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Additional file 1: Table S1. Read codes used for covid-19 vaccination records and diagnosed SARS-CoV-2 infection. Figure S1. A directed acyclic graph of the comparative effectiveness of BNT162b2 and ChAdOx1 nCoV-19 vaccines against COVID-19 and potential confounders.

Additional file 2: Supplemental Figure 2. Sox9, Col2a1, Acan and Mmp-13 genes expression. Mouse chondrocytes were cultured under different magnesium conditions (0.7mM, 0,4mM and 0.1mM) with or without treatment of Rapa. Sox9, Col2a1, Acan and Mmp-13 genes expression were assessed by qRT-PCR (n = 5). Hprt1 was used as housekeeping gene. Data were expressed as the mean ± SD and analyzed by one-way ANOVA test. (*P

Additional file 5: Supplemental Figure 5. Catenin, Wnt3a, Wnt5a, Wnt5b and Wnt16 genes expression. Mouse chondrocytes were cultured under different magnesium conditions (0.7mM, 0,4mM and 0.1mM). mRNA levels of Catenin, Wnt3a, Wnt5a, Wnt5b and Wnt16 were investigated by qRT-PCR (n = 5). Hprt1 was used as housekeeping gene. Data were expressed as the mean ± SD and analyzed by one-way ANOVA test. (*P

Additional file 6: Supplemental Table 1. Ct values of Wnt ligands normalized to β-actin in qRT-PCR.

Additional File 1 .

Additional file 4: Supplemental Figure 4. Immunohistochemistry analysis of Beclin-1. (A, B) Immunostaining and quantitative analysis of cells positive for Beclin-1 in sham and DMM-induced OA mice fed with diets containing different content of magnesium (500 mg/kg, 300 mg/kg, 100 mg/kg) (n = 9). Scale bar: 100 μm. Data were expressed as the mean ± SEM and analyzed by one-way ANOVA test (*P

Additional file 1: Supplemental Figure 1. Body weight of mice over time. Body weight of sham and DMM-induced OA mice fed with diets containing different content of magnesium (500 mg/kg, 300 mg/kg, 100 mg/kg) measured weekly. No statistical significance was observed between different groups at the same age.

Additional file 3: Supplemental Figure 3. Immunohistochemistry analysis of LC3-II. (A, B) Immunostaining and quantitative analysis of cells positive for LC3-II in sham and DMM-induced OA mice fed with diets containing different content of magnesium (500 mg/kg, 300 mg/kg, 100 mg/kg) (n = 9). Scale bar: 100 μm. Data were expressed as the mean ± SEM and analyzed by one-way ANOVA test (*P

Additional file 1: Supplemental Figure 1. Recruitment and enrollment of study participants in Xiangya Osteoarthritis Study (XO Study). Supplemental Figure 2. Longitudinal ultrasonographic scan of suprapatellar recess (B mode). SH, synovial hypertrophy; E, joint effusion. Supplemental Figure 3. Longitudinal ultrasonographic scan of suprapatellar recess (Power Doppler mode). Power Doppler signal (PDS) at synovial membrane was scored using a semi-quantitative grading system, from 0 to 3 (0=absent, 1=mild, 2=moderate, 3=marked or severe). (A) grade 0, (B) grade 1, (C) grade 2. We did not detected grade 3 PDS in knee joints of participants of our study. Supplemental Figure 4. Bilateral weight-bearing posterior-anterior tibio-femoral radiographs, assessed according to Kellgren and Lawrence (KL) criteria: (A) grade 0, (B) grade 1, (C) grade 2, (D) grade 3 and (E) grade 4. Supplemental Figure 5. Skyline views of patellofemoral radiographs, assessed according to Kellgren and Lawrence (KL) criteria: (A) grade 0, (B) grade 1, (C) grade 2, (D) grade 3 and (E) grade 4. Supplemental Table 1. The intra- and inter-rater reliability for ultrasound-detected synovial abnormalities and Kellgren-Lawrence grade of knee radiography. Supplemental Table 2. Prevalence of knee synovial abnormalities on ultrasound among middle-aged and elderly persons, according to age group and sex. Supplemental Table 3. Association of knee synovial abnormalities on ultrasound and knee pain. Supplemental Table 4. Association of knee synovial abnormalities on ultrasound and knee pain among people with two knees discordant for knee pain. Supplemental Table 5. Association of knee synovial abnormalities on ultrasound and knee radiographic osteoarthritis. Supplemental Table 6. Association of knee pain stratified by knee synovial abnormalities on ultrasound and radiographic osteoarthritis status among people with two knees discordant for knee pain.

Several professional organizations have recommended tramadol as one of the first-line or second-line therapies for patients with chronic noncancer pain and its prescription has been increasing rapidly worldwide; however, the safety profile of tramadol, such as risk of fracture, remains unclear. This study aimed to examine the association of tramadol with risk of hip fracture. Among individuals age 50 years or older without a history of hip fracture, cancer, or opioid use disorder in The Health Improvement Network (THIN) database in the United Kingdom general practice (2000-2017), five sequential propensity score-matched cohort studies were assembled, ie, participants who initiated tramadol or those who initiated one of the following medications: codeine (n = 146,956) (another commonly used weak opioid), naproxen (n = 115,109) or ibuprofen (n = 107,438) (commonly used nonselective nonsteroidal anti-inflammatory drugs [NSAIDs]), celecoxib (n = 43,130), or etoricoxib (n = 27,689) (cyclooxygenase-2 inhibitors). The outcome was incident hip fracture over 1 year. After propensity-score matching, the included participants had a mean age of 65.7 years and 56.9% were women. During the 1-year follow-up, 518 hip fracture (3.7/1000 person-years) occurred in the tramadol cohort and 401 (2.9/1000 person-years) occurred in the codeine cohort. Compared with codeine, hazard ratio (HR) of hip fracture for tramadol was 1.28 (95% confidence interval [CI] 1.13 to 1.46). Risk of hip fracture was also higher in the tramadol cohort than in the naproxen (2.9/1000 person-years for tramadol, 1.7/1000 person-years for naproxen; HR = 1.69, 95% CI 1.41 to 2.03), ibuprofen (3.4/1000 person-years for tramadol, 2.0/1000 person-years for ibuprofen; HR = 1.65, 95% CI 1.39 to 1.96), celecoxib (3.4/1000 person-years for tramadol, 1.8/1000 person-years for celecoxib; HR = 1.85, 95% CI 1.40 to 2.44), or etoricoxib (2.9/1000 person-years for tramadol, 1.5/1000 person-years for etoricoxib; HR = 1.96, 95% CI 1.34 to 2.87) cohort. In this population-based cohort study, the initiation of tramadol was associated with a higher risk of hip fracture than initiation of codeine and commonly used NSAIDs, suggesting a need to revisit several guidelines on tramadol use in clinical practice. © 2020 American Society for Bone and Mineral Research.

AimsThere is an increasing demand for hip arthroplasty in China. We aimed to describe trends in in-hospital mortality after this procedure in China and to examine the potential risk factors.Patients and methodsWe included 210 450 patients undergoing primary hip arthroplasty registered in the Hospital Quality Monitoring System in China between 2013 and 2016. In-hospital mortality after hip arthroplasty and its relation to potential risk factors were assessed using multivariable Poisson regression.ResultsDuring the study period, 626 inpatient deaths occurred within 30 days after hip arthroplasty. Mortality decreased from 2.9% in 2013 to 2.6% in 2016 (p for trend = 0.02). Compared with their counterparts, old age, male sex, and divorced or widowed patients had a higher rate of mortality (all p < 0.05). Risk ratio (RR) for mortality after arthroplasty for fracture was two-fold higher (RR 2.0, 95% confidence interval (CI) 1.5 to 2.6) than that for chronic disease. RRs for mortality were 3.3 (95% CI 2.7 to 3.9) and 8.2 (95% CI 6.5 to 10.4) for patients with Charlson Comorbidity Index (CCI) of 1 to 2 and CCI ≥ 3, respectively, compared with patients with CCI of 0. The rate of mortality varied according to geographical region, the lowest being in the East region (1.8%), followed by Beijing (2.1%), the North (2.9%), South-West (3.6%), South-Central (3.8%), North-East (4.1%), and North-West (5.2%) regions.ConclusionWhile in-hospital mortality after hip arthroplasty in China appears low and declined during the study period, discrepancies in mortality after this procedure exist according to sociodemographic factors. Healthcare resources should be allocated more to underdeveloped regions to further reduce mortality. Cite this article: Bone Joint J 2019;101-B:1209-1217.