Publications by authors named "David J Hunter"

961 Publications

Monitoring work-related physical activity and estimating lower-limb loading: a proof-of-concept study.

BMC Musculoskelet Disord 2021 Jun 18;22(1):552. Epub 2021 Jun 18.

Department of Rheumatology, Royal North Shore Hospital, Institute of Bone and Joint Research, Kolling Institute, University of Sydney, 2065, St Leonards, Sydney, New South Wales, Australia.

Background: Physical activity (PA) is important to general health and knee osteoarthritis (OA). Excessive workplace PA is an established risk factor for knee OA however, appropriate methods of measurement are unclear. There is a need to examine and assess the utility of new methods of measuring workplace PA and estimating knee load prior to application to large-scale, knee OA cohorts. Our aims, therefore, were to monitor workplace PA and estimate lower-limb loading across different occupations in health participants.

Methods: Twenty-four healthy adults, currently working full-time in a single occupation (≥ 35 h/week) and free of musculoskeletal disease, comorbidity and had no history of lower-limb injury/surgery (past 12-months) were recruited across New South Wales (Australia). A convenience sample was recruited with occupations assigned to levels of workload; sedentary, light manual and heavy manual. Metrics of workplace PA including tasks performed (i.e., sitting), step-count and lower-limb loading were monitored over 10 working days using a daily survey, smartwatch, and a smartphone.

Results: Participants of light manual occupations had the greatest between-person variations in mean lower-limb load (from 2 to 59 kg*m/s3). Lower-limb load for most participants of the light manual group was similar to a single participant in heavy manual work (30 kg*m/s3) and was at least three times greater than the sedentary group (2 kg*m/s3). The trends of workplace PA over working hours were largely consistent, per individual, but rare events of extreme loads were observed across all participants (up to 760 kg*m/s3).

Conclusions: There are large interpersonal variations in metrics of workplace PA, particularly among light and heavy manual occupations. Our estimates of lower-limb loading were largely consistent with pre-conceived levels of physical demand. We present a new approach to monitoring PA and estimating lower-limb loading, which could be applied to future occupational studies of knee OA.
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http://dx.doi.org/10.1186/s12891-021-04409-zDOI Listing
June 2021

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

Semin Arthritis Rheum 2021 May 5;51(4):749-760. Epub 2021 May 5.

Institute of Bone and Joint Research, Kolling Institute, The University of Sydney, Sydney, Australia; Department of Rheumatology, Royal North Shore Hospital, Sydney, Australia.

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.
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http://dx.doi.org/10.1016/j.semarthrit.2021.04.017DOI Listing
May 2021

Risk of Breast Cancer Among Carriers of Pathogenic Variants in Breast Cancer Predisposition Genes Varies by Polygenic Risk Score.

J Clin Oncol 2021 Jun 8:JCO2001992. Epub 2021 Jun 8.

Population Health Sciences Department, Weill Cornell Medicine, New York, NY.

Purpose: This study assessed the joint association of pathogenic variants (PVs) in breast cancer (BC) predisposition genes and polygenic risk scores (PRS) with BC in the general population.

Methods: A total of 26,798 non-Hispanic white BC cases and 26,127 controls from predominately population-based studies in the Cancer Risk Estimates Related to Susceptibility consortium were evaluated for PVs in , , , , , , , , and . PRS based on 105 common variants were created using effect estimates from BC genome-wide association studies; the performance of an overall BC PRS and estrogen receptor-specific PRS were evaluated. The odds of BC based on the PVs and PRS were estimated using penalized logistic regression. The results were combined with age-specific incidence rates to estimate 5-year and lifetime absolute risks of BC across percentiles of PRS by PV status and first-degree family history of BC.

Results: The estimated lifetime risks of BC among general-population noncarriers, based on 10th and 90th percentiles of PRS, were 9.1%-23.9% and 6.7%-18.2% for women with or without first-degree relatives with BC, respectively. Taking PRS into account, more than 95% of , , and carriers had > 20% lifetime risks of BC, whereas, respectively, 52.5% and 69.7% of and carriers without first-degree relatives with BC, and 78.8% and 89.9% of those with a first-degree relative with BC had > 20% risk.

Conclusion: PRS facilitates personalization of BC risk among carriers of PVs in predisposition genes. Incorporating PRS into BC risk estimation may help identify > 30% of and nearly half of carriers below the 20% lifetime risk threshold, suggesting the addition of PRS may prevent overscreening and enable more personalized risk management approaches.
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http://dx.doi.org/10.1200/JCO.20.01992DOI Listing
June 2021

Superficial cartilage transverse relaxation time is associated with osteoarthritis disease progression - data from the FNIH biomarker study of the osteoarthritis initiative.

Arthritis Care Res (Hoboken) 2021 May 10. Epub 2021 May 10.

Department of Imaging and Functional Musculoskeletal Research, Institute of Anatomy and Cell Biology, Paracelsus Medical University Salzburg and Nuremberg, Salzburg, Austria.

Objective: To study whether layer-specific cartilage transverse relaxation time (T2), and/or longitudinal change is associated with clinically relevant knee osteoarthritis (OA) disease progression.

Methods: The FNIH biomarker consortium was a nested case-control study on 600 knees from 600 Osteoarthritis Initiative participants. Progressor knees had both medial tibiofemoral radiographic joint space width (JSW) loss (≥0.7 mm) and a persistent increase in WOMAC pain (≥9 on a 0-100 scale) at 24-48 month from baseline (n=194). Multi-echo spin-echo (MESE) MRIs for cartilage T2 analysis had been acquired in the right knees only (97 progressor knees). These were compared to 104 control knees without JSW or pain progression. 53 knees had JSW progression, and 57 pain progression only. Cartilage thickness segmentations obtained from DESS MRI were matched to MESE MRI, to extract superficial and deep femorotibial cartilage T2. Superficial medial femorotibial compartment (MFTC) T2 at baseline was the primary, and change in deep MFTC T2 between baseline and 12 months the secondary analytic outcome of this post-hoc exploratory study.

Results: Baseline superficial MFTC T2 was significantly elevated in progressor knees (adjusted mean 47.2ms [95% confidence interval [CI] 46.5, 48.0]) and JSW progression only knees (adjusted mean 47.3ms [95% confidence interval [CI] 46.3, 48.3]), respectively, vs non-progressor knees (45.8ms [95% CI 45.0, 46.5]) after adjustment for age, sex, BMI, WOMAC pain, and medial JSN grade (ANCOVA). Change in T2 was not significantly associated with case status.

Conclusions: Baseline superficial, but not deep, medial cartilage T2 is associated with clinically relevant disease progression in knee OA.
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http://dx.doi.org/10.1002/acr.24627DOI Listing
May 2021

Recent Injury, Severe Radiographic Change, and Lower Quadriceps Strength Increase Risk of Knee Pain Exacerbation During Walking: A Within-Person Knee-Matched Study.

J Orthop Sports Phys Ther 2021 06 10;51(6):298-304. Epub 2021 May 10.

Objective: To examine the associations of knee injury, radiographic osteoarthritis severity, and quadriceps strength with knee pain exacerbation during walking.

Design: Within-person knee-matched case-control study.

Methods: Participants from the Osteoarthritis Initiative who completed a 20-m walking test at the 24-month visit were included. Pain exacerbation was defined as an increase in pain intensity of 1 or more on a numeric rating scale (0 as no pain and 10 as the worst imaginable pain) while completing the 20-m walking test. We used conditional logistic regression to assess the relation of recent knee injury, Kellgren-Lawrence (KL) grade, and quadriceps strength to unilateral knee pain exacerbation during walking.

Results: We included 277 people who experienced unilateral knee pain exacerbation during the walking test. Recent knee injury was associated with pain exacerbation during walking, with an odds ratio of 3.4 (95% confidence interval [CI]: 1.3, 9.2). Compared with knees with a KL grade of 0, the odds ratios of pain exacerbation during walking were 1.3 (95% CI: 0.7, 2.7), 3.3 (95% CI: 1.5, 7.1), and 8.1 (95% CI: 3.1, 21.1) for knees with KL grades of 2, 3, and 4, respectively. Painful knees with a deficit in quadriceps strength of greater than or equal to 4% had a 1.4-fold (95% CI: 1.0, 1.9) higher risk of pain exacerbation during walking than their pain-free counterparts.

Conclusion: Recent knee injury, more severe radiographic osteoarthritis, and lower quadriceps strength were associated with an increased risk of knee pain exacerbation during walking. .
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http://dx.doi.org/10.2519/jospt.2021.9735DOI Listing
June 2021

Endorsement of the domains of knee and hip osteoarthritis (OA) flare: A report from the OMERACT 2020 inaugural virtual consensus vote from the flares in OA working group.

Semin Arthritis Rheum 2021 Jun 20;51(3):618-622. Epub 2021 Mar 20.

Department of Physical Therapy, The University of British Columbia, Arthritis Research Canada, Canada.

Objective: Towards developing an instrument to measure knee and hip osteoarthritis (KHOA) flare, the Outcome Measures in Rheumatology (OMERACT) Flares in OA Working Group first sought to identify and define relevant domains of flare in KHOA.

Methods: Guided by OMERACT Filter 2.1, candidate domains were identified from data generated in interviews, in English or French, with persons with KHOA and health professionals (HPs) who treat OA. The first and second rounds of an online Delphi process with patients and HPs, including researchers, selected relevant domains. The third round provided agreement on the selected domains and their definitions. At the virtual OMERACT 2020 workshop, the proposed domains and their definitions were discussed in facilitated breakout groups with patients and HPs. Participants then voted, with consensus set at ≥70%.

Results: Qualitative interviews characterizing OA flare were completed with 29 persons with KHOA and 16 HPs. Content was analyzed and grouped into nine clusters. These candidate domains were included in two Delphi rounds, completed by 91 patients and 165 HPs then 50 patients and 116 HPs, per round, respectively. This resulted in selecting five relevant domains. A final Delphi round, completed by 38 patients and 89 HPs, provided agreement on these domains and their definitions. The OMERACT virtual vote included 27 patients and 106 HPs. The domains and their definitions were endorsed with ≥98% agreement. Domains include: Pain, Swelling, Stiffness, Psychological aspects, and Impact of symptoms, all defined "during flare".

Conclusion: Using OMERACT methodology, we have developed five domains of KHOA flare that were highly endorsed by patients and HPs.
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http://dx.doi.org/10.1016/j.semarthrit.2021.03.010DOI Listing
June 2021

Osteoarthritis in 2020 and beyond - Authors' reply.

Lancet 2021 Mar;397(10279):1060

The Lancet, Sydney, Australia.

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http://dx.doi.org/10.1016/S0140-6736(21)00205-1DOI Listing
March 2021

Genetically predicted circulating concentrations of micronutrients and risk of colorectal cancer among individuals of European descent: a Mendelian randomization study.

Am J Clin Nutr 2021 06;113(6):1490-1502

Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Background: The literature on associations of circulating concentrations of minerals and vitamins with risk of colorectal cancer is limited and inconsistent. Evidence from randomized controlled trials (RCTs) to support the efficacy of dietary modification or nutrient supplementation for colorectal cancer prevention is also limited.

Objectives: To complement observational and RCT findings, we investigated associations of genetically predicted concentrations of 11 micronutrients (β-carotene, calcium, copper, folate, iron, magnesium, phosphorus, selenium, vitamin B-6, vitamin B-12, and zinc) with colorectal cancer risk using Mendelian randomization (MR).

Methods: Two-sample MR was conducted using 58,221 individuals with colorectal cancer and 67,694 controls from the Genetics and Epidemiology of Colorectal Cancer Consortium, Colorectal Cancer Transdisciplinary Study, and Colon Cancer Family Registry. Inverse variance-weighted MR analyses were performed with sensitivity analyses to assess the impact of potential violations of MR assumptions.

Results: Nominally significant associations were noted for genetically predicted iron concentration and higher risk of colon cancer [ORs per SD (ORSD): 1.08; 95% CI: 1.00, 1.17; P value = 0.05] and similarly for proximal colon cancer, and for vitamin B-12 concentration and higher risk of colorectal cancer (ORSD: 1.12; 95% CI: 1.03, 1.21; P value = 0.01) and similarly for colon cancer. A nominally significant association was also noted for genetically predicted selenium concentration and lower risk of colon cancer (ORSD: 0.98; 95% CI: 0.96, 1.00; P value = 0.05) and similarly for distal colon cancer. These associations were robust to sensitivity analyses. Nominally significant inverse associations were observed for zinc and risk of colorectal and distal colon cancers, but sensitivity analyses could not be performed. None of these findings survived correction for multiple testing. Genetically predicted concentrations of β-carotene, calcium, copper, folate, magnesium, phosphorus, and vitamin B-6 were not associated with disease risk.

Conclusions: These results suggest possible causal associations of circulating iron and vitamin B-12 (positively) and selenium (inversely) with risk of colon cancer.
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http://dx.doi.org/10.1093/ajcn/nqab003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168352PMC
June 2021

Prevalence and determinants of hypertension control among almost 100 000 treated adults in the UK.

Open Heart 2021 02;8(1)

Nuffield Department of Population Health, University of Oxford, Oxford, Oxfordshire, UK.

Objective: To identify factors associated with hypertension control among treated middle-aged UK adults.

Methods: A cross-sectional population-based study including 99 468 previously diagnosed, treated hypertensives enrolled in the UK Biobank. Hypertension control was defined as systolic blood pressure <140 mm Hg and diastolic blood pressure <90 mm Hg.

Results: Median age was 62.3 years (IQR 57.3 to 66.0), 45.9% female, 92.0% white, 40.1% obese, 9.3% current smokers and 19.4% had prior cardiovascular disease. 38.1% (95% CI 37.8% to 38.4%) were controlled. In multivariable logistic regression, associations with lack of hypertension control included: older age (OR 0.61, 95% CI 0.58 to 0.64 for 60-69 years compared with age 40-50 years), higher alcohol use (OR 0.61, 95% CI 0.58 to 0.64, for consuming >30 units per week compared with none), black ethnicity (OR 0.73, 95% CI 0.65 to 0.82 compared with white), obesity (OR 0.73, 95% CI 0.71 to 0.76 compared with normal body mass index). The strongest positive association with control was having ≥3 comorbidities (OR 2.09, 95% CI 1.95 to 2.23). Comorbidities associated with control included cardiovascular disease (OR 2.11, 95% CI 2.04 to 2.19), migraines (OR 1.68, 95% CI 1.56 to 1.81), diabetes (OR 1.32, 95% CI 1.27 to 1.36) and depression (OR 1.27, 95% CI 1.20 to 1.34).

Conclusions: In one of the largest population-based analyses of middle-aged adults with measured blood pressure, the majority of treated hypertensives were uncontrolled. Risk factors for hypertension were associated with a lower probability of control. Having a comorbidity was associated with higher probability of control, possibly due to more frequent interaction with the healthcare system and/or appropriate management of those at greater cardiovascular risk.
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http://dx.doi.org/10.1136/openhrt-2020-001461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957140PMC
February 2021

Efficacy of a Combination of Conservative Therapies vs an Education Comparator on Clinical Outcomes in Thumb Base Osteoarthritis: A Randomized Clinical Trial.

JAMA Intern Med 2021 Apr;181(4):429-438

Institute of Bone and Joint Research, Kolling Institute of Medical Research, The University of Sydney, Sydney, New South Wales, Australia.

Importance: A combination of conservative treatments is commonly used in clinical practice for thumb base osteoarthritis despite limited evidence for this approach.

Objective: To determine the efficacy of a 6-week combination of conservative treatments compared with an education comparator.

Design, Setting, And Participants: Randomized, parallel trial with 1:1 allocation ratio among people aged 40 years and older with symptomatic and radiographic thumb base osteoarthritis in a community setting in Australia.

Interventions: The intervention group (n = 102) received education on self-management and ergonomic principles, a base-of-thumb splint, hand exercises, and diclofenac sodium, 1%, gel. The comparator group (n = 102) received education on self-management and ergonomic principles alone. Intervention use was at participants' discretion from 6 to 12 weeks.

Main Outcomes And Measures: Hand function (Functional Index for Hand Osteoarthritis; 0-30) and pain (visual analog scale; 0-100 mm) were measured at week 6 (primary time point) and week 12. An α of .027 was used at week 6 to account for co-primary outcomes.

Results: Of the 204 participants randomized, 195 (96%) and 194 (95%) completed follow-ups at 6 and 12 weeks, respectively; the mean (SD) age of the population was 65.6 (8.1) years, and 155 (76.0%) were female. At week 6, hand function improved significantly more in the intervention group than the comparator (between-group difference, -1.7 units; 97.3% CI, -2.9 to -0.5; P = .002). This trend was sustained at 12 weeks (-2.4 units; 95% CI, -3.5 to -1.3; P < .001). Pain scores improved similarly at week 6 (between-group difference, -4.2 mm; 97.3% CI, -11.3 to 3.0; P = .19). At week 12, pain reduction was significantly greater in the intervention group (-8.6 mm; 95% CI, -15.2 to -2.0; P = .01). There were 34 nonserious adverse events, all in the intervention group-mostly skin reactions and exercise-related pain exacerbations.

Conclusions And Relevance: In this randomized clinical trial of people with thumb base osteoarthritis, combined treatments provided small to medium and potentially clinically beneficial effects on hand function but not pain.

Trial Registration: Australian New Zealand Clinical Trials Registry Identifier: ACTRN12616000353493.
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http://dx.doi.org/10.1001/jamainternmed.2020.7101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941246PMC
April 2021

Integrated Polygenic Tool Substantially Enhances Coronary Artery Disease Prediction.

Circ Genom Precis Med 2021 Apr 2;14(2):e003304. Epub 2021 Mar 2.

Genomics plc, Oxford, United Kingdom (F.R.-M., M.E.W., R.M., S.S., E.K., R.M.S., W.A.T., P.S., A.S.L., J.A.G., A.S., C.C.A.S., V.P., P.D.).

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 resource, we developed our own polygenic risk score for coronary artery disease (CAD). We used an additional 60 000 UK Biobank individuals to develop an integrated risk tool (IRT) that combined our polygenic risk score with established risk tools (either the American Heart Association/American College of Cardiology pooled cohort equations [PCE] or UK QRISK3), and we tested our IRT in an additional, independent set of 186 451 UK Biobank individuals.

Results: The novel CAD polygenic risk score shows superior predictive power for CAD events, compared with other published polygenic risk scores, and is largely uncorrelated with PCE and QRISK3. When combined with PCE into an IRT, 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 with 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 the best performance in 40- to 54-year-old 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 United States over a 5-year period.

Conclusions: An IRT 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.
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http://dx.doi.org/10.1161/CIRCGEN.120.003304DOI Listing
April 2021

Societal Cost of Opioid Use in Symptomatic Knee Osteoarthritis Patients in the United States.

Arthritis Care Res (Hoboken) 2021 Feb 24. Epub 2021 Feb 24.

Orthopaedic and Arthritis Center for Outcomes Research, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.

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.
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http://dx.doi.org/10.1002/acr.24581DOI Listing
February 2021

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.

Nat Commun 2021 02 17;12(1):1078. Epub 2021 Feb 17.

Copenhagen General Population Study, Herlev and Gentofte Hospital Copenhagen University Hospital, Herlev, Denmark.

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies. Other mutation carrier-specific susceptibility variants may exist but studies of mutation carriers have so far been underpowered. We conduct a novel case-only genome-wide association study comparing genotype frequencies between 60,212 general population BC cases and 13,007 cases with BRCA1 or BRCA2 mutations. We identify robust novel associations for 2 variants with BC for BRCA1 and 3 for BRCA2 mutation carriers, P < 10, at 5 loci, which are not associated with risk in the general population. They include rs60882887 at 11p11.2 where MADD, SP11 and EIF1, genes previously implicated in BC biology, are predicted as potential targets. These findings will contribute towards customising BC polygenic risk scores for BRCA1 and BRCA2 mutation carriers.
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http://dx.doi.org/10.1038/s41467-020-20496-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890067PMC
February 2021

Effect of High-Intensity Strength Training on Knee Pain and Knee Joint Compressive Forces Among Adults With Knee Osteoarthritis: The START Randomized Clinical Trial.

JAMA 2021 02;325(7):646-657

Division of Rheumatology, Allergy and Immunology and the Thurston Arthritis Research Center, University of North Carolina School of Medicine, Chapel Hill.

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.
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http://dx.doi.org/10.1001/jama.2021.0411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887656PMC
February 2021

Presence of MRI-defined inflammation particularly in overweight and obese women increases risk of radiographic knee osteoarthritis: the POMA Study.

Arthritis Care Res (Hoboken) 2021 Feb 2. Epub 2021 Feb 2.

Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, S700 Biomedical Science Tower, 3500 Terrace Street, Pittsburgh, PA, 15261, USA.

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.
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http://dx.doi.org/10.1002/acr.24568DOI Listing
February 2021

Association between current medication use and progression of radiographic knee osteoarthritis: data from the Osteoarthritis Initiative.

Rheumatology (Oxford) 2021 Jan 27. Epub 2021 Jan 27.

Institute of Bone and Joint Research, Rheumatology Department, Royal North Shore Hospital, University of Sydney, Sydney, New South Wales, Australia.

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.
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http://dx.doi.org/10.1093/rheumatology/keab059DOI Listing
January 2021

Breast Cancer Risk Factors and Survival by Tumor Subtype: Pooled Analyses from the Breast Cancer Association Consortium.

Cancer Epidemiol Biomarkers Prev 2021 Apr 26;30(4):623-642. Epub 2021 Jan 26.

Gynaecology Research Unit, Hannover Medical School, Hannover, Germany.

Background: It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype.

Methods: We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer-specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype.

Results: There was no evidence of heterogeneous associations between risk factors and mortality by subtype ( > 0.30). The strongest associations were between all-cause mortality and BMI ≥30 versus 18.5-25 kg/m [HR (95% confidence interval (CI), 1.19 (1.06-1.34)]; current versus never smoking [1.37 (1.27-1.47)], high versus low physical activity [0.43 (0.21-0.86)], age ≥30 years versus <20 years at first pregnancy [0.79 (0.72-0.86)]; >0-<5 years versus ≥10 years since last full-term birth [1.31 (1.11-1.55)]; ever versus never use of oral contraceptives [0.91 (0.87-0.96)]; ever versus never use of menopausal hormone therapy, including current estrogen-progestin therapy [0.61 (0.54-0.69)]. Similar associations with breast cancer mortality were weaker; for example, 1.11 (1.02-1.21) for current versus never smoking.

Conclusions: We confirm associations between modifiable lifestyle factors and 10-year all-cause mortality. There was no strong evidence that associations differed by ER status or intrinsic-like subtype.

Impact: Given the large dataset and lack of evidence that associations between modifiable risk factors and 10-year mortality differed by subtype, these associations could be cautiously used in prognostication models to inform patient-centered care.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0924DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026532PMC
April 2021

CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers.

Br J Cancer 2021 02 26;124(4):842-854. Epub 2021 Jan 26.

Molecular Epidemiology Group, C080, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Background: Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk.

Methods: We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry.

Results: For pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (-49.2%, 95% CI -56.1% to -41.1%, P = 3.1 × 10); in follow-up analyses, rs45446698-C was also associated with lower progesterone (-26.7%, 95% CI -39.4% to -11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82-0.91, P = 6.9 × 10).

Conclusions: The CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women.
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http://dx.doi.org/10.1038/s41416-020-01185-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884683PMC
February 2021

Serum uric acid and knee osteoarthritis in community residents without gout: a longitudinal study.

Rheumatology (Oxford) 2021 Jan 25. Epub 2021 Jan 25.

Division of Rheumatology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Republic of Korea.

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.
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http://dx.doi.org/10.1093/rheumatology/keab048DOI Listing
January 2021

A Population-Based Study of Genes Previously Implicated in Breast Cancer.

N Engl J Med 2021 02 20;384(5):440-451. Epub 2021 Jan 20.

From Mayo Clinic, Rochester, MN (C. Hu, S.N.H., R.G., K.Y.L., J.N., J.L., S. Yadav, N.J.B., T.L., J.E.O., C.S., C.M.V., E.C.P., F.J.C.); Harvard University T.H. Chan School of Public Health (H.H., C.G., D.J.H., P.K.), Slone Epidemiology Center at Boston University (K.A.B., J.R.P., L.R.), and Brigham and Women's Hospital (H.E.) - all in Boston; Qiagen, Hilden, Germany (R.S., J.K.); Roswell Park Comprehensive Cancer Center, Buffalo (C.B.A., S. Yao), and Weill Cornell Medicine, New York (R.T.) - both in New York; the University of California, Irvine (H.A.-C., A.Z.), Beckman Research Institute of City of Hope, Duarte (L.B., H.M., S.N., J.N.W.), Keck School of Medicine, University of Southern California, Los Angeles (C. Haiman), and Stanford University School of Medicine, Stanford (E.M.J., A.W.K.) - all in California; the University of Wisconsin-Milwaukee Joseph J. Zilber School of Public Health, Milwaukee (P.A.), and the University of Wisconsin-Madison, Madison (E.S.B., I.M.O., A.T.-D.); the Cancer Prevention and Control Program, Rutgers Cancer Institute of New Jersey, State University of New Jersey, New Brunswick (E.V.B.); the Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta (B.D.C., S.M.G., M.G., J.M.H., E.J.J., A.V.P.); the University of Oxford, Oxford, United Kingdom (D.J.H.); the Fred Hutchinson Cancer Research Center (C.K., P.A.N.) and the Department of Epidemiology, University of Washington (S.L.) - both in Seattle; the Epidemiology Program, University of Hawaii Cancer Center, Honolulu (L.L.M.); the National Institute of Environmental Health Sciences, Durham, NC (K.M.O., D.P.S., J.A.T., C.W.); Vanderbilt University, Nashville (T.P., S.R.); the University of Utah, Salt Lake City (D.E.G.); and the Department of Medicine and the Basser Center for BRCA, Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (S.M.D., K.L.N.).

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 and 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 were associated with a moderate risk (odds ratio, 3.83; 95% CI, 2.68 to 5.63). Pathogenic variants in , , and were associated with increased risks of estrogen receptor-negative breast cancer and triple-negative breast cancer, whereas pathogenic variants in , , and 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 , 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.).
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http://dx.doi.org/10.1056/NEJMoa2005936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127622PMC
February 2021

Participatory health through behavioural engagement and disruptive digital technology for postoperative rehabilitation: protocol of the PATHway trial.

BMJ Open 2021 01 17;11(1):e041328. Epub 2021 Jan 17.

University of Sydney Institute of Bone and Joint Research, Saint Leonards, New South Wales, Australia.

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.
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http://dx.doi.org/10.1136/bmjopen-2020-041328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7813372PMC
January 2021

Multivariable modeling of biomarker data from the phase 1 Foundation for the NIH Osteoarthritis Biomarkers Consortium.

Arthritis Care Res (Hoboken) 2021 Jan 9. Epub 2021 Jan 9.

Duke Molecular Physiology Institute and Division of Rheumatology, Department of Medicine, Duke University School of Medicine, Durham, NC, 27701, USA.

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.
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http://dx.doi.org/10.1002/acr.24557DOI Listing
January 2021

Exercise therapy and patient education versus intra-articular saline injections in the treatment of knee osteoarthritis: an evidence-based protocol for an open-label randomised controlled trial (the DISCO trial).

Trials 2021 Jan 6;22(1):18. Epub 2021 Jan 6.

The Parker Institute, Copenhagen University Hospital Bispebjerg-Frederiksberg, Copenhagen, Denmark.

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.
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http://dx.doi.org/10.1186/s13063-020-04952-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787248PMC
January 2021

Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.

Nat Genet 2021 01 4;53(1):65-75. Epub 2021 Jan 4.

Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.
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http://dx.doi.org/10.1038/s41588-020-00748-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148035PMC
January 2021

How can neighborhood environments facilitate management of osteoarthritis: A scoping review.

Semin Arthritis Rheum 2021 02 18;51(1):253-265. Epub 2020 Dec 18.

Institute of Bone and Joint Research, The Kolling Institute, The University of Sydney, Australia.

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.
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http://dx.doi.org/10.1016/j.semarthrit.2020.09.019DOI Listing
February 2021

A Deep Learning Automated Segmentation Algorithm Accurately Detects Differences in Longitudinal Cartilage Thickness Loss - Data from the FNIH Biomarkers Study of the Osteoarthritis Initiative.

Arthritis Care Res (Hoboken) 2020 Dec 18. Epub 2020 Dec 18.

Department of Imaging and Functional Musculoskeletal Research, Institute of Anatomy and Cell Biology, Paracelsus Medical University Salzburg and Nuremberg, Salzburg, Austria.

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.
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http://dx.doi.org/10.1002/acr.24539DOI Listing
December 2020

Covid-19 mass testing: throwing the baby out with the bathwater?

BMJ 2020 Dec 10;371:m4782. Epub 2020 Dec 10.

School of Public Health, Imperial College London, and Imperial College Healthcare NHS Trust, London, UK.

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http://dx.doi.org/10.1136/bmj.m4782DOI Listing
December 2020

Does screening for depressive symptoms help optimize duloxetine use in knee OA patients with moderate pain? A cost-effectiveness analysis.

Arthritis Care Res (Hoboken) 2020 Nov 30. Epub 2020 Nov 30.

Orthopaedic and Arthritis Center for Outcomes Research (OrACORe) and Policy and Innovation eValuation in Orthopaedic Treatments (PIVOT) Center, Department of Orthopaedic Surgery Brigham and Women's Hospital, Boston, MA, 02115, USA.

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.
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http://dx.doi.org/10.1002/acr.24519DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164641PMC
November 2020