title: Evaluation of the Quality of Prognosis Studies in Systematic Reviews Quadriceps strength and the risk of cartilage loss and symptom progression in knee osteoarthritis. Nonsteroidal anti-inflammatory drug or glucosamine reduced pain and improved muscle strength with resistance training in a randomized controlled trial of knee osteoarthritis patients. Physical function and properties of quadriceps femoris muscle in men with knee osteoarthritis. Osteoarthritis of the knee: isokinetic quadriceps exercise versus an educational intervention. Development and validation of a lower-extremity activity scale. Use for patients treated with revision total knee arthroplasty. The efficacy of home based progressive strength training in older adults with knee osteoarthritis: a randomized controlled trial. Which patientswith osteoarthritis of hip and/or knee benefit most from behavioral graded activity? Determinants of self-report outcome measures in people with knee osteoarthritis. Predicting the course of functional limitation among older adults with knee pain: do local signs, symptoms and radiographs add anything to general indicators?
abstract: Prognosis studies are investigations of future events or the evaluation of associations between risk factors and health outcomes in population s of patients ( 1 ) . The results of such studies improve our underst and ing of the clinical course of a disease and assist clinicians in making informed decisions about how best to manage patients . Prognostic research also informs the design of intervention studies by helping define subgroups of patients who may benefit from a new treatment and by providing necessary information about the natural history of a disorder ( 2 ) . There has recently been a rapid increase in the use of systematic review methods to synthesize the evidence on research questions related to prognosis . It is essential that investigators conducting systematic review s thoroughly appraise the method ologic quality of included studies to be confident that a study 's design , conduct , analysis , and interpretation have adequately reduced the opportunity for bias ( 3 , 4 ) . Caution is warranted , however , because inclusion of method ologically weak studies can threaten the internal validity of a systematic review ( 4 ) . This follows abundant empirical evidence that inadequate attention to biases can cause invalid results and inferences ( 5 - 9 ) . However , there is limited consensus on how to appraise the quality of prognosis studies ( 1 ) . A useful framework to assess bias in such studies follows the basic principles of epidemiologic research ( 10 , 11 ) . We focus on 6 areas of potential bias : study participation , study attrition , prognostic factor measurement , confounding measurement and account , outcome measurement , and analysis . The main objectives of our review of review s are to describe methods used to assess the quality of prognosis studies and to describe how well current practice s assess potential biases . Our secondary objective is to develop recommendations to guide future quality appraisal , both within single studies of prognostic factors and within systematic review s of the evidence . We hope this work facilitates future discussion and research on biases in prognosis studies and systematic review s. Methods Literature Search and Study Selection We identified systematic review s of prognosis studies by search ing MEDLINE ( 1966 to October 2005 ) using the search strategy recommended by McKibbon and colleagues ( 12 ) . This strategy combines broad search terms for systematic review s ( systematic review .mp ; meta- analysis .mp ) and a sensitive search strategy for prognosis studies ( cohort , incidence , mortality , follow-up studies , prognos * , predict * , or course ) . We also search ed the reference lists of included review s and method ologic papers to identify other relevant publications . We restricted our search to English- language publications . One review er conducted the search and selected the studies . Systematic review s , defined as review s of published studies with a comprehensive search and systematic selection , were included if they assessed the method ologic quality of the included studies by using 1 or more explicit criteria . We excluded studies if they were meta-analyses of independent patient data only , if their primary goal was to investigate the effectiveness of an intervention or specific diagnostic or screening tests , or if they included studies that were not done on humans . Data Extraction and Synthesis Individual items included in the quality assessment of the systematic review s were recorded as they were reported in the publication ( that is , the information that would be available to readers and future review ers ) . We review ed journal Web sites and contacted the authors of the systematic review s for additional information when authors made such an offer in their original papers . When review s assessed different study design s by using different sets of quality items , we extracted only those items used to assess cohort studies . We constructed a comprehensive list of distinct items that the review s used to assess the quality of their included studies . The full text of each review was screened . All items used by the review authors to assess the quality of studies were extracted into a computerized spreadsheet by 1 review er . Two experienced review ers , a clinical epidemiologist and an epidemiologist , independently synthesized the quality items extracted from the prognosis review s to determine how well the systematic review s assessed potential biases . We did this in 3 steps : 1 ) identified distinct concepts or domains addressed by the quality items ; 2 ) grouped each extracted quality item into the appropriate domain or domains ; and 3 ) identified the domains necessary to assess potential biases in prognosis studies . We then used this information to assess how well the review s ' quality assessment included items from the domains necessary to assess potential biases . After completing each of the first 3 steps , the review ers met to attempt to reach a consensus . The consensus process involved each review er presenting his or her observations and results , followed by discussion and debate . A third review er was available in cases of persistent disagreement or uncertainty . In the first step , all domains addressed by the quality items were identified . The first review er iteratively and progressively defined the domains as items were extracted from the included review s. The second review er defined domains from a r and om list of all extracted quality items . Limited guidance was provided to the review ers so that their assessment s and definitions of domains would be independent . The review ers agreed on a final set of domains that adequately and completely defined all of the extracted items . In the second step , review ers independently grouped each extracted item into the appropriate domains . Review ers considered each extracted item by asking , What is each particular quality item addressing ? or What are the review 's authors getting at with the particular quality assessment item ? . Items were grouped into the domain or domains that best represented the concepts being addressed . For example , the extracted items at least 80 % of the group originally identified was located for follow-up and follow-up was sufficiently complete or does n't jeopardize validity were each independently classified by both review ers as assessing the domain completeness of follow-up adequate , whereas the extracted item quantification and description of all subjects lost to follow-up was classified as assessing the domain completeness of follow-up described . In the third step , we identified the domains necessary to assess potential biases . Each review er considered the ability of the identified domains to adequately address , at least in part , 1 of the following 6 potential biases : 1 ) study participation , 2 ) study attrition , 3 ) prognostic factor measurement , 4 ) confounding measurement and account , 5 ) outcome measurement , and 6 ) analysis . Domains were considered to adequately address part of the framework if information garnered from that domain would inform the assessment of potential bias . For example , both review ers judged that the identified domain study population represents source population or population of interest assessed potential bias in a prognosis study , whereas the domain research question definition did not , although the latter is an important consideration in assessing the inclusion of studies in a systematic review . Finally , on the basis of our previous ratings , we looked at whether each review included items from the domains necessary to assess the 6 potential biases . We calculated the frequency of systematic review s by assessing each potential bias and the number of review s that adequately assessed bias overall . From this systematic synthesis , we developed recommendations for improving quality appraisal in future systematic review s of prognosis studies . We used Microsoft Access and Excel 2002 ( Microsoft Corp. , Redmond , Washington ) for data management and SAS for Windows , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) for descriptive statistics . Role of the Funding Sources The funding sources , the Canadian Institutes of Health Research , the Canadian Chiropractic Research Foundation , the Ontario Chiropractic Association , and the Ontario Ministry of Health and Long Term Care , did not have a role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results We identified 1384 potentially relevant articles . Figure 1 shows a flow chart of studies that were included and excluded . Figure 2 shows the number of review s identified by year of publication . We excluded 131 systematic review s of prognosis studies that did not seem to include any quality assessment of the included studies ; this represented 44 % of prognosis review s. We included 163 review s of prognosis studies in our analysis ( 13 - 175 ) . The most common topics were cancer ( 15 % ) , musculoskeletal disorders and rheumatology ( 13 % ) , cardiovascular ( 10 % ) , neurology ( 10 % ) , and obstetrics ( 10 % ) . Other review s included a wide range of health and health care topics . Sixty-three percent of the review s investigated the association between a specific prognostic factor and a particular outcome ; the remainder investigated multiple prognostic factors or models . The number of primary studies included in each systematic review ranged from 3 to 167 ( median , 18 [ interquartile range , 12 to 31 ] ) . A complete description of the included review s is available from the authors on request . Figure 1 . Flow diagram of inclusion and exclusion criteria of systematic review s. Figure 2 . Number of systematic review s of prognosis studies identified over time . Quality Items One hundred fifty-three review s provided adequate detail to allow extraction of quality items . Eight hundred eighty-two distinct quality items were extracted from the review s. Most review s developed their own set of quality items , with only a few applying criteria from previous review s. Most quality items OBJECTIVE To determine the effect of quadriceps strength in individuals with knee osteoarthritis ( OA ) on loss of cartilage at the tibiofemoral and patellofemoral joints ( assessed by magnetic resonance imaging [ MRI ] ) and on knee pain and function . METHODS We studied 265 subjects ( 154 men and 111 women , mean+/-SD age 67+/-9 years ) who met the American College of Rheumatology criteria for symptomatic knee OA and who were participating in a prospect i ve , 30-month natural history study of knee OA . Quadriceps strength was measured at baseline , isokinetically , during concentric knee extension . MRI of the knee at baseline and at 15 and 30 months was used to assess cartilage loss at the tibiofemoral and patellofemoral joints , with medial and lateral compartments assessed separately . At baseline and at followup visits , knee pain was assessed using a visual analog scale , and physical function was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index . RESULTS There was no association between quadriceps strength and cartilage loss at the tibiofemoral joint . Results were similar in malaligned knees . However , greater quadriceps strength was protective against cartilage loss at the lateral compartment of the patellofemoral joint ( for highest versus lowest tertile of strength , odds ratio 0.4 [ 95 % confidence interval 0.2 , 0.9 ] ) . Those with greater quadriceps strength had less knee pain and better physical function over followup ( P<0.001 ) . CONCLUSION Greater quadriceps strength had no influence on cartilage loss at the tibiofemoral joint , including in malaligned knees . We report for the first time that greater quadriceps strength protected against cartilage loss at the lateral compartment of the patellofemoral joint , a finding that requires confirmation . Subjects with greater quadriceps strength also had less knee pain and better physical function over followup OBJECTIVES To investigate the effect of 12 weeks of strength training in combination with a nonsteroidal anti-inflammatory drug ( NSAID ) , glucosamine , or placebo on muscle cross-sectional area ( CSA ) , strength ( primary outcome parameters ) , and function , power , pain , and satellite cell number ( secondary outcome parameters ) in patients with knee osteoarthritis ( OA ) . DESIGN Double-blinded , r and omized controlled trial . SETTING Hospital . PARTICIPANTS Patients ( N=36 ; 20 women , 16 men ; age range , 50 - 70y ) with bilateral tibiofemoral knee OA . A total of 181 patients were approached , and 145 were excluded . INTERVENTIONS Patients were r and omly assigned to treatment with the NSAID ibuprofen ( n=12 ) , glucosamine ( n=12 ) , or placebo ( n=12 ) during 12 weeks of quadriceps muscle strength training . MAIN OUTCOME MEASURES Muscle CSA and strength . RESULTS No differences between groups were observed in gains in muscle CSA . Training combined with ibuprofen increased maximal isometric strength by an additional .22Nm/kg ( 95 % confidence interval [ CI ] , .01-.42 ; P=.04 ) , maximal eccentric muscle strength by .38Nm/kg ( 95 % CI , .05-.70 ; P=.02 ) , and eccentric muscle work by .27J/kg ( 95 % CI , .01-.53 ; P=.04 ) in comparison with placebo . Training combined with glucosamine increased maximal concentric muscle work by an additional .24J/kg versus placebo ( 95 % CI , .06-.42 ; P=.01 ) . CONCLUSIONS In patients with knee OA , NSAID or glucosamine administration during a 12-week strength-training program did not improve muscle mass gain , but improved maximal muscle strength gain in comparison with treatment with placebo . However , we do not find that the benefits are large enough to justify taking NSAIDs or glucosamine OBJECTIVES To examine the objective physical function of the lower extremities , to measure the properties of quadriceps femoris muscle ( QFM ) , and to assess subjective disabilities in men with knee osteoarthritis ( OA ) and to compare the results with those obtained from age- and sex-matched control subjects . DESIGN Cross-sectional study . SETTING Rehabilitation clinic in a university hospital . PARTICIPANTS Male volunteers ( n=54 ) ( age range , 50 - 69y ) with knee OA and r and omly selected healthy , age- and sex-matched control subjects ( n=53 ) . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Physical function evaluated with a test battery including the QFM composition measurement , the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) , and the R AND 36-Item Short-Form Health Survey , version 1.0 .  RESULTS Knee OA patients had 13 % to 26 % poorer ( P range , .050-.001 ) physical function and muscle strength compared with the controls . There were also significant differences in QFM composition . WOMAC ( P range , .050-.001 ) and muscle strength ( P<.001 ) associated with physical function tests , but subjective pain correlated with neither physical function nor muscle strength in knee OA patients . The radiographic knee OA grade did not have any significant effect on physical function , but passive knee motion , knee extension strength , and WOMAC were related to the severity of the disease ( P<.05 ) . CONCLUSIONS The patients with knee OA exhibited impaired physical function and muscle strength and QFM composition compared with healthy controls . The severity of radiographic knee OA clearly had adverse effects on functional ability at the later stages of the disease . The results highlight the effect of QFM strength on physical function as well as the importance of patient 's subjective and objective physical function when deciding on knee OA treatment policy OBJECTIVE To evaluate the effects of isokinetic exercise versus a program of patient education on pain and function in older persons with knee osteoarthritis . DESIGN A r and omized , comparative clinical trial , with interventions lasting 8 weeks and evaluations of 12 weeks . SETTING An outpatient Veterans Affairs Medical Center clinic and an affiliated university hospital . PATIENTS One hundred thirteen men and women between 50 and 80 years old with diagnosed osteoarthritis of the knee ; 98 completed the entire assigned treatment . INTERVENTION Patients received either a regimen of isokinetic exercise of the quadriceps muscle three times weekly over 8 weeks or a series of 4 discussion s and lectures led by health care professionals . MAIN OUTCOME MEASURES Variables studied for change were isokinetic and isometric quadriceps strength , pain and function determined by categorical and visual analog scales , and overall status using physician and patient global evaluations by the Arthritis Impact Scale , version 2 , Western Ontario McMaster 's Arthritis Index , and Medical Outcome Study Short Form 36 . RESULTS Both treatment groups showed significant strength gains ( p < .05 ) , which occurred over a wider velocity spectrum for the exercise group . Exercised patients also had improved pain scores for more of the variables measured than those receiving education . Both groups had positive functional outcomes and slightly improved measures of overall status . CONCLUSIONS Isokinetic exercise is an effective and well-tolerated treatment for knee osteoarthritis , but a much less costly education program also showed some benefits BACKGROUND Valid outcome measurement tools are required to reliably demonstrate the effectiveness and clinical outcomes of lower-extremity arthroplasty . Having ascertained a lack of a practical and valid measure of the change in actual daily physical activity that occurs prior to and following lower-limb arthroplasty , we developed and vali date d a lower-extremity activity scale . METHODS The eighteen-level self-administered scale was developed with the aid of content experts to ensure face validity . Validity and reliability were assessed with the use of ( 1 ) pedometer measurements of seventy subjects over seven days ;  ( 2 )  next-of-kin proxy measurements of the activity levels of ninety patients before they underwent lower-limb arthroplasty ;  and ( 3 ) application , and correlation with the Western Ontario and McMaster Universities Osteoarthritis Index scores , in a prospect i ve seventeen-center clinical study of 297 consecutive patients undergoing revision total knee arthroplasty . In this latter study , demographic and comorbidity data were also collected . Univariate and bivariate correlations were performed , and a multivariate structured equation modeling approach was used to further test responsiveness , reliability , and validity of the lower-extremity activity scale . RESULTS Pedometer readings correlated with the activity levels derived with the lower-extremity activity scale ( r = 0.79 ) . Of note was the finding that age , weight , and body mass index did not correlate well with the average number of steps per day ( r = -0.32 , -0.32 , and -0.25 , respectively ) . A significant correlation was found between the lower-extremity activity scores recorded by the patients and those reported by their next of kin ( Pearson correlation , r = 0.715 ; p = 0.0001 ) and between the initial lower-extremity activity scores and two-week-retest scores ( intraclass correlation = 0.9147 ; p < 0.0001 ) , demonstrating the validity and reliability of the scale . The  lower-extremity activity scale was responsive , accurately reflecting changes in the patient 's condition between baseline and the time of follow-up ( p < 0.001 ) , and it was reliable , with baseline values correlating with follow-up scores ( p < 0.001 ) . The convergent validity of the lower-extremity activity scale was established by correlations with the function scores ( r = -0.301 , p < 0.001 ) and pain scores ( r = -0.241 , p < 0.001 ) derived with the Western Ontario and McMaster Universities Osteoarthritis Index and with a higher number of comorbidities ( r = -0.244 , p < 0.001 ) . Multivariate path modeling further demonstrated diminished activity in patients who had more difficulty in functioning and a greater number of comorbidities . CONCLUSIONS We developed a lower-extremity activity scale and vali date d that it was an effective instrument for the assessment of patients ' actual activity levels . It is easy to apply and interpret , and it is valid and ready for use in the clinical setting . This scale will allow more accurate analysis and prediction of outcomes . Consequently , it will become a useful , practical adjunct to objective clinical decision-making and intervention for patients undergoing arthroplasty OBJECTIVE To test the effects of a high intensity home-based progressive strength training program on the clinical signs and symptoms of osteoarthritis ( OA ) of the knee . METHODS Forty-six community dwelling patients , aged 55 years or older with knee pain and radiographic evidence of knee OA , were r and omized to a 4 month home based progressive strength training program or a nutrition education program ( attention control ) .  Thirty-eight patients completed the trial with an adherence of 84 % to the intervention and 65 % to the attention control . The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis ( WOMAC ) index pain and physical function subscales . Secondary outcomes included clinical knee examination , muscle strength , physical performance measures , and question naires to measure quality of life variables . RESULTS Patients in the strength training group who completed the trial had a 71 % improvement in knee extension strength in the leg reported as most painful versus a 3 % improvement in the control group ( p < 0.01 ) . In a modified intent to treat analysis , self-reported pain improved by 36 % and physical function by 38 % in the strength training group versus 11 and 21 % , respectively , in the control group ( p = 0.01 for between group comparison ) . In addition , those patients in the strength training group who completed the trial had a 43 % mean reduction in pain ( p = 0.01 vs controls ) , a 44 % mean improvement in self-reported physical function ( p < 0.01 vs controls ) , and improvements in physical performance , quality of life , and self-efficacy when compared to the control group . CONCLUSION High intensity , home based strength training can produce substantial improvements in strength , pain , physical function and quality of life in patients with knee OA Our objective was to investigate whether behavioral grade d activity ( BGA ) has particular benefit in specific subgroups of osteoarthritis ( OA ) patients . Two hundred participants with OA of hip or knee , or both ( clinical American College of Rheumatology , ACR , criteria ) participated in a r and omized clinical trial on the efficacy of BGA compared to treatment according to the Dutch physiotherapy guideline ( usual care ; UC ) . Changes in pain ( Visual Analog Scale , VAS ) , physical functioning ( Western Ontario and McMaster Universities Osteoarthritis Index , WOMAC , and McMaster Toronto Arthritis Question naire , MACTAR ) , and patient global assessment were compared for specific subgroups . Subgroups were assigned by the median split method and were analyzed using analysis of covariance . Beneficial effects of BGA were found for patients with a relatively low level of physical functioning ( p?0.03 ) . Furthermore , beneficial effects of BGA  in patients with a low level of internal locus of control were marginally significant ( p = .05 ) . Patients with a relatively low level of physical functioning  benefit more from BGA compared to UC . Compared to UC , BGA is the preferred treatment option in patients with a low level of physical functioning OBJECTIVES To identify the determinants of self-report mobility measures in people with knee osteoarthritis ( OA ) and to compare self-report measures with physical performance . DESIGN Cross-sectional , prospect i ve . SETTING Motor performance laboratory and human mobility research center . PARTICIPANTS A convenient sample of 54 participants with medial compartment knee OA ( 32 women , 22 men ; age 68.3+/-8.7y ; range , 50 - 87y ) . Three participants were excluded because of the presence of lateral knee OA on radiographs . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Self-reports were recorded by using the Western Ontario McMaster Universities Osteoarthritis Index ( WOMAC ) and the Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ) . Performance measures included the  six-minute walk test ( 6MWT ) , Timed Up & Go ( TUG ) test , and a st and ardized stair-climbing task ( STR ) . RESULTS Stepwise linear regression analysis identified models that included pain , quadriceps and hamstrings strength , and depression to explain 62 % to 73 % of the variance in scores on the physical functioning subscale of the WOMAC and the SF-36 . These self-report measures had a moderate relation ( r range , .46-.64 ) with performance measures ( 6MWT , TUG , STR ) . CONCLUSIONS Self-report measures were strongly related to pain ; physical performance measures were strongly related to self-efficacy . Regression models showed that self-report scores reflect pain , knee strength , and depression . The relation between self-report and performance measures was moderate , suggesting that these examine different aspects of mobility Objective : To determine the additional prognostic value of clinical history , physical examination and x-ray findings to a previously derived simple generic model ( age , body mass index , anxiety and pain severity ) in a cohort of older adults with knee pain . Methods : Prospect i ve cohort study in community-dwelling adults in North Staffordshire . 621 participants ( aged ⩾50 years ) reporting knee pain who attended a research clinic at recruitment and were followed up by postal question naire at 18 months . Poor functional outcome was measured by the Physical Functioning Scale of the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) at 18-month follow-up defined in 60 % of participants . Results : Three clinical history variables ( bilateral knee pain , duration of morning stiffness and inactivity gelling ) were independently associated with poor outcome . The addition of the “ clinical history ” model to the “ generic ” model led to a statistical improvement in model fit ( likelihood ratio ( LR ) = 24.84 , p = 0.001 ) . Two physical examination variables ( knee tender point count and single-leg balance ) were independently associated with poor outcome but did not lead to a significant improvement when added to the “ clinical history and generic ” model ( LR = 6.34 , p = 0.50 ) . Functional outcome was significantly associated with severity of knee radiographic osteoarthritis ( OA ) , but did not lead to any improvement in fit when added to the “ generic , clinical history and physical examination ” model ( LR = 1.86 , p = 0.39 ) . Conclusions : Clinical history , physical examination and severity of radiographic knee OA are of limited value over generic factors when trying to predict which older adults with knee pain will experience progressive or persistent functional difficulties
target: In knee OA , strong evidence was found that avoidance of activities is associated with activity limitations via muscle weakness ( mediation by muscle weakness ) , strong evidence was found for an association between muscle weakness and activity limitations , and weak evidence was found that pain and psychological distress are associated with muscle weakness via avoidance of activities ( mediation by avoidance ) .
  In hip OA , weak evidence was found for mediation by muscle weakness ; and strong evidence was found for an association between muscle weakness and activity limitations .
background: The avoidance model in patients with knee and hip osteoarthritis ( OA ) hypothesizes that pain and psychological distress lead to avoidance of activities , and thereby to muscle weakness and activity limitations .
  This paper systematic ally review s the scientific evidence for the validity of this avoidance model .