Refracture following vertebral fragility fracture when bone fragility is not recognized: summarizing findings from comparator arms of randomized clinical trials.

PURPOSE: Since vertebral fragility fractures (VFFs) might increase the risk of subsequent fractures, we evaluated the incidence rate and the refracture risk of subsequent vertebral and non-vertebral fragility fractures (nVFFs) in untreated patients with a previous VFF. METHODS: We systematically searched PubMed, Embase, and Cochrane Library up to February 2022 for randomized clinical trials (RCTs) that analyzed the occurrence of subsequent fractures in untreated patients with prior VFFs. Two authors independently extracted data and appraised the risk of bias in the selected studies. Primary outcomes were subsequent VFFs, while secondary outcomes were further nVFFs. The outcome of refracture within ≥ 2 years after the index fracture was measured as (i) rate, expressed per 100 person-years (PYs), and (ii) risk, expressed in percentage. RESULTS: Forty RCTs met our inclusion criteria, ranging from medium to high quality. Among untreated patients with prior VFFs, the rate of subsequent VFFs and nVFFs was 12 [95% confidence interval (CI) 9-16] and 6 (95% CI 5-8%) per 100 PYs, respectively. The higher the number of previous VFFs, the higher the incidence. Moreover, the risk of VFFs and nVFFs increased within 2 (16.6% and 8%) and 4 years (35.1% and 17.4%) based on the index VFF. CONCLUSION: The highest risk of subsequent VFFs or nVFFs was already detected within 2 years following the initial VFF. Thus, prompt interventions should be designed to improve the detection and treatment of VFFs, aiming to reduce the risk of future FFs and properly implement secondary preventive measures.

The integrated structure of care: evidence for the efficacy of models of clinical governance in the prevention of fragility fractures after recent sentinel fracture after the age of 50 years.

Randomized clinical trials and observational studies on the implementation of clinical governance models, in patients who had experienced a fragility fracture, were examined. Literature was systematically reviewed and summarized by a panel of experts who formulated recommendations for the Italian guideline. PURPOSE: After experiencing a fracture, several strategies may be adopted to reduce the risk of recurrent fragility fractures and associated morbidity and mortality. Clinical governance models, such as the fracture liaison service (FLS), have been introduced for the identification, treatment, and monitoring of patients with secondary fragility fractures. A systematic review was conducted to evaluate the association between multidisciplinary care systems and several outcomes in patients with a fragility fracture in the context of the development of the Italian Guidelines. METHODS: PubMed, Embase, and the Cochrane Library were investigated up to December 2020 to update the search of the Scottish Intercollegiate Guidelines Network. Randomized clinical trials (RCTs) and observational studies that analyzed clinical governance models in patients who had experienced a fragility fracture were eligible. Three authors independently extracted data and appraised the risk of bias in the included studies. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Effect sizes were pooled in a meta-analysis using random-effects models. Primary outcomes were bone mineral density values, antiosteoporotic therapy initiation, adherence to antiosteoporotic medications, subsequent fracture, and mortality risk, while secondary outcomes were quality of life and physical performance. RESULTS: Fifteen RCTs and 62 observational studies, ranging from very low to low quality for bone mineral density values, antiosteoporotic initiation, adherence to antiosteoporotic medications, subsequent fracture, mortality, met our inclusion criteria. The implementation of clinical governance models compared to their pre-implementation or standard care/non-attenders significantly improved BMD testing rate, and increased the number of patients who initiated antiosteoporotic therapy and enhanced their adherence to the medications. Moreover, the treatment by clinical governance model respect to standard care/non-attenders significantly reduced the risk of subsequent fracture and mortality. The integrated structure of care enhanced the quality of life and physical function among patients with fragility fractures. CONCLUSIONS: Based on our findings, clinicians should promote the management of patients experiencing a fragility fracture through structured and integrated models of care. The task force has formulated appropriate recommendations on the implementation of multidisciplinary care systems in patients with, or at risk of, fragility fractures.

A systematic review on the performance of fracture risk assessment tools: FRAX, DeFRA, FRA-HS.

PURPOSE: Preventing fragility fractures by treating osteoporosis may reduce disability and mortality worldwide. Algorithms combining clinical risk factors with bone mineral density have been developed to better estimate fracture risk and possible treatment thresholds. This systematic review supported panel members of the Italian Fragility Fracture Guidelines in recommending the use of best-performant tool. The clinical performance of the three most used fracture risk assessment tools (DeFRA, FRAX, and FRA-HS) was assessed in at-risk patients. METHODS: PubMed, Embase, and Cochrane Library were searched till December 2020 for studies investigating risk assessment tools for predicting major osteoporotic or hip fractures in patients with osteoporosis or fragility fractures. Sensitivity (Sn), specificity (Sp), and areas under the curve (AUCs) were evaluated for all tools at different thresholds. Quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies-2; certainty of evidence (CoE) was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Forty-three articles were considered (40, 1, and 2 for FRAX, FRA-HS, and DeFRA, respectively), with the CoE ranging from very low to high quality. A reduction of Sn and increase of Sp for major osteoporotic fractures were observed among women and the entire population with cut-off augmentation. No significant differences were found on comparing FRAX to DeFRA in women (AUC 59-88% vs. 74%) and diabetics (AUC 73% vs. 89%). FRAX demonstrated non-significantly better discriminatory power than FRA-HS among men. CONCLUSION: The task force formulated appropriate recommendations on the use of any fracture risk assessment tools in patients with or at risk of fragility fractures, since no statistically significant differences emerged across different prediction tools.

Which physical activity in patients affected by hypoparathyroidism? A review of the literature and practical recommendations.

BACKGROUND: Hypoparathyroidism (HypoP) is a rare endocrine condition characterized by hypocalcaemia and hyperphosphatemia, as a consequence of absent or improperly low parathyroid hormone (PTH) levels. Patients affected by HypoP have a clinical condition often characterized by paresthesias and muscle spasms, as well as long-term consequences as nephrolithiasis, extraskeletal calcification, and fractures. In the literature, likely due to these symptoms, few data exist regarding the appropriate physical activity (PA) in subjects suffering from HypoP. PURPOSE: This review evaluates the literature on exercise-based approaches to the management of individuals affected by HypoP and evaluates: (1) the effects of physical exercise on muscle cramps and other clinical symptoms; (2) the effects of exercise on PTH and calcium level; (3) the most suitable clinical exercise testing; and (4) the most suitable exercise combination. METHODS AND RESULTS: A systematic search was conducted using the databases MEDLINE, Google Scholar using "hypoparathyroidism AND Physical Activity", "Training AND hypoparathyroidism", "Exercise AND muscle cramps", "Exercise AND Fatigue" as keywords. In addition, references list from the included articles were searched and cross-checked to identify any further potentially eligible studies. A total of 50 manuscripts were found among which 39 manuscripts were selected. A few clinical studies have been performed in HypoP patients to evaluate PA training protocols. CONCLUSION: Although further research is needed to draw solid conclusions regarding best PA protocols in subjects affected by HypoP, a PA protocol has been proposed within the manuscript to encourage patients to attempt exercise to improve their clinical conditions and their quality of life.

Influence of sex and gender on the management of late-stage knee osteoarthritis.

PURPOSE: The exact nature of sex and gender differences in knee osteoarthritis (OA) among patient candidates for total knee arthroplasty (TKA) remains unclear and requires better elucidation to guide clinical practice. The purpose of this investigation was to survey physician practices and perceptions about the influence of sex and gender on knee OA presentation, care, and outcomes after TKA. METHODS: The survey questions were elaborated by a multidisciplinary scientific board composed of 1 pain specialist, 4 orthopedic specialists, 2 physiatrists, and 1 expert in gender medicine. The survey included 5 demographic questions and 20 topic questions. Eligible physician respondents were those who treat patients during all phases of care (pain specialists, orthopedic specialists, and physiatrists). All survey responses were anonymized and handled via remote dispersed geographic participation. RESULTS: Fifty-six physicians (71% male) accepted the invitation to complete the survey. In general, healthcare professionals expressed that women presented worse symptomology, higher pain intensity, and lower pain tolerance and necessitated a different pharmacological approach compared to men. Pain and orthopedic specialists were more likely to indicate sex and gender differences in knee OA than physiatrists. Physicians expressed that the absence of sex and gender-specific instruments and indications is an important limitation on available studies. CONCLUSIONS: Healthcare professionals perceive multiple sex and gender-related differences in patients with knee OA, especially in the pre- and perioperative phases of TKA. Sex and gender bias sensitivity training for physicians can potentially improve the objectivity of care for knee OA among TKA candidates.

How can the orthopedic surgeon ensure optimal vitamin D status in patients operated for an osteoporotic fracture?

In this narrative review, the role of vitamin D deficiency in the pathophysiology, healing of fragility fractures, and rehabilitation is discussed. Vitamin D status can be assessed by measuring serum 25(OH)-vitamin D level with standardized assays. There is a high prevalence of vitamin D insufficiency (25(OH)D < 50 nmol/l (i.e., 20 ng/mL)) or deficiency (25(OH)D < 25 nmol/l (i.e., 10 ng/mL)) in patients with fragility fractures and especially in those with a hip fracture. The evidence on the effects of vitamin D deficiency and/or vitamin D supplementation on fracture healing and material osseointegration is still limited. However, it appears that vitamin D have a rather positive influence on these processes. The fracture liaison service (FLS) model can help to inform orthopedic surgeons, all caregivers, and fractured patients about the importance of optimal vitamin D status in the management of patients with fragility fractures. Therefore, vitamin D status should be included in Capture the Fracture® program as an outcome of FLS in addition to dual-energy X-ray absorptiometry (DXA) and specific antiosteoporosis medication. Vitamin D plays a significant role in the pathophysiology and healing of fragility fractures and in rehabilitation after fracture. Correction of vitamin D deficiency should be one of the main outcomes in fracture liaison services.

The role of bone anabolic drugs in the management of periodontitis: a scoping review.

The aim of this scoping review was to summarise current knowledge about the effects of bone anabolic drugs on periodontitis, in order to identify new therapeutic strategies for preventing disease progression and reducing tooth loss. A technical expert panel (TEP) was established of 11 medical specialists, including periodontists and bone specialists that followed the PRISMA-ScR model to perform the scoping review and considered for eligibility both pre-clinical and clinical studies published in the English language up to September 2020. 716 items were initially found. After duplicate removal and screening of articles for eligibility criteria, 25 articles published between 2001 and 2019 were selected. Only studies concerning teriparatide, strontium ranelate, sclerostin antibodies and DKK1 antibodies met the eligibility criteria. In particular, only for teriparatide were there both clinical studies and experimental studies available, while for other bone anabolic drugs only animal studies were found. Available evidence about the use of bone anabolic drugs in periodontology demonstrates beneficial effects of these agents on biological pathways and histological parameters involved in periodontal tissue regeneration that suggest relevant clinical implications for the management of periodontitis.

One-year follow-up showing effects of single intra-articular injection of hyaluronic acid (1,500-2,000 kDa) in symptomatic knee osteoarthritis.

Clinical evidence on knee osteoarthritis suggests that intra-articular administration of hyaluronic acid may be useful in the management of patients with persistent pain. This study assesses the duration of effectiveness of a single intra-articular hyaluronic acid injection in a large population of patients with knee osteoarthritis. This retrospective post-marketing cohort study collected data from the ANTIAGE Registry (http://www.antiagefbf.it/registro), selecting patients of age ≥ 40 years, with symptomatic knee osteoarthritis (Kellgren-Lawrence grade I-III) of ≥ 12 months duration, and ≥12 months of follow-up. Patients had received a single intra-articular injection of high molecular weight hyaluronic acid (1,500-2,000 kDa) at baseline. WOMAC Osteoarthritis Index total scores measured using the LK 3.1 scale and 10 cm VAS pain scores were evaluated before IA Injection and at 6, 9, 10, 11 and 12 months. Blood cell counts, uricemia, erythrocyte sedimentation rates and levels of C-reactive protein were measured at baseline and 12 months. Time from initial treatment to second injection up to 12 months was recorded to assess event-free survival. Included patients (n=187) were 53.5% female and had a mean (±SD) age at baseline of 62 (±16.6) years and mean (±SD) body mass index of 26.2 (±2.5) kg/m2. Mean (±SD) WOMAC index total score and VAS pain scores were 60.9 (±7.1) and 5.9 cm (±1.8), respectively. There were statistically significant reductions compared to baseline in mean WOMAC index total score and VAS pain score at all time points (p less than0.01 at 6 and 9 months; p less than 0.05 at 10, 11 and 12 months for both parameters). These results support the clinical effectiveness and safety of hyaluronic acid for up to 12 months for pain relief and function improvement in patients with knee osteoarthritis, confirming previous data on intra-articular administration of hyaluronic acid as chronic therapy in the management of knee osteoarthritis.

Persistence with denosumab therapy in women affected by osteoporosis with fragility fractures: a multicenter observational real practice study in Italy.

BACKGROUND: Persistence is commonly considered a key factor for the successful management of osteoporosis and fragility fractures. Denosumab is the first biologic agent developed for the treatment of osteoporosis with satisfying data regarding the persistence with this therapy. AIM: The purpose of this multicenter observational real practice study was to evaluate the persistence with denosumab treatment in post-menopausal women affected by osteoporosis. MATERIAL/SUBJECTS AND METHODS: Women were recruited in four specialized centers for the management of osteoporosis in North, Center and South of Italy. We included women with a diagnosis of post-menopausal osteoporosis, aged >50 years, able to obtain a prescription according to the Italian reimbursement criteria in force during the study period for anti-osteoporotic pharmacological treatment. They initiated a treatment with subcutaneous denosumab (Prolia®) 60 mg/every 6 months between November 2011 and May 2016. Women who had received aromatase inhibitors were excluded. Patients were assessed at baseline and every 6 months for all treatment length. Persistence data were evaluated for a total of 36 months. RESULTS: Eight hundred seventy women were enrolled; mean aged 70 years, with a mean body mass index of 24.8 ± 4.1 kg/m2. At the Dual-energy X-ray absorptiometry assessment, the mean lumbar spine T-score was -2.76 ± 1.14 standard deviations (SD) and the mean femoral neck T-score was -2.49 ± 0.80 SD. During the study, the total persistence was 91.4%. Total dropouts were 75 (8.6%), higher within the initial 6-month period of treatment. CONCLUSIONS: Persistence to denosumab treatment in our observational real practice study was very high. These results suggest that factors such as frequency of visits, pharmacological schedule, and opportunity to call the doctor might play an important role in the persistence and adherence to treatment to obtain maximum therapeutic effect and avoid further fragility fractures.

Are Dietary Supplements and Nutraceuticals Effective for Musculoskeletal Health and Cognitive Function? A Scoping Review.

OBJECTIVE: The aim of our scoping review was to summarize the state of the art regarding micronutrients in order to identify which of them might effectively improve health status in the areas typically impaired in older people: bone, skeletal muscle, and cognitive function. DESIGN: Scoping review. METHODS: The Italian Study Group on Healthy Aging by Nutraceuticals and Dietary Supplements (HANDS) performed this scoping review, based on the following steps: doing a list of micronutrients related with musculoskeletal or cognitive functions, included in dietary supplements and nutraceuticals commercialized in Italy; planning a research on PubMed, according to an evidence-based approach, in order to the most relevant positive study for each micronutrient into each of the three areas involved (bone, skeletal muscle and cognitive function); identifying the micronutrients effective in maintaining or achieving an adequate health status in older people, specifying the effective and safe daily doses, according to the selected studies. RESULTS: In literature we found 12 relevant positive studies (1 international society guidelines/recommendations, 1 systematic review, 7 randomized controlled trials, and 3 prospective cohort studies). We showed that only 16 micronutrients resulted to have appropriate scientific evidences in terms of improving musculoskeletal health and/or cognitive function in older people: beta-alanine, calcium, creatine, fluorides, leucine, magnesium, omega-3 fatty acids, potassium, vitamin B6, vitamin B9, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K2, and zinc. CONCLUSION: This scoping review showed that selected micronutrients in adequate doses might have an ancillary role in musculoskeletal health and cognitive functions in older people.

Classification of functioning and assessment of fracture risk of a large Italian osteoporotic population. The Physiatric Approach To Osteoporosis project.

BACKGROUND: Osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture. Osteoporotic fractures cause significant morbidity, disability, and decrease in quality of life. AIM: The aims of the Physiatric Approach To Osteoporosis (PATO) project were to classify osteoporotic patients with or without fragility fractures, using the Brief ICF (International Classification of Functioning, Disability and Health) Core Set for Osteoporosis and to calculate the fracture risk with the WHO FRAX® (World Health Organization Fracture Risk Assessment Tool) algorithm. DESIGN: Cross-sectional survey. SETTING: Seventy-nine Italian Rehabilitation Services distributed throughout Italy. POPULATION: Osteoporotic patients. METHODS: Each physiatrist involved in the survey was asked systematically to record demographic data, presence of fragility fractures, anamnestic risk factors included in the FRAX® Assessment Tool, ICF categories as they are listed in the Brief ICF Core Set for Osteoporosis, and treatment data of 100 osteoporotic patients (50 with at least a clinical fragility fracture and 50 without). RESULTS: In accordance with the FRAX® algorithm, the 35.22% of the interviewed osteoporotic patients had a FRAX® MAJ≥20.00 and the 70.32% had a FRAX® HIP≥3.00. The most commonly impaired ICF categories were the sensation of pain for the body functions, the structure of the trunk for body structures, lifting and carrying objects for the domain of activities and participation, and products or substances for personal consumption for the environmental factors. CONCLUSION: The FRAX® Assessment tool has been recognized as useful to identify people at high risk of fracture and the Brief ICF Core Set seems to be an important framework to be followed when dealing with osteoporotic patients in an outpatient setting or for clinical studies. CLINICAL REHABILITATION IMPACT: Osteoporosis is well recognized as a disabling disease, posing a significant challenge for the society, therefore physiatrists should always be involved, from prevention to treatment.

Effects of focal muscle vibration on physical functioning in patients with knee osteoarthritis: a randomized controlled trial.

BACKGROUND: Knee osteoarthritis (OA) is a chronic condition characterized by pain, stiffness and functional limitations. According to the OsteoArthritis Research Society International (OARSI) recommendations, patients with knee OA should undertake regular quadriceps muscle strengthening exercises. Whole body vibration (WBV) proved its effectiveness in strengthening of the quadriceps muscles and improving balance in chronic knee OA patients. To date, there are no published studies that investigated the effects of focal muscle vibration (FMV) in these patients. AIM: The aim of the present study was to evaluate the effects of FMV on physical functioning in patients with symptomatic knee OA. DESIGN: Randomized controlled trial. SETTING: Outpatient clinic, University Hospital. POPULATION: Men and women aged 60 years or older with radiographic diagnosis of mild to moderate monolateral knee OA (Kellgren-Lawrence grade II or III) and chronic knee pain. METHODS: Patients were randomized in two groups (treatment group and placebo control group). The treatment group received FMV treatment, according to the "repeated muscle vibration" protocol. The control group received a sham treatment. The primary outcome measure was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Secondary outcome measures were the Short Physical Performance Battery (SPPB) and the Performance-Oriented Mobility Assessment (POMA). Follow up evaluations were done at 3 and 6 months. RESULTS: Fifty patients were recruited and randomly assigned to either the study or control group. There was a statistical significant difference between the two groups both for primary (WOMAC) and secondary (SPPB and POMA) outcomes. CONCLUSIONS: In this study, FMV therapy has proven to be effective and safe in improving functioning of patients affected by mild to moderate chronic knee OA. CLINICAL REHABILITATION IMPACT: The use of FMV therapy might be an additional and safe tool in the conservative management of knee OA.

NSAIDs and opioids in management of fragility fractures.

Fragility fractures and their care are a major burden on individuals, health systems, and social care systems in industrialized countries. Fragility fracture can lead to long lasting painful and disabling condition. The level of pain is a major determinant for the outcome of any treatment of these fractures regardless of its location. The treatment of pain in patient with fragility fracture is rarely considered a priority in the care pathway.

Mechanobiology of bone.

Bone is a tissue that dynamically adapts mass and architecture to the mechanical loads that occur in daily life in a world with gravity. Bone architecture and mass are influenced by the applied tension peak, whereas the bone formation rate is modulated by the stimulus frequency. In bone tissue, osteocytes govern the detection of mechanical afferents and their transformation into biochemical messages, therefore these cells can be considered a mechanosensor that directs osteogenesis to where it is most needed to increase bone strength. The stimulation of osteocytes occurs with several modalities: shear stress and stretch, extracellular pressure modifications, strains, variations of electric field in and around osteocytes lacunae. The osteocyte network, under physiological conditions, activates osteoclastogenesis and suppresses osteoblast function enhancing bone resorption and inhibiting bone formation. In the unloaded condition, the functions of the osteocyte network are augmented, whereas exercise could decrease inhibitory effects on bone mass by reducing both osteoclastogenesis and inhibition on osteoblast function.

Sarcopenia in women with vertebral fragility fractures.

We performed a pilot study with the purpose to evaluate the prevalence of sarcopenia in osteoporotic women with vertebral fractures. Dual-energy X-ray absorptiometry (DXA) was used to measure the whole and regional body composition. Appendicular lean mass (aLM) was calculated as the sum of lean mass in arms and legs. We calculated the skeletal muscle mass index (aLM/h(2)), and we measured bone mineral density and T scores by DXA scan at total-body and at femoral neck. Participants were divided according to the number of vertebral fractures (single or multiple fractures). A total of 67 women were included. Thirty-five women (52.23%) had a vertebral fracture, of them 8 (22.85%) were sarcopenic and 32 women (47.76%) had multiple vertebral fractures, of them 14 (43.75%) were sarcopenic. Our results suggest that sarcopenia is common among osteoporotic women increasing along with the number of vertebral fragility fractures.

Rehabilitative approach in patients with vertebral fragility fracture.

Osteoporosis is a skeleton disease characterized by low bone mineral density and deterioration of bone tissue, resulting in an increased risk of fragility fracture. Osteoporotic vertebral fractures are recognized as a significant health problem particularly in older people with an impact on the quality of life, mobility and mortality. A well-timed diagnosis and treatment is necessary in preventing further vertebral fracture and their consequences. Exercise alone or as part of physical therapy management is often recommended as a non-pharmacological intervention. The exercise protocols, designed specifically for individuals with vertebral fracture, should include postural correction, trunk and lower extremity muscle strengthening, balance exercises and falls prevention program. The aim of this short communication is to examine the rationale of a rehabilitation protocol after a vertebral fracture.

Characteristics and circumstances of falls in hip fractures.

Osteoporosis is a chronic disease characterized by a loss of bone mass and deterioration of bone microstructure that lead to a greater risk of fragility fractures. Fall is generally the main cause of fractures. Hip fractures are the most common ones and are usually correlated to a greater morbidity and mortality. The aim of our observational study was to evaluate, among patients with hip fragility fracture, characteristics and circumstances of falls. We conducted a national epidemiological survey, involving 80 physiatrists. They were asked to collect data on patients over 55 years of age who underwent a fragility fracture in the 12 months prior to recruitment. For each patient they had to fill a form including questions on different aspects of patients' medical history: age, gender, reason for the visit, type of fracture, number of falls in the last year and the year before the fall. Among 419 patients who sustained hip fracture, 70 had experienced a fall, while 119 were incurred in more falls in the 12 months before the fracture. In most people of our cohort, hip fracture was caused by a fall that occurred on the side during the morning.

Effects of denosumab on cortical and trabecular microarchitecture: evidences from clinical studies.

Excess of bone remodeling is still the major pathogenic factor in involutional osteoporosis. This phenomenon is linked to an imbalance between neoformation (by osteoblasts) and resorption (by osteoclasts). Recently, research in drug development is focused on new and more "physiological" approach to balance bone remodeling. The efficacy of denosumab was proved in the prevention of vertebral and non-vertebral fractures and related to the ability of the drug to penetrate in cortical and trabecular bone. Recently, data from several clinical studies confirm that denosumab improves fracture outcomes, also at skeletal sites rich in cortical bone.

Post-surgical rehabilitative approach to fragility fractures.

Osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture. The most frequent sites of fragility fractures are the hip, the distal radius, the spine, the proximal humerus, and the ankle. In most cases, a surgical approach with subsequent rehabilitative treatment is required. The general aims of rehabilitation are to increase functioning and improve patients' activities, participation level, and quality of life.