Definition: To what extent does the study allow us to draw conclusions about a causal effect between two or more constructs? Issues: Selection, maturation, history, mortality, testing, regression towrd the mean, selection by maturation, treatment by mortality, treatment by testing, measured treatment variables Increase: Eliminate the threats, above all do experimental manipulations, random assignment, and counterbalancing.

Reliability and validity

This review concerns the applications of some polysaccharides in the domain of biomaterials and bioactive polymers. Natural polysaccharides from different sources have been studied for a long time, and their main properties are summarized in this paper; some of their derivatives obtained by chemical modification are also described. The main polysaccharides currently used in the biomedical and pharmaceutical domains are chitin and its derivative chitosan, hyaluronan and alginates. Alginates are well known for their property of forming a physical gel in the presence of divalent counterions (Ca, Ba, Sr) whereas carrageenans form a thermoreversible gel; these seaweed polysaccharides are mainly used to encapsulate different materials (cells, bacteria, fungi). Other promising systems are the electrostatic complexes formed when an anionic polysaccharide is mixed with a cationic polysaccharide (e.g. alginate/chitosan or hyaluronan/chitosan). An important development of the applications of polysaccharides can be predicted for the next few years in relation to their intrinsic properties such as biocompatibility and biodegradability in the human body for some of them; they are also renewable and have interesting physical properties (film-forming, gelling and thickening properties). In addition, they are easily processed in different forms such as beads, films, capsules and fibres. Copyright © 2007 Society of Chemical Industry

Main properties and current applications of some polysaccharides as biomaterials

Background Osteoarthritis (OA) is the most prevalent chronic joint disorder worldwide and is associated with significant pain and disability. Objectives To assess the effects of viscosupplementation in the treatment of OA of the knee. The products were hyaluronan and hylan derivatives (Adant, Arthrum H, Artz (Artzal, Supartz), BioHy (Arthrease, Euflexxa, Nuflexxa), Durolane, Fermathron, Go-On, Hyalgan, Hylan G-F 20 (Synvisc Hylan G-F 20), Hyruan, NRD-101 (Suvenyl), Orthovisc, Ostenil, Replasyn, SLM-10, Suplasyn, Synject and Zeel compositum). Search strategy MEDLINE (up to January (week 1) 2006 for update), EMBASE, PREMEDLINE, Current Contents up to July 2003, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched. Specialised journals and reference lists of identified randomised controlled trials (RCTs) and pertinent review articles up to December 2005 were handsearched. Selection criteria RCTs of viscosupplementation for the treatment of people with a diagnosis of OA of the knee were eligible. Single and double-blinded studies, placebo-based and comparative studies were eligible. At least one of the four OMERACT III core set outcome measures had to be reported (Bellamy 1997). Data collection and analysis Each trial was assessed independently by two reviewers for its methodological quality using a validated tool. All data were extracted by one reviewer and verified by a second reviewer. Continuous outcome measures were analysed as weighted mean differences (WMD) with 95% confidence intervals (CI). However, where different scales were used to measure the same outcome, standardized mean differences (SMD) were used. Dichotomous outcomes were analyzed by relative risk (RR). Main results Seventy-six trials with a median quality score of 3 (range 1 to 5) were identified. Follow-up periods varied between day of last injection and eighteen months. Forty trials included comparisons of hyaluronan/hylan and placebo (saline or arthrocentesis), ten trials included comparisons of intra-articular (IA) corticosteroids, six trials included comparisons of nonsteroidal anti-inflammatory drugs (NSAIDs), three trials included comparisons of physical therapy, two trials included comparisons of exercise, two trials included comparisons of arthroscopy, two trials included comparisons of conventional treatment, and fifteen trials included comparisons of other hyaluronans/hylan. The pooled analyses of the effects of viscosupplements against 'placebo' controls generally supported the efficacy of this class of intervention. In these same analyses, differential efficacy effects were observed for different products on different variables and at different timepoints. Of note is the 5 to 13 week post injection period which showed a percent improvement from baseline of 28 to 54% for pain and 9 to 32% for function. In general, comparable efficacy was noted against NSAIDs and longer-term benefits were noted in comparisons against IA corticosteroids. In general, few adverse events were reported in the hyaluronan/hylan trials included in these analyses. Authors' conclusions Based on the aforementioned analyses, viscosupplementation is an effective treatment for OA of the knee with beneficial effects: on pain, function and patient global assessment; and at different post injection periods but especially at the 5 to 13 week post injection period. It is of note that the magnitude of the clinical effect, as expressed by the WMD and standardised mean difference (SMD) from the RevMan 4.2 output, is different for different products, comparisons, timepoints, variables and trial designs. However, there are few randomised head-to-head comparisons of different viscosupplements and readers should be cautious, therefore, in drawing conclusions regarding the relative value of different products. The clinical effect for some products, against placebo, on some variables at some timepoints is in the moderate to large effect-size range. Readers should refer to relevant tables to review specific detail given the heterogeneity in effects across the product class and some discrepancies observed between the RevMan 4.2 analyses and the original publications. Overall, the analyses performed are positive for the HA class and particularly positive for some products with respect to certain variables and timepoints, such as pain on weight bearing at 5 to 13 weeks postinjection. In general, sample-size restrictions preclude any definitive comment on the safety of the HA class of products; however, within the constraints of the trial designs employed no major safety issues were detected. In some analyses viscosupplements were comparable in efficacy to systemic forms of active intervention, with more local reactions but fewer systemic adverse events. In other analyses HA products had more prolonged effects than IA corticosteroids. Overall, the aforementioned analyses support the use of the HA class of products in the treatment of knee OA.

/pdf/viscosupplementation-for-the-treatment-of-osteoarthritis-of-3irfb0d2h5.pdf

Viscosupplementation for the treatment of osteoarthritis of the knee

Background
Knee osteoarthritis (OA) is a major public health issue because it causes chronic pain, reduces physical function and diminishes quality of life. Ageing of the population and increased global prevalence of obesity are anticipated to dramatically increase the prevalence of knee OA and its associated impairments. No cure for knee OA is known, but exercise therapy is among the dominant non-pharmacological interventions recommended by international guidelines.

Objectives
To determine whether land-based therapeutic exercise is beneficial for people with knee OA in terms of reduced joint pain or improved physical function and quality of life.

Search methods
Five electronic databases were searched, up until May 2013.

Selection criteria
All randomised controlled trials (RCTs) randomly assigning individuals and comparing groups treated with some form of land-based therapeutic exercise (as opposed to exercise conducted in the water) with a non-exercise group or a non-treatment control group.

Data collection and analysis
Three teams of two review authors independently extracted data, assessed risk of bias for each study and assessed the quality of the body of evidence for each outcome using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach. We conducted analyses on continuous outcomes (pain, physical function and quality of life) immediately after treatment and on dichotomous outcomes (proportion of study withdrawals) at the end of the study; we also conducted analyses on the sustained effects of exercise on pain and function (two to six months, and longer than six months).

Main results
In total, we extracted data from 54 studies. Overall, 19 (20%) studies reported adequate random sequence generation and allocation concealment and adequately accounted for incomplete outcome data; we considered these studies to have an overall low risk of bias. Studies were largely free from selection bias, but research results may be vulnerable to performance and detection bias, as only four of the RCTs reported blinding of participants to treatment allocation, and, although most RCTs reported blinded outcome assessment, pain, physical function and quality of life were participant self-reported.

High-quality evidence from 44 trials (3537 participants) indicates that exercise reduced pain (standardised mean difference (SMD) -0.49, 95% confidence interval (CI) -0.39 to -0.59) immediately after treatment. Pain was estimated at 44 points on a 0 to 100-point scale (0 indicated no pain) in the control group; exercise reduced pain by an equivalent of 12 points (95% CI 10 to 15 points). Moderate-quality evidence from 44 trials (3913 participants) showed that exercise improved physical function (SMD -0.52, 95% CI -0.39 to -0.64) immediately after treatment. Physical function was estimated at 38 points on a 0 to 100-point scale (0 indicated no loss of physical function) in the control group; exercise improved physical function by an equivalent of 10 points (95% CI 8 to 13 points). High-quality evidence from 13 studies (1073 participants) revealed that exercise improved quality of life (SMD 0.28, 95% CI 0.15 to 0.40) immediately after treatment. Quality of life was estimated at 43 points on a 0 to 100-point scale (100 indicated best quality of life) in the control group; exercise improved quality of life by an equivalent of 4 points (95% CI 2 to 5 points).

High-quality evidence from 45 studies (4607 participants) showed a comparable likelihood of withdrawal from exercise allocation (event rate 14%) compared with the control group (event rate 15%), and this difference was not significant: odds ratio (OR) 0.93 (95% CI 0.75 to 1.15). Eight studies reported adverse events, all of which were related to increased knee or low back pain attributed to the exercise intervention provided. No study reported a serious adverse event.

In addition, 12 included studies provided two to six-month post-treatment sustainability data on 1468 participants for knee pain and on 1279 (10 studies) participants for physical function. These studies indicated sustainability of treatment effect for pain (SMD -0.24, 95% CI -0.35 to -0.14), with an equivalent reduction of 6 (3 to 9) points on 0 to 100-point scale, and of physical function (SMD -0.15 95% CI -0.26 to -0.04), with an equivalent improvement of 3 (1 to 5) points on 0 to 100-point scale.

Marked variability was noted across included studies among participants recruited, symptom duration, exercise interventions assessed and important aspects of study methodology. Individually delivered programmes tended to result in greater reductions in pain and improvements in physical function, compared to class-based exercise programmes or home-based programmes; however between-study heterogeneity was marked within the individually provided treatment delivery subgroup.

Authors' conclusions
High-quality evidence indicates that land-based therapeutic exercise provides short-term benefit that is sustained for at least two to six months after cessation of formal treatment in terms of reduced knee pain, and moderate-quality evidence shows improvement in physical function among people with knee OA. The magnitude of the treatment effect would be considered moderate (immediate) to small (two to six months) but comparable with estimates reported for non-steroidal anti-inflammatory drugs. Confidence intervals around demonstrated pooled results for pain reduction and improvement in physical function do not exclude a minimal clinically important treatment effect. Since the participants in most trials were aware of their treatment, this may have contributed to their improvement. Despite the lack of blinding we did not downgrade the quality of evidence for risk of performance or detection bias. This reflects our belief that further research in this area is unlikely to change the findings of our review.

Exercise for osteoarthritis of the knee

Diagnosis and Treatment of Overactive Bladder (Non-Neurogenic) in Adults: AUA/SUFU Guideline

The aim of this study was to develop a Turkish version of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and assess its reliability, validity, and sensitivity to change. The Turkish version was obtained after a translation and back-translation process. Seventy-one patients with ankylosing spondylitis were assessed with it. To assess its validity, patients were also evaluated with the Turkish version of the Bath Ankylosing Spondylitis Functional Index (BASFI), the Bath Ankylosing Spondylitis Metrology Index (BASMI), the Bath Ankylosing Spondylitis Patient Global Score (BAS-G), and physicians' assessments of disease activity. Over 24 h, the Turkish BASDAI did not show significant differences between the two assessments (P>0.05). Correlations were found between BASDAI and all of the evaluation parameters except BASMI (P<0.01). Both BASDAI and BASMI showed significant improvements after 8-week home exercise programmes. The results of this study show that the Turkish version of the BASDAI is reliable, valid, and sensitive to change.

A turkish version of the bath ankylosing spondylitis disease activity index : reliability and validity

AIM The aim of the study was to compare the effects of conventional exercise (CE), swimming and walking on the pulmonary functions, aerobic capacity, quality of life, Bath indexes and psychological symptoms in patients with ankylosing spondylitis (AS). METHODS Forty-five patients were randomised into either swimming (group 1), walking (group 2), CE group (group 3). Patients in Group 1 performed CE and swimming, patients in Group 2 performed CE and walking and patients in Group 3 performed CE only. Exercise sessions were performed three times a week for a period of six weeks. Patients were assessed before and after the rehabilitation program, with respect to, pulmonary function test (forced vital capacity [FVC, mL], forced expiration volume in one second [FEV1, mL], FEV1/FVC (%) and vital capacity [VC, mL]), maximal oxygen uptake (pV.O2), 6-minute walking test (6MWT), Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Metrology Index, Nottingham Health Profile and Beck Depression Inventory. RESULTS There were significant increases in pVO2 and 6MWT after treatment in Groups 1 and 2 (P<0.05). FeV1, FVC and VC improved significantly with treatment in all three groups (P<0.05). A statistically significant improvement was observed in energy, emotional reaction and physical mobility sub-scores of NHP in three exercise groups after completion of the exercise program (P<0.05). CONCLUSIONS Swimming, walking and CE had beneficial effects on the quality of life and pulmonary functions. Aerobic exercises such as swimming and walking in addition to CE increased functional capacities of patients.

Are swimming or aerobic exercise better than conventional exercise in ankylosing spondylitis patients? A randomized controlled study.

The objective of this non-randomised controlled trial was to evaluate the impact of group-based exercise programme and a home-based exercise programme on Bath Ankylosing Spondylitis Indices, depression and quality of life in patients with ankylosing spondylitis (AS). Approximately 41 patients in a rehabilitation unit were divided into two groups, either group- or home-based exercise programme. Exercise sessions were performed three times a week for a period of 6 weeks. The patients were compared before and after the rehabilitation programme, with respect to Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Disease Assessment Index (BASDAI), Bath Ankylosing Spondylitis Metrology Index (BASMI), Beck Depression Inventory (BDI) and The Nottingham Health Profile (NHP). A statistically significant improvement was observed on BASDAI, BASMI and energy, pain, reaction of emotional and sleep subscores of NHP in both exercise groups after the exercise programme (p 0.05). No statistically significant differences were found between the two exercise programmes (p > 0.05). Group and home-based exercise programmes are efficient in improving symptoms and mobility and had an important effect on quality of life in patients with AS. Home-based exercise programme, as it is cheaper, more easily performed and efficient, may be preferable for the management programme in AS.

Comparison of group-based exercise versus home-based exercise in patients with ankylosing spondylitis: effects on Bath Ankylosing Spondylitis Indices, quality of life and depression.

In this clinical trial, we examined the efficacy of intra-articular hyaluronic acid (HA) treatment in 38 patients with reducing displaced disc of the temporomandibular joint (TMJ). Subjects received two unilateral upper space injections of HA or physiological saline solution with 1 week apart. Efficacy was based on the following measurements: pain and sound intensity of the joint measured by visual analogue scale (VAS), modified Helkimo's clinical dysfunction index and the intensity of joint vibration during opening and closing the mouth measured by accelerometers. These measurements were performed before the first injection and 1 and 6 months after the last injection. In the treatment group (n=19), all measurements improved significantly at month 1 and at month 6 compared with the baseline (P < 0.01). The same measurements, in the placebo group (n=19), did not show any change, except for the pain intensity which improved at month 1 and month 6 (P < 0.05). The change in baseline measurements of all of the efficacy criteria at month 1 and at month 6 in the treatment group was significantly better compared with the change obtained with placebo at the same time intervals. This study demonstrates that intra-articular sodium hyaluronate (Orthovisc) injection into the TMJ is an effective treatment for a reducing displaced disc.

The efficacy of intra-articular sodium hyaluronate in patients with reducing displaced disc of the temporomandibular joint.

The aim of this study was to compare the effects of physical therapy agents (PTA) and two different intra-articular hyaluronan drugs (sodium hyaluronate (NaHA) and hylan G-F 20) on knee osteoarthritis (OA). The randomised, single-blind study, with 12 months of follow-up, was performed on 80 patients diagnosed as knee OA. The patients were randomly divided into two treatment groups: patients in group 1 were given weekly intra-articular hyaluronan treatment which consisted of either hylan G-F 20 or NaHA during the first 3 weeks and in the sixth month; PTA was applied to each patient in group 2 five times a week for 3 weeks with a series of infrared, short-wave diathermy-pulsed patterns and interferential therapy. Clinical assessments for each patient were made at 1, 3, 6, 9 and 12 months using the following measures: spontaneous pain, pain at rest, pain at night, pain on touch, pain on movement, 15 m walking time, range of motion, short form 36 (SF-36), Western Ontario and McMaster University Osteoarthritis Index (WOMAC) global assessment. There was significant improvement in all variables measured in both groups during the follow-up except the WOMAC-stiffness and range of the motion. The improvement of pain (at night, at rest, SF-36) and SF-36 social functioning subscales was greater in the PTA group. Consequently, in the subgroup analyses, there was no difference between PTA and hylan groups for this improvement. In the comparison of two drugs, the reduction of pain on touch and WOMAC-function was greater in hylan group than that of NaHA. No serious local or systemic effects were observed following injections. Although all patients had improvement, PTA was superior to hyaluronan group for no activity-related pain and functional performance. On the other hand, this study supports the preferential use of hylan over NaHA in patients with knee OA.

Yesim Akkoc

Papers

A turkish version of the bath ankylosing spondylitis disease activity index : reliability and validity

Are swimming or aerobic exercise better than conventional exercise in ankylosing spondylitis patients? A randomized controlled study.

Comparison of group-based exercise versus home-based exercise in patients with ankylosing spondylitis: effects on Bath Ankylosing Spondylitis Indices, quality of life and depression.

The efficacy of intra-articular sodium hyaluronate in patients with reducing displaced disc of the temporomandibular joint.

A comparison of two different intra-articular hyaluronan drugs and physical therapy in the management of knee osteoarthritis