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1.
Artigo em Inglês | MEDLINE | ID: mdl-33651632

RESUMO

Background - There is considerable interest in whether genetic data can be used to improve standard cardiovascular disease risk calculators, as the latter are routinely used in clinical practice to manage preventative treatment. Methods - Using the UK Biobank (UKB) resource, we developed our own polygenic risk score (PRS) for coronary artery disease (CAD). We used an additional 60,000 UKB individuals to develop an integrated risk tool (IRT) that combined our PRS with established risk tools (either the American Heart Association/American College of Cardiology's Pooled Cohort Equations (PCE) or UK's QRISK3), and we tested our IRT in an additional, independent, set of 186,451 UKB individuals. Results - The novel CAD PRS shows superior predictive power for CAD events, compared to other published PRSs and is largely uncorrelated with PCE and QRISK3. When combined with PCE into an integrated risk tool, it has superior predictive accuracy. Overall, 10.4% of incident CAD cases were misclassified as low risk by PCE and correctly classified as high risk by the IRT, compared to 4.4% misclassified by the IRT and correctly classified by PCE. The overall net reclassification improvement for the IRT was 5.9% (95% CI 4.7-7.0). When individuals were stratified into age-by-sex subgroups the improvement was larger for all subgroups (range 8.3%-15.4%), with best performance in 40-54yo men (15.4%, 95% CI 11.6-19.3). Comparable results were found using a different risk tool (QRISK3), and also a broader definition of cardiovascular disease. Use of the IRT is estimated to avoid up to 12,000 deaths in the USA over a 5-year period. Conclusions - An integrated risk tool that includes polygenic risk outperforms current risk stratification tools and offers greater opportunity for early interventions. Given the plummeting costs of genetic tests, future iterations of CAD risk tools would be enhanced with the addition of a person's polygenic risk.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33617972

RESUMO

OBJECTIVE: The RADIANT study aimed to investigate the efficacy and safety of a complementary medicine supplement combination in people with hand osteoarthritis (HOA). METHOD: This was an internet-based, double-blind, randomised, placebo-controlled trial. Participants aged over 40 years with symptomatic HOA with radiographic confirmation (Kellgren Lawrence grade ≥ 2) throughout Australia were recruited and randomly assigned (1:1) to receive either a supplement combination composed of Boswellia serrata extract 250 mg/day, pine bark extract 100 mg/day, methylsulfonylmethane 1500 mg/day and curcumin 168 mg/day or placebo for 12 weeks. The primary outcome was change in hand pain assessed using a visual analogue scale (VAS 0-100) from baseline to week 12. A range of secondary outcomes and additional measures were recorded. Adverse events were monitored weekly. RESULTS: One hundred and six participants were included with mean age 65.6 years and 81% were women. 45% of the participants were graded as KLG 4, 40% KLG 3 and 39 (37%) had erosive OA. There was no significant difference in pain VAS reduction between groups. The adjusted between group difference in means (95%CI) was 5.34 (-2.39 to 13.07). Five participants (10%) in the supplement combination group discontinued study treatment due to AE versus four participants (7%) in the placebo group. CONCLUSION: There were no significant differences in symptomatic relief between the two groups over 12 weeks. These findings do not support the use of the supplement combination for treating hand pain in people with HOA. REGISTRATION: Prospectively registered (Australian New Zealand Clinical Trials Registry ACTRN12619000835145, 31/05/2019).

3.
JAMA ; 325(7): 646-657, 2021 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-33591346

RESUMO

Importance: Thigh muscle weakness is associated with knee discomfort and osteoarthritis disease progression. Little is known about the efficacy of high-intensity strength training in patients with knee osteoarthritis or whether it may worsen knee symptoms. Objective: To determine whether high-intensity strength training reduces knee pain and knee joint compressive forces more than low-intensity strength training and more than attention control in patients with knee osteoarthritis. Design, Setting, and Participants: Assessor-blinded randomized clinical trial conducted at a university research center in North Carolina that included 377 community-dwelling adults (≥50 years) with body mass index (BMI) ranging from 20 to 45 and with knee pain and radiographic knee osteoarthritis. Enrollment occurred between July 2012 and February 2016, and follow-up was completed September 2017. Interventions: Participants were randomized to high-intensity strength training (n = 127), low-intensity strength training (n = 126), or attention control (n = 124). Main Outcomes and Measures: Primary outcomes at the 18-month follow-up were Western Ontario McMaster Universities Osteoarthritis Index (WOMAC) knee pain (0 best-20 worst; minimally clinically important difference [MCID, 2]) and knee joint compressive force, defined as the maximal tibiofemoral contact force exerted along the long axis of the tibia during walking (MCID, unknown). Results: Among 377 randomized participants (mean age, 65 years; 151 women [40%]), 320 (85%) completed the trial. Mean adjusted (sex, baseline BMI, baseline outcome values) WOMAC pain scores at the 18-month follow-up were not statistically significantly different between the high-intensity group and the control group (5.1 vs 4.9; adjusted difference, 0.2; 95% CI, -0.6 to 1.1; P = .61) or between the high-intensity and low-intensity groups (5.1 vs 4.4; adjusted difference, 0.7; 95% CI, -0.1 to 1.6; P = .08). Mean knee joint compressive forces were not statistically significantly different between the high-intensity group and the control group (2453 N vs 2512 N; adjusted difference, -58; 95% CI, -282 to 165 N; P = .61), or between the high-intensity and low-intensity groups (2453 N vs 2475 N; adjusted difference, -21; 95% CI, -235 to 193 N; P = .85). There were 87 nonserious adverse events (high-intensity, 53; low-intensity, 30; control, 4) and 13 serious adverse events unrelated to the study (high-intensity, 5; low-intensity, 3; control, 5). Conclusions and Relevance: Among patients with knee osteoarthritis, high-intensity strength training compared with low-intensity strength training or an attention control did not significantly reduce knee pain or knee joint compressive forces at 18 months. The findings do not support the use of high-intensity strength training over low-intensity strength training or an attention control in adults with knee osteoarthritis. Trial Registration: ClinicalTrials.gov Identifier: NCT01489462.


Assuntos
Articulação do Joelho/fisiologia , Osteoartrite do Joelho/terapia , Manejo da Dor/métodos , Treinamento de Resistência/métodos , Idoso , Índice de Massa Corporal , Força Compressiva , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/fisiopatologia , Dor/etiologia , Dor/reabilitação , Medição da Dor , Método Simples-Cego
4.
Artigo em Inglês | MEDLINE | ID: mdl-33629485

RESUMO

BACKGROUND: Symptomatic knee osteoarthritis (SKOA) is a chronic, disabling condition, requiring long-term pain management; over 800,000 SKOA patients in the USA use opioids chronically. We aim to characterize the societal economic burden of opioid use in this population. METHODS: We used the Osteoarthritis Policy Model, a validated computer simulation of SKOA, to estimate the opioid-related lifetime and annual cost generated by the USA SKOA population. We included direct medical, lost productivity, criminal justice, and diversion costs. We modeled the SKOA cohort with mean (SD) age 54 (14) years and Western Ontario and McMaster University pain score 29 (17) (0-100, 100-worst). We estimated annual costs of strong ($1,381) and weak ($671) opioid regimens using Medicare fee schedules, Red Book, the Federal Supply Schedule, and published literature. The annual lost productivity and criminal justice costs of opioid use disorder (OUD), obtained from published literature, were $11,387 and $4,264, per-person. The 2015-2016 Medicare Current Beneficiary Survey provided OUD prevalence. We conducted sensitivity analyses to examine the robustness of our estimates to uncertainty in input parameters. RESULTS: Assuming 5.1% prevalence of chronic strong opioid use, the total lifetime opioid-related cost generated by the USA SKOA population was estimated at $14.0 billion, of which only $7.45 billion (53%) were direct medical costs. CONCLUSIONS: Lost productivity, diversion, and criminal justice costs comprise about half of opioid-related costs generated by the USA SKOA population. Reducing chronic opioid use may lead to a meaningful reduction in societal costs that can be used for other public health causes.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33527736

RESUMO

OBJECTIVE: Aims were to assess 1.) whether odds for incident radiographic osteoarthritis (ROA) differ between men and women in regard to body mass index (BMI) and inflammatory magnetic resonance imaging (MRI) markers one and two years prior and 2.) whether presence of inflammation on MRI differs between normal-weight, and overweight/obese persons that develop ROA up to four years prior. METHODS: We studied 355 knees from the Osteoarthritis Initiative study that developed incident ROA and 355 matched controls. MRIs were read for effusion-synovitis and Hoffa-synovitis for up to four consecutive annual time points. Subjects were classified as normal-weight (BMI < 25), overweight (BMI ≥25/<30) or obese (BMI ≥30). Conditional logistic regression was used to assess odds of incident ROA for effusion-synovitis and Hoffa-synovitis at one and two years prior ROA incidence (i.e. "P-1" and "P-2") considering BMI category. Bivariate logistic regression was used to assess odds of inflammation for cases only. RESULTS: 178 (25.1%) participants were normal-weight, 283 (39.9%) overweight and 249 (35.1%) obese. At P-2 being overweight with Hoffa-synovitis (OR 3.26, 95%CI 1.39,7.65) or effusion-synovitis (3.56, 95%CI 1.45,8.75) was associated with greater odds of incident ROA in women. For those with incident ROA there were no increased odds of synovitis in the overweight/obese subgroup for most time points but increased odds for effusion-synovitis were observed at P-2 (OR 2.21, 95%CI 1.11,4.43). CONCLUSIONS: Presence of inflammatory markers seems to play a role especially in overweight women while obese women have increased odds for ROA also in the absence of these markers.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33502488

RESUMO

OBJECTIVE: Use of specific medications may accelerate the progression of radiographic knee osteoarthritis (RKOA). Our aim was to examine the effect of medication use on the progression of RKOA. METHODS: We used longitudinal data from the Osteoarthritis Initiative (OAI); an observational study of risk factors for knee OA. At baseline, we selected participants with RKOA (KL grade ≥2) and excluded those with a history of knee-related injury/surgery and other musculoskeletal disorders. Current medication use (use/non-use in the previous 30 days) and radiographic medial minimum joint space width (mJSW) data were available at baseline and annually up to 96-months follow-up. We used random-effects, panel-regression to assess the association between current medication use (non-users as reference group) and change in mJSW. RESULTS: Of 2,054 eligible participants, 2,003 participants with baseline mJSW data were included (55.7% female, mean age 63.3 (SD 8.98) years). Of 7 medication classes, at baseline non-steroidal anti-inflammatory drugs (NSAIDs) were the most frequently used analgesia (14.7%), anti-histamine (10.4%) use were frequent and, the following comorbidity medications were used most frequently; i) statins (27.4%), ii) anti-hypertensives (up to 15.0%), iii) anti-depressant/anxiolytics/psychotropics (14.0%), iv) osteoporosis-related medication (10.9%) and v) diabetes-related medication (6.9%). Compared with current non-users, current use of NSAIDs was associated with a loss of mJSW (b = -0.042, 95% CI -0.08 to -0.0004). No other associations were observed. CONCLUSIONS: In current users of NSAIDs, mJSW loss was increased compared with current non-users in participants with RKOA. Clinical trials are required to assess the potential disease-modifying effects of these medications.

7.
BMJ Open ; 11(1): e041328, 2021 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-33455931

RESUMO

INTRODUCTION: Postsurgical rehabilitation is critical for optimal recovery in people undergoing orthopaedic surgery. Currently, knee and lumbar spine postsurgical care is not standardised, economically sustainable, nor based on quality evidence, contributing to substantial clinical variation, poor outcomes and increasing healthcare costs. This protocol describes the design of a randomised controlled trial aiming to evaluate the effectiveness and cost-effectiveness of a postsurgical clinical pathway augmented by disruptive technology and compared with standardised rehabilitation alone, in decreasing pain and improving function after total knee replacement (TKR) or lumbar laminectomy (with or without fusion). METHODS: An assessor-blinded, parallel group, randomised controlled trial will be conducted to recruit 204 consenting participants (102 per arm) of whom 50% are undergoing TKR and 50% lumbar surgery. The intervention group will receive a 6-month technology-enabled rehabilitation package in addition to usual postsurgical care. The package includes (1) an exercise program delivered via the Physitrack app on the iPad, (2) a health-coaching program delivered via video calls and motivational messages, (3) use of physical activity tracker with goal setting and motivational reminders (Fitbit). For those undergoing TKR, the intervention will also include knee joint range of motion self-monitoring via the Goniometer app. The control group will receive usual postsurgical care. Participants will be followed up at 3, 6 and 12 months from the enrolment date. The primary outcome is pain measured with the Numerical Rating Scale at 3 months. Secondary outcomes include pain-related disability, quality of life, computer self-efficacy, physical activity participation and sedentary behaviour. Data analysis will be blinded and by intention-to-treat. A trial-based cost-effectiveness analysis will determine the potential incremental cost per quality-adjusted life-year gained. ETHICS AND DISSEMINATION: This protocol is approved by the human research ethics committee of the University of Sydney. Dissemination will occur through lay summary, infographics, conferences and journal publications. TRIAL REGISTRATION NUMBER: ACTRN12618001448235.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33421361

RESUMO

OBJECTIVE: To determine the optimal combination of imaging and biochemical biomarkers to predict knee osteoarthritis (OA) progression. METHODS: Nested case-control study from the FNIH OA Biomarkers Consortium of participants with Kellgren-Lawrence grade 1-3 and complete biomarker data (n=539 to 550). Cases were knees with radiographic and pain progression between 24-48 months from baseline. Radiographic progression only was assessed in secondary analyses. Biomarkers (baseline and 24-month changes) with p<0.10 in univariate analysis were selected, including MRI (quantitative (Q) cartilage thickness and volume; semi-quantitative (SQ) MRI markers; bone shape and area; Q meniscal volume), radiographic (trabecular bone texture (TBT)), and serum and/or urine biochemical markers. Multivariable logistic regression models were built using three different step-wise selection methods (complex vs. parsimonious models). RESULTS: Among baseline biomarkers, the number of locations affected by osteophytes (SQ), Q central medial femoral and central lateral femoral cartilage thickness, patellar bone shape, and SQ Hoffa-synovitis predicted progression in most models (C-statistics 0.641-0.671). 24-month changes in SQ MRI markers (effusion-synovitis, meniscal morphology, and cartilage damage), Q central medial femoral cartilage thickness, Q medial tibial cartilage volume, Q lateral patellofemoral bone area, horizontal TBT (intercept term), and urine NTX-I predicted progression in most models (C-statistics 0.680-0.724). A different combination of imaging and biochemical biomarkers (baseline and 24-month change) predicted radiographic progression only, with higher C-statistics (0.716-0.832). CONCLUSION: This study highlights the combination of biomarkers with potential prognostic utility in OA disease-modifying trials. Properly qualified, these biomarkers could be used to enrich future trials with participants likely to progress.

9.
Trials ; 22(1): 18, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407791

RESUMO

BACKGROUND: Knee osteoarthritis (OA) is a highly prevalent musculoskeletal condition causing pain, physical disability, and reduced quality of life. Exercise and patient education are non-pharmacological interventions for knee OA unanimously recommended as first-line treatments based on extensive research evidence. However, none of the numerous randomised controlled trials of exercise and education for knee OA has used adequate sham/placebo comparison groups because the 'active' ingredients are unknown. Designing and executing an adequate and 'blindable placebo' version of an exercise and education intervention is impossible. Therefore, using an open-label study design, this trial compares the efficacy of a widely used 'state-of-art' exercise and education intervention (Good Life with osteoarthritis in Denmark; GLAD) with presumably inert intra-articular saline injections on improvement in knee pain in patients with knee OA. METHODS: In this open-label randomised trial, we will include 200 patients with radiographically verified OA of the knee and randomly allocate them to one of two interventions: (i) 8 weeks of exercise and education (GLAD) or (ii) Intra-articular injections of 5 ml isotonic saline every second week for a total of 4 injections. Outcomes are taken at baseline, after 8 weeks of treatment (week 9; primary endpoint) and after an additional 4 weeks of follow-up (week 12). The primary outcome is change from baseline in the Knee Injury and Osteoarthritis Outcome Score questionnaire (KOOS) pain subscale score. Secondary outcomes include the Physical function in Activities of Daily Living, Symptoms, and Knee-related Quality of Life subscales of the KOOS, the patients' global assessment of disease impact, physical performance tests, and presence of knee joint swelling. DISCUSSION: This current trial compares a presumably active treatment (GLAD) with a presumably inert treatment (IA saline injections). Both study interventions have well-established and anticipated similar effects on knee OA symptoms, but the underlying mechanisms are unknown. The interpretation of the results of this trial will likely be difficult and controversial but will contribute to a better understanding of the bias introduced in the effect estimation of classically unblindable exercise and education interventions for knee OA. TRIAL REGISTRATION: www.ClinicalTrials.gov NCT03843931 . Prospectively registered on 18 February 2019.

10.
Semin Arthritis Rheum ; 51(1): 253-265, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33387921

RESUMO

OBJECTIVE: The association between neighborhood environments and health outcomes has long been recognized, but the importance of environmental factors is less well examined in osteoarthritis (OA). We aimed to give an overview of the literature examining the role of neighborhood built environments in the context of OA self-management. MATERIAL AND METHODS: A literature search between 2000 and 2019 was performed using a scoping methodology. Literature examining the influence of neighborhood built environments on health and other outcomes in people with OA, mixed or unspecified arthritis were screened by two independent reviewers. Seven domains were pre-determined based on the World Health Organization European Healthy Cities Framework. Sub-domains and themes were synthesized from the literature. RESULTS: We included 27 studies across seven pre-determined domains, 23 sub-domains. We identified 6 key outcomes of physical activity, quality of life, community participation, resource use, psychological health, and other physical health. The majority of studies emphasized the importance of neighborhood built environment on supporting OA self-management, particularly for facilitating physical activity. The impacts on other outcomes were also considered important but were less well studied, especially access to healthy food. CONCLUSIONS: This review highlights the potential of better using the built environment to support OA management to address many different outcomes. Understanding the impacts of different environments is the first step, and designing new and novel ways to utilize neighborhoods is needed. Implementing strategies and public policies at a neighborhood level may be a more viable way to curb further increases in the OA epidemic than addressing individual factors alone.

11.
N Engl J Med ; 384(5): 440-451, 2021 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-33471974

RESUMO

BACKGROUND: Population-based estimates of the risk of breast cancer associated with germline pathogenic variants in cancer-predisposition genes are critically needed for risk assessment and management in women with inherited pathogenic variants. METHODS: In a population-based case-control study, we performed sequencing using a custom multigene amplicon-based panel to identify germline pathogenic variants in 28 cancer-predisposition genes among 32,247 women with breast cancer (case patients) and 32,544 unaffected women (controls) from population-based studies in the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. Associations between pathogenic variants in each gene and the risk of breast cancer were assessed. RESULTS: Pathogenic variants in 12 established breast cancer-predisposition genes were detected in 5.03% of case patients and in 1.63% of controls. Pathogenic variants in BRCA1 and BRCA2 were associated with a high risk of breast cancer, with odds ratios of 7.62 (95% confidence interval [CI], 5.33 to 11.27) and 5.23 (95% CI, 4.09 to 6.77), respectively. Pathogenic variants in PALB2 were associated with a moderate risk (odds ratio, 3.83; 95% CI, 2.68 to 5.63). Pathogenic variants in BARD1, RAD51C, and RAD51D were associated with increased risks of estrogen receptor-negative breast cancer and triple-negative breast cancer, whereas pathogenic variants in ATM, CDH1, and CHEK2 were associated with an increased risk of estrogen receptor-positive breast cancer. Pathogenic variants in 16 candidate breast cancer-predisposition genes, including the c.657_661del5 founder pathogenic variant in NBN, were not associated with an increased risk of breast cancer. CONCLUSIONS: This study provides estimates of the prevalence and risk of breast cancer associated with pathogenic variants in known breast cancer-predisposition genes in the U.S. population. These estimates can inform cancer testing and screening and improve clinical management strategies for women in the general population with inherited pathogenic variants in these genes. (Funded by the National Institutes of Health and the Breast Cancer Research Foundation.).


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença/genética , Variação Genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Mutação , Razão de Chances , Risco , Análise de Sequência de DNA , Adulto Jovem
12.
Artigo em Inglês | MEDLINE | ID: mdl-33493331

RESUMO

OBJECTIVES: Emerging evidence suggests a potential link between osteoarthritis (OA) and gout; however, the association between serum uric acid (UA) itself and knee OA remains uncertain due to a lack of longitudinal studies. Here, we investigated the association between serum UA and knee OA according to cartilage status in elderly community residents without gout. METHODS: In this longitudinal study, participants without a history of gout were recruited from among the Korean cohort of the Hallym Aging Study (n = 296 for radiography study and n = 223 for MRI study). Weight-bearing knee radiographs and 1.5-T MRI scans, along with blood collection for analysis of serum UA, were performed at baseline and after 3 years. The severity and structural progression of knee OA were evaluated using the Kellgren-Lawrence grading system and the Whole-Organ MRI Score (WORMS) cartilage scoring method. Multivariable logistic regression analysis was conducted using generalized estimating equation (GEE) models. RESULTS: Serum UA levels were not associated with radiographic progression after adjusting for age, sex, and body mass index (BMI). There was no significant association between serum UA and tibiofemoral cartilage loss on MRI. However, baseline serum UA levels were negatively associated with patellofemoral cartilage loss over 3 years (adjusted odd ratio 0.70, 95% confidence interval 0.49-0.98). CONCLUSION: In this population-based cohort, serum UA was not a risk factor for knee OA progression. Further large-scale longitudinal studies in other populations are needed to validate the effects of UA on cartilage damage.

13.
Int J Cancer ; 148(2): 307-319, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-32851660

RESUMO

Blood lipids have been associated with the development of a range of cancers, including breast, lung and colorectal cancer. For endometrial cancer, observational studies have reported inconsistent associations between blood lipids and cancer risk. To reduce biases from unmeasured confounding, we performed a bidirectional, two-sample Mendelian randomization analysis to investigate the relationship between levels of three blood lipids (low-density lipoprotein [LDL] and high-density lipoprotein [HDL] cholesterol, and triglycerides) and endometrial cancer risk. Genetic variants associated with each of these blood lipid levels (P < 5 × 10-8 ) were identified as instrumental variables, and assessed using genome-wide association study data from the Endometrial Cancer Association Consortium (12 906 cases and 108 979 controls) and the Global Lipids Genetic Consortium (n = 188 578). Mendelian randomization analyses found genetically raised LDL cholesterol levels to be associated with lower risks of endometrial cancer of all histologies combined, and of endometrioid and non-endometrioid subtypes. Conversely, higher genetically predicted HDL cholesterol levels were associated with increased risk of non-endometrioid endometrial cancer. After accounting for the potential confounding role of obesity (as measured by genetic variants associated with body mass index), the association between genetically predicted increased LDL cholesterol levels and lower endometrial cancer risk remained significant, especially for non-endometrioid endometrial cancer. There was no evidence to support a role for triglycerides in endometrial cancer development. Our study supports a role for LDL and HDL cholesterol in the development of non-endometrioid endometrial cancer. Further studies are required to understand the mechanisms underlying these findings.

14.
BMJ ; 371: m4782, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33303582
15.
Artigo em Inglês | MEDLINE | ID: mdl-33337584

RESUMO

OBJECTIVE: To study the longitudinal performance of fully automated cartilage segmentation in knees with radiographic osteoarthritis (ROA). We evaluate the sensitivity to change in progressor knees from the Foundation National Institutes of Health OA Biomarkers Consortium between the automated and previously reported manual expert segmentation, and whether differences in progression rates between predefined cohorts can be detected by the fully automated approach. METHODS: The Osteoarthritis Initiative Biomarker Consortium was a nested case-control study. Progressor knees had both medial tibiofemoral radiographic joint space width loss (≥0.7 mm) and a persistent increase in WOMAC pain (≥9 on a 0-100 scale) after two years from baseline (n=194), whereas non-progressor knees did not have either of both (n=200). Deep learning automated algorithms trained on ROA or healthy reference (HRC) knees were used to automatically segment medial (MFTC) and lateral femorotibial cartilage on baseline and two-year follow-up MRIs. Findings were compared with previously published manual expert segmentation. RESULTS: The MFTC cartilage loss in the progressor cohort was -181±245µm by manual (SRM=-0.74), -144±200µm by ROA-based model (SRM=-0.72), and -69±231µm by HRC-based model segmentation (SRM=-0.30). The Cohen's D for rates of progression between progressor vs. non-progressor cohort was -0.84 (p<0.001) for manual, -0.68 (p<0.001) for automated ROA-model, and -0.14 (p=0.18) for automated HRC-model segmentation. CONCLUSIONS: A fully automated deep learning segmentation approach not only displayed similar sensitivity to change of longitudinal cartilage thickness loss in knee OA as manual expert segmentation, but also effectively differentiates longitudinal rates of cartilage thickness loss between cohorts with different progression profiles.

16.
Lancet ; 396(10264): 1711-1712, 2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-33159851
17.
Arthritis Rheumatol ; 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-33169542

RESUMO

Osteoarthritis (OA) is an extraordinarily prevalent and disabling disease [1]. Current management options for pain and functional limitation are constrained by modest efficacy or a range of unwanted side effects. Our society is being impacted through underemployment and the opioid epidemic and our health care systems are overstretched, as a consequence of the trajectory of increasing joint replacement requirements [2]. In this context, development of new treatments or identification of efficacy of existing therapies to address the huge unmet need of pain are strongly desired.

18.
N Engl J Med ; 2020 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-33176081
19.
Artigo em Inglês | MEDLINE | ID: mdl-33253496

RESUMO

OBJECTIVE: Duloxetine is an FDA-approved treatment for both osteoarthritis (OA) pain and depression, but uptake of duloxetine in knee OA management varies. We examined the cost-effectiveness of adding duloxetine to knee OA care with or without depression screening. METHODS: We used the Osteoarthritis Policy Model, a validated computer microsimulation of knee OA, to examine the value of duloxetine for knee OA patients with moderate pain by comparing three strategies: 1) usual care (UC); 2) duloxetine for those who screen positive for depression on the Patient Health Questionnaire 9 (PHQ-9) + UC; and 3) universal duloxetine + UC. Outcomes included quality-adjusted life years (QALYs), lifetime direct medical costs, and incremental cost-effectiveness ratios (ICERs), discounted at 3% annually. Model inputs, drawn from published literature and national databases, included: annual cost of duloxetine, $721-$937; average pain reduction for duloxetine, 17.5 points on the WOMAC pain scale (0-100); likelihood of depression remission with duloxetine, 27.4%. We considered two willingness-to-pay (WTP) thresholds of $50,000/QALY and $100,000/QALY. We varied parameters related to the PHQ-9 and duloxetine's cost, efficacy, and toxicities to address uncertainty in model inputs. RESULTS: The screening strategy led to an additional 17 QALYs per 1,000 subjects and increased costs by $289/subject (ICER=$17,000/QALY). Universal duloxetine led to an additional 31 QALYs per 1,000 subjects and $1,205/subject (ICER=$39,300/QALY). Under the majority of sensitivity analyses, universal duloxetine was cost-effective at the $100,000/QALY threshold. CONCLUSION: Adding duloxetine to usual care for knee OA patients with moderate pain, regardless of depressive symptoms, is cost-effective at frequently-used WTP thresholds.

20.
BMJ Open ; 10(10): e043088, 2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-33099502

RESUMO

INTRODUCTION: The infrapatellar fat pad (IPFP) is commonly resected during total knee arthroplasty (TKA) for better exposure. However, our previous studies have suggested that IPFP size was protective against, while IPFP signal intensity alteration was detrimental on knee symptoms and structural abnormalities. We hypothesise that an IPFP with normal qualities, rather than abnormal qualities, should be preserved during TKA. The aim of this study is to compare, over a 1-year period, the postoperative clinical outcomes of IPFP preservation versus resection after TKA in patients with normal or abnormal IPFP signal intensity alteration on MRI. METHODS AND ANALYSIS: Three hundred and sixty people with end-stage knee osteoarthritis and on the waiting list for TKA will be recruited and identified as normal IPFP quality (signal intensity alteration score ≤1) or abnormal IPFP quality (signal intensity alteration score ≥2). Patients in each hospital will then be randomly allocated to IPFP resection group or preservation group. The primary outcomes are the summed score of self-reported Knee Injury and Osteoarthritis Outcome Score (KOOS), KOOS subscales assessing function in daily activities and function in sport and recreation. Secondary endpoints will be included: KOOS subscales (pain, symptoms and quality of life), Knee Society Score, 100 mm Visual Analogue Scale (VAS) Pain, timed up-and-go test, patellar tendon shortening, 100 mm VAS self-reported efficacy of reduced pain and increased quality of life, and Insall-Salvati index assessed on plain X-ray. Adverse events will be recorded. Intention-to-treat analyses will be used. ETHICS AND DISSEMINATION: The study is approved by the local Medical Ethics Committee (Zhujiang Hospital Ethics Committee, reference number 2017-GJGBK-001) and will be conducted according to the principle of the Declaration of Helsinki (64th, 2013) and the Good Clinical Practice standard, and in compliance with the Medical Research Involving Human Subjects Act . Data will be published in peer-reviewed journals and presented at conferences, both nationally and internationally. TRIAL REGISTRATION NUMBER: This trial was registered at Clinicaltrial.gov website on 19 October 2018 with identify number NCT03763448.

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