Clinical value of questionnaires & physical tests for patellofemoral pain: Validity, reliability and predictive capacity

RESEARCH ARTICLE Clinical value of questionnaires & physical tests for patellofemoral pain: Validity, reliability and predictive capacity Gema Chamorro-MorianaID 1,2 *, Fernando Espuny-RuizID 1 *, Carmen Ridao-Ferna ´ndez 1,2 , Eleonora Magni 3 1Department of Physiotherapy, Faculty of Nursing, Physiotherapy and Podiatry, University of Seville, Seville, Spain, 2Research Group “Area of Physiotherapy CTS305”, Spain, 3Department of Nursing, Faculty of Nursing, Physiotherapy and Podiatry, University of Seville, Seville, Spain *[email protected] (FER); [email protected] (GCM) Abstract Objectives To determine the most appropriate method of functional assessment for "patellofemoral pain" (PFP)/“chondromalacia patella” for its diagnostic value, (validity, reliability, sensitivity, specificity, predictive value and clinical applicability); to outline initial interpretations of the questionnaires and their appropriateness, through the cut-off points determined in their scores based on physical test and Magnetic Resonance Imaging (MRI); to establish which methods should be used in conjunction with each other to obtain clinical diagnoses that are robust effective and efficient. Methods (1)Intraand inter-observer reliability and of the relationship among PFP questionnaires/ physical tests validated. (2)Predictive capacity of the questionnaires. Subject: 113 knees with PFP, assessed using “Knee-injury-and-Osteoarthritis Outcome-Score-for-Patellofemoral-pain-and-osteoarthritis” (KOOS-PF), “Kujala-Patellofemoral-Score” (KPS), “Victorian-Institute-of-Sports-Assessment-for-Patellar-tendons-questionnaire” (VISA-P), and the physical tests: “patellar-palpation”,“patellar-tilt”,“patellar-apprehension”,“Clarke” and “squat”. Results Questionnaires correlations themselves was 0.78<r<0.86. Tests intra-rater reliability was “excellent”. Squat inter-rater reliability was “excellent”/“good”.Palpation,tilt,Clarke and squat showed a statistically significant relationship (p<0.05) with all questionnaires/specific items. AUC of the questionnaires showed a "useful" accuracy, except for Tilt. No statistically significant differences were found between grades 0 and 1 chondromalacia (by MRI) knee scores, but between 1 and �2. AUC of the questionnaires showed "useful" accuracy. PLOS ONE PLOS ONE | https://doi.org/10.1371/journal.pone.0302215 April 17, 2024 1 / 23 a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 OPEN ACCESS Citation: Chamorro-Moriana G, Espuny-Ruiz F, Ridao-Ferna ´ndez C, Magni E (2024) Clinical value of questionnaires & physical tests for patellofemoral pain: Validity, reliability and predictive capacity. PLoS ONE 19(4): e0302215. https://doi.org/10.1371/journal.pone.0302215 Editor: Mehrnaz Kajbafvala, Iran University of Medical Sciences, ISLAMIC REPUBLIC OF IRAN Received: December 22, 2023 Accepted: March 30, 2024 Published: April 17, 2024 Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. The editorial history of this article is available here: https://doi.org/10.1371/journal.pone.0302215 Copyright: ©2024 Chamorro-Moriana et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the manuscript and its Supporting Information files. Conclusions KOOS-PF, KPS and VISA-P demonstrated their diagnostic value in PFP/chondromalacia (validity, reliability, sensitivity, specificity, predictive value and clinical applicability). KOOSPF was the most versatile, and the most appropriate in mild cases and for early detection and prevention. Squat was the best due to its reliability and clinical relationship with the questionnaires, which predicted it correctly. The functional assessment tools discussed should be applied by combining them with each other. Introduction Patellofemoral Pain (PFP), also known as Patellofemoral Pain Syndrome [1], is a condition characterized by retropatellar or peripatellar pain [1–3] often of insidious onset [4] associated primarily with activities where the support of body weight in knee flexion positions loads the patellofemoral joint [2,3]. It is often considered a chronic overuse injury [5], with symptoms persisting for up to 20 years [6] leading to a diminished quality of life [7]. Chondromalacia patella (CP) can be used as a PFP synonym if there is structural cartilage damage [8] diagnosed by imaging [9], or simply grade I cartilage softening and inflammation, according to several commonly used classifications, such as Outerbridge [10], Insall [11], Noyes [11] or even Modified Noyes [12]. It has a high prevalence, especially among the military, adolescents and athletes in general [5]. For example, in 2016, it affected 22.7% of the UK population [5] although some authors estimate this figure at over 40% [13,14]. Women are twice as likely to suffer from PFP [5], possibly due to anatomical and biomechanical variations, including thinner cartilage, greater Qangle, greater dynamic valgus [4,15], etc. The pathogenesis of PFP is multifactorial [15,16]. Thus, quadriceps weakness or quadriceps muscle imbalance [15,16], patellar instability [1], foot or hip dysfunction [15], activities such as running, squats or stair climbing [6], and dynamic valgus in women [15], among other factors, lead to incorrect patellar tracking [15], hypermobile [1,15] or lateralised patellae [15], etc. This, together with the influence of abnormal morphological features [17,18] regarding patellar type [19], sulcus depth of femoral condyles [17–19], patellar tilt angles [17], etc., results in ongoing patellofemoral friction that contributes or predisposes to the onset of pain and even cartilage deterioration [18]. The diverse etiopathology must be taken into account in the assessment and subsequent medical and physiotherapeutic process [20]. Numerous methods have been used to assess PFP [21]. For example, imaging is useful to objectively confirm whether there is structural damage to the cartilage [9]. Magnetic Resonance Imaging (MRI), which appears to be accurate in high grades [22], and arthroscopies; show low correlation between degrees and symptoms [22]. On the other hand, MRI, computed tomography, ultrasound and X-ray are useful for locating the patella in different degrees of flexion, although the first three are only used in unloaded flexion [23]. Thus, they provide interesting but incomplete data based on the preceding paragraph. Non-technological methods, i.e. functional assessment questionnaires and physical tests [21, 24,25], stand out for their efficiency, clinical feasibility and focus mainly on symptomatology. Few questionnaires are validated and created specifically for these patellofemoral conditions, i.e. Kujala Patellofemoral Score (KPS) [26]. Since cross-cultural language adaptations are not always available or they are not accessible to researchers and clinicians, among others, nonPLOS ONE Functional valuation of patellofemoral pain PLOS ONE | https://doi.org/10.1371/journal.pone.0302215 April 17, 2024 2 / 23 Funding: The author(s) received no specific funding for this work. Competing interests: The authors have declared that no competing interests exist. specific questionnaires are also frequently used to assess PFP [20,21,27]. This is the case of Fulkerson Knee Instability Scale (FKIS) [28]. KPS is considered the reference standard, among other reasons because of how long it has been in use (since 1993) and its methodological quality [29,30]. The most common physical tests are: medial/lateral patellar palpation [2,9,31,32], Clarke test [2,9,31,32] as specific palpation and mobility tests, and the squat test [2,9,32,33] as a general pain provocation test. Up to now, it has not been possible to identify a benchmark physical test, which is needed [31,32] in clinical and research settings in order to apply it in isolation or in combination with other tests [34]. The difficulty involved in diagnosing PFP due to its multifactorial nature [15,16] and the differential diagnoses it entails, such as bursitis, patellar tendinopathy or rheumatoid arthritis [35], lead to an in-depth examination of the efficiency of existing assessment methods and the identification of clinically feasible tools. This could help to improve assessment [25,33], especially early ones, and consequently therapeutic protocols, whether preventive or curative. The high prevalence of patellofemoral conditions [5], the poor long-term prognosis [1,4,6,36] due to cartilage degeneration [18], its association with disability and chronicity [6,7], and the economic and health care costs involved [5] are other issues that would justify the need to further develop the existing assessment methods for PFP. Since, so far, there is no evidence in the literature of a functional assessment method that provides all of the above-mentioned characteristics and is also useful especially in initial; this study aimed to determine the most appropriate method of functional assessment to evaluate "patellofemoral pain" and/or “CP” for its diagnostic value, according to its validity, reliability, sensitivity, specificity, predictive value and clinical applicability. A second objective was to outline initial interpretations of the questionnaires and their appropriateness, through the cut-off points determined in their scores based on physical and MRI tests. Lastly, this study is aimed to establish which methods should be used in conjunction with each other in order to obtain clinical diagnoses that are robust, effective and efficient. Materials and methods Study 1: intraand inter-observer reliability and of the relationship among PFP functional assessment methods: questionnaires validated and/or applied in PFP and cross-culturally adapted to Spanish, as well as physical tests validated in PFP. Study 2: predictive capacity of the above-mentioned questionnaires. Participants and sample Participants were recruited using non-random convenience sampling. Inclusion criteria were: subjects with symptomatic PFP with or without cartilage damage (note: by PFP we mean the patellofemoral joint conflict that produces friction between the facet joints due to non-traumatic causes such as knee valgus, muscle imbalance between the vastus medialis and vastus lateralis, etc., as shown in the introduction section); between 16 and 55 years old to avoid late symptoms of apophysitis (Osgood-Schlatter or Sinding-Larssen-Johansson) and early symptoms of osteoarthritis [37]; and native Spanish speakers. Exclusion criteria were: subjects with severe cognitive or coordination impairment, severe cardiovascular or respiratory conditions and PFP symptomatology common to other affected knee dysfunction such as femoral condyle or patella fractures affecting the facet joints, knee prosthesis, etc.; and disorders of other joints such as hip, ankle or femorotibial joint, which prevent the performance of physical tests or bias the tests results. PLOS ONE Functional valuation of patellofemoral pain PLOS ONE | https://doi.org/10.1371/journal.pone.0302215 April 17, 2024 3 / 23 The study considered the affected knees as the sample, except for the descriptives, where it was the participants. Functional assessment methods used Following a literature review using Pubmed, Web of Science, Scopus, Cinahl and Dialnet, we selected three validated self-administered functional assessment questionnaires, transculturally adapted to Spanish and applied to PFP. Knee injury and Osteoarthritis Outcome Score for Patellofemoral pain and osteoarthritis (KOOS-PF), which assesses PFP and/or osteoarthritis [30], addressing pain especially, stiffness, and quality of life. KPS, which assesses patellofemoral pathologies [26] considering pain and physical alterations, functional limitation and difficulty in sports activities. Victorian Institute of Sports Assessment for Patellar tendons questionnaire (VISA-P), which is applied in PFP [29], although it was designed specifically for patellar tendinopathy [38]. It especially considers pain and the ability to engage in physical activity and sport. The scores of the three questionnaires ranged 0–100 (optimal/asymptomatic). The regular functional tests selected, all of which were dichotomous (positive/negative), were: patellar palpation test [31], positive if tenderness or discomfort is present in any of the medial or lateral facets; patellar tilt test [31], positive if the lateral outer edge of the patella is not elevated or does not separate from the femur; patellar apprehension test [31], positive if there is a withdrawal manoeuvre by the patient when the patella is displaced outwards; Clarke test, positive if there is pain on isometric contraction of the quadriceps and cranial displacement of the patella rubbing against the femur or if the contraction is avoided for fear of pain [39]; and the squat test with 90˚ of knee flexion, positive if it causes pain or if pain prevents them from performing the test [40]. Magnetic Resonance Imaging (MRI) MRI has been used in this study to establish cut-off points in the questionnaire scores according to the CP degrees it determines. The degrees [10] are: I, cartilage softening and swelling; II, fissures <0.5 inches in diameter not reaching the subchondral bone; III, fissures >0.5 inches reaching the subchondral bone; and IV, erosion that exposes subchondral bone. Action protocol Evaluations were conducted between 01 December 2022 and 28 February 2023. Each subject was assessed in two sessions, 7–10 days apart; enough time to avoid recall of their answers, but not too long after to avoid clinical changes in PFP [29,41], since the purpose of the study was not to assess the effect of an intervention. Session 1. 1 st Completion of the informed consent form and collection of descriptive data on the subject, both general information and regarding PFP (affected knee, summary of the process and Q-angle assessment of the affected knee(s). 2 nd Self-completion of questionnaires in the following order: “KOOS-PF”, “KPS”, “VISA-P”. They were able to ask the investigators any questions they had. 3 rd Application of physical assessment tests by two physiotherapists on two alternative occasions (FE-CR-FE-CR) in the following order: patellar palpation,patellar tilt,patellar apprehension,Clarke and squat. Since the last two could cause pain, they were left for last to avoid apprehension regarding the other tests [39]. Session 2. 1 st Self-completion of the questionnaires as in session 1. 2 nd Battery of physical tests only performed by a physiotherapist (FE-FE). PLOS ONE Functional valuation of patellofemoral pain PLOS ONE | https://doi.org/10.1371/journal.pone.0302215 April 17, 2024 4 / 23 Statistical analysis Sample size calculation was based on a related study that examined the combination of history elements and physical tests for PFP [25]. The following conditions were used: KOOS-PF mean standard deviations (s), 20.22; confidence interval of 95% and error (E), 4. The following formula used was: n¼z2 a=2�s2 E2 The sample size obtained was 99 affected knees. Our sample included a few more subjects following COSMIN recommendations [42] (optimum �100) and anticipating possible dropouts. The description of the participants and their condition considered absolute (N) and relative (%) frequencies in qualitative variables. The normality of quantitative variables was analysed using the Shapiro-Wilk test, considering mean and standard deviation for parametric variables, and median and interquartile range for non-parametric variables. To assess the relationship between the two measurement moments of the questionnaires, we used: the t-Test for related samples in normal distributions, and the Wilcoxon SignedRank Test for related samples in non-normal distributions. We applied a double correlation analysis among questionnaires, one for each session (time). Pearson’s correlation coefficient (r) and Spearman’s Rho were used, depending on whether the distribution was normal or not, respectively, where: r>0.7 strong, 0.7�r>0.5 moderate, 0.5�r>0.25 weak and r�0.25 rare correlation [43]. The same correlation analysis was applied among some specific items of the questionnaires due to their direct link to the squat test. The inter-observer and intra-observer agreement of the tests was analyzed using Cohen’s Kappa Index (k). Inter-observer reliability was analyzed twice: between the 1st FE and CR measurements (session 1); and between the 2nd FE and CR measurements (session 1). Intraobserver reliability was analyzed twice: between the 1st and 2nd FE measurements (session 1) and between the next 2 FE measurements (session 2). It was graded according to Landis JR et al [44] where: k>0.8 excellent, 0.8�k>0.6 good, 0.6�k>0.4 acceptable and k�0.4 unacceptable. The relationships among questionnaires and physical tests were analyzed with t-Test for independent samples in variables with normal distributions, and Mann-Whitney U-test for independent samples in non-normal distributions. The 2 measurement moments of the questionnaires and the physical tests were taken into account. Notice that only those test measurements where the positive/negative ratio 6¼1 at each point in time were considered for the comparative analysis. For each questionnaire the following was calculated: area under curve (AUC) (between 0–1), represented by a ROC curve, cut-off point to discriminate between positive and negative results in each physical test, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) (CI = 95%). AUC was graded according to Swets JA [45] where: 0.5–0.7 = “low” accuracy, 0.7–0.9 = “useful” accuracy, >0.9 = “high” accuracy. The ROC curve shows the probability of the questionnaire being able to discriminate between positive and negative physical test results. On the other hand, the same statistical tests mentioned in the previous paragraph were carried out for some specific items associated with the patellar tilt test,Clarke test and squat test. Similarly, a comparative analysis between CP grades (0, 1 and �1) by MRI and questionnaire scores was carried out with a sub-sample of the study. Cluster analysis was performed to establish groupings in the sample based on overall questionnaire scores, physical test results, gender, height and Q-angle. Moreover, this analysis will make it possible to establish the relationships between the variables of the study based on the association between gender, height and QPLOS ONE Functional valuation of patellofemoral pain PLOS ONE | https://doi.org/10.1371/journal.pone.0302215 April 17, 2024 5 / 23 angle. Only results of cohesion and separation silhouette measurement >0.5 (<0.2 = “poor”; 0.2–0.5 = “sufficient”; >0.5 = "good") were considered valid [46]. p<0.05 values were considered statistically significant in general. CI95%>0.5 were considered statistically significant for AUC [47]. IBM SPSS STATISTICS 251software was used for the analysis. This research was conducted in accordance with the Declaration of Helsinki and approved on 3 December 2021 by the Research Ethics Committee of the Virgen Macarena-Virgen del Rocı ´o Hospitals of the Andalusian Public Health System (C.I.0162-N-21). Before starting the fieldwork (request for personal data and functional assessment), all participants received a written information sheet about the study together with the informed consent to sign. They were able to ask questions and solve any doubts about these documents with the researchers before signing the consent, which did not prevent the subject from leaving the study if he/she wanted to. All patients gave written informed consent after reading the user information sheet. For those subjects under 18 (inclusion criterion: minimum 16 years), the consent signatures of the parent or legal guardian and the informed assent of the minor, i.e. in age-appropriate language, were expressly required. All the above was included in the application submitted to the Ethics Committee for approval. Results A total of 113 affected knees of 80 participants were assessed. The description of both variables is detailed in Table 1. Analysis of assessment questionnaires The relationship between the measurement moments of the assessment questionnaires is shown in Table 2. Bilaterally affected participants answered for each of their affected knees in Table 1. Descriptive characteristics of the participants and sample. Men (n = 29) Women (n = 51) Total (n = 80) Age (years) Med 30.5 29 30 IQR 22.3–49.0 23.0–48.5 23–49 Height (cm) μ181 166 172 SD 6 6 9 BMI Med 24.7 23 24.4 IQR 23.5–29.2 20.8–26.1 22.0–27.9 Time with pain (months) Med 66 54 60 IQR 27–120 24–84 24–99 Impairment Bilateral N11 22 33 %14% 27.5% 41.5% Unilateral N18 29 47 %22.5% 36% 58.5% Impaired limb*Dominant N11 17 28 %24% 36% 60% Nondominant N7 12 19 %15% 25% 40% Affected knees Q-angle (degrees) Med 16 19 18 IQR 14–18 17–24 16–22 Abbreviations: BMI, body mass index; Med, median; IQR, interquartile range. a Only unilateral affected subjects considered. https://doi.org/10.1371/journal.pone.0302215.t001 PLOS ONE Functional valuation of patellofemoral pain PLOS ONE | https://doi.org/10.1371/journal.pone.0302215 April 17, 2024 6 / 23 the questions that required them to do so. The sample in the following tables was thus the knees, not the participants. Statistically significant differences were found in KOOS-PF. Table 3 shows the correlation of the rating questionnaires with each other at the two measurement moments. The 3 questionnaires showed statistically significant correlation among them (p<0.05) at the two moments in time analyzed. In fact, all were p<0.001, their correlation coefficients being >0.78. Analysis of physical assessment tests The intra-observer and inter-observer agreement analyses of the different physical tests are shown in Table 4. Summarizing the table above, the inter-observer reliability of the tests analyzed showed results ranging from “excellent” (k>0.8) [44] to “acceptable” (0.4<k<0.6) [44]. The squat test stood out with an “excellent” (k>0.8) [44] result in the first measurement, and “good” (0.6<k<0.8) [44] in the second. In terms of intra-observer reliability, the analyses of all tests produced “excellent” (k<0.8) [44] results. Analysis of the relationships among questionnaires and physical assessment tests The relationship among questionnaires and tests is summarized in Tables 5and 6.Table 5 shows whether subjects with scores on the questionnaires referring to milder pathology were more likely to have a negative test result (absence of symptoms) and viceversa. Table 6 shows Table 2. Relationship between the two measurement moments of the rating questionnaires. μSD Med IQR p KOOS-PF m1 54.5 22.8 59.1 34.1–69.4 <0.001* m2 60.5 23.0 63.6 47.7–77.3 KPS m1 73.5 17.6 78 62.0–86.5 0.078* m2 74.7 18.3 80 65–89 VISA-P m1 55.6 21.3 56 41–73 0.249 a m2 56.8 22.5 57 41–73 Abbreviations: m1, measurement 1; m2, measurement 2; μ, media; SD, standard deviation; Med, median; IQR, interquartile range. a Wilcoxon signed-rank test for paired samples. b T-test for paired samples. Questionnaires score ranges: 0–100. https://doi.org/10.1371/journal.pone.0302215.t002 Table 3. Correlation among rating questionnaires at the two measurement moments. rMeasurement 1 Measurement 2 KOOS-PF KPS KOOS-PF KPS KPS 0.825 0.865 VISA-P 0.851 0.788 0.860 0.819 Abbreviation: r, correlation coefficient. Note: all coefficients were analyzed using Spearman’s Rho. All values were p<0.001. https://doi.org/10.1371/journal.pone.0302215.t003 PLOS ONE Functional valuation of patellofemoral pain PLOS ONE | https://doi.org/10.1371/journal.pone.0302215 April 17, 2024 7 / 23 the capacity of the questionnaires and some of their specific items to predict test outcome, and the cut-off points of the questionnaire scores from which they are predicted. Patellar apprehension test is not reflected in the following tables because all test measurements were negative. Patellar palpation test,patellar tilt test,Clarke test and squat test showed a statistically significant relationship (p<0.05) with all 3 questionnaires and specific items, i.e. positive tests corresponded to lower scores (higher in KOOS-PF items). All values were p<0.001, except for tilt test. The AUC values of the 3 questionnaires were significant (CI95% >0.5) showing a "useful" accuracy (0.7–0.9) [45], except for the patellar tilt test. Associations with the squat test (>0.8) were notable. The AUC values of the 7 specific items analysed, also significant, indicated a "useful" accuracy (0.7–0.9) [45], except KPS-4 with squat. The representation of the ROC curves is shown in Fig 1. All CI95% of the sensitivity, specificity, PPV and NPV of the three questionnaires with the squat were >50%. The CI95% for the sensitivity of the 7 specific items were >50%, although none scored >50% for all statistics. Table 7 shows the correlation between the specific items associated with the squat test. All items associated with the squat test showed statistically significant correlations (p<0.001). Analysis of the relationships among questionnaries and CP degree according to MRI The relationship among questionnaires and CP is summarized in Tables 8and 9.Table 8 shows whether subjects with higher scores in the questionnaires (milder pathology), were more likely to have lower degrees of CP (less structural damage). Table 9 shows the ability of the questionnaires to predict the degree of CP and the cut-off points of the questionnaire scores from which they are predicted. No statistically significant differences were found between grade 0 and grade 1 CP knee scores, but there were differences between grade 1 and �2 grades. All AUC values for the 3 questionnaires were statistically significant and of "useful" accuracy (0.7–0.9) [45]. The representation of the ROC curves is shown in Fig 2. Cluster analysis Finally, the sample clusters are shown by cluster analysis in relation to the questionnaires, gender, height and Q-angle. Note: all physical tests were discarded by the statistical test itself. The optimal algorithm generated presented 3 clusters with 6 entries, in agreement with the good Table 4. Reliability of physical assessment tests. Physical tests Inter-rater Intra-rater 1FE-1CR 2FE-2CR 1FE-2FE 3FE-4FE Patellar palpation 0.619 0.697 0.809 0.942 Patellar tilt 0.505 0.540 0.826 0.954 Clarke 0.600 0.554 0.849 0.858 Squat 0.862 0.732 0.904 0.903 Abbreviations: 1FE, 1 st measurement FE; 2FE, 2 nd measurement FE; 3F, 3 rd measurement FE; 4F, 4 th measurement FE; 1CR, 1 st measurement CR; 2CR, 2 nd measurement CR. https://doi.org/10.1371/journal.pone.0302215.t004 PLOS ONE Functional valuation of patellofemoral pain PLOS ONE | https://doi.org/10.1371/journal.pone.0302215 April 17, 2024 8 / 23 Table 5. Descriptive and comparative analysis of the overall scores of the questionnaires and specific items according to the results of the physical tests. Physical tests N(knees) μ SD Med IQR P Questionnaires KOOS-PF Patellar palpation - 82 69.4 19.1 68.2 61.4–84.7 <0.001 a + 142 50.6 22.5 55.7 34.1–68.2 Patellar tilt - 58 64.2 22.3 68.2 46.0–77.9 0.007 a + 156 54.9 22.7 59 37.0–72.7 Clarke - 126 67.0 18.0 68.2 56.2–77.9 <0.001 a + 80 42.0 22.5 37.5 21.1–61.4 Squat - 148 67.0 17.3 68.2 56.8–77.3 <0.001 a + 76 39.1 21.8 34.1 20.5–56.8 KPS Patellar palpation - 82 81.7 13.8 85 76–91 <0.001 a + 142 69.6 18.7 76 53.8–83.0 Patellar tilt - 58 79.2 16.1 84 67.8–91.3 0.004 a + 156 72.2 18.3 78 62–85 Clarke - 126 81.5 12.1 83 74–91 <0.001 a + 80 61.7 19.4 62 43.0–80.8 Squat - 148 81.0 13.5 82 76–91 <0.001 a + 76 60.5 17.9 61 43–78 VISA-P Patellar palpation - 82 67.4 18.2 66.5 53–83 <0.001 b + 142 49.6 21.3 51 34–64 Patellar tilt - 58 62.5 23.1 60.5 43.5–85.0 0.031 a + 156 54.0 21.1 55 38.3–69.8 Clarke - 126 64.8 17.6 64.5 51–78 <0.001 b + 80 42.7 20.7 42 27.0–56.8 Squat - 148 64.9 18.3 63.5 53.3–78.8 <0.001 b + 76 39.1 18.4 38.5 25.3–52.0 Specific items KPS-13 Patellar tilt - 58 4.1 1.4 5 3–5 0.004 a + 156 3.8 1.3 3 3–5 VISA-P-3 Clarke - 126 8.6 1.8 9 8–10 <0.001 a + 80 6.2 2.6 6 4.0–8.8 KOOS-PF-4 Squat - 148 1.1 0.9 1 0–2 <0.001 a + 76 1.9 1.1 2 1–3 KOOS-PF-6 - 148 1.5 1.1 1 1–2 <0.001 a + 76 2.7 1.1 3 2–4 KPS-4 - 148 7.9 1.8 8 8–10 <0.001 a + 76 6.6 1.8 5 5–8 KPS-5 - 148 3.7 0.8 4 3–4 <0.001 a + 76 2.8 1.3 3 2–4 VISA-P-2 - 148 8.6 1.8 9 8–10 <0.001 a + 76 6.1 2.7 6 4–9 VISA-P-5 - 148 7.6 2.3 8 7–10 <0.001 a + 76 6.3 2.6 7 4–8 Abbreviations: μ, media; SD, standard deviation; Med, median; IQR, interquartile range. *The + and–signs indicate the results of the physical test. ** The pvalue indicates the statistical significance of the dependence between the test result and the scale/item scores. The greater the difference in scores among those scales that correspond to positive test results and those that correspond to negative test results, the greater the statistical significance. a Mann-Whitney U test for non-paired samples. b T-test for non-paired samples. Items: KPS-13, “Flexion deficiency”; VISA-P-3, “Do you have pain at the knee with full active non weight bearing knee extension?”; KOOS-PF-4, “Rising from sitting”; KOOS-PF-6, “Squatting”; KPS-4, “Stairs”; KPS-5, “Squatting”; VISA-P-2, “Do you have pain walking down stairs with a normal gait cycle?”; VISA-P-5, “Do you have problems squatting?”. Score ranges: questionnaires (0–100); KOOS-PF items (0–4); KPS-4 (0–10); KPS-5 and KPS-13 (0–5); VISA-P items (0–10). https://doi.org/10.1371/journal.pone.0302215.t005 PLOS ONE Functional valuation of patellofemoral pain PLOS ONE | https://doi.org/10.1371/journal.pone.0302215 April 17, 2024 9 / 23 regarding when to consider it positive or negative. As with the patellar tilt test, some authors [2,31] do not recommend its use. In general, although the inter-observer reliability of the tests analyzed was at least “acceptable”, clinical interpretation leads us to believe that this level of reliability is too low for a test to be applied in isolation or independently [32]. In the same vein, the authors of this study advocate greater precision in clinical assessments. In contrast, intra-observer reliability not only showed homogeneity between the two analyses performed, but they were all “excellent”. Thus, they seem to be useful tools as long as the same therapist monitors the patient. It is difficult to get different therapists to agree on the pressure to be applied or degrees of mobility to be detected, and these tests are more useful when only one therapist applies them [51]. About the relationships among functional assessment methods: Prediction capacity of questionnaires To find scientific evidence on the relationship among functional assessment questionnaires [24,27] or among physical tests [32] is not uncommon. However, this is not the case among questionnaires and physical tests, especially for PFP. This research complemented its results in a new way with statistics linking these two types of PFP assessment methods. Thus, four of the physical tests analyzed, patellar palpation,patellar tilt,Clarke and squat, showed statistically significant relationships with the questionnaires. The relationship was logically with all questionnaires, given the strong correlation among them, i.e., subjects with high scores on the questionnaires would probably get negative tests. In fact, all values obtained were p<0.001 except for the patellar tilt, possibly due to their "acceptable" inter-observer reliability values. Statistically significant results were also found regarding the specific items analysed associated with the squat test, the patellar tilt test and the Clarke test. The item associated with patellar tilt, "Flexion deficiency" (KPS-13) was the least significant. A positive result of this would imply a patella attached to the femur, and consequently stiffness, although clinically there are other factors such as the misalignment of the patella, its morphology or the inflammation of the knee itself which can also influence this stiffness [17]. As for the items associated with the squat test and the Clarke test, both stood out positively. On the one hand, squat-related items: “Rising from sitting” (KOOS-PF-4), “Squatting” (KOOS-PF6), “Stairs” (KPS-4), “Squatting” (KPS-5), “Do you have pain walking down stairs with a normal gait cycle?”(VISA-P-2) and “Do you have problems squatting?”(VISA-P-5); clearly involved knee flexion-extension under load. On the other hand, the Clarke-related item, “Do you have pain at the knee with full active non weight bearing knee extension?”(VISA-P-3) generates an open kinetic chain contraction of the quadriceps to full extension causing the patella to bind to the femur, as well as aggressive rubbing [39]. In an innovative way, the results of this study showed cut-off points in the scores of the questionnaires that led to negative results when applying the physical tests. Thus, the KPS cut-off points stood out as the highest (72.5–79.5) for predicting a negative test result. Likewise, it is striking that the questionnaire scores for patellar palpation and patellar tilt are always higher than for Clarke and squat. This could be because the latter two tests look for patellar involvement by gliding over the femoral groove (patellar tracking) with pain [39,40], as opposed to patellar tilt and patellar palpation. That is, our results match squat with Clarke, as well as clearly indicating that a person with mild impairment is more likely to score positive on Clarke and squat than on patellar tilt and patellar palpation. In relation to the predictive capacity of the questionnaires, squat was the most predictable physical test for both positive and negative results. Moreover, all three questionnaires were PLOS ONE Functional valuation of patellofemoral pain PLOS ONE | https://doi.org/10.1371/journal.pone.0302215 April 17, 2024 16 / 23 good at predicting only negative results in the Clarke test; and KOOS-PF and KPS were good at predicting only positive results in patellar palpation. As the results on the relationships between assessment methods showed (see above), patellar tilt was the most difficult to predict. Finally, it should be noted that no single questionnaire was able to accurately predict the physical tests as a whole, i.e. the positive and negative results for patellar palpation,patellar tilt,Clarke and squat. In relation to the specific items, none was a good predictor of the physical test with which it was associated. This is striking in the items associated with the squat test. KOOS-PF-6, which asks for "Squatting" pain, is only adequate to predict negative test results; and KOOS-PF-4, which asks for "Rising from sitting" pain, does not correctly predict any results. The difference between them can be explained by the fact that KOOS-PF-4 assesses only concentric extension of the knee after a period of inactivity and knee flexion. In fact, these two items have a weak correlation between them, which justifies them both being in the same questionnaire. With regard to KOOS-PF-6, the results are especially striking as it asks for the squat test gesture. However, some subjects commented, regarding squats, that one squat would not hurt, but doing several in a row would, while others said that the pain decreased or disappeared as they did more. In KOOS-PF-4, the lack of good results could be due to the fact that only a concentric contraction of the quadriceps is performed in the eccentric phase when the amount of friction of the patella with the femur doubles and the cartilage suffers more pressure [52]. KPS-5, which asks about the functional limitation caused by squatting pain, and VISA-P-5 ("Do you have problems squatting?"), which addresses the intensity of pain in the same gesture, are excellent predictors of negative squat test results. It is possibly not a good predictor of positive results because, when translating both items into English, the term "squat" was replaced by "cuclillas", which is associated with a deep squat (maximum knee flexion), instead of "sentadilla", which implies only 90˚ flexion [40]; moreover, when squatting, the load is on the forefoot, increasing patellofemoral pressure more than in a squat. Therefore, they would not be optimal items for predicting a positive squat test result. Finally, two other items related to stairs were associated with squat test: pain ascending or descending "Stairs" (KPS-4); and "Do you have pain walking downstairs with a normal gait cycle?", asking for pain intensity (VISA-P-2). Although both refer to stairs, they differ in that one considers the ability to perform the task and the other the pain of performing the task. This is in addition to the aforementioned greater patellofemoral involvement when descending stairs compared to ascending stairs. Thus, an inverse correlation was found between the two items. Regarding predictive ability, both KPS-4 and VISA-P-2 were shown to be good predictors of good predictors for the squat test, but only for negative results, since squatting is a less aggressive activity for the patellofemoral joint than stairs. i.e., squatting carries bilateral loading within the base of support while ascending or descending stairs implies unilateral loading outside the base of support. As for VISA-P-3, “Do you have pain at the knee with full active non weight bearing knee extension?”, its association with the Clarke test was analysed as it is a gesture of quadriceps contraction in open kinetic chain up to full extension. However, it is not a good predictor of a positive Clarke test. We consider the Clarke test to be a significantly more severe test than the knee extension without pressure from the assessor, which is also very subjective. The inter-observer reliability median results of this study supported this idea. Predictive capacity of questionnaires on MRI-diagnosed CP grades Although this study assesses subjects with PFP in general, a representative subsample was diagnosed with CP by MRI. Thus, the relationships obtained between degrees of CP were assessed regarding the scores on the three questionnaires. No statistically or clinically significant differences were found between grades 0 and 1, in agreement with Thomas et al [22] and Flanigan PLOS ONE Functional valuation of patellofemoral pain PLOS ONE | https://doi.org/10.1371/journal.pone.0302215 April 17, 2024 17 / 23 et al [53], who considered MRI to be an inaccurate tool for the diagnosis of CP, especially for low grades [22]. However, we did find differences between grades 1 and above, i.e. 2 and even 3 and 4, with severe structural damage. Furthermore, there is evidence of low correlation between grades and symptoms [22], the latter associated with functional assessment questionnaires. Other recent evidence, 2020 [12], with a substantial sample size (n = 230), even found asymptomatic subjects with structural damage of the patellofemoral cartilage on MRI in 57% of cases. This would justify the poor relationship between the questionnaires and the MRIs. Consequently, the predictive ability of the questionnaires on CP grades set by this objective method was not particularly good. According to the previous paragraph, it was not possible to determine the relative predictive ability for the pair grades 0 and 1. For the pair 1 and greater than 1, only KOOS-PF and VISA-P had a relative predictive capacity. According to the cut-off points, scores below 53.4 and 48.5, respectively, predicted grades higher than 1. However, the 95% IC of the PPV was not adequate, so the predictive capacity for grade 1 should be considered with caution until a larger sample size is available. As with the results discussed in previous sections, this analysis yields new data that lead therapists to decide whether or not to apply certain methods, but also to encourage appropriate combinations among them, in this case among questionnaires and tests that, because of their relationship, confirm an assessment or diagnosis. This study advocates the efficiency of functional assessment questionnaires, although it understands that they are insufficient in this case as they are patient reported outcome measures (PROMs). That is, they provide information on symptomatology and only consider the subjectivity of the user. Similarly, specific physical tests do not consider the multifactorial aspect of PFP, as mentioned in the introduction, focusing primarily on the presence of pain. We believe it is essential to collect information on the factors that influence the development of the pathology. Thus, a holistic and individualized assessment would allow the establishment of medical (i.e. pharmacological, surgical), orthopaedic (insoles, knee braces) and physiotherapeutic (i.e. electrotherapy, massage therapy, therapeutic taping, therapeutic exercise) goals and procedures, associated both to the symptomatology and to the possible existing structural damage, but also to the factors that work against PFP. For example, if there is patellar hypermobility due to quadriceps weakness, this muscle should be strengthened. Or if there is patellar lateralisation caused by asymmetry between the muscle tone of the vastus externus and quadriceps internus or retraction of either of them, they should be balanced to re-centre the patella. In this way, the functional recovery of the user would be optimized and aggravations, relapses and sequelae could be prevented. Association among functional assessment methods, Q-angle, gender and height Although the cluster analysis included all methods of functional assessment, the presence of physical tests prevented the clusters from being appropriate, and therefore logical. Therefore, the statistical test ruled them out. This fact, together with the associations obtained between the questionnaires, gender, height and Q-angle, led us to believe that the questionnaires assessed are more reliable methods to be applied in PFP and/or CP. Thus, the results clearly indicated a differentiation by gender and height. Both variables, according to authors such as Kasitinon et al [54], influence the Q-angle, and this in turn, the patellofemoral involvement. Men are associated with a lower Q-angle than women and tall people are associated with a smaller Q-angle than short people [54]. As for the three clusters generated, two of them (clusters 1 and 3) included subjects with healthier outcomes according PLOS ONE Functional valuation of patellofemoral pain PLOS ONE | https://doi.org/10.1371/journal.pone.0302215 April 17, 2024 18 / 23 to the scores of all questionnaires. One of the groups obtained consisted of relatively tall men and therefore with a reduced Q-angle (cluster 1). The other two groups were made up of women, with the taller women (cluster 3) having a lower Q-angle than the shorter women (cluster 2). However, the group of men (taller than tall women) had a smaller Q-angle than tall women. These findings would also enable practitioners to predict the trend of questionnaire scores, i.e. intensity of symptomatology, from simple anthropometric data linked to gender. Consequently, this information would make it easier to prevent an unfavourable evolution of the pathology, especially in early stages. Regarding the strengths of the study, questionnaires that, although validated, did not have cross-cultural adaptations in Spanish were excluded, while maintaining an appropriate level of methodological quality. In fact, this led to a limitation, namely the exclusion of validated and specific questionnaires in common use. Prospectively, other cross-cultural adaptations of questionnaires of scientific interest should be carried out, both into Spanish and other languages. Furthermore, this study suggests the creation of assessment protocols that take into account factors that negatively influence PFP, enabling them to be minimized during the functional recovery process. Finally, the results obtained in the analysis regarding MRI-mediated CP grades should be treated with caution due to the size of the subsample (see above). On the basis of this new limitation, we propose the consideration of a large sample that provides robust evidence. Conclusions Regarding the questionnaires, KOOS-PF, KPS and VISA-P demonstrated their diagnostic value in “patellofemoral pain” and/or “chondromalacia patella”, based on their validity, reliability, sensitivity, specificity, predictive value and clinical applicability. All of them showed their predictive capacity and logical groupings by clusters, with respect to gender, height and Q-angle. Taller women were associated with a higher Q-angle and higher scores on all questionnaires. No single questionnaire could accurately predict all physical tests in their entirety, i.e., the positive and negative results of patellar palpation,patellar tilt,Clarke and squat. KOOS-PF and KPS were better overall predictors of the physical tests, although KOOS-PF was more demanding due to its lower cut-off points, and therefore more suitable for mild symptomatology and functional limitations. All three were suitable predictors of negative squat and Clarke tests. They were also good predictors of chondromalacia patella grades by magnetic resonance imaging, with KOOS-PF and VISA P being better predictors of grades greater than one, with intermediate cut-off points. Although the questionnaires analysed were found to be clinically feasible, KOOS-PF appeared to be the most versatile of the three, and, in general, the most appropriate in mild cases and for early detection and prevention. KPS is the most advisable in severe cases. With regard to the physical tests, the squat test was the most appropriate and stood out positively for its reliability and its clinical relationship with the questionnaires, which predicted it correctly. However, of the items associated with it, not even the one that asks directly about pain with such a gesture, KOOS-PF-6, offered good predictive capacity for negative test results. For this reason, and because the other physical tests are not fully predicted by the questionnaires, we suggest that all physical tests be complemented by at least one assessment questionnaire, choosing the most appropriate according to the context. PLOS ONE Functional valuation of patellofemoral pain PLOS ONE | https://doi.org/10.1371/journal.pone.0302215 April 17, 2024 19 / 23 Furthermore, with the exception of the squat test, it should preferably be applied by a single examiner according to the levels of inter-observer reliability found, or at least be complemented by other methods. This study also advocates improving, clarifying and unifying the definitions and interpretations of the physical tests, especially the squat test, and the items associated with this gesture, in order to achieve results with greater scientific rigour. Height, Q-angle and gender are simple data that can predict and prevent the unfavourable evolution of the pathology, especially in the early stages. In general, functional assessment methods, although specific to PFP, should be applied by combining them with each other. They should also be complemented by data on PFP influencing factors. Moreover, imaging tests could be useful if structural damage to the cartilage is suspected. Supporting information S1 Data. Matrix including outcomes about study variables. (XLSX) Acknowledgments The authors would like to thank the Research Group “Area of Physiotherapy CTS-305” of the University of Seville, Spain; for its contribution in this study. Author Contributions Conceptualization: Gema Chamorro-Moriana, Carmen Ridao-Ferna ´ndez. Data curation: Fernando Espuny-Ruiz, Carmen Ridao-Ferna ´ndez. Formal analysis: Fernando Espuny-Ruiz, Eleonora Magni. Investigation: Gema Chamorro-Moriana, Eleonora Magni. Methodology: Gema Chamorro-Moriana, Eleonora Magni. Project administration: Fernando Espuny-Ruiz, Carmen Ridao-Ferna ´ndez. Resources: Gema Chamorro-Moriana, Carmen Ridao-Ferna ´ndez. 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