Background: Postoperative infection is a common complication in hip fracture patients and the risk appears to have increased during the last decade. However, the impact of infection on mortality after hip fracture surgery remains unclear. Purpose: We aimed to examine the association between infection (any, as well as specific infections), with all-cause mortality following hip fracture surgery. Methods: Using Danish nationwide registries, we conducted a population-based cohort study on 74,771 hip fracture patients ≥ 65 years old operated from 2005-2016. We included hospital-treated infection as a time-varying exposure, and calculated 30-days mortality rate per 1000 person-years (PY). We used time-varying Cox Proportional Hazard Regression to compute 30-days adjusted hazards ratios (aHRs) with 95 % confidence interval (CI) comparing the mortality of hip fracture patients with and without infections. We adjusted for sex, age, comorbidities, medication use, and marital status. Results: Within 30 days of surgery, 9,592 (12.8%) patients developed a hospital-treated infection. Among these, 30-days mortality was 8.43 per 1000 PY compared with 3.34 among patients without infection (aHR=2.72, 95 % CI: 2.56-2.88). For patients who developed pneumonia, aHR was 4.18 (95 % CI: 3.91-4.48), whereas the aHR was 8.86 (95 % CI: 7.88-9.95) for patients who developed systemic sepsis. For patients who sustained reoperation due to infection, aHR was 2.95 (95 %CI: 1.88-4.64). The mortality was higher in infected vs. noninfected patients irrespective of patients' age, sex and comorbidity. Conclusion: Infection within 30 days of hip fracture surgery is associated with substantially increased mortality risk. Further research should improve our knowledge about patients at increased risk and prevention measures for specific infections.

Purpose: We examined the association between delay in surgery and hospital-treated infections in hip fracture patients with and without known comorbidities. Patients and methods: All hip fracture patients aged ≥65 years registered in the Danish Multidisciplinary Hip Fracture Registry from 2005 to 2016 were included (n=72,520). Delay in surgery was defined as the time in hours from admission to surgery and was divided into 3 groups (12, 24 and 48 hrs). The outcomes were hospital-treated pneumonia, urinary tract infection and reoperation due to infection 0–30 days after surgery. As a measure of comorbidity, we used the Charlson Comorbidity Index (CCI): none (no registered comorbidities prior to the fracture), medium (1–2 points) and high (≥3 points). Results: Overall, there was an association between a delay of 12 hrs and pneumonia. A delay of 12 hrs was associated with an increased risk of pneumonia in patients with no comorbidities (adjusted hazard ratio (HR) 1.20, confidence interval (CI) 1.03–1.40) and a delay of 24 hrs was associated with an increased risk of pneumonia in patients with a medium level of comorbidity (HR 1.12, CI (1.02–1.23)). Overall, delay was associated with reoperation due to infection, particularly among patients with comorbidities, although the confidence intervals of some of the estimates were wide. A delay of 48 hrs was associated with an increased risk of reoperation due to infection in patients with a high level of comorbidity (HR 2.36, CI 1.19–4.69). Conclusion: Delay in surgery was associated with an increased risk of hospital-treated pneumonia and reoperations due to infection within 30 days of surgery. The number of postoperative hospital-treated infections within 30 days may be reduced by continuously targeting pre-, per- and postoperative optimization not only for patients with high level of comorbidity but also for hip fracture patients without known comorbidities prior to surgery.

We aimed to examine trends in the incidence of treated infections following hip fracture surgery in Denmark from 2005 to 2016. We conducted a nationwide cohort study using individual‐level linked data from Danish population‐based registries. We calculated cumulative incidence considering death as competing risk and, based on the pseudo‐observation method, risk ratios (RRs) with 95% confidence interval (CI) using the period 2005–2006 as a reference. RRs were adjusted for age, sex, and comorbidity. A total of 74,771 patients aged 65 years or older with first‐time hip fracture surgery were included. The risk of postoperative (at 15, 30, 90, and 365 days) infections increased during 2005–2016. The 30‐day cumulative incidence of all hospital‐treated infections increased from 10.8% (95% CI, 10.2% to 11.3%) in 2005–2006 to 14.3% (95% CI, 13.7% to 15.0%) in 2015–2016 (adjusted RR 1.32; 95% CI, 1.23 to 1.42). Adjusted RR for 30‐day hospital‐treated pneumonia was 1.70 (95% CI, 1.49 to 1.92). The 30‐day cumulative incidence of redeeming community‐based antibiotic prescriptions increased from 17.5% (95% CI, 16.8% to 18.2%) in 2005–2006 to 27.1% (95% CI, 26.3% to 27.9%) in 2015–2016 (adjusted RR 1.54; 95% CI, 1.47 to 1.62). The largest increase was observed for broad‐spectrum antibiotic use (adjusted RR 1.79; 95% CI, 1.68 to 1.90). During 2005–2016, risk of infections was substantially higher in hip fracture patients than in the general population. The risk of hospital‐treated pneumonia and antibiotic prescriptions increased more over time among hip fracture patients. We found increased risks of postoperative treated infections following hip fracture surgery during the 12‐year study period, which could not entirely be explained by similar infection trends in the general population. Given the high mortality following infections in the elderly, further research is needed to identify patients at increased risk to target preventive treatment and potentially reduce complications and mortality in hip fracture patients. © 2018 American Society for Bone and Mineral Research.

BackgroundTapering of disease modifying antirheumatic drugs (DMARDs) to achieve drug-free remission is a goal for the growing group of rheumatoid arthritis (RA) patients in remission. However, the long-term effects of tapering or withdrawal of DMARDs remain unclear.ObjectivesTo compare the 3-year clinical and radiographic outcomes of three conventional synthetic DMARD (csDMARD) treatment strategies (continued stable treatment, half-dose treatment and tapering to withdrawal) among patients in sustained RA remission.MethodsARCTIC REWIND was a randomized, multicenter, open-label, clinical trial enrolling 160 RA patients in sustained remission for ≥1 year on stable csDMARD therapy from 10 different Norwegian rheumatology departments.(1) At baseline, patients were randomized 2:1:1 to stable csDMARDs, half-dose csDMARDs, or half-dose csDMARDs for one year, followed by withdrawal of all csDMARDs (“tapering to withdrawal”). The primary endpoint was absence of disease activity flare over the 3-year study period. A flare was defined as a combination of disease activity score (DAS)>1.6, an increase in DAS ≥0.6 units since the previous visit and ≥2 swollen joints, or if the physician and patient agreed that a clinically significant flare had occurred. Full-dose csDMARD treatment was reinstated upon flare. Secondary endpoints included remission (DAS, ACR/EULAR Boolean) at 1, 2 and 3 years, and 3-year change in radiographic joint damage evaluated by van der Heijde-Sharp score (vdHSS). Data were analyzed using Kaplan-Meier, Mann-Whitney test, Cox and mixed effect logistic regression, with stratification or adjustment for study center.ResultsOf 156 patients who received the allocated treatment strategy, 139 patients completed 3-years follow-up without major protocol violation. Mean baseline methotrexate dose/week was 19.0 mg in the stable group, 19.4 mg in half-dose, and 19.5 mg in the withdrawal group, and mean DAS at baseline was 0.8 in all groups. During the 3-year study period, 80.1% remained flare-free in the stable csDMARD group, 59.5% in the half-dose and 40.8% in the withdrawal group (Figure 1), with corresponding adjusted hazard ratio (aHR) for flare of 2.7 (95% CI: 1.3 to 5.5) in the half-dose group and 4.1 (2.1 to 8.0) in the withdrawal group, compared to stable csDMARD. The aHR was 1.5 (0.8 to 3.0) in the withdrawal group compared to the half-dose group. For all groups, a majority were in remission at 1, 2 and 3 years(Table 1), with the only significant group difference for ACR/EULAR Boolean remission at 3 years, with risk difference for withdrawal vs stable dose -25% (-45 to -6). Mean/median change in vdHSS after 3 years were 0.3/0.0 in the stable group, 1.0/0.5 in the half-dose group, and 0.7/0.0 in the tapering to withdrawal group, with significant difference between the stable and half-dose group, p<0.01. Sensitivity analyses in the full analysis population gave similar results.ConclusionThese 3-year data show that 41% of patients in the tapering to withdrawal arm achieved long-term drug-free remission, indicating that this is a realistic option for some RA patients in sustained remission. The two tapering strategies were associated with an increased risk of flares compared to full-dose csDMARD, and the half-dose group had more radiographic change. However, there were no differences in DAS-remission at the end of the study period. Further research identifying prognostic factors for successful tapering is needed.Reference[1]Lillegraven S et al. JAMA 2021Table 1.Remission at 12, 24 and 36 monthsStable doseHalf-doseTapered to withdrawal*DAS remission 12 months71/77 (92%)34/39 (87%)29/36 (81%) 24 months64/73 (88%)33/37 (89%)33/35 (94%) 36 months64/67 (96%)34/36 (94%)31/34 (91%)ACR/EULAR 2011 Boolean remission 12 months56/77 (73%)25/39 (64%)22/36 (61%) 24 months47/73 (64%)21/37 (57%)20/35 (57%) 36 months55/67 (82%)25/36 (69%)19/34 (56%)*12 months half-dose, thereafter withdrawalAcknowledgements:NIL.Disclosure of InterestsKaja Kjørholt: None declared, Nina Paulshus Sundlisæter: None declared, Anna-Birgitte Aga Speakers bureau: AbbVie, Eli Lilly, Novartis, Pfizer, Consultant of: AbbVie, Eli Lilly, Novartis, Pfizer, Joseph Sexton: None declared, Inge Olsen: None declared, Hallvard Fremstad: None declared, Cristina Spada Consultant of: Advisory board UCB November 2022, Tor Magne Madland Speakers bureau: Cellgene (2017), Novartis (2018), Boehringer (2022), Christian A. Høili: None declared, Gunnstein Bakland Consultant of: Consultant fee from UCB, Åse Lexberg: None declared, Inger Johanne Widding Hansen: None declared, Inger M. Hansen: None declared, Hilde Haukeland Consultant of: Advisory board for UCB Pharma 2x in 2022, NovartisNorge 2017 and 2018, Abbot 2012, Maud-Kristine A Ljosa Consultant of: Advisory Board for Abbvie i 2022, Ellen Moholt: None declared, Till Uhlig Speakers bureau: Lilly, Galapagos, Pfizer, UCB, Consultant of: Lilly, Galapagos, Pfizer, UCB, Tore K. Kvien Speakers bureau: Grünenthal, Sandoz, UCB, Consultant of: AbbVie, Amgen, Celltrion, Gilead, Novartis, Pfizer, Sandoz, UCB, Grant/research support from: AbbVie, Amgen, BMS, Galapagos, Novartis, Pfizer, UCB, Daniel Solomon Grant/research support from: Abbvie, Amgen, CorEvitas, Moderna, and Janssen, Désirée van der Heijde Consultant of: AbbVie, Bayer, BMS, Cyxone, Eisai, Galapagos, Gilead, Glaxo-Smith-Kline, Janssen, Lilly, Novartis, Pfizer, UCB Pharma Director of Imaging Rheumatology bv, Espen A Haavardsholm Speakers bureau: Pfizer, UCB, Consultant of: AbbVie, Boehringer Ingelheim, Eli Lilly, Gilead, Siri Lillegraven Grant/research support from: Boehringer Ingelheim.