Daniel Uebelhart

Physical Exercise in Cancer Patients During and After Medical Treatment: A Systematic Review of Randomized and Controlled Clinical Trials

PURPOSE To systematically review the methodologic quality of, and summarize the evidence from trials examining the effectiveness of physical exercise in improving the level of physical functioning and psychological well-being of cancer patients during and after medical treatment. METHODS Thirty-four randomized clinical trials (RCTs) and controlled clinical trials were identified, reviewed for substantive results, and assessed for methodologic quality. RESULTS Four of 34 trials met all (seven of seven) methodologic criteria on the Delphi criteria list. Failure to conceal the sequencing of treatment allocation before patient recruitment, failure to blind the outcome assessor, and failure to employ an intention-to-treat analysis strategy were the most prevalent methodologic shortcomings. Various exercise modalities have been applied, differing in content, frequency, intensity, and duration. Positive results have been observed for a diverse set of outcomes, including physiologic measures, objective performance indicators, self-reported functioning and symptoms, psychological well-being, and overall health-related quality of life. CONCLUSION The trials reviewed were of moderate methodologic quality. Together they suggest that cancer patients may benefit from physical exercise both during and after treatment. However, the specific beneficial effects of physical exercise may vary as a function of the stage of disease, the nature of the medical treatment, and the current lifestyle of the patient. Future RCTs should use larger samples, use appropriate comparison groups to rule out the possibility of an attention-placebo effect, use a comparable set of outcome measures, pay greater attention to issues of motivation and adherence of patients participating in exercise programs, and examine the effect of exercise on cancer survival.

Effects of oral chondroitin sulfate on the progression of knee osteoarthritis: a pilot study

The aim of this study was to assess the clinical, radiological and biological efficacy and tolerability of the SYSADOA, chondroitin 4- and 6-sulfate (CS, Condrosulf, IBSA, Lugano, Switzerland), in patients suffering from knee osteoarthritis. This was a 1-year, randomized, double-blind, controlled pilot study which included 42 patients of both sexes, aged 35-78 years with symptomatic knee OA. Patients were treated orally with 800 mg chondroitin sulfate (CS) per day or with a placebo (PBO) administered in identical sachets. The main outcome criteria were the degree of spontaneous joint pain and the overall mobility capacity. Secondary outcome criteria included the actual joint space measurement and the levels of biochemical markers of bone and joint metabolism. This limited study confirmed that chondroitin sulfate was well-tolerated and both significantly reduced pain and increased overall mobility capacity. Treatment with CS was also associated in a limited group of patients with a stabilization of the medial femoro-tibial joint width, measured with a digitized automatic image analyzer, whereas joint space narrowing did occur in placebo-treated patients. In addition, the metabolism of bone and joint assessed by various biochemical markers also stabilized in the CS patients whereas it was still abnormal in the PBO patients. These results confirm that oral chondroitin 4- and 6-sulfate is an effective and safe symptomatic slow-acting drug for the treatment of knee OA. In addition, CS might be able to stabilize the joint space width and to modulate bone and joint metabolism. This is the first preliminary demonstration that a SYSADOA might influence the natural course of OA in humans.

Long-term effects of chondroitins 4 and 6 sulfate on knee osteoarthritis: The study on osteoarthritis progression prevention, a two-year, randomized, double-blind, placebo-controlled trial

OBJECTIVE To assess the long-term effects of chondroitins 4 and 6 sulfate (CS) on the radiographic progression of, and symptom changes associated with, knee osteoarthritis (OA). METHODS We performed an international, randomized, double-blind, placebo-controlled trial in which 622 patients with knee OA were randomly assigned to receive either 800 mg CS (n = 309 patients) or placebo (n = 313 patients) once daily for 2 years. Radiographs of the target knee, using the Lyon schuss view, were obtained at the time of enrollment and at 12, 18, and 24 months. The minimum joint space width (JSW) of the medial compartment of the tibiofemoral joint was assessed by digital image analysis. The primary outcome was the loss in minimum JSW over 2 years. RESULTS The intent-to-treat analysis demonstrated a significant reduction (P < 0.0001) in minimum JSW loss in the CS group (mean +/- SEM -0.07 +/- 0.03 mm) as compared with the placebo group (-0.31 +/- 0.04 mm). The percentage of patients with radiographic progression > or =0.25 mm was significantly reduced in the CS group compared with the placebo group (28% versus 41% [P < 0.0005]; relative risk reduction 33% [95% confidence interval 16-46%]). The number of patients needed to treat was 8 (95% confidence interval 5-17). Pain improved significantly faster in the CS group than in the placebo group (P < 0.01). There were no differences in safety between groups. CONCLUSION The long-term combined structure-modifying and symptom-modifying effects of CS suggest that it could be a disease-modifying agent in patients with knee OA.

Effects of denosumab on bone turnover markers in postmenopausal osteoporosis.

Denosumab, a fully human monoclonal antibody to RANKL, decreases bone remodeling, increases bone density, and reduces fracture risk. This study evaluates the time course and determinants of bone turnover marker (BTM) response during denosumab treatment, the percentage of denosumab‐treated women with BTMs below the premenopausal reference interval, and the correlations between changes in BTMs and bone mineral density (BMD). The BTM substudy of the Fracture REduction Evaulation of Denosumab in Osteoporosis every 6 Months (FREEDOM) Trial included 160 women randomized to subcutaneous denosumab (60 mg) or placebo injections every 6 months for 3 years. Biochemical markers of bone resorption (serum C‐telopeptide of type I collagen [CTX] and tartrate‐resistant acid phosphatise [TRACP‐5b]) and bone formation (serum procollagen type I N‐terminal propeptide [PINP] and bone alkaline phosphatase [BALP]) were measured at baseline and at 1, 6, 12, 24, and 36 months. Decreases in CTX were more rapid and greater than decreases in PINP and BALP. One month after injection, CTX levels in all denosumab‐treated subjects decreased to levels below the premenopausal reference interval. CTX values at the end of the dosing period were influenced by baseline CTX values and the dosing interval. The percentage of subjects with CTX below the premenopausal reference interval before each subsequent injection decreased from 79% to 51% during the study. CTX and PINP remained below the premenopausal reference interval at all time points in 46% and 31% denosumab‐treated subjects, respectively. With denosumab, but not placebo, there were significant correlations between CTX reduction and BMD increase (r = −0.24 to −0.44). The BTM response pattern with denosumab is unique and should be appreciated by physicians to monitor this treatment effectively.

Wearable systems for monitoring mobility-related activities in older people: a systematic review:

Objective: The use of wearable motion-sensing technology offers important advantages over conventional methods for obtaining measures of physical activity and/or physical functioning in aged individuals. This review aims to identify the actual state of applying wearable systems for monitoring mobility-related activity in older populations. In this review we focus on technologies and applications, research designs, feasibility and adherence aspects, and clinical relevance of wearable motion-sensing technology. Data sources: PubMed (MEDLINE since 1990), Ovid (BIOSIS, CINAHL), and Cochrane (Central) and reference lists of all relevant articles were searched. Review methods: Two authors independently reviewed randomized and non-randomized trials on people above 65 years systematically. Quality of selected articles was scored and study results were summarised and discussed. Results: Two hundred and twenty-seven abstracts were considered. After application of inclusion criteria and full text reading, 42 articles were taken into account in a full text review. Twenty of these papers evaluated walking with step counters, other papers used varying accelerometry approaches for obtaining overall activity measures (n = 16), or for monitoring changes in body postures and activity patterns (n = 17). Seven studies explicitly mentioned feasibility and/or adherence aspects. Eight studies presented outcome evaluations of interventions. Eight articles were representing descriptive research designs, three articles were using mixed descriptive and exploratory research designs, 23 articles used exploratory research-type designs, and eight articles used experimental research designs. Conclusion: Although feasible methods for monitoring human mobility are available, evidence-based clinical applications of these methods in older populations are in need of further development.

Protective effect of exogenous chondroitin 4,6-sulfate in the acute degradation of articular cartilage in the rabbit

The injection of 2.0 mg chymopapain into the adolescent rabbit knee causes severe loss of articular cartilage proteoglycans (PG). Although chondrocytes attempt to restore lost PG, failure to repair ensues. Pure chondroitin 4,6-sulfate (Condrosulf, IBSA Lugano, Switzerland) has been used in clinical studies of human osteoarthritis (OA) as a slow-acting drug for OA (SYSADOA). Using our model of articular cartilage injury, we examined the effects of oral and intramuscular administration of Condrosulf after chymopapain-induced cartilage injury. In this study, animals received an injection of 2.0 mg chymopapain (Chymodiactin, Boots Pharmaceuticals) into the left knee and were sacrificed after 84 days. The contralateral right knee served as a noninjected control. Some animals received oral Condrosulf while others received intramuscular injections of Condrosulf. Serum keratan sulfate (KS) levels were monitored to ensure degradation of the cartilage PG. Those animals not exhibiting at least a 100% increase of serum KS following chymopapain injection were excluded from the study. At sacrifice, cartilage PG contents were markedly reduced in animals receiving an injection of 2.0 mg chymopapain with no further treatment. In contrast, oral administration of Condrosulf beginning 11 days prior to chymopapain injury resulted in significantly higher (P = 0.0036) cartilage PG contents. Intramuscular administration of Condrosulf resulted in higher, but less significantly so (P = 0.0457), cartilage PG contents. These results suggest that daily Condrosulf treatment prior to and continuing after chymopapain injury may have a protective effect on the damaged cartilage, allowing it to continue to re-synthesize matrix PG after the treatment is discontinued.

Effects of exercise and nutrition on postural balance and risk of falling in elderly people with decreased bone mineral density: randomized controlled trial pilot study

Objective : To compare the effect of calcium/vitamin D supplements with a combination of calcium/vitamin D supplements and exercise/protein on risk of falling and postural balance. Design : Randomized clinical trial. Setting : University hospital physiotherapy department. Subjects : Twenty-four independently living elderly females aged 65 years and older with osteopenia or osteoporosis and mean total hip T-score (SD) of —1.8 (0.8). Interventions : A three-month programme consisting of exercise/protein including training of muscular strength, co-ordination, balance and endurance. Calcium/ vitamin D was supplemented in all participants for a 12-month period. Outcome measures : Assessment took place prior to and following the months 3, 6, 9 and at the end of the study; primary dependent variables assessed were risk of falling (Berg Balance Test) and postural balance (forceplate). Secondary measures included body composition, strength, activity level, number of falls, bone mineral content, biochemical indices, nutritional status and general health. Results : Significant reductions of risk of falling (repeated measures ANOVA F = 8.90, P = 0.008), an increase in muscular strength (ANOVA F = 3.0, P = 0.03), and an increase in activity level (ANOVA F = 3.38, P = 0.02) were found in the experimental group as compared to the control group. Further on, there was 89% reduction of falls reported in the experimental group (experimental pre/post 8/1 falls; control group pre/post 5/6 falls). Conclusion : This study provides support for our intervention programme aimed at reducing the risk of falling in elderly participants diagnosed with osteopenia or osteoporosis. The data obtained from the pilot study allow the calculation of the actual sample size needed for a larger randomized trial.

F-18 FDG whole-body PET for the assessment of disease activity in patients with rheumatoid arthritis

Purpose of Report: F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) can be used to image synovitis in patients with rheumatoid arthritis (RA). The aim of this study was to evaluate if a simple scoring system based on visual assessment of FDG joint uptake correlates with the clinical assessment of patients with RA undergoing antiinflammatory treatment. Materials and Methods: Seven patients with active RA underwent whole-body FDG PET and clinical assessment before and after treatment with the antitumor necrosis factor alpha antibody (infliximab). A PET total joint score, ie, the sum of all scores based on FDG uptake intensity between zero and 4 in 28 joints, was correlated with a total joint score based on the clinical disease activity in the same joints using a Spearman rank correlation. Results: The PET based total joint score was similarly high before onset as was the clinical total joint score. The decrease of FDG joint uptake in the follow-up PET scans correlated significantly with the clinical assessment. Additionally, synovial FDG uptake was found in extraarticular sites such as tendon sheaths and bursae. Conclusions: Visual assessment of FDG uptake shows a significant correlation with clinical evaluation of disease activity in patients with RA undergoing antiinflammatory treatment.

Falls prediction in elderly people: A 1-year prospective study

The aim of the present study was to determine whether force plate variables in single- and dual-task situations are able to predict the risk of multiple falls in a community-dwelling elderly population. Two hundred and seventy elderly persons (225 females, 45 males; age, 73+/-7 years) performed balance assessment with and without vision. Seven force plate variables were assessed to predict the risk of multiple falls; maximum displacement in the anteroposterior and medial-lateral directions (Max-AP, Max-ML), mean displacement in the medial-lateral direction (MML), the root mean square amplitude in anteroposterior and medial-lateral directions (RMS-AP, RMS-ML), the average speed of displacement (V), and the area of the 95th percentile ellipse (AoE). Falls were prospectively recorded during the following year. A total of 437 registered falls occurred during monitoring period. The force plate variable RMS-ML in the single-task condition (odds ratio, 21.8) predicted multiple falls together with the following covariables: history of multiple falls (odds ratio, 5.6), use of medications (fall-risk medications or multiple medicine use; odds ratio, 2.3), and gender (odds ratio, 0.34). Multiple fallers had a narrower stance width than non-fallers.

Cortical and trabecular bone density and structure in anorexia nervosa

The aim of the study was to examine bone density and architecture with three different measurement methods in a sample of young women with anorexia nervosa (AN) and in an age-matched control group of women. Three-dimensional periphery quantitative computer tomography (3D-pQCT) at the ultradistal radius, a new technology providing measures of cortical and trabecular bone density and architecture, was performed, as well as quantitative ultrasound (QUS) at the heel, and dual energy X-ray absorptiometry (DXA) at the spine and hip. Thirty-six women with AN aged 18–30 years (mean duration of AN: 5.8 years) and 30 age-matched women were assessed. Bone mineral density measured by DXA at the spine and hip, and broadband ultrasound attenuation measured by QUS at the heel were significantly lower in patients than controls. 3D-pQCT demonstrated a highly significant deficit in the absolute number of bone trabecules and a significant reduction of cortical thickness. Severity of underweight was significantly associated with bone deficits at the hip measured by DXA. 3D-pQCT revealed mostly deficits of cortical bone related with age of onset of eating disorder. Using three different methods to measure bone density and bone structure at the hip, spine, heel and ultradistal radius, significant deficits in bone mineral density both in trabecular and cortical bone, as well in trabecular structure could be demonstrated in the AN patients.