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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]

Nonsteroidal antiinf lammatory drugs (NSAIDs) remain the mainstay of the pharmacologic management for relieving osteoarthritis pain, and low-dose aspirin is often prescribed to osteoarthritis patients who are at high risk of cardiovascular disease (CVD). We conducted cohort studies using data from The Health Improvement Network (THIN) database (2000–2019) to assess whether the relationship of initiation of naproxen or ibuprofen vs. initiation of other NSAIDs (excluding both naproxen and ibuprofen), respectively, to the risk of CVD was modified by coprescription of low-dose aspirin among the participants with osteoarthritis. Among participants without coprescription of aspirin, the risk of CVD was lower in naproxen initiators (10.3/1000 person-years) than in other NSAIDs initiators (13.2/1000 person-years; hazard ratio = 0.71, 95% confidence interval: 0.60, 0.85). Among participants with coprescription of aspirin, however, the risk of CVD was higher among naproxen initiators (36.9/1000 person-years) than that among other NSAIDs initiators (34.8/1000 person-years; hazard ratio = 1.48, 95% confidence interval: 1.12, 1.84). The association was significantly modified by coprescription of aspirin (P  < 0.001). Similar findings were observed in the association of initiation of ibuprofen vs. other NSAIDs with the risk of CVD, which was significantly modified by coprescription of aspirin (P  < 0.001). These findings suggest that osteoarthritis patients and clinicians should be aware of the potential CVD risk of concurrently taking naproxen or ibuprofen and low-dose aspirin. [ABSTRACT FROM AUTHOR]

Objectives Angiotensin II is implicated in GCA pathology. We examined whether the use of angiotensin receptor blockers (ARBs) is associated with GCA risk compared with angiotensin-converting enzyme inhibitors (ACEis) or other antihypertensives. Methods We performed a matched cohort study including adults who were initiators of antihypertensives in UK primary care data between 1995 and 2019. Treatment-naïve individuals without prior GCA or PMR were categorized into three groups—ARB initiators, ACEi initiators, or other antihypertensive initiators (beta-blockers, calcium channel blockers, diuretics or alpha-adrenoceptor blockers)—and followed for up to 5 years. Incident GCA was defined using validated Read codes, with age of onset ≥50 years and two or more glucocorticoid prescriptions. Inverse probability–weighted Cox models were used to model outcome risk, adjusting for lifestyle parameters, comorbidities and comedications. Results Among >1 million new starters of antihypertensives (81 780 ARBs, 422 940 ACEis and 873 066 other antihypertensives), the incidence rate of GCA per 10 000 patient-years was 2.73 (95% CI 2.12, 3.50) in the ARB group, 1.76 (95% CI 1.25, 2.39) in the ACEi group and 1.90 (95% CI 1.37, 2.56) in the other antihypertensives group. The hazard of GCA was higher in ARB initiators [hazard ratio (HR) 1.55; 95% CI 1.16, 2.06] than initiators of ACEis, but similar between initiators of other antihypertensives and ACEis (HR 1.08; 95% CI 0.87, 1.35). Conclusions Initiation of ARBs is associated with a higher risk of GCA compared with ACEis or other antihypertensives. Mechanistic studies of angiotensin receptor biology will provide further clarity for our findings. [ABSTRACT FROM AUTHOR]

Objective: Gout patients often have multiple comorbidities, making them susceptible to SARS–CoV‐2 infection and poor outcomes. This study was undertaken to examine the association between gout and the risk of SARS–CoV‐2 infection and severe outcomes, especially in patients who have received a SARS–CoV‐2 vaccine. Methods: We conducted 2 cohort studies using The Health Improvement Network in the UK. Individuals with gout and those without gout from the general population were followed up from December 8, 2020 to October 31, 2021. We estimated the rate difference (RD) and hazard ratio (HR) of SARS–CoV‐2 infection and severe outcomes (i.e., hospitalization and death within 30 days after SARS–CoV‐2 infection) for individuals with gout versus those without gout using a Cox proportional hazards model according to SARS–CoV‐2 vaccination status. We adjusted for potential confounders by using overlap weighting of exposure scores. Results: Among the vaccinated cohort, 1,955 cases of breakthrough COVID‐19 infection occurred in 54,576 individuals with gout (4.68 cases per 1,000 person‐months), and 52,468 cases occurred in 1,336,377 individuals without gout (3.76 cases per 1,000 person‐months). The partially adjusted RD of breakthrough infection was 0.91 cases per 1,000 person‐months (95% confidence interval [95% CI] 0.62–1.20 cases per 1,000 person‐months), and the partially adjusted HR was 1.24 (95% CI 1.19–1.30). Gout was also associated with an increased risk of hospitalization (adjusted HR 1.30 [95% CI 1.10–1.53]) and death (adjusted HR 1.36 [95% CI 0.87–2.13]). Women with gout had an increased risk of hospitalization (adjusted HR 1.55 [95% CI 1.15–2.10]) and death (adjusted HR 2.46 [95% CI 1.12–5.41]). Similar associations with gout were observed in the unvaccinated cohort. Conclusion: These general population data suggest that individuals with gout, especially women, have higher risks of SARS–CoV‐2 infection and severe outcomes, even when vaccinated. [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]

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]

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: This study aimed at examining the association between symptomatic knee osteoarthritis and all-cause mortality based on four population-based longitudinal surveys. Method: Data were retrieved from the English Longitudinal Study of Aging (ELSA), the Survey of Health, Aging and Retirement in Europe (SHARE), the Korean Longitudinal Study of Aging (KLoSA), and the Indonesian Family Life Survey (IFLS). The association between symptomatic knee osteoarthritis and all-cause mortality over the 8- to 12-year follow-up period was assessed using Cox-proportional hazard models. Results: In the entire sample of 59,522 participants (4823 with symptomatic knee osteoarthritis; 54,699 without symptomatic knee osteoarthritis [control group]; mean age: 61.8 years; female percentage: 55.3%), 8375 died (937 in the symptomatic knee osteoarthritis group, 7438 in the control group) during the follow-up period. Patients with symptomatic knee osteoarthritis had a higher risk of all-cause mortality than control group without adjusting for potential confounders in each survey, and the unadjusted hazard ratios (HRs) of all-cause mortality were 1.32 (95% confidence interval [CI] 1.18 to 1.47) in ELSA, 1.40 (95%CI 1.24 to 1.56) in SHARE, 1.25 (95%CI 1.06 to 1.47) in KLoSA, and 1.65 (95%CI 1.31 to 2.07) in IFLS. However, with adjustment of potential confounders, the corresponding HRs dropped to 1.07 (95%CI 0.94 to 1.20) in ELSA, 1.08 (95%CI 0.97 to 1.22) in SHARE, 0.91 (95%CI 0.77 to 1.08) in KLoSA, and 0.89 (95%CI 0.66 to 1.21) in IFLS, respectively. Conclusions: In these four population-based longitudinal studies, no association between symptomatic knee osteoarthritis and increased risk of all-cause mortality was observed after adjusting for potential confounders. Key Points • This study evaluated the association between symptomatic knee OA and the risk of all-cause mortality among the participants retrieved from four large population-based longitudinal studies across the world. • No association between symptomatic knee osteoarthritis and increased risk of all-cause mortality was observed after considering potential confounders, and our findings were consistent with the results derived from four independent longitudinal studies. • The present study included four international population-based longitudinal studies, comprising both developed and developing areas, which allowed the findings to be interpreted under larger circumstance. [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]