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Objective: The current guidelines recommend weight loss for patients with overweight or obesity and knee or hip osteoarthritis (OA); however, there is a paucity of data on the relation of weight loss to death among patients with OA. We aimed to examine the relation of the rate of weight loss induced by antiobesity medications over one year to all‐cause mortality among patients with overweight or obesity and knee or hip OA. Methods: Using the IQVIA Medical Research Database, we identified people with overweight or obesity and knee or hip OA. We emulated analyses of a hypothetical target trial to assess the effect of slow‐to‐moderate (2%–10%) or fast (≥10%) weight loss induced by the initiation of antiobesity medications within one year on all‐cause mortality and secondary outcomes over five years' follow‐up. Results: Among 6,524 participants, the five‐year all‐cause mortality rates were 5.3%, 4.0%, and 5.4% for weight gain or stable, slow‐to‐moderate weight loss, and fast weight loss arms, respectively. Compared with the weight gain or stable arm, hazard ratios of all‐cause mortality were 0.72 (95% confidence interval [CI] 0.56–0.92) for the slow‐to‐moderate weight loss arm and 0.99 (95% CI 0.67–1.44) for the fast weight loss arm. We found dose–response protective effects of weight loss on incident hypertension, type 2 diabetes, and venous thromboembolism but a slightly higher risk of cardiovascular disease, albeit not statistically significant, in the fast rate of weight loss arm than in the weight gain or stable arm and no significant relations of weight loss to the risk of cancer. Conclusion: In this population‐based study, a slow‐to‐moderate, but not fast, rate of weight loss induced by antiobesity medications is associated with a lower risk of all‐cause mortality in people with overweight or obesity and knee or hip OA. [ABSTRACT FROM AUTHOR]

Objective: Gout is associated with a higher risk of fracture; however, findings on the associations of hyperuricemia and urate‐lowering therapy (ULT) with the risk of fracture have been inconsistent. We examined whether lowering serum urate (SU) levels with ULT to a target level (i.e., <360 μmoles/liter) reduces the risk of fracture among individuals with gout. Methods: We emulated analyses of a hypothetical target trial using a "cloning, censoring, and weighting" approach to examine the association between lowering SU with ULT to the target levels and the risk of fracture using data from The Health Improvement Network, a UK primary care database. Individuals with gout who were age 40 years or older and for whom ULT was initiated were included in the study. Results: Among 28,554 people with gout, the 5‐year risk of hip fracture was 0.5% for the "achieving the target SU level" arm and 0.8% for the "not achieving the target SU level" arm. The risk difference and hazard ratio for the "achieving the target SU level" arm was –0.3% (95% confidence interval [95% CI] –0.5%, –0.1%) and 0.66 (95% CI 0.46, 0.93), respectively, compared with the "not achieving the target SU level" arm. Similar results were observed when the associations between lowering SU level with ULT to the target levels and the risk of composite fracture, major osteoporotic fracture, vertebral fracture, and nonvertebral fracture were assessed. Conclusion: In this population‐based study, lowering the SU level with ULT to the guideline‐based target level was associated with a lower risk of incident fracture in people with gout. [ABSTRACT FROM AUTHOR]

Background: Two recent randomized clinical trials of escalating doses of allopurinol for the progression of chronic kidney disease (CKD) reported no benefits but potentially increased risk for death. Whether the risk could occur in patients with gout and concurrent CKD remains unknown.Objective: To examine the relation of allopurinol initiation, allopurinol dose escalation, and achieving target serum urate (SU) level after allopurinol initiation to all-cause mortality in patients with both gout and CKD.Design: Cohort study.Setting: The Health Improvement Network U.K. primary care database (2000 to 2019).Participants: Patients aged 40 years or older who had gout and concurrent moderate-to-severe CKD.Measurements: The association between allopurinol initiation and all-cause mortality over 5-year follow-up in propensity score (PS)-matched cohorts was examined. Analysis of hypothetical trials were emulated: achieving target SU level (<0.36 mmol/L) versus not achieving target SU level and dose escalation versus no dose escalation for mortality over 5-year follow-up in allopurinol initiators.Results: Mortality was 4.9 and 5.8 per 100 person-years in 5277 allopurinol initiators and 5277 PS-matched noninitiators, respectively (hazard ratio [HR], 0.85 [95% CI, 0.77 to 0.93]). In the target trial emulation analysis, the HR of mortality for the achieving target SU level group compared with the not achieving target SU level group was 0.87 (CI, 0.75 to 1.01); the HR of mortality for allopurinol in the dose escalation group versus the no dose escalation group was 0.88 (CI, 0.73 to 1.07).Limitation: Residual confounding cannot be ruled out.Conclusion: In this population-based data, neither allopurinol initiation, nor achieving target SU level with allopurinol, nor allopurinol dose escalation was associated with increased mortality in patients with gout and concurrent CKD.Primary Funding Source: Project Program of National Clinical Research Center for Geriatric Disorders. [ABSTRACT FROM AUTHOR]

Objective: Hyperuricemia is a precursor to gout and is often present in other metabolic diseases that are promoted by microbiome dysbiosis. We undertook this study to examine the association of gut microbiota with hyperuricemia and serum urate levels in humans. Methods: Study participants were derived from a community‐based observational study, the Xiangya Osteoarthritis Study (discovery cohort). Hyperuricemia was defined as the presence of a serum urate level >357 μmoles/liter in women and >416 μmoles/liter in men. Gut microbiota were analyzed using 16S ribosomal RNA sequencing of stool samples. We examined the relationship of microbiota dysbiosis (i.e., richness, diversity, composition, and relative abundance of microbiota taxa) and predicted functional pathways to prevalent hyperuricemia and serum urate levels. We verified the associations in an independent observational study, the Step Study (validation cohort). Results: The discovery cohort consisted of 1,392 subjects from rural areas (mean age 61.3 years, 57.4% women, 17.2% with hyperuricemia). Participants with hyperuricemia had decreased richness and diversity, altered composition of microbiota, and lower relative abundances of genus Coprococcus compared to those with normouricemia. Predicted KEGG metabolism pathways including amino acid and nucleotide metabolisms were significantly altered in subjects with hyperuricemia compared to those with normouricemia. Gut microbiota richness, diversity, and low relative abundances of genus Coprococcus were also associated with high levels of serum urate. These findings were replicated in the validation cohort with 480 participants. Conclusion: Gut microbiota dysbiosis is associated with elevated serum urate levels. Our study examines the possibility that microbiota dysbiosis may modulate these levels. [ABSTRACT FROM AUTHOR]

Background: Having a senior surgeon present for high-risk patients is an important safety measure in emergency surgery, but 24-h consultant cover is not efficient. We aimed to develop a user-friendly toolbox (risk identification, outcome prediction and patient stratification) to support when to involve a senior surgeon.Materials and Methods: We included 11,901 general surgery patients (10.0% emergencies) in a multicenter prospective cohort in China (2015-2016). Patient information and surgeons' seniority were compared between emergency and elective surgery with the same procedure codes. Risk indicators common in these two surgical timings and specific to emergency surgery were identified, and their clinical importance was evaluated by a working group of 48 experienced surgeons. Predictive models for mortality and morbidity were built using logistic regression models. Stratification rules were created to balance patients' risk and surgeons' caseload with an Acute Call Team (ACT) model.Results: Emergency patients had significantly higher risks of mortality (3.6% vs 0.6%) and morbidity (7.8% vs 4.3%) than elective patients, but disproportionally fewer senior surgeons (59.9% vs 91.4%) were present. Using three risk indicators (American Society of Anesthesiologists score, age, blood urea nitrogen), C-statistic (95% CI) for prediction of emergency mortality was high [0.90 (0.84-0.96)]. It was less complex but equally accurate as two existing and validated models (0.86 [0.79-0.93] and 0.86 [0.77-0.95]). Using five indicators, C-statistic (95% CI) was moderate for prediction of overall morbidity [0.77 (0.72-0.83)], but high for severe morbidity [0.92 (0.88-0.97)]. Based on stratification rules of the ACT model, patient mortality and morbidity were 0.5% and 5.3% in the low-risk stratum (composing 64.6% of emergency caseload), and 15.9% and 29.0% in the very high-risk stratum (6.9% of caseload).Conclusion: These findings show the practical feasibility of using a risk assessment tool to direct senior surgeons' involvement in emergency general surgery. [ABSTRACT FROM AUTHOR]

Objectives: Osteoarthritis is a leading cause of immobility and joint replacement, two strong risk factors for venous thromboembolism (VTE). We aimed to examine the relation of knee, hip and hand osteoarthritis to the risk of VTE and investigate joint replacement as a potential mediator.Methods: We conducted three cohort studies using data from The Health Improvement Network. Up to five individuals without osteoarthritis were matched to each case of incident knee (n=20 696), hip (n=10 411) or hand (n=6329) osteoarthritis by age, sex, entry time and body mass index. We examined the relation of osteoarthritis to VTE (pulmonary embolism and deep vein thrombosis) using a multivariable Cox proportional hazard model.Results: VTE developed in 327 individuals with knee osteoarthritis and 951 individuals without osteoarthritis (2.7 vs 2.0 per 1000 person-years), with multivariable-adjusted HR being 1.38 (95% CI 1.23 to 1.56). The indirect effect (HR) of knee osteoarthritis on VTE through knee replacement was 1.07 (95% CI 1.01 to 1.15), explaining 24.8% of its total effect on VTE. Risk of VTE was higher in hip osteoarthritis than non-osteoarthritis (3.3 vs 1.8 per 1000 person-years; multivariable-adjusted HR=1.83, 95% CI 1.56 to 2.13). The indirect effect through hip replacement yielded an HR of 1.14 (95% CI 1.04 to 1.25), explaining 28.1% of the total effect. No statistically significant difference in VTE risk was observed between hand osteoarthritis and non-osteoarthritis (1.5 vs 1.6 per 1000 person-years; multivariable-adjusted HR=0.88, 95% CI 0.67 to 1.16).Conclusion: Our large population-based cohort study provides the first evidence that knee or hip osteoarthritis, but not hand osteoarthritis, was associated with an increased risk of VTE, and such an association was partially mediated through knee or hip replacement. [ABSTRACT FROM AUTHOR]

Background: Denosumab is effective for osteoporosis, but discontinuation leads to rapid reversal of its therapeutic effect.Objective: To estimate the risk for fracture among users of denosumab who delayed subsequent doses compared with users who received doses on time.Design: Population-based cohort study.Setting: The Health Improvement Network U.K. primary care database, 2010 to 2019.Patients: Persons aged 45 years or older who initiated denosumab therapy for osteoporosis.Measurements: Observational data were used to emulate an analysis of a hypothetical trial with 3 dosing intervals: subsequent denosumab injection given within 4 weeks after the recommended date ("on time"), delay by 4 to 16 weeks ("short delay"), and delay by more than 16 weeks ("long delay"). The primary outcome was a composite of all fracture types at 6 months after the recommended date. Secondary outcomes were major osteoporotic fracture, vertebral fracture, hip fracture, and nonvertebral fracture.Results: Investigators identified 2594 patients initiating denosumab therapy. The risk for composite fracture over 6 months was 27.3 in 1000 for on-time dosing, 32.2 in 1000 for short delay, and 42.4 in 1000 for long delay. Compared with on-time injections, short delay had a hazard ratio (HR) for composite fracture of 1.03 (95% CI, 0.63 to 1.69) and long delay an HR of 1.44 (CI, 0.96 to 2.17) (P for trend = 0.093). For vertebral fractures, short delay had an HR of 1.48 (CI, 0.58 to 3.79) and long delay an HR of 3.91 (CI, 1.62 to 9.45).Limitation: Dosing schedules were not randomly assigned.Conclusion: Although delayed administration of subsequent denosumab doses by more than 16 weeks is associated with increased risk for vertebral fracture compared with on-time dosing, evidence is insufficient to conclude that fracture risk is increased at other anatomical sites with long delay.Primary Funding Source: National Clinical Research Center for Orthopedics, Sports Medicine & Rehabilitation. [ABSTRACT FROM AUTHOR]

Objective Statins are reported to have a potential benefit on progression of OA and on disease activity in RA, but existing evidence is conflicting. Our objective was to examine whether statins associate with reduction in the risk for joint replacement due to OA and RA. Methods This was a propensity score-matched cohort study. Electronic health records from the UK Clinical Practice Research Datalink were used. We selected people prescribed statins and people never prescribed statins. Each statin user was matched to a non-user by age, gender, practice and propensity score for statin prescription. The main outcome measures were knee or hip joint replacement overall, and specifically because of OA or RA. The association between statins and risk of joint replacement was assessed using Cox proportional hazard regression. Statin exposure was categorized according to the potency of reducing low-density lipoprotein as low (21–28%), medium (32–38%) or high (42–55%) intensity. Results A total of 178 467 statin users were matched with 178 467 non-users by age, gender, practice and propensity score. Overall, statin was not associated with reduced risk of knee or hip replacement (hazard ratio 0.99, 95% CI: 0.97, 1.03), unless prescribed at high strength (0.86, 0.75–0.98). The reduced risk was only observed for joint replacement due to RA (0.77, 0.63–0.94) but not OA (0.97, 0.94–1.01). Conclusion Statins at high intensity may reduce the risk of hip or knee replacement. This effect may be RA specific. Further studies to investigate mechanisms of risk reduction and the impact in people with RA are warranted. [ABSTRACT FROM AUTHOR]

Objective: The aim was to examine the association between dietary selenium intake and nonalcoholic fatty liver disease (NAFLD) in a large group of middle-aged and elderly Chinese persons.Method: The data included in this analysis were from a population-based study, the Xiangya Hospital Health Management Center Study. NAFLD was diagnosed by (1) imaging or histological evidence of hepatic steatosis; (2) absence of specific etiologies of NAFLD; and (3) no heavy consumption of alcohol. Dietary selenium intake was assessed using a validated semi-quantitative food frequency questionnaire. The association between dietary selenium intake and the prevalence of NAFLD was evaluated using logistic and spline regression in a cross-sectional study of 5436 subjects.Results: The prevalence of NAFLD was 36.8%. Compared with the lowest quintile, the energy-adjusted odds ratios for NAFLD were 1.27 (95% confidence interval [CI], 1.07-1.52), 1.30 (95% CI, 1.09-1.55), and 1.58 (95% CI, 1.33-1.89) for the third, fourth, and fifth quintiles of selenium intake, respectively, and there was a positive dose-response relationship (r = 0.88, p for trend = 0.008). Similar results were observed for men and women separately. The findings were not materially altered by adjustment for potential confounders (i.e., age, gender, body mass index, smoking status, diabetes, hypertension, activity level, nutritional supplements, energy intake, fat intake, fiber intake, cholesterol and saturated fatty acid intake).Conclusions: In this middle-aged and elderly population, subjects with higher dietary selenium intake, even below the recommended nutrient intake in China, had higher prevalence of NAFLD in a dose-response relationship manner. [ABSTRACT FROM AUTHOR]

Importance: An American Academy of Orthopaedic Surgeons guideline recommends tramadol for patients with knee osteoarthritis, and an American College of Rheumatology guideline conditionally recommends tramadol as first-line therapy for patients with knee osteoarthritis, along with nonsteroidal anti-inflammatory drugs.Objective: To examine the association of tramadol prescription with all-cause mortality among patients with osteoarthritis.Design, Setting, and Participants: Sequential, propensity score-matched cohort study at a general practice in the United Kingdom. Individuals aged at least 50 years with a diagnosis of osteoarthritis in the Health Improvement Network database from January 2000 to December 2015, with follow-up to December 2016.Exposures: Initial prescription of tramadol (n = 44 451), naproxen (n = 12 397), diclofenac (n = 6512), celecoxib (n = 5674), etoricoxib (n = 2946), or codeine (n = 16 922).Main Outcomes and Measures: All-cause mortality within 1 year after initial tramadol prescription, compared with 5 other pain relief medications.Results: After propensity score matching, 88 902 patients were included (mean [SD] age, 70.1 [9.5] years; 61.2% were women). During the 1-year follow-up, 278 deaths (23.5/1000 person-years) occurred in the tramadol cohort and 164 (13.8/1000 person-years) occurred in the naproxen cohort (rate difference, 9.7 deaths/1000 person-years [95% CI, 6.3-13.2]; hazard ratio [HR], 1.71 [95% CI, 1.41-2.07]), and mortality was higher for tramadol compared with diclofenac (36.2/1000 vs 19.2/1000 person-years; HR, 1.88 [95% CI, 1.51-2.35]). Tramadol was also associated with a higher all-cause mortality rate compared with celecoxib (31.2/1000 vs 18.4/1000 person-years; HR, 1.70 [95% CI, 1.33-2.17]) and etoricoxib (25.7/1000 vs 12.8/1000 person-years; HR, 2.04 [95% CI, 1.37-3.03]). No statistically significant difference in all-cause mortality was observed between tramadol and codeine (32.2/1000 vs 34.6/1000 person-years; HR, 0.94 [95% CI, 0.83-1.05]).Conclusions and Relevance: Among patients aged 50 years and older with osteoarthritis, initial prescription of tramadol was associated with a significantly higher rate of mortality over 1 year of follow-up compared with commonly prescribed nonsteroidal anti-inflammatory drugs, but not compared with codeine. However, these findings may be susceptible to confounding by indication, and further research is needed to determine if this association is causal. [ABSTRACT FROM AUTHOR]

Background: Physical distancing measures taken to contain COVID-19 transmission may substantially reduce physical activity levels and cause individuals to adopt a more sedentary lifestyle.Objective: The objective of this study is to determine if there was any change in daily steps, an important component of daily physical activity, and examine risk factors for frequent low daily steps during the COVID-19 epidemic.Methods: We used data collected from the Step Study, a population-based longitudinal study of walking activity among residents aged ≥40 years in Changsha, China. Daily steps were collected via a smartphone linked to WeChat, a social networking platform. We plotted mean daily steps and the prevalence of low daily steps (≤1500 steps/day) 30 days before (reference period) and 30 days after (epidemic period) January 21, 2020 (date of the first COVID-19 case diagnosed in Changsha), and compared it with the same corresponding period from 2019. We examined the association of risk factors with the prevalence of frequent low daily steps (≤1500 steps/day for ≥14 days) using logistic regression.Results: Among 3544 participants (mean age 51.6 years; n=1226 females, 34.6%), mean daily steps dropped from 8097 to 5440 and the prevalence of low daily steps increased from 3% (2287/76,136 person-day) to 18.5% (12,951/70,183 person-day) during the reference and epidemic periods, respectively. No such phenomenon was observed during the corresponding period in 2019. Older age (P for interaction=.001) and female sex (P for interaction<.001) were both associated with a higher prevalence of frequent low daily steps and were more pronounced during the epidemic period. More education was associated with a lower prevalence of frequent low daily steps during the reference period but not the epidemic period (P for interaction=.34). Body mass index or comorbidity were not associated with frequent low daily steps during either period.Conclusions: Daily steps of Changsha residents aged ≥40 years dropped significantly during the COVID-19 period, especially among older adults and females. Although successful physical distancing, measured by the rapid downward trend in daily step counts of residents, played a critical role in the containment of the COVID-19 epidemic, our findings of an increase in the prevalence of frequent low daily steps raise concerns about unintended effects on physical activity. [ABSTRACT FROM AUTHOR]