To update and expand upon prior Osteoarthritis Research Society International (OARSI) guidelines by developing patient-focused treatment recommendations for individuals with Knee, Hip, and ...Polyarticular osteoarthritis (OA) that are derived from expert consensus and based on objective review of high-quality meta-analytic data.
We sought evidence for 60 unique interventions. A systematic search of all relevant databases was conducted from inception through July 2018. After abstract and full-text screening by two independent reviewers, eligible studies were matched to PICO questions. Data were extracted and meta-analyses were conducted using RevMan software. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Evidence Profiles were compiled using the GRADEpro web application. Voting for Core Treatments took place first. Four subsequent voting sessions took place via anonymous online survey, during which Panel members were tasked with voting to produce recommendations for all joint locations and comorbidity classes. We designated non-Core treatments to Level 1A, 1B, 2, 3, 4A, 4B, or 5, based on the percentage of votes in favor, in addition to the strength of the recommendation.
Core Treatments for Knee OA included arthritis education and structured land-based exercise programs with or without dietary weight management. Core Treatments for Hip and Polyarticular OA included arthritis education and structured land-based exercise programs. Topical non-steroidal anti-inflammatory drugs (NSAIDs) were strongly recommended for individuals with Knee OA (Level 1A). For individuals with gastrointestinal comorbidities, COX-2 inhibitors were Level 1B and NSAIDs with proton pump inhibitors Level 2. For individuals with cardiovascular comorbidities or frailty, use of any oral NSAID was not recommended. Intra-articular (IA) corticosteroids, IA hyaluronic acid, and aquatic exercise were Level 1B/Level 2 treatments for Knee OA, dependent upon comorbidity status, but were not recommended for individuals with Hip or Polyarticular OA. The use of Acetaminophen/Paracetamol (APAP) was conditionally not recommended (Level 4A and 4B), and the use of oral and transdermal opioids was strongly not recommended (Level 5). A treatment algorithm was constructed in order to guide clinical decision-making for a variety of patient profiles, using recommended treatments as input for each decision node.
These guidelines offer comprehensive and patient-centered treatment profiles for individuals with Knee, Hip, and Polyarticular OA. The treatment algorithm will facilitate individualized treatment decisions regarding the management of OA.
ABSTRACT
We present a blind time-delay cosmographic analysis for the lens system DES J0408−5354. This system is extraordinary for the presence of two sets of multiple images at different redshifts, ...which provide the opportunity to obtain more information at the cost of increased modelling complexity with respect to previously analysed systems. We perform detailed modelling of the mass distribution for this lens system using three band Hubble Space Telescope imaging. We combine the measured time delays, line-of-sight central velocity dispersion of the deflector, and statistically constrained external convergence with our lens models to estimate two cosmological distances. We measure the ‘effective’ time-delay distance corresponding to the redshifts of the deflector and the lensed quasar $D_{\Delta t}^{\rm eff}=$$3382_{-115}^{+146}$ Mpc and the angular diameter distance to the deflector Dd = $1711_{-280}^{+376}$ Mpc, with covariance between the two distances. From these constraints on the cosmological distances, we infer the Hubble constant H0= $74.2_{-3.0}^{+2.7}$ km s−1 Mpc−1 assuming a flat ΛCDM cosmology and a uniform prior for Ωm as $\Omega _{\rm m} \sim \mathcal {U}(0.05, 0.5)$. This measurement gives the most precise constraint on H0 to date from a single lens. Our measurement is consistent with that obtained from the previous sample of six lenses analysed by the H0 Lenses in COSMOGRAIL’s Wellspring (H0LiCOW) collaboration. It is also consistent with measurements of H0 based on the local distance ladder, reinforcing the tension with the inference from early Universe probes, for example, with 2.2σ discrepancy from the cosmic microwave background measurement.
Estimates of the prevalence of Parkinson's disease in North America have varied widely and many estimates are based on small numbers of cases and from small regional subpopulations. We sought to ...estimate the prevalence of Parkinson's disease in North America by combining data from a multi-study sampling strategy in diverse geographic regions and/or data sources. Five separate cohort studies in California (2), Minnesota (1), Hawaii USA (1), and Ontario, Canada (1) estimated the prevalence of PD from health-care records (3), active ascertainment through facilities, large group, and neurology practices (1), and longitudinal follow-up of a population cohort (1). US Medicare program data provided complementary estimates for the corresponding regions. Using our age- and sex-specific meta-estimates from California, Minnesota, and Ontario and the US population structure from 2010, we estimate the overall prevalence of PD among those aged ≥45 years to be 572 per 100,000 (95% confidence interval 537-614) that there were 680,000 individuals in the US aged ≥45 years with PD in 2010 and that that number will rise to approximately 930,000 in 2020 and 1,238,000 in 2030 based on the US Census Bureau population projections. Regional variations in prevalence were also observed in both the project results and the Medicare-based calculations with which they were compared. The estimates generated by the Hawaiian study were lower across age categories. These estimates can guide health-care planning but should be considered minimum estimates. Some heterogeneity exists that remains to be understood.
Summary Objectives To recommend a consensus-derived set of performance-based tests of physical function for use in people diagnosed with hip or knee osteoarthritis (OA) or following joint ...replacement. Methods An international, multidisciplinary expert advisory group was established to guide the study. Potential tests for consideration in the recommended set were identified via a survey of selected experts and through a systematic review of the measurement properties for performance-based tests. A multi-phase, consensus-based approach was used to prioritize and select performance-based tests by applying decision analysis methodology (1000Minds software) via online decision surveys. The recommended tests were chosen based on available measurement-property evidence, feasibility of the tests, scoring methods and expert consensus. Results Consensus incorporated the opinions of 138 experienced clinicians and researchers from 16 countries. The five tests recommended by the advisory group and endorsed by Osteoarthritis Research Society International (OARSI) were the 30-s chair-stand test, 40 m fast-paced walk test, a stair-climb test, timed up-and-go test and 6-min walk test. The first three were recommended as the minimal core set of performance-based tests for hip or knee OA. Conclusion The OARSI recommended set of performance-based tests of physical function represents the tests of typical activities relevant to individuals diagnosed with hip or knee OA and following joint replacements. These tests are complementary to patient-reported measures and are recommended as prospective outcome measures in future OA research and to assist decision-making in clinical practice. Further research should be directed to expanding the measurement-property evidence of the recommended tests.
To develop sets of core and optional recommended domains for describing and evaluating Osteoarthritis Management Programs (OAMPs), with a focus on hip and knee Osteoarthritis (OA).
We conducted a ...3-round modified Delphi survey involving an international group of researchers, health professionals, health administrators and people with OA. In Round 1, participants ranked the importance of 75 outcome and descriptive domains in five categories: patient impacts, implementation outcomes, and characteristics of the OAMP and its participants and clinicians. Domains ranked as “important” or “essential” by ≥80% of participants were retained, and participants could suggest additional domains. In Round 2, participants rated their level of agreement that each domain was essential for evaluating OAMPs: 0 = strongly disagree to 10 = strongly agree. A domain was retained if ≥80% rated it ≥6. In Round 3, participants rated remaining domains using same scale as in Round 2; a domain was recommended as “core” if ≥80% of participants rated it ≥9 and as “optional” if ≥80% rated it ≥7.
A total of 178 individuals from 26 countries participated; 85 completed all survey rounds. Only one domain, “ability to participate in daily activities”, met criteria for a core domain; 25 domains met criteria for an optional recommendation: 8 Patient Impacts, 5 Implementation Outcomes, 5 Participant Characteristics, 3 OAMP Characteristics and 4 Clinician Characteristics.
The ability of patients with OA to participate in daily activities should be evaluated in all OAMPs. Teams evaluating OAMPs should consider including domains from the optional recommended set, with representation from all five categories and based on stakeholder priorities in their local context.
To identify research gaps and inform implementation we systematically reviewed the literature evaluating cost-effectiveness of recommended treatments (education, exercise and diet) for the management ...of hip and/or knee OA.
We searched Medline, Embase, Cochrane Central Register of Controlled Trials, National Health Services Economic Evaluation Database, and EconLit from inception to November 2019 for trial-based economic evaluations investigating hip and/or knee OA core treatments. Two investigators screened relevant publications, extracted data and synthesized results. Risk of bias was assessed using the Consensus on Health Economic Criteria list.
Two cost-minimization, five cost-effectiveness and 16 cost-utility analyses evaluated core treatments in six health systems. Exercise therapy with and without education or diet was cost-effective or cost-saving compared to education or physician-delivered usual care at conventional willingness to pay (WTP) thresholds in 15 out of 16 publications. Exercise interventions were cost-effective compared to physiotherapist-delivered usual care in three studies at conventional WTP thresholds. Education interventions were not cost-effective compared to usual care or placebo at conventional WTP thresholds in three out of four publications.
Structured core treatment programs were clinically effective and cost-effective, compared to physician-delivered usual care, in five health care systems. Providing education about core treatments was not consistently cost-effective. Implementing structured core treatment programs into funded clinical pathways would likely be an efficient use of health system resources and enhance physician-delivered usual primary care.
Summary Objective To evaluate the clinical effectiveness of manual physiotherapy and/or exercise physiotherapy in addition to usual care for patients with osteoarthritis (OA) of the hip or knee. ...Design In this 2 × 2 factorial randomized controlled trial, 206 adults (mean age 66 years) who met the American College of Rheumatology criteria for hip or knee OA were randomly allocated to receive manual physiotherapy ( n = 54), multi-modal exercise physiotherapy ( n = 51), combined exercise and manual physiotherapy ( n = 50), or no trial physiotherapy ( n = 51). The primary outcome was change in the Western Ontario and McMaster osteoarthritis index (WOMAC) after 1 year. Secondary outcomes included physical performance tests. Outcome assessors were blinded to group allocation. Results Of 206 participants recruited, 193 (93.2%) were retained at follow-up. Mean (SD) baseline WOMAC score was 100.8 (53.8) on a scale of 0–240. Intention to treat analysis showed adjusted reductions in WOMAC scores at 1 year compared with the usual care group of 28.5 (95% confidence interval (CI) 9.2–47.8) for usual care plus manual therapy, 16.4 (−3.2 to 35.9) for usual care plus exercise therapy, and 14.5 (−5.2 to 34.1) for usual care plus combined exercise therapy and manual therapy. There was an antagonistic interaction between exercise therapy and manual therapy ( P = 0.027). Physical performance test outcomes favoured the exercise therapy group. Conclusions Manual physiotherapy provided benefits over usual care, that were sustained to 1 year. Exercise physiotherapy also provided physical performance benefits over usual care. There was no added benefit from a combination of the two therapies. Trial registration number Australian New Zealand Clinical Trials Registry ACTRN12608000130369.
The rhesus macaque (
) is the most widely studied nonhuman primate (NHP) in biomedical research. We present an updated reference genome assembly (Mmul_10, contig N50 = 46 Mbp) that increases the ...sequence contiguity 120-fold and annotate it using 6.5 million full-length transcripts, thus improving our understanding of gene content, isoform diversity, and repeat organization. With the improved assembly of segmental duplications, we discovered new lineage-specific genes and expanded gene families that are potentially informative in studies of evolution and disease susceptibility. Whole-genome sequencing (WGS) data from 853 rhesus macaques identified 85.7 million single-nucleotide variants (SNVs) and 10.5 million indel variants, including potentially damaging variants in genes associated with human autism and developmental delay, providing a framework for developing noninvasive NHP models of human disease.
Supported Au−Pd catalysts have been shown to exhibit superior catalytic performances when compared to their monometallic counterparts in a variety of reactions. In addition, the nature of the support ...often plays a critical role in reactivity. To gain a deeper understanding of the structure−reactivity relationship of the Au−Pd catalysts, here we have employed model systems where monometallic and bimetallic Au−Pd nanoparticles are deposited on well-ordered thin films of reducible and irreducible oxides (i.e., Fe3O4(111), MgO(100), and CeO2(111)). Surface structures of the model systems were characterized by temperature-programmed desorption, sum frequency generation, and infrared reflection absorption spectroscopy of CO as a probe molecule. In agreement with previous studies, the results show segregation of gold to the surface. Density functional theory calculations confirm that Au prefers to be at the edges of AuPd alloy particles under vacuum conditions. Strong similarities between the spectral features observed for metal particles on these oxide substrates suggest that the reducibility of the support does not affect the surface structure.
We have developed a protocol suitable for high-throughput lipidomic analysis of human brain samples. The traditional Folch extraction (using chloroform and glass–glass homogenization) was compared to ...a high-throughput method combining methyl-
tert
-butyl ether (MTBE) extraction with mechanical homogenization utilizing ceramic beads. This high-throughput method significantly reduced sample handling time and increased efficiency compared to glass–glass homogenizing. Furthermore, replacing chloroform with MTBE is safer (less carcinogenic/toxic), with lipids dissolving in the upper phase, allowing for easier pipetting and the potential for automation (i.e., robotics). Both methods were applied to the analysis of human occipital cortex. Lipid species (including ceramides, sphingomyelins, choline glycerophospholipids, ethanolamine glycerophospholipids and phosphatidylserines) were analyzed via electrospray ionization mass spectrometry and sterol species were analyzed using gas chromatography mass spectrometry. No differences in lipid species composition were evident when the lipid extraction protocols were compared, indicating that MTBE extraction with mechanical bead homogenization provides an improved method for the lipidomic profiling of human brain tissue.
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