Arthroscopic partial meniscectomy vs non-surgical or sham treatment in patients with MRI-confirmed degenerative meniscus tears: a systematic review and meta-analysis with individual participant data from 605 randomised patients.

OBJECTIVE: To identify subgroups of patients with magnetic resonance imaging (MRI)-confirmed degenerative meniscus tears who may benefit from arthroscopic partial meniscectomy (APM) in comparison with non-surgical or sham treatment. METHODS: Individual participant data (IPD) from four RCTs were pooled (605 patients, mean age: 55 (SD: 7.5), 52.4% female) as to investigate the effectiveness of APM in patients with MRI-confirmed degenerative meniscus tears compared to non-surgical or sham treatment. Primary outcomes were knee pain, overall knee function, and health-related quality of life, at 24 months follow-up (0-100). The IPD were analysed in a one- and two-stage meta-analyses. Identification of potential subgroups was performed by testing interaction effects of predefined patient characteristics (e.g., age, gender, mechanical symptoms) and APM for each outcome. Additionally, generalized linear mixed-model trees were used for subgroup detection. RESULTS: The APM group showed a small improvement over the non-surgical or sham group on knee pain at 24 months follow-up (2.5 points (95% CI: 0.8-4.2) and 2.2 points (95% CI: 0.9-3.6), one- and two-stage analysis, respectively). Overall knee function and health-related quality of life did not differ between the two groups. Across all outcomes, no relevant subgroup of patients who benefitted from APM was detected. The generalized linear mixed-model trees did also not identify a subgroup. CONCLUSIONS: No relevant subgroup of patients was identified that benefitted from APM compared to non-surgical or sham treatment. Since we were not able to identify any subgroup that benefitted from APM, we recommend a restrained policy regarding meniscectomy in patients with degenerative meniscus tears.

Changes in physical activity and the association between pain and physical activity - a longitudinal analysis of 17,454 patients with knee or hip osteoarthritis from the GLA:D® registry.

OBJECTIVE: Investigate change in physical activity following an 8-week education and exercise therapy program for patients with knee/hip osteoarthritis, focusing on those with low physical activity level. Furthermore, to evaluate associations between changes in pain intensity and physical activity. METHOD: Data from the Good Life with osteoArthritis in Denmark (GLA:D®) registry, at baseline, immediately after completion, and 12 months after entering the program was used. Measures of interest were UCLA activity scale (1-10) and Visual Analog Scale for pain intensity (0-100 mm). Changes in physical activity levels (low 1-4, moderate 5-6, and high 7-10) over three time points were investigated. Asymmetric fixed effects regression models were used to evaluate the association between clinically relevant change in pain (≥15 mm) and change in physical activity level from baseline to 12 months. RESULTS: 37% with low activity level at baseline (n = 4,836) and 69% of all patients (n = 17,454) reached or maintained at least a moderate physical activity level at follow-ups. Surprisingly, both an improvement (ß = 1.44, P < 0.001) and a worsening (ß = 1.18, P < 0.001) in pain intensity was associated with increased physical activity in low activity patients. For all patients a similar trend was observed (ß = 0.51, P < 0.001 and ß = 0.11, P = 0.215, respectively). CONCLUSION: In low active knee or hip OA patients, a third of patients participating in an education and exercise therapy program reached and maintained at least a moderate physical activity level for 1 year. The improvement in physical activity was not dependent on pain reduction.

Chronic opioid use before and after exercise therapy and patient education among patients with knee or hip osteoarthritis.

OBJECTIVE: To investigate changes in opioid use after supervised exercise therapy and patient education among knee or hip osteoarthritis patients with chronic opioid use. METHOD: In this cohort study, we linked data from the Good Life with osteoArthritis in Denmark register (GLA:D®; standardised treatment program for osteoarthritis; January 2013 to November 2018) with national health registries. Among 35,549 patients, 1,262 were classified as chronic opioid users based on amount and temporal distribution of dispensed opioids the year before the intervention. We investigated changes in opioid use, measured as mg oral morphine equivalents (OMEQs), from the year before the intervention to the year after using generalized estimating equations. RESULTS: We found a 10% decrease in mg OMEQs from the year before to the year after the intervention (incidence rate ratio [IRR]: 0.90, 95% confidence interval [CI]: 0.86, 0.94). Additional analyses suggested this decrease to be mainly attributable to regulatory actions targeting opioid prescribing during the study period (IRR among patients participating in the intervention before: 0.98 [95% CI: 0.89, 1.07] vs after: 0.83 [0.74, 0.93] regulatory actions). In a random general population sample of matched chronic opioid users, a similar opioid use pattern was observed over time, further supporting the impact of regulatory actions on the opioid use in the study population. CONCLUSION: Among patients with knee or hip osteoarthritis and chronic opioid use, a standardised treatment program did not change opioid use when regulatory changes in opioid prescribing were taken into account.

Knee and hip osteoarthritis are more alike than different in baseline characteristics and outcomes: a longitudinal study of 32,599 patients participating in supervised education and exercise therapy.

OBJECTIVE: Compare baseline characteristics and change in outcomes in patients with symptomatic knee or hip OA participating in patient education and exercise therapy. DESIGN: Longitudinal cohort study. Good Life with osteoArthritis in Denmark (GLA:D®) is an 8-week patient education and supervised exercise program delivered by certified clinicians. Changes in pain intensity, Knee injury/Hip disability Osteoarthritis Outcome Scores' subscale Quality of Life (K/HOOS QOL), EuroQoL 5-Dimensions 5-Level (EQ-5D) and 40 m walk test at ∼3 and 12 months were compared between knee and hip patients. RESULTS: 24,241 knee and 8,358 hip patients were included, with response rates of 75% and 60% at ∼3 and 12 months. Age, gender, symptom duration, pain medication use, pain intensity, physical function and quality of life were alike. More knee than hip patients were obese and had bilateral symptoms. At 3 months, clinically relevant improvements were seen in both knee and hip OA patients with clinically irrelevant between groups differences; 2.1 (1.5; 2.8) mm in pain intensity, -1.1 (-1.5; -0.7) point in K/HOOS QOL score, -0.010 (-0.013; -0.007) in EQ-5D index score and -0.02 (-0.02; -0.01) m/sec in walking speed. At 12 months the slight immediate differences were equalized. CONCLUSION: Patients presenting with knee and hip OA in primary care were on average more alike than different. Following treatment, clinically relevant improvements were seen in both knee and hip OA patients at 3 and 12 months. Patients with knee and hip OA should be prioritized alike for treatment with patient education and supervised exercise therapy.

Dietary Fibers: Effects, Underlying Mechanisms and Possible Role in Allergic Asthma Management.

The prevalence of asthma is increasing, but the cause remains under debate. Research currently focuses on environmental and dietary factors that may impact the gut-lung axis. Dietary fibers are considered to play a crucial role in supporting diversity and activity of the microbiome, as well as immune homeostasis in the gut and lung. This review discusses the current state of knowledge on how dietary fibers and their bacterial fermentation products may affect the pathophysiology of allergic asthma. Moreover, the impact of dietary fibers on early type 2 asthma management, as shown in both pre-clinical and clinical studies, is described. Short-chain fatty acids, fiber metabolites, modulate host immunity and might reduce the risk of allergic asthma development. Underlying mechanisms include G protein-coupled receptor activation and histone deacetylase inhibition. These results are supported by studies in mice, children and adults with allergic asthma. Fibers might also exert direct effects on the immune system via yet to be elucidated mechanisms. However, the effects of specific types of fiber, dosages, duration of treatment, and combination with probiotics, need to be explored. There is an urgent need to further valorize the potential of specific dietary fibers in prevention and treatment of allergic asthma by conducting more large-scale dietary intervention trials.

A lifespan approach to osteoarthritis prevention.

Prevention is an attractive solution for the staggering and increasingly unmanageable burden of osteoarthritis. Despite this, the field of osteoarthritis prevention is relatively immature. To date, most of what is known about preventing osteoarthritis and risk factors for osteoarthritis is relative to the disease (underlying biology and pathophysiology) of osteoarthritis, with few studies considering risk factors for osteoarthritis illness, the force driving the personal, financial and societal burden. In this narrative review we will discuss what is known about osteoarthritis prevention, propose actionable prevention strategies related to obesity and joint injury which have emerged as important modifiable risk factors, identify where evidence is lacking, and give insight into what might be possible in terms of prevention by focussing on a lifespan approach to the illness of osteoarthritis, as opposed to a structural disease of the elderly. By targeting a non-specialist audience including scientists, clinicians, students, industry employees and others that are interested in osteoarthritis but who do not necessarily focus on osteoarthritis, the goal is to generate discourse and motivate inquiry which propel the field of osteoarthritis prevention into the mainstream.

Symptoms of lumbar spinal stenosis in people with knee or hip osteoarthritis or low back pain: a cross-sectional study of 10,234 participants in primary care.

OBJECTIVE: The aims of this study were to evaluate: the proportion of people reporting symptoms associated with lumbar spinal stenosis (LSS) in primary care programs for knee or hip osteoarthritis (OA) or persistent low back pain (LBP) and; the prevalence of self-reported clinical LSS in these three cohorts, according to two sets of adapted criteria. METHOD: A cross-sectional analysis of baseline data from the Good Life with osteoArthritis in Denmark primary care programs. Self-report LSS symptom questions were administered to participants with knee OA, hip OA, and persistent LBP. The prevalence of eleven LSS symptoms and clinical LSS were calculated for each cohort. RESULTS: A total of 10,234 participants were included in the analysis. A similar proportion of participants in each cohort were female (69%), with a 6- and 7-year older mean age in the knee and hip cohorts compared to the back cohort. A greater proportion of participants with LBP reported LSS symptoms (range 11-71%) than in the hip (11-50%) and knee (8-40%) cohorts. This pattern was observed for all but one symptom. The same pattern was observed for the prevalence of clinical LSS with less than 10% of people in each cohort satisfying the clinical criteria. CONCLUSION: Self-reported LSS symptoms are commonly reported by people treated in primary care for knee or hip OA, although not as frequently as reported by those with LBP. Despite symptoms of LSS being common, only a small proportion of people were classified as having self-reported clinical LSS.

Immediate outcomes following the GLA:D® program in Denmark, Canada and Australia. A longitudinal analysis including 28,370 patients with symptomatic knee or hip osteoarthritis.

OBJECTIVE: To report outcomes across three countries for patients with symptomatic knee or hip OA attending the evidence-based education and exercise therapy program Good Life with osteoArthritis from Denmark (GLA:D®). DESIGN: GLA:D® is a structured treatment program including 2-3 patient education sessions and 12 supervised exercise sessions delivered over 8 weeks by certified health care practitioners. The program was introduced in Denmark in 2013, in Canada 2015 and in Australia 2016. Absolute mean change in pain intensity, number of chair stands in 30 s, 40 m walk test time and Knee injury and Osteoarthritis Outcome Score (KOOS)/Hip dysfunction and Osteoarthritis Outcome Score (HOOS) QOL subscale scores from baseline to immediately after treatment were reported as means and 95 % CIs and proportion of responders for each country. RESULTS: Patients from the three countries improved 26-33% in mean pain intensity, 8-12% in walking speed, 18-30% in chair stand ability and 12-26% in joint-related quality of life from baseline to immediately after treatment, with no clinically relevant differences between patients with hip and knee OA. These improvements correspond with moderate to large within-group effect sizes and 43-47 % of the patients experienced clinically relevant pain reductions. CONCLUSION: About half or more of patients across the three countries were categorized as responders for pain and objective function following the implementation of GLA:D®. These findings indicate positive patient outcomes associated with GLA:D® participation across varying health care systems from implementation of guideline-based patient education and exercise therapy for knee and hip OA.

The clinical profile of people with knee osteoarthritis and a self-reported prior knee injury: A cross-sectional study of 10,973 people.

BACKGROUND: Little is known about how a prior knee injury affects the clinical profile of individuals with knee osteoarthritis (KOA) although this is potentially important to personalize care. OBJECTIVES: To compare individual and clinical characteristics of individuals with KOA with and without a self-reported prior knee injury. DESIGN: Secondary data analysis of baseline data from the Good Life with osteoArthritis in Denmark (GLA:D®) registry. METHODS: Individuals with symptomatic KOA, self-reporting a prior knee injury requiring a doctor's assessment, were compared to individuals without prior knee injury on a range of individual and clinical characteristics using multivariable logistic regression. RESULTS: The analysis included 10,973 individuals with KOA of which 54% self-reported a prior knee injury. The average age was 64 years and 73% were female. We found that being male (Odds Ratio (OR): 0.99), having longer symptom duration of knee pain (OR: 1.07), having more painful body sites (OR: 1.03), being able to do more chair rises (OR: 1.02) and being more physically active in a week (2-4 days; OR:1.33) (>4 days; OR: 1.24) were associated with self-reporting a prior knee injury whereas being older (OR: 0.99), having higher BMI (OR: 0.99) and higher quality of life (OR: 0.98) were not associated with reporting a prior knee injury. CONCLUSION: The overall pattern of our findings rather than specific characteristics indicates that individuals with KOA and a history of a self-reported knee injury have a somewhat different clinical profile than their non-injured peers.

Associations between comorbidities and immediate and one-year outcomes following supervised exercise therapy and patient education - A cohort study of 24,513 individuals with knee or hip osteoarthritis.

OBJECTIVE: To investigate if comorbidities are associated with change in health outcomes following an 8-week exercise and education program in knee and hip osteoarthritis (OA). METHODS: We included 24,513 individuals with knee or hip OA from the Good Life with osteoArthritis in Denmark (GLA:D®). GLA:D® consists of two patient education sessions and 12 supervised exercise sessions. Before the program, individuals self-reported having one or more of 11 common comorbidities. Physical function was assessed using the 40-m Fast-Paced Walk Test (FPWT, m/sec) before and immediately after the program. Pain intensity and health-related quality of life was self-reported before, immediately after, and at 12 months post-intervention using a visual analogue scale (VAS, 0-100) and the EQ-5D-5L index (-0.624 to 1.000), respectively. Associations of comorbidity combinations with change in outcomes immediately and at 12 months was estimated using mixed linear regression. RESULTS: Individuals with OA improved on average 0.12 m/s (95%CI 0.12 to 0.13) in 40-m FPWT, -12.7 mm (95%CI -13.2 to -12.2) in VAS, and 0.039 (95%CI 0.036 to 0.041) in EQ-5D-5L from before to immediately after the intervention with minor additional improvements at 12 months. Despite that individuals with comorbidities had worse baseline scores in all outcomes than individuals without comorbidities, they had similar levels of improvement immediately and 12 months after the intervention. CONCLUSION: Comorbidities are not associated with worse nor better health outcomes following an 8-week exercise and education program in individuals with OA, suggesting exercise as a viable treatment option for individuals with OA, irrespective of comorbidities.

Individualized predictions of changes in knee pain, quality of life and walking speed following patient education and exercise therapy in patients with knee osteoarthritis - a prognostic model study.

OBJECTIVE: To facilitate shared decision-making for patients with knee osteoarthritis (OA), we aimed at building clinically applicable models to predict the individual change in pain intensity (VAS scale 0-100), knee-related quality of life (QoL) (KOOS QoL score 0-100) and walking speed (m/sec) immediately following two educational and 12 supervised exercise therapy sessions. METHODS: We used data from patients with knee OA from the 'Good Life with osteoArthritis in Denmark' (GLA:D®) registry (n = 6,767). From 51 patient characteristics, we selected the best performing variables to predict the outcomes via random forest regression. We evaluated model performance via R2. Lastly, we validated and compared our models with the average improvements via the mean differences in an independent validation data set from the GLA:D® registry (n = 2,896) collected 1 year later than the data used to build the models. RESULTS: Validating our models including the best performing variables yielded R2s of 0.34 for pain intensity, 0.18 for knee-related QoL, and 0.07 for walking speed. The absolute mean differences between model predictions and the true outcomes were 14.65 mm, 10.32 points, and 0.14 m/s, respectively, and similar to the absolute mean differences of 17.64, 11.28 and 0.14 observed when we subtracted the average improvements from the true outcomes. CONCLUSION: Despite including 51 potential predictors, we were unable to predict changes in individuals' pain intensity, knee-related QoL and walking speed with clinically relevant greater precision than the respective group average outcomes. Therefore, average prediction values can be used to inform patients about expected outcomes.

Comorbidities and their link with individual health status: A cross-sectional analysis of 23,892 people with knee and hip osteoarthritis from primary care.

OBJECTIVES: Robust data on the impact of comorbidities on health in people with osteoarthritis (OA) are lacking, despite its potential importance for patient management. Objectives were to determine coexisting conditions in people with OA in primary care and whether more comorbidities were linked with individual health status. METHODS: A retrospective analysis of 23,892 patients with knee and hip OA was conducted to determine comorbidities present (number/clusters) and how these linked with pain intensity (0-100), widespread pain (site numbers), medication usage (paracetamol, nonsteroidal anti-inflammatory drugs, opioids), quality of life EuroQol five dimension scale (EQ-5D), and physical function (walking speed) using independent t-tests or χ 2 test. RESULTS: Sixty-two percent of people with OA treated in primary care had at least one comorbidity; hypertension (37%), heart disease (8%), and diabetes (7%) being most common. Outcome measures worsened with more comorbidities (0-4+ comorbidities); pain intensity [mean (SD)] 46(22)-57(21); number of painful sites 3.7(3.0)-6.3(5.4); quality of life 0.73(0.10)-0.63(0.15); walking speed 1.57 m/s (0.33)-1.24 m/s (0.31), while the proportion of people using pain medication increased from 0 to 2 comorbidities (58-69%; p < 0.001), with an increase in opioid use from 4.6% to 19.5% with more comorbidities (0-4+ comorbidities). CONCLUSION: Most people with knee or hip OA in primary care have at least one other long-term condition. A greater number of comorbidities is linked with worsening health, highlighting the importance of screening for comorbidities when treating patients with OA. It is important for clinicians to consider how OA treatments will interact and affect other common comorbidities.

Sex Differences in Symptom Presentation in Acute Coronary Syndromes: A Systematic Review and Meta-analysis.

Background Timely recognition of patients with acute coronary syndromes (ACS) is important for successful treatment. Previous research has suggested that women with ACS present with different symptoms compared with men. This review assessed the extent of sex differences in symptom presentation in patients with confirmed ACS. Methods and Results A systematic literature search was conducted in PubMed, Embase, and Cochrane up to June 2019. Two reviewers independently screened title-abstracts and full-texts according to predefined inclusion and exclusion criteria. Methodological quality was assessed using the Newcastle-Ottawa Scale. Pooled odds ratios (OR) with 95% CI of a symptom being present were calculated using aggregated and cumulative meta-analyses as well as sex-specific pooled prevalences for each symptom. Twenty-seven studies were included. Compared with men, women with ACS had higher odds of presenting with pain between the shoulder blades (OR 2.15; 95% CI, 1.95-2.37), nausea or vomiting (OR 1.64; 95% CI, 1.48-1.82) and shortness of breath (OR 1.34; 95% CI, 1.21-1.48). Women had lower odds of presenting with chest pain (OR 0.70; 95% CI, 0.63-0.78) and diaphoresis (OR 0.84; 95% CI, 0.76-0.94). Both sexes presented most often with chest pain (pooled prevalences, men 79%; 95% CI, 72-85, pooled prevalences, women 74%; 95% CI, 72-85). Other symptoms also showed substantial overlap in prevalence. The presence of sex differences has been established since the early 2000s. Newer studies did not materially change cumulative findings. Conclusions Women with ACS do have different symptoms at presentation than men with ACS, but there is also considerable overlap. Since these differences have been shown for years, symptoms should no longer be labeled as "atypical" or "typical."

Percentile curves for the knee injury and osteoarthritis outcome score in the middle-aged Dutch population.

OBJECTIVE: To improve the interpretation of the Knee injury and Osteoarthritis Outcome Score (KOOS) in individual patients, we explored associations with age, sex, BMI, history of knee injury and presence of clinical knee osteoarthritis, and developed percentile curves. METHODS: We used cross-sectional data of middle-aged individuals from the population-based Netherlands Epidemiology of Obesity (NEO) study. Clinical knee osteoarthritis was defined using the ACR classification criteria. KOOS scores were handled according to the manual (zero = extreme problems, 100 = no problems). Patient characteristics associated with KOOS were explored using ordered logistic regression, and sex and body mass index (BMI)-specific percentile curves were developed using quantile regression with fractional polynomials. The curves were applied as a benchmark for comparison of KOOS scores of participants with knee osteoarthritis and comorbidities. RESULTS: The population consisted of 6,643 participants (56% women, mean (SD) age 56(6) years). Population-based KOOS subscale scores (median; interquartile range) near optimum: pain (100;94-100), symptoms (96;86-100), ADL function (100;96-100), sport/recreation function (100;80-100), quality of life (100;75-100). Worse KOOS scores were observed in women and in participants with higher BMI. Clinical knee osteoarthritis was defined in 15% of participants, and was, in comparison to other patient characteristics, associated with the highest odds of worse KOOS scores. Furthermore, presence of any comorbidity and cardiovascular disease specifically, was associated with worse KOOS scores, particularly in women. CONCLUSIONS: In the middle-aged Dutch population KOOS scores were generally good, but worse in women and with higher BMI. These percentile curves may be used as benchmarks in research and clinical practice.

Cost-effectiveness of 12 weeks of supervised treatment compared to written advice in patients with knee osteoarthritis: a secondary analysis of the 2-year outcome from a randomized trial.

OBJECTIVE: To assess the 24-month cost-effectiveness of supervised treatment compared to written advice in knee osteoarthritis (OA). DESIGN: 100 adults with moderate-severe OA not eligible for total knee replacement (TKR) randomized to a 12-week individualized, supervised treatment (exercise, education, diet, insoles and pain medication) or written advice. Effectiveness was measured as change in quality-adjusted life years (QALYs) from baseline to 24 months, including data from baseline, 3, 6, 12 and 24 months, while healthcare costs and transfer payments were derived from national registries after final follow-up. Incremental costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated. A sensitivity analysis resampling existing data was conducted and the probability of cost-effectiveness was estimated using a 22,665 Euros/QALY threshold. In a sensitivity analysis, cost-effectiveness was calculated for different costs of the supervised treatment (actual cost in study; cost in private practice; and in-between cost). RESULTS: Average costs were similar between groups (6,758 Euros vs 6,880 Euros), while the supervised treatment were close to being more effective (incremental effect (95% CI) of 0.075 (-0.005 to 0.156). In the primary analysis excluding deaths, this led the supervised treatment to be cost-effective, compared to written advice. The sensitivity analysis demonstrated that the results were sensitive to changes in the cost of treatment, but in all scenarios the supervised treatment was cost-effective (ICERs of 6,229 to 20,688 Euros/QALY). CONCLUSIONS: From a 24-month perspective, a 12-week individualized, supervised treatment program is cost-effective compared to written advice in patients with moderate-severe knee OA not eligible for TKR. TRIAL REGISTRATION: ClinicalTrials.gov number: NCT01535001.

Development of osteoarthritis in patients with degenerative meniscal tears treated with exercise therapy or surgery: a randomized controlled trial.

OBJECTIVE: To evaluate progression of individual radiographic features 5 years following exercise therapy or arthroscopic partial meniscectomy as treatment for degenerative meniscal tear. DESIGN: Randomized controlled trial including 140 adults, aged 35-60 years, with a magnetic resonance image verified degenerative meniscal tear, and 96% without definite radiographic knee osteoarthritis. Participants were randomized to either 12-weeks of supervised exercise therapy or arthroscopic partial meniscectomy. The primary outcome was between-group difference in progression of tibiofemoral joint space narrowing and marginal osteophytes at 5 years, assessed semi-quantitatively by the OARSI atlas. Secondary outcomes included incidence of radiographic knee osteoarthritis and symptomatic knee osteoarthritis, medial tibiofemoral fixed joint space width (quantitatively assessed), and patient-reported outcome measures. Statistical analyses were performed using a full analysis set. Per protocol and as treated analysis were also performed. RESULTS: The risk ratios (95% CI) for progression of semi-quantitatively assessed joint space narrowing and medial and lateral osteophytes for the surgery group were 0.89 (0.55-1.44), 1.15 (0.79-1.68) and 0.77 (0.42-1.42), respectively, compared to the exercise therapy group. In secondary outcomes (full-set analysis) no statistically significant between-group differences were found. CONCLUSION: The study was inconclusive with respect to potential differences in progression of individual radiographic features after surgical and non-surgical treatment for degenerative meniscal tear. Further, we found no strong evidence in support of differences in development of incident radiographic knee osteoarthritis or patient-reported outcomes between exercise therapy and arthroscopic partial meniscectomy. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT01002794).