Structural Foot Characteristics in People With Midfoot Osteoarthritis: Cross-Sectional Findings From the Clinical Assessment Study of the Foot.

OBJECTIVE: This study compared radiographic measures of foot structure between people with and without symptomatic radiographic midfoot osteoarthritis (OA). METHODS: This was a cross-sectional study of adults aged 50 years and older registered with four UK general practices who reported foot pain in the past year. Bilateral weightbearing dorsoplantar and lateral radiographs were obtained. Symptomatic radiographic midfoot OA was defined as midfoot pain in the last 4 weeks, combined with radiographic OA in one or more midfoot joints (first cuneometatarsal, second cuneometatarsal, navicular-first cuneiform, and talonavicular). Midfoot OA cases were matched 1:1 for sex and age to controls with a 5-year age tolerance. Eleven radiographic measures were extracted and compared between the groups using independent sample t-tests and effect sizes (Cohen's d). RESULTS: We identified 63 midfoot OA cases (mean ± SD age was 66.8 ± 8.0 years, with 32 male and 31 female participants) and matched these to 63 controls (mean ± SD age was 65.9 ± 7.8 years). There were no differences in metatarsal lengths between the groups. However, those with midfoot OA had a higher calcaneal-first metatarsal angle (d = 0.43, small effect size, P = 0.018) and lower calcaneal inclination angle (d = 0.46, small effect size, P = 0.011) compared with controls. CONCLUSIONS: People with midfoot OA have a flatter foot posture compared with controls. Although caution is required when inferring causation from cross-sectional data, these findings are consistent with a pathomechanical pathway linking foot structure to the development of midfoot OA. Prospective studies are required to determine the temporal relationships between foot structure, function, and the development of this common and disabling condition.

Plantar pressures in people with midfoot osteoarthritis: cross-sectional findings from the Clinical Assessment Study of the Foot.

BACKGROUND: Midfoot osteoarthritis (OA) is a common condition, however its aetiology is not well understood. Understanding how plantar pressures differ between people with and without midfoot OA may provide insight into the aetiology and how best to manage this condition. RESEARCH QUESTION: To compare plantar pressures between people with and without symptomatic radiographic midfoot OA. METHODS: This was a cross-sectional study of adults aged ≥ 50 years registered with four UK general practices who reported foot pain in the past year. Symptomatic radiographic midfoot OA was defined as midfoot pain in the last four weeks, combined with radiographic OA in one or more midfoot joints. Cases were matched 1:1 for sex and age ( ± 5 years) to controls. Peak plantar pressure and maximum force in 10 regions of the foot were determined using a pressure platform (RSscan International, Olen, Belgium) and compared between the groups using independent samples t-tests and effect sizes (Cohen's d). RESULTS: We included 61 midfoot OA cases (mean age 67.0, SD 8.1, 31 males, 30 females) and matched these to 61 controls (mean age 66.0, SD 7.9). Midfoot OA cases displayed greater force (d=0.79, medium effect size, p = <0.001) and pressure at the midfoot (d=0.70, medium effect size, p = <0.001), greater force at the fourth metatarsophalangeal (MTP) joint (d=0.28, small effect size, p = 0.13), and fifth MTP joint (d=0.37, small effect size, p = 0.10) and greater pressure at the fifth MTP joint (d=0.34, small effect size, p = 0.13). They also displayed lower force (d=0.40, small effect size, p = 0.02) and pressure at the hallux (d=0.50, medium effect size, p = <0.001) and lower force (d=0.54, medium effect size, p = <0.001) and pressure at the lesser toes (d=0.48, small effect size, p = <0.001) compared with controls. SIGNIFICANCE: Midfoot OA appears to be associated with lowering of the medial longitudinal arch, greater lateral push off and less propulsion at toe off. Longitudinal studies are needed to establish causal relationships.

A scoping review of patient self-report measures of flare in knee and hip osteoarthritis (OA): A report from the OMERACT flares in OA working group.

PURPOSE: We aimed to analyze the content validity/domain match and feasibility of self-report instruments that could measure flare in osteoarthritis (OA), by extending our 2017 literature review on the definition of flare in knee and hip OA. METHOD: We searched PubMed (Medline), Web of Science and PsycInfo (Ebsco Host) databases for original articles reporting research about flare (or synonyms) in humans with knee and hip OA, between 2017 and 2023. Four experts worked independently, checking the records, and assessing content validity and feasibility, writing justification for exclusion. RESULTS: At literature review phase, 575 papers were filtered. After experts' analysis, 59 studies were included, and 44 instruments associated with flare in OA were identified. Most were studies about pain in knee or hip OA (35 %), cultural adaptation of a measure (33 %) or studies investigating psychometric properties of full (16 %) or short form (4 %) instruments. The assessment of domain match and feasibility revealed that 15 instruments were assigned a label of 'yes' or 'uncertain' as to whether or not there was a good match with the domain concept or whether the instrument was considered feasible to use. DISCUSSION: Most identified instruments considered different aspects of pain and the associated discomfort in performing daily activities but did not include the central aspects of flare in OA, i.e. the change of state, nor the additional Outcome Measures in Rheumatology (OMERACT) endorsed domains for OA flare namely stiffness, swelling, psychological aspects, impact of symptoms including fatigue and sleep disturbance. Although it is possible that the period specified to conduct this literature review may have led to some recognized instruments being excluded, this review demonstrates the need for the research community to reach consensus on the best way to measure self-reported flares in future clinical trials and observational studies.

An Evaluation of Different Strategies for Sampling Controls in an Online Case-Crossover Study of Acute Flares in Knee Osteoarthritis.

Objective: To evaluate bias and precision of exposure-outcome effect estimates from three control sampling strategies in a case-crossover study. Methods: Online case-crossover study investigating eight physical activity-related triggers for acute flares in knee osteoarthritis. Exposures were measured in hazard periods (≤24 hours before self-declared flare onset). Control period exposure was measured in three ways: (1) four scheduled questionnaires over 13-weeks, (2) "usual" physical activity levels ascertained at baseline, (3) over three days before flare onset. Derived odds ratios, 95% confidence intervals and standard errors were compared. Results: Of 744 participants (mean age 62.1 [SD 10.2] years; 61% female), 493 reported 714 flares. Selecting controls from scheduled questionnaires, independent of hazard periods, yielded predominantly odds ratios in the expected direction (exposure "a lot" versus exposure "not at all", range: 0.57-3.22). When controls were sampled at baseline (range: 0.01-1.42) or immediately before a flare (range: 0.30-1.27) most odds ratio estimates were inverted. Standard errors of the log odds ratios were smallest when controls were sampled from scheduled questionnaires (range: 0.264-0.473) compared to controls sampled at baseline (range: 0.267-0.589) or immediately before a flare (range: 0.319-0.621). Conclusion: Our findings are sensitive to control sample selection. Under certain conditions, different patterns could be attributed to over reporting and social desirability bias, where people may want to present themselves more positively about their "usual" physical activity levels, at baseline. Exposure measurement at the time of a flare may be less precise and more susceptible to recall bias due to systematically reporting exposures differently during a flare, compared to control measurement independent of flares.

Identifying Long-Term Trajectories of Foot Pain Severity and Potential Prognostic Factors: A Population-Based Cohort Study.

OBJECTIVES: To identify distinct foot pain trajectories over 7 years and examine their associations with potential prognostic factors. METHODS: Adults ages ≥50 years and registered with 4 general practices in North Staffordshire, UK were mailed a baseline health survey. Those reporting current or recent foot pain were invited to attend a research assessment clinic. Follow-up was by repeated postal surveys at 18, 36, 54, and 84 months. Distinct trajectories of foot pain were explored using latent class growth analysis (LCGA). Subsequently, identified trajectories were combined into most and least progressive groups, and covariate-adjusted associations with a range of prognostic factors were examined. RESULTS: Of 560 adults with foot pain attending baseline research clinics, 425 (76%) provided data at baseline and 2 or more follow-up time points. LCGA for foot pain severity (0-10 numerical rating scale) identified a 4-trajectory model: "mild, improving" (37%); "moderate, improving" (33%); "moderate-severe, persistent" (24%); and "severe, persistent" (6%). Compared with individuals in more favorable (improving) pain trajectories, those in less favorable (persistent) pain trajectories were more likely to be obese, have routine/manual and intermediate occupations, have poorer physical and mental health, have catastrophizing beliefs, have greater foot-specific functional limitation, and have self-assessed hallux valgus at baseline. CONCLUSIONS: Four distinct trajectories of foot pain were identified over a 7-year period, with one-third of individuals classified as having pain that is persistently moderate-severe and severe in intensity. The effect of intervening to target modifiable prognostic factors such as obesity and hallux valgus on long-term outcomes in people with foot pain requires investigation.

Incidence and Progression of Hallux Valgus: A Prospective Cohort Study.

OBJECTIVE: Hallux valgus is a common and disabling condition. The objective of the present study was to identify factors associated with hallux valgus incidence and progression. METHODS: Participants were from a population-based prospective cohort study, the Clinical Assessment Study of the Foot. All adults ages ≥50 years who were registered at 4 general practices in North Staffordshire, UK, were invited to take part in a postal survey at baseline and at 7-year follow-up, which included health questionnaires and self-assessment of hallux valgus using line drawings. RESULTS: Complete baseline and follow-up data were available for 1,482 participants (739 women and 743 men, mean ± SD age 62.9 ± 8.1 years), of whom 450 (30.4%) had hallux valgus in at least 1 foot at baseline. Incident hallux valgus was identified in 207 (20.1%) participants (349 [15.4%] feet) and was associated with baseline age, poorer physical health, foot pain, and wearing shoes with a very narrow toe-box shape between the ages of 20 and 29 years. Hallux valgus progression was identified in 497 (33.6%) participants (719 [24.3%] feet) but was not associated with any baseline factors. CONCLUSION: Incident hallux valgus develops in 1 in 5 adults ages ≥50 years over a 7-year period and is related to age, poorer physical health, foot pain, and previous use of constrictive footwear. Progression occurs in 1 in 3 adults. These findings suggest that changes in first metatarsophalangeal joint alignment may still occur beyond the age of 50 years.

Prediction Models to Estimate the Future Risk of Osteoarthritis in the General Population: A Systematic Review.

OBJECTIVE: To evaluate the performance and applicability of multivariable prediction models for osteoarthritis (OA). METHODS: This was a systematic review and narrative synthesis using 3 databases (EMBASE, PubMed, and Web of Science) from inception to December 2021. We included general population longitudinal studies reporting derivation, comparison, or validation of multivariable models to predict individual risk of OA incidence, defined by recognized clinical or imaging criteria. We excluded studies reporting prevalent OA and joint arthroplasty outcome. Paired reviewers independently performed article selection, data extraction, and risk-of-bias assessment. Model performance, calibration, and retained predictors were summarized. RESULTS: A total of 26 studies were included, reporting 31 final multivariable prediction models for incident knee (23), hip (4), hand (3) and any-site OA (1), with a median of 121.5 (range 27-12,803) outcome events, a median prediction horizon of 8 years (range 2-41), and a median of 6 predictors (range 3-24). Age, body mass index, previous injury, and occupational exposures were among the most commonly included predictors. Model discrimination after validation was generally acceptable to excellent (area under the curve = 0.70-0.85). Either internal or external validation processes were used in most models, although the risk of bias was often judged to be high with limited applicability to mass application in diverse populations. CONCLUSION: Despite growing interest in multivariable prediction models for incident OA, focus remains predominantly on the knee, with reliance on data from a small pool of appropriate cohort data sets, and concerns over general population applicability.

Osteoarthritis Flares.

The phenomenon of flares is a common feature in the daily life of people with osteoarthritis (OA). Characterized by episodes of sudden-onset increases in signs and symptoms, their impact can often be distressing and disabling. Despite their potential to have both short-term and long-term consequences for patients across the whole course of the condition, their occurrence and optimal management are not fully understood. This article provides a contemporary perspective on defining OA flares and their potential triggers, and offers suggestions for how health professionals might explore flare patterns with patients in clinical practice and frame timely best-practice treatment approaches.

Identification of Radiographic Foot Osteoarthritis: Sensitivity of Views and Features Using the La Trobe Radiographic Atlas.

OBJECTIVE: To compare the sensitivity of alternative case finding approaches for the identification of foot osteoarthritis (OA) based on the La Trobe radiographic atlas. METHODS: This was a cross-sectional study of 533 adults age ≥50 years with foot pain in the past year. Weightbearing dorsoplantar (DP) and lateral radiographs were taken of both feet. The La Trobe radiographic atlas was used to document the presence of osteophytes (OPs) and joint space narrowing (JSN). The prevalence of OA in each joint was documented using both views and features in combination (as recommended in the original atlas), and by using a single view (DP or lateral only) and a single feature (OP or JSN only). RESULTS: Compared to the recommended case definition based on OPs and JSN using both views, a DP-only view identified between 15% and 77% of OA cases, while a lateral-only view identified between 28% and 97% of OA cases. Compared to the recommended case definition of using both features, using only OPs identified between 46% and 94% of OA cases, while using only JSN identified between 19% and 76% of OA cases. CONCLUSION: Applying the La Trobe radiographic atlas but using only 1 radiograph view (DP or lateral) or 1 feature (OP or JSN) in isolation misses a substantial number of OA cases, and the sensitivity of these approaches varies considerably between different foot joints. These findings indicate that, where possible, the atlas should be administered according to the original description to avoid under-ascertainment of radiographic foot OA.

Best-practice clinical management of flares in people with osteoarthritis: A scoping review of behavioral, lifestyle and adjunctive treatments.

INTRODUCTION: Transient episodes of increased pain, stiffness or swelling are common in people with osteoarthritis (OA). Yet, evidence-based management strategies for lessening the impact of OA flares are rarely covered in clinical guidelines and have been identified as a gap by clinicians delivering OA care. We aimed to identify evidence on behavioral, lifestyle or other adjunctive flare management strategies that could be used by clinicians or consumers. MATERIALS AND METHODS: A literature search between 1990-2020 was performed in three databases using a scoping methodology. We included qualitative or quantitative studies, and reviews that examined OA flare management, or that reported OA flare outcomes at timepoints ≤2 weeks post-intervention. Outcomes included any physical or psychological OA outcome treatable with a therapeutic intervention. RESULTS: We included 9 studies, all of which examined the relationship between therapeutic exercise/ physical activity and OA flares. All studies reported pain outcomes at the knee. Two also included the hip. Only two studies examined specific management strategies for OA flares. Both favorably reported the benefits of undertaking an exercise program modified accordingly during an episode, but the quality of the evidence was low. DISCUSSION: This scoping review highlights the paucity of evidence available on non-pharmacological treatments of OA flare management that could influence clinical practice. At present, there is no robust evidence to support or reject any specific therapies for OA flare management in clinical practice. Future work is needed, particularly around outcomes beyond pain, trajectories of symptom improvement, and for joints other than the knee.

Self-management advice, exercise and foot orthoses for plantar heel pain: the TREADON pilot and feasibility randomised trial.

BACKGROUND: Plantar heel pain (PHP) is common and impacts negatively on physical function and quality of life. Initial treatment usually comprises analgesia and self-management advice (SMA), with referral to a physiotherapist or podiatrist recommended only when symptoms persist. Systematic reviews highlight limitations of existing evidence for the effectiveness of exercises and orthoses. The objective of the TREADON pilot and feasibility trial was to inform the design of a future main trial to compare the clinical and cost-effectiveness of self-management advice (SMA), individualised exercises and foot orthoses for PHP. METHODS: This was a four-arm randomised feasibility and pilot trial with 12-week follow-up. Adults aged ≥ 18 years with PHP were identified from primary care by general practice consultation, retrospective general practice medical record review or a population survey. Participants were randomised to either (i) SMA, (ii) SMA plus individualised exercises (SMA-exercises), (iii) SMA plus prefabricated foot orthoses (SMA-orthoses) or (iv) SMA plus combined individualised exercises and prefabricated foot orthoses (SMA-combined). Feasibility outcomes were recruitment; retention; intervention adherence, credibility and satisfaction; performance of three potential primary outcome measures (pain numeric rating scale (NRS), Foot Function Index-pain subscale (FFI-pain), Manchester Foot Pain and Disability Index-pain subscale (MFPDI-pain)); and parameters for informing the main trial sample size calculation. RESULTS: Eighty-two participants were recruited. All three identification methods met the target number of participants. Retention at 12 weeks was 67%. All interventions were successfully delivered as per protocol. Adherence (range over 12 weeks 64-100%) and credibility (93%) were highest in the SMA-combined arm. Satisfaction with treatment was higher for the three clinician-supported interventions (SMA 29%, SMA-exercises 72%, SMA-orthoses 71%, SMA-combined 73%). Responsiveness (baseline to 12 weeks) was higher for FFI-pain (standardised response mean 0.96) and pain NRS (1.04) than MFPDI-pain (0.57). Conservative sample size parameter estimates for standard deviation were pain NRS 2.5, FFI-pain 25 and MFPDI-pain 4, and baseline-outcome correlations were 0.5-0.6, 0.4 and < 0.3, respectively. CONCLUSIONS: We demonstrated the feasibility of conducting a future main randomised clinical trial comparing the clinical and cost-effectiveness of SMA, exercises and/or foot orthoses for PHP. TRIAL REGISTRATION NUMBER: ISRCTN 12160508 . Prospectively registered 5th July 2016.

Identification of patterns of foot and ankle pain in the community: Cross-sectional findings from the clinical assessment study of the foot.

OBJECTIVES: To investigate patterns of foot and ankle pain locations and symptoms, socio-demographic and comorbid characteristics to examine whether there are distinct foot and ankle pain phenotypes. METHODS: Adults aged ≥50 years registered with four general practices in North Staffordshire were mailed a Health Survey questionnaire. Participants reporting foot pain in the last month indicated foot pain location on a foot manikin. Foot and ankle pain patterns were investigated by latent class analysis. Associations between the classes with foot pain symptoms, socio-demographic and comorbid characteristics were assessed. RESULTS: Four thousand four hundred fifty-five participants with complete foot pain and manikin data were included in this analysis (mean age 65 years [SD 9.8], 49% male). Of those with foot and ankle pain (n = 1356), 90% had pain in more than one region. Six distinct classes of foot and ankle pain were identified: no pain (71%), bilateral forefoot/midfoot pain (4%), bilateral hindfoot pain (5%), left forefoot/midfoot pain (8%), right forefoot/midfoot pain (5%) and bilateral widespread foot and ankle pain (6%). People with bilateral widespread foot and ankle pain were more likely to be female, obese, depressed, anxious, have/had a manual occupation, have comorbidities, lower SF-12 scores and greater foot-specific disability. Age did not differ between classes. CONCLUSIONS: Six distinct classes of foot and ankle pain locations were identified, and those with bilateral widespread foot and ankle pain had distinct characteristics. Further investigation of these individuals is required to determine if they have poorer outcomes over time and whether they would benefit from earlier identification and treatment.

Hallux valgus severity, great toe pain, and plantar pressures during gait: A cross-sectional study of community-dwelling adults.

BACKGROUND: Hallux valgus (HV) is a common disabling condition affecting 36% of adults aged 65 years and over. Identifying whether the severity of the deformity alters weight-bearing patterns during walking may assist clinicians optimize offloading interventions. Therefore, we examined how plantar pressure distributions during walking are affected by HV severity. METHODS: Plantar pressures and maximum forces in ten regions of the foot were obtained from 120 participants (40 men, 80 women) aged ≥50 years using a pressure platform (RSscan® International, Olen, Belgium). HV severity was documented using a validated line-drawing instrument with participants separated into four groups: none (n = 30), mild (n = 30), moderate (n = 30) and severe (n = 30). Pressure and force values were compared across HV severity, stratified by the presence or absence of great toe pain. RESULTS: Participants with severe HV were more likely to have great toe pain. More severe HV was associated with significant reductions in peak pressure and maximum force under the hallux but not at other sites of the foot. This association appeared strongest in those reporting great toe pain. CONCLUSIONS: Greater HV severity is associated with great toe pain and reduced loading under the hallux when walking. These observed changes in plantar pressure and maximum force may reflect a pain avoidance mechanism.

Relative prevalence and distribution of knee, hand and foot symptomatic osteoarthritis subtypes in an English population.

In this brief report, we used data from a series of three related cohorts on pain and osteoarthritis (OA) of the knee, hand and foot, which were conducted in North Staffordshire, England. We used a common approach for sampling, data collection and coding, to estimate the relative prevalence of 10 different symptomatic radiographic OA subtypes in the knee, hand and foot and to compare their association with age, sex, socioeconomic position and body mass index. Overall, symptomatic hand OA was more common than knee or foot OA (22.4% vs 17.4% vs 16.5%), due mainly to the high prevalence of nodal interphalangeal joint OA among women. The first carpometacarpal joint OA was the most frequent subtype, with patellofemoral, tibiofemoral, (nodal) interphalangeal and midfoot OA also common. Of the risk factors examined, the greatest differences between subtypes appeared to be their associations with sex and obesity: sex differences were noticeably greater for all forms of hand OA except non-nodal interphalangeal joint OA, while obesity appeared most strongly associated with forms of knee OA. The prevalence of all subtypes was higher among older ages, and among those with lower educational attainment.

Associations Between Calcaneal Enthesophytes and Osteoarthritis of the Hands and Feet.

OBJECTIVE: To examine associations between calcaneal enthesophytes and osteoarthritis (OA) in the hands and feet, and to provide insights into the role of biomechanical and systemic processes in the development of OA. METHODS: Adults ages ≥50 years who were registered with 4 general practices were mailed a Health Survey. Responders reporting foot pain within the last 12 months underwent a detailed assessment, including hand and foot radiographs. Calcaneal enthesophytes (plantar and posterior) and OA features (osteophytes and joint space narrowing) were documented. Associations between enthesophytes and hand and foot OA (including OA phenotypes and OA features at individual joints) were explored using generalized estimating equations, adjusting for age, sex, and body mass index. RESULTS: Data were available from 532 participants (298 women, mean ± SD age 64.9 ± 8.4 years). Calcaneal enthesophytes were not associated with hand OA phenotypes or OA at individual hand joints. In contrast, plantar calcaneal enthesophytes were positively associated with polyarticular foot OA (odds ratio [OR] 1.80 [95% confidence interval (95% CI) 1.02-3.17]). When individual foot joints were examined, posterior enthesophytes were associated with talonavicular joint OA (OR 1.58 [95% CI 1.02-2.44]) and plantar enthesophytes were associated with first metatarsophalangeal joint OA (OR 0.67 [95% CI 0.49-0.98]) and navicular-cuneiform joint OA (OR 2.30 [95% CI 1.40-3.79]). Patterns of association were similar for osteophytes and joint space narrowing. CONCLUSION: Calcaneal enthesophytes are associated with foot OA but not hand OA. The pattern of association is indicative of a local, biomechanical rather than systemic bone-forming process.

Risk factors for episodes of back pain in emerging adults. A systematic review.

BACKGROUND AND OBJECTIVE: The transition from adolescence to adulthood is a sensitive period in life for health outcomes, including back pain. The objective was to synthesize evidence on risk factors for new episodes of back pain in emerging adults (18-29 years). METHODS: The protocol was registered in PROSPERO (CRD42016046635). We searched Medline; EMBASE; AMED and other databases up to September 2018 for prospective cohort studies that estimated the association between risk factor(s) and self-reported back pain. Risk factors could be measured before or during the age range 18-29 years, and back pain could be measured during or after this age range, with at least 12 months between assessments. Risk factors assessed in ≥3 studies were summarized. Risk of bias was assessed using a 6-item checklist. RESULTS: Forty-nine studies were included with more than 150 different risk factors studied. Nine studies had low risk of bias, 26 had moderate and 14 had high risk of bias. Age, sex, height, body mass index (BMI), smoking, physical activity level, a history of back pain, job satisfaction and structural imaging findings were investigated in three or more studies. History of back pain was the only risk factor consistently associated with back pain after adjustment (nine studies). CONCLUSION: There is moderate quality evidence that a history of back pain is a risk factor for back pain. There are inconsistent associations for age, sex, height, BMI, smoking and activity level. No associations were found between job satisfaction and structural imaging findings and back pain. SIGNIFICANCE: Emerging adulthood is a transitional period of life with changes in life style, potentially influencing future musculoskeletal health. This systematic review included 49 articles evaluating more than 150 potential risk factors for back pain, one of the most prevalent musculoskeletal disorders. No consistent results were found for life style factors such as physical activity level or BMI, both highlighted as important risk factors in previous literature. Importantly, a previous episode of back pain was a consistent risk factor for a new episode of back pain across several studies, and further investigation of risk factors for the first back pain episode is needed.

Short-Term Recovery Trajectories of Acute Flares in Knee Pain: A UK-Netherlands Multicenter Prospective Cohort Analysis.

OBJECTIVE: To identify distinct recovery trajectories of acute flares of knee pain and associated participant characteristics. METHODS: Data were from the FLARE randomized controlled trial, a multicenter trial in 27 primary care centers in the UK and Netherlands of 3 regimes of oral nonsteroidal antiinflammatory therapy for acute flares of knee pain. Individuals with a history of inflammatory/crystal arthritis, fibromyalgia, and chronic pain syndrome were excluded. Latent class growth analysis was applied to measures of pain intensity repeated over 5 days to identify distinct recovery trajectories. The concurrent courses of interference with activity, stiffness, and swelling for each trajectory group were modelled using generalized estimating equations. Participant age, sex, obesity, and osteoarthritis diagnosis were described for each trajectory group. RESULTS: A total of 449 participants were included (median age 55 years, 41% female, 35% obese, and 42% diagnosed with osteoarthritis). A 6-group cubic model was deemed optimal, with trajectories distinguished by rate of pain reduction and absolute level at final measurement. At the extremes were rapid and near-complete resolution (n = 41, 9%) and persistent, high pain (n = 25, 6%), but most participants showed a reduction and plateau in pain severity within 3-5 days. Within each pain trajectory group, interference with activity, stiffness, and swelling followed the same course as pain. Baseline characteristics did not differ substantially between trajectory groups. CONCLUSION: Even under a well-adhered to regime of oral nonsteroidal antiinflammatory medication, recovery following acute flares of knee pain is heterogeneous. Our observations that favorable trajectories are apparent within 3-5 days can help to inform treatment decision-making in the patient-health care professional consultation.