelines. People with MM were interested in exercise programs (55%) that are low-cost (77%), offered at flexible times (74%), and at locations close to home (69%), both during active treatment and remission (57%), and supervised by an exercise oncology specialist (48%). People with MM, particularly those insufficiently active prior to diagnosis, should be offered convenient, low-cost exercise programs supervised by an exercise oncology specialist to increase PA participation.

The Barker hypothesis confirmed: association of low birth weight with all-cause natural deaths in young adult life in a remote Australian Aboriginal community.

Barker et al. proposed that low birth weight predisposes to higher death rates in adult life. We previously confirmed this fact in a cohort of young adults who were born in a remote Australian Aboriginal community between 1956 and 1985. We now present data in these same people with four more years of follow-up and a greater number of deaths. The fates of participants were documented from age 15 years until death, start of dialysis, or until the end of 2010 and causes of death were derived from clinic narratives and dialysis records. Rates of natural deaths were compared by birth cohorts and birth weight, and hazard ratios were calculated using Cox proportional hazards methods, by birth weight and adjusted for birth cohort and sex. Over follow-up of 19,661 person-years, 61 people died of natural causes between age 15 and the censor date. Low birth weights (<2.5 kg) were associated with higher rates of natural death, with HR (95% CI) 1.76 (1.1-2.9, P=0.03), after adjustment for year of birth and sex. The effect was particularly prominent for deaths at <41 years of age, and with deaths from respiratory conditions/sepsis and unusual causes. A predisposing effect of low birth weight on adult deaths was confirmed. This phenomenon, occurring in the context of dramatically improved survivals of lower birth weight infants and children since the early 1960s, helps explain the current epidemic of chronic disease in Aboriginal people. Birth weights continue to improve, so excess deaths from this source should progressively be minimized.

Birthweight and natural deaths in a remote Australian Aboriginal community.

OBJECTIVES: To describe associations between birthweight and infant, child and early adult mortality from natural causes in a remote Australian Aboriginal community against a background of rapidly changing mortality due to better health services. DESIGN, PARTICIPANTS AND SETTING: Cohort study of 995 people with recorded birthweights who were born between 1956 and 1985 to an Aboriginal mother in a remote Australian Aboriginal community. Participants were followed through to the end of 2006. MAIN OUTCOME MEASURES: Rates of natural deaths of infants (aged 0 to < 1 year), children (aged 1 to < 15 years) and adults (aged 15 to < 37 years), compared by birth intervals (1956-1965, 1966-1975 and 1976-1985 for infants and children, and 1956-1962 and 1963-1969 for adults) and by birthweight. RESULTS: Birthweights were low, but increased over time. Deaths among infants and children decreased dramatically over time, but deaths among adults did not. Lower birthweights were associated with higher mortality. Adjusted for birth interval, hazard ratios for deaths among infants, children and adults born at weights below their group birthweight medians were 2.30 (95% CI, 1.13-4.70), 1.78 (95% CI, 1.03-3.07) and 3.49 (95% CI, 1.50-8.09), respectively. The associations were significant individually for deaths associated with diarrhoea in infants, with cardiovascular and renal disease in adults, and marginally significant for deaths from pulmonary causes in children and adults. CONCLUSION: The striking improvements in infant and child survival over time must be applauded. We confirmed a predisposing effect of lower birthweights on deaths in infants and children, and showed, for the first time, an association between lower birthweights and deaths in adults. Together, these factors are probably contributing to the current epidemic of chronic disease in Aboriginal people, an effect that will persist for decades. Similar phenomena are probably operating in developing countries.

Predictive value of nephelometric and high-performance liquid chromatography assays of urine albumin for mortality in a high-risk Aboriginal population.

BACKGROUND: Urine albumin assays by high-performance liquid chromatography (HPLC) yield greater values than immunoassays at lower albumin levels. We compared predictive values of albumin-creatinine ratios (ACRs) by these 2 techniques for mortality in Aboriginal people. STUDY DESIGN & SETTING: This was a longitudinal study of 741 adults in a remote Aboriginal community who participated in a baseline health survey between 1992 and 1998 at ages ranging from 18 to 84 years (mean, 34 years). All natural deaths were documented on follow-up until 2006. Urine albumin concentrations were measured simultaneously by using both nephelometric and HPLC techniques on baseline urine samples retrieved from -70 degrees C storage, as well as creatinine concentrations, and ACRs were derived. Age- and sex-specific tertiles of ACR were compiled. Cox regression analyses were used to evaluate the predictive value of ACR for natural deaths by ACR tertiles and again by z score changes in ACRs as continuous variables. RESULTS: Participants were followed up for a median of 11 years, during which a total of 119 natural deaths were documented. ACRs on baseline urine samples were greater by HPLC than immunoassay at lower ACR ranges, but were fairly concordant at levels greater than 100 mg/mmol. Levels of ACR by both techniques were strong predictors of death, but correlations of death with ACR tertiles and with ACR levels on a continuum were similar for the 2 techniques. LIMITATIONS: The age- and sex-specific tertiles used might introduce some risk of bias in the assessment of predictive value. In addition, assays were performed on urine after more than 10 years of cold storage. CONCLUSION: Despite different absolute values, this study did not show that ACR level by either technique was superior in predicting deaths.

A comparison of pathomolecular markers of fibrosis and morphology in kidney from autopsies of African Americans and whites.

African Americans have an increased incidence of chronic kidney disease (CKD) due to hypertension and arteriosclerosis and increased death due to coronary artery disease, compared with whites. The pathogenesis of CKD involves the increased presence and activation of myofibroblasts and macrophages, promotion of tubulointerstitial fibrosis, and effects of tubulointerstitial cell mitosis and apoptosis. We hypothesized that increased risk of hypertensive vascular disease may be identified by renal pathomolecular markers that are associated with progressive CKD. Renal sections were available from 50 autopsies of 33 African Americans (55% males) and 17 whites (76% males) undergoing forensic autopsy for unexpected death. Sclerotic glomeruli, severity of cortical fibrosis, and renal arteriolosclerosis, total glomerular number (N (glom)), average glomerular volume (V (glom)), birth weights, and blood pressure were known. Presence and locality of markers for myofibroblasts (alpha-SMA), macrophages (CD68), collagen, pro-fibrotic transforming growth factor-beta1 were scored in renal autopsies, and tubulointerstitial apoptosis was recorded. The results demonstrated a strong positive correlation between age, cortical fibrosis and alpha-SMA (p<0.05), and between CD68 and hypertension and coronary artery disease (p<0.05). The findings confirm the role of myofibroblasts and macrophages in pathogenesis of human CKD. However, the markers showed no significant relationships to V (glom), N (glom), birth weight, or race.

How many glomerular profiles must be measured to obtain reliable estimates of mean glomerular areas in human renal biopsies?

The objective of this study was to investigate the number of glomerular profiles that are required for accurate estimates of mean profile area in a renal biopsy series. Slides from 384 renal biopsies from one center were reviewed. They contained a median of seven glomerular profiles or of four profiles without sclerosis. Profile areas were measured using stereologic point counting. The "true individual mean" for each biopsy was calculated and the "true population mean" for groups of biopsies derived. Individual and population "random sample means" then were calculated from a random sampling of profiles in each biopsy and were compared with true means for the same biopsies. The effect on the true population means of the entire group of biopsies was also assessed, as the minimum number of glomerular profiles that were required for inclusion was changed. In a single biopsy, random sampling of > or =10 profiles without exclusions and of eight profiles or more without sclerosis reliably estimated the true mean areas. In a group of 30 biopsies, random sampling of five or more glomeruli per biopsy reliably estimated the true population mean. In the aggregate series, inclusion of all 384 biopsies produced the most robust true population mean; the reliability of the estimates decreased as the numbers of eligible biopsies diminished with increasing requisite minimum numbers of profiles per biopsy. We conclude that, while > or =10 profiles might be needed for reliable area estimates in a single biopsy, far fewer profiles per biopsy can suffice when groups of biopsies are studied. In analyses of groups of biopsies, all available biopsies should be used without consideration of the number of glomerular profiles in each. Stipulation of a specific minimum number of glomeruli in each biopsy for inclusion reduces the power of analyses because fewer biopsies are available for evaluation.

Clinical outcomes associated with changes in a chronic disease treatment program in an Australian Aboriginal community.

In late 1995, a treatment program for renal disease and hypertension was introduced into a remote Aboriginal community. Over the next 3.5 years, mean blood pressure levels were markedly reduced, renal function stabilised, and rates of both renal and non-renal deaths declined significantly. In 1999-2000, responsibility for the program was passed to the community's local Health Board, which subsequently faced deficiencies in clinical information systems and a shortfall in funding. After the handover, the intensity of the program declined, and compliance with medicines fell. Blood pressures in the treatment cohort increased, renal function deteriorated, and rates of deaths from natural causes subsequently rose. From 2002 to mid-2003, the adjusted risks of renal and non-renal deaths in the treatment cohort were three and 9.5 times the respective risks of people during the first 18 months of treatment in the systematic phase of the program. Sustained vigorous activity, both in treatment of people already identified and in community screening for treatment eligibility, is required to maintain good results in any chronic disease program. Adequate resources and well supported staff are essential, and constant evaluation is needed to follow outcomes and modify strategies as necessary.