The impact of comorbidity status on knee function 1 year after total knee arthroplasty: a population-based cohort study.

BACKGROUND AND PURPOSE: Few studies have examined the impact of comorbidity on functional and clinical knee scores after primary total knee arthroplasty (TKA). We compared the effect of having a high Charlson Comorbidity Index (CCI), relative to a low CCI, on changes in the American Knee Society Score (AKSS) functional and clinical scores from baseline to week 52 after TKA in patients with knee osteoarthritis (OA). METHODS: This population-based cohort study included 22,533 patients identified in the Danish Knee Arthroplasty Register from 1997 to 2021. Patients were classified as having low, medium, or high comorbidity based on CCI. The outcome was defined as the mean change (from preoperative to 1-year post-TKA) in functional and clinical knee scores measured by the AKSS (0-100). The association was analyzed using multiple linear regression by calculating mean change scores adjusting for sex, age, weight, cohabiting status, and baseline AKSS. RESULTS: The prevalence of patients with low, medium, and high comorbidity was 75%, 21%, and 4%, respectively. The mean change score in functional AKSS for patients with high comorbidity was -6 points (95% confidence interval [CI] -7 to -5) compared with low comorbidity. The mean change score in clinical AKSS for patients with high comorbidity was -1 point (CI -2 to 0) compared with low comorbidity. CONCLUSION: Patients with knee OA and medium or high comorbidity can expect similar improvements in functional and clinical AKSS after TKA to patients with low comorbidity.

Epidemiology of male osteoporosis in Denmark (1996-2018).

Osteoporosis in men may be underdiagnosed. One in four men in Denmark will develop osteoporosis after age of 50 years, with fracture as a common presenting symptom. PURPOSE: The aim of this study was to describe epidemiology of male osteoporosis in Denmark. METHODS: In this nationwide registry-based cohort study, we identified men with osteoporosis, 50 years or older, residing in Denmark, during the years 1996-2018. Osteoporosis was defined as one of the following: a hospital diagnosis of osteoporosis; a hospital diagnosis of osteoporosis fracture; or an outpatient dispensing of an anti-osteoporosis medication. We reported annual incidence and prevalence and described the distribution of fractures, comorbidities, socioeconomic status, and initiation of anti-osteoporosis therapy among men with osteoporosis. Selected characteristics were also described among men without osteoporosis of similar age. RESULTS: There were 171,186 men fulfilling the study criteria for osteoporosis. The overall age-standardized incidence rate of osteoporosis was 8.6 per 1000 person-years (95% confidence interval (CI), 8.5-8.6), varying between 7.7 and 9.7, while the prevalence increased from 4.3% (95% CI, 4.2-4.3) to 7.1% (95% CI, 7.0-7.1) during the 22-year period. The remaining-lifetime risk of developing osteoporosis after age of 50 years was close to 30%. The proportion of men initiating anti-osteoporosis treatment within 1 year of diagnosis increased from 6.9% to 29.8%. Men with osteoporosis had more comorbidities and redeemed more medication than did men without osteoporosis of similar age. CONCLUSION: Osteoporosis among men may be undertreated despite increasing treatment initiation.

Optimized medial unicompartmental knee arthroplasty outcome: learning from 20 years of propensity score matched registry data.

BACKGROUND AND PURPOSE: Unicompartmental knee arthroplasty (UKA) has increased in use. We investigated changes to UKA revision risk over the last 20 years compared with total knee arthroplasty (TKA), examined external and patient factors for correlation to UKA revision risk, and described the survival probability for current UKA and TKA practice. PATIENTS AND METHODS: All knee arthroplasties reported to the Danish Knee Arthroplasty Register from 1997 to 2017 were linked to the National Patient Register and the Civil Registration System for comorbidity, emigration, and mortality information. All primary UKA and TKA patients with primary osteoarthritis were included and propensity score matched 4 TKAs to 1 UKA. Revision and mortality were analyzed using competing risk cox regression with a shared gamma frailty component. RESULTS: The matched cohort included 48,195 primary knee arthroplasties (9,639 UKAs). From 1997-2001 to 2012-2017 the 3-year hazard ratio decreased from 5.5 (95% CI 2.7-11) to 1.5 (CI 1.2-1.8) due to increased UKA survival. Cementless fixation, a high percentage usage of UKA, and increased surgical volume decreased UKA revision risk, and increased in occurrence parallel to the decreasing revision risks. Current UKA practice using cementless fixation at a high usage unit has a 3-year implant survival of 96% (CI 97-95), 1.1% lower than current TKA practice. INTERPRETATION: UKA revision risk has decreased over the last 20 years, nearing that of TKA surgery. High usage rates, surgical volume, and the use of cementless fixation have increased during the study and were associated with decreased UKA revision risks.

Association of perioperative thromboprophylaxis on revision rate due to infection and aseptic loosening in primary total hip arthroplasty - new evidence from the Nordic Arthroplasty Registry Association (NARA).

BACKGROUND AND PURPOSE: Results regarding the impact of anticoagulants on revision rate are conflicting. We examined the association between the use of low molecular weight heparin (LMWH) or non-vitamin K oral anticoagulants (NOACs) as thromboprophylaxis after primary total hip arthroplasty (THA) and the revision rate due to infection, aseptic loosening, and all causes. PATIENTS AND METHODS: We conducted a cohort study (n = 53,605) based on prospectively collected data from the national hip arthroplasty registries from Denmark and Norway. The outcome was time to revision due to infection, aseptic loosening, and all causes, studied separately. Kaplan-Meier (KM) survival analysis and a Cox proportional hazard model was used to estimate implant survival and cause-specific hazard ratios (HRs) with 95% confidence intervals (CI) adjusting for age, sex, Charlson Comorbidity Index, fixation type, start, and duration of thromboprophylaxis, and preoperative use of Vitamin K antagonists, NOAC, aspirin, and platelet inhibitors as confounders. RESULTS: We included 40,451 patients in the LMWH group and 13,154 patients in the NOAC group. Regarding revision due to infection, the 1-year and 5-year KM survival was 99% in both the LMWH group and in the NOAC group. During the entire follow-up period, the adjusted HR for revision due to infection was 0.9 (CI 0.7-1.1), 1.6 (CI 1.3-2.1) for aseptic loosening, and 1.2 (CI 1.1-1.4) for all-cause revision for the NOAC compared with the LMWH group. The absolute differences in revision rates between the groups varied from 0.2% to 1%. INTERPRETATION: Compared with LMWH, NOACs were associated with a slightly lower revision rate due to infection, but higher revisions rates due to aseptic loosening and all-cause revision. The absolute differences between groups are small and most likely not clinically relevant. In addition, the observed associations might partly be explained by selection bias and unmeasured confounding, and should be a topic for further research.

Hospital variation in the risk of infection after hip fracture surgery: a population-based cohort study including 29,598 patients from 2012-2017.

Background and purpose - Understanding the key drivers of hospital variation in postoperative infections after hip fracture surgery is important for directing quality improvements. Therefore, we investigated variation in the risk of any infection, and subgroups of infections including pneumonia and sepsis after hip fracture surgery.Methods - In this nationwide population-based cohort study, all Danish patients aged ≥ 65 undergoing surgery for an incident hip fracture from 2012 to 2017 were included. Risk of postoperative infections, based on data from hospital registration (hospital-treated infections) and antibiotic dispensing (community-treated infections), were calculated using multilevel Poisson regression analysis. Hospital variation was evaluated by intra-class coefficient (ICC) and median risk ratio (MRR).Results - The risk of hospital-treated infection was 15%. The risk of community-treated infection was 24%. The adjusted risk varied between hospitals from 7.8-25% for hospital-treated infection and 16-34% for community-treated infection. The ICC indicated that 19% of the adjusted variance was due to hospital level for hospital-treated infection. The ICC for community-treated infections was 13%. The MRR showed a 2-fold increased risk for the average patient acquiring a hospital-treated infection at the highest risk hospital compared with the lowest risk hospital. For community-treated infection, the MRR was 1.4.Interpretation - Our results suggest that 20% of infections could be reduced by applying the top performing hospitals' approach. Nearly a 5th of the variation was at the hospital level. This suggests a more standardized approach to avoid postoperative infection after hip fracture surgery.Hip fracture is a leading cause of hospital admission among the elderly. The 30-day mortality following hip fracture surgery has been approximately 10% during the last few years in Denmark (Pedersen et al. 2017). Higher mortality after hip fracture has been associated with a range of hospital factors (Kristensen et al. 2016, Sheehan et al. 2016) and patient factors in observational studies (Roche et al. 2005). Furthermore, variation in 30-day mortality after hip fracture surgery has been observed between Danish hospitals, but not fully explained (Kristensen et al. 2019).

Mortality and revision risk after femoral neck fracture: comparison of internal fixation for undisplaced fracture with arthroplasty for displaced fracture: a population-based study from Danish National Registries.

Background and purpose - Hemiarthroplasty has lower reoperation frequency and better mobilization compared with internal fixation (IF) in patients with undisplaced femoral neck fractures (FNF), which might translate into lower mortality. In this population-based cohort study we compare the risk of mortality and reoperation in undisplaced FNF treated with IF and displaced FNF treated with arthroplasty in patients older than 70 years old. We assume that, per se, there is no difference in mortality risk between patients with a displaced and an undisplaced FNF.Patients and methods - Hip fracture patients were identified in the Danish Multidisciplinary Hip Fracture Registry during 2005-2015. Data on medication, comorbidities, reoperation, and mortality were retrieved from other Danish medical databases. IF and arthroplasty patients were compared with regards to mortality and reoperation up to 5 years postoperatively. We calculated hazard ratios (HR) with 95% confidence intervals (CI) adjusting for relevant confounders.Results - We included 19,260 FNF treated with arthroplasty and 10,337 FNF with IF. There was an increased risk of mortality for arthroplasty within 30 days, HR 1.3 (95% CI 1.3-1.4), compared with IF but not after 1 and 5 years. Arthroplasty patients had adjusted HRs for reoperation of 0.8 (0.8-0.9) within 1 year, 0.8 (0.7-0.9) within 2 years, and 0.8 (0.8-0.9) within 5 years postoperatively compared with IF.Interpretation - Patients treated for a displaced FNF with arthroplasty had a higher risk of 30-day mortality compared with patients who had an undisplaced FNF treated with IF. It has to be considered that there were baseline differences in the groups but there was no difference in mortality risk up to 5 years post-surgery. Concerning reoperation, patients with a displaced FNF treated with arthroplasty had a lower risk of reoperation compared with IF for undisplaced FNF.

20-year trends of distal femoral, patellar, and proximal tibial fractures: a Danish nationwide cohort study of 60,823 patients.

Background and purpose - Knee fracture treatment burden remains unknown, impeding proper use of hospital resources. We examined 20-year trends in incidence rates (IRs) and patient-, fracture-, and treatment-related characteristics of knee fracture patients.Patients and methods - This nationwide cohort study of prospectively collected data including patients with distal femoral, patellar, and proximal tibial fractures from the Danish National Patient Registry during 1998-2017, assesses IRs of knee fractures (per 105 inhabitants) as well as patient-, fracture-, and treatment-related characteristics of knee fracture patients.Results - During 1998-2017, 60,823 patients (median age 55; 57% female) sustained 74,106 knee fractures. 74% of the study population had a Charlson Comorbidity Index (CCI) of 0 and 18% a CCI of ≥ 2. 51% were proximal tibial fractures, 31% patellar fractures, and 18% distal femoral fractures. At the time of knee fracture, 20% patients had concomitant near-knee fractures (femur/tibia/fibula shaft/hip/ankle), 13% concomitant fractures (pelvic/spine/thorax/upper extremities), 5% osteoporosis, and 4% primary knee osteoarthritis. Over 1/3 knee fractures were surgically treated and of these 86% were open-reduction internal fixations, 9% external fixations, and 5% knee arthroplasties. The most common surgery type was proximal tibia plating (n = 4,868; 60% female). Knee fracture IR increased 12% to 70, females aged > 51 had the highest knee fracture IR, proximal tibial fracture had the highest knee fracture type IR (32) and surgically treated knee fracture IR increased 35% to 23.Interpretation - Knee fracture IRs, especially of surgically treated knee fractures, are increasing and proximal tibial fracture has the highest knee fracture type IR. Females aged > 51 and patients with comorbidity are associated with knee fracture, proximal tibial fracture, proximal tibial fracture surgery, and posttraumatic knee arthroplasty.

A population-based cohort study of rheumatoid arthritis-associated interstitial lung disease: comorbidity and mortality.

OBJECTIVES: To compare mortality risks in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and patients with RA without ILD. DESIGN: Matched cohort study. SETTING: The study was conducted in Denmark, using nationwide, prospectively collected data. PARTICIPANTS: Among patients with RA diagnosed between 2004 and 2016, 679 patients with RA-ILD were matched for birth year, gender and age at RA diagnosis with 11 722 patients with RA but without ILD. MAIN OUTCOME MEASURES: Mortality risks were assessed using Kaplan-Meier mortality curves, and hazard rate ratios (HRRs) for death were estimated using Cox proportional hazards regression models. RESULTS: The number of prevalent RA patients more than doubled from 15 352 to 35 362 individuals during the study period. RA-ILD was seen in 2.2% of incident RA patients. 34.0% of RA-ILD cases were diagnosed within 1 year prior to and 1 year after the RA diagnosis. One-year mortality was 13.9% (95% CI, 11.4% to 16.7%) in RA-ILD and 3.8% (95% CI, 3.5% to 4.2%) in non-ILD RA, 5-year mortality was 39.0% (34.4% to 43.5%) and 18.2% (17.3% to 19.1%) and 10-year mortality was 60.1% (52.9% to 66.5%) and 34.5% (32.8% to 36.1%), respectively. The HRRs for death were 2 to 10 times increased for RA-ILD compared with non-ILD RA, irrespective of follow-up period. Stratified analysis showed that the HRR for death was highest in the first months after the diagnosis of RA-ILD was made, especially in patients diagnosed with RA before diagnosis of ILD. HRR was higher in males and in patients without comorbidity as assessed by the Charlson Comorbidity Index. CONCLUSIONS: ILD is a serious complication in RA, with a significantly increased mortality compared with a large matched cohort of RA comparisons without ILD.

Is the higher mortality among men with hip fracture explained by sex-related differences in quality of in-hospital care? A population-based cohort study.

Background: mortality after hip fracture is two-fold higher in men compared with women. It is unknown whether sex-related differences in the quality of in-hospital care contribute to the higher mortality among men. Objective: to examine sex-related differences in quality of in-hospital care, 30-day mortality, length of hospital stay and readmission among patients with hip fracture. Design: population-based cohort study. Measures: using prospectively collected data from the Danish Multidisciplinary Hip Fracture Registry, we identified 25,354 patients ≥65 years (29% were men). Outcome measures included quality of in-hospital care as reflected by seven process performance measures, 30-day mortality, length of stay (LOS) and readmission within 30 days after discharge. Data were analysed using multivariable regression techniques. Results: in general, there were no substantial sex-related differences in quality of in-hospital care. The relative risk for receiving the individual process performance measure ranged from 0.91 (95% confidence interval (CI) 0.85-0.97) to 0.97 (95% CI 0.94-0.99) for men compared with women. The 30-day mortality was 15.9% for men and 9.3% for women corresponding to an adjusted odds ratio (OR) of 2.30 (95% CI 2.09-2.54). The overall readmission risk within 30 days after discharge was 21.6% for men and 16.4% for women (adjusted OR of 1.38 (95% CI 1.29-1.47)). No difference in LOS was observed between men and women. Conclusions: sex differences in the quality of in-hospital care appeared not to explain the higher mortality and risk of readmission among men hospitalised with hip fracture.

Increased Mortality After Prosthetic Joint Infection in Primary THA.

BACKGROUND: Revision for prosthetic joint infection (PJI) has a major effect on patients' health but it remains unclear if early PJI after primary THA is associated with a high mortality. QUESTIONS/PURPOSES: (1) Do patients with a revision for PJI within 1 year of primary THA have increased mortality compared with patients who do not undergo revision for any reason within 1 year of primary THA? (2) Do patients who undergo a revision for PJI within 1 year of primary THA have an increased mortality risk compared with patients who undergo an aseptic revision? (3) Are there particular bacteria among patients with PJI that are associated with an increased risk of death? METHODS: This population-based cohort study was based on the longitudinally maintained Danish Hip Arthroplasty Register on primary THA performed in Denmark from 2005 to 2014. Data from the Danish Hip Arthroplasty Register were linked to microbiology databases, the National Register of Patients, and the Civil Registration System to obtain data on microbiology, comorbidity, and vital status on all patients. Because reporting to the register is compulsory for all public and private hospitals in Denmark, the completeness of registration is 98% for primary THA and 92% for revisions (2016 annual report). The mortality risk for the patients who underwent revision for PJI within 1 year from implantation of primary THA was compared with (1) the mortality risk for patients who did not undergo revision for any reason within 1 year of primary THA; and (2) the mortality risk for patients who underwent an aseptic revision. A total of 68,504 primary THAs in 59,954 patients were identified, of those 445 primary THAs underwent revision for PJI, 1350 primary THAs underwent revision for other causes and the remaining 66,709 primary THAs did not undergo revision. Patients were followed from implantation of primary THA until death or 1 year of followup, or, in case of a revision, 1 year from the date of revision. RESULTS: Within 1 year of primary THA, 8% (95% CI, 6%-11%) of patients who underwent revision for PJI died. The adjusted relative mortality risk for patients with revision for PJI was 2.18 (95% CI, 1.54-3.08) compared with the patients who did not undergo revision for any cause (p < 0.001). The adjusted relative mortality risk for patients with revisions for PJI compared with patients with aseptic revision was 1.87 (95% CI, 1.11-3.15; p = 0.019). Patients with enterococci-infected THA had a 3.10 (95% CI, 1.66-5.81) higher mortality risk than patients infected with other bacteria (p < 0.001). CONCLUSIONS: Revision for PJI within 1 year after primary THA induces an increased mortality risk during the first year after the revision surgery. This study should incentivize further studies on prevention of PJI and on risk to patients with the perspective to reduce mortality in patients who have had THA in general and for patients with PJI specifically. LEVEL OF EVIDENCE: Level III, therapeutic study.

Increased risk of early and medium-term revision after post-fracture total knee arthroplasty.

Background and purpose - Total knee arthroplasty (TKA) due to posttraumatic fracture osteoarthritis (PTFA) may be associated with inferior prosthesis survival. This study is the first registry-based study solely addressing this issue. Both indications and predictors for revision were identified. Patients and methods - 52,518 primary TKAs performed between 1997 and 2013 were retrieved from the Danish Knee Arthroplasty Register (DKR). 1,421 TKAs were inserted due to PTFA and 51,097 due to primary osteoarthritis (OA). Short-term (< 1 year), medium-term (1-5 years), and long-term (> 5 years) implant survival were analyzed using Kaplan-Meier analysis and Cox regression after age stratification (< 50, 50-70, and >70 years). In addition, indications for revision and characteristics of TKA patients with subsequent revision were determined. Results - During the first 5 years, TKAs inserted due to PTFA had a higher risk of revision than OA (with adjusted hazard ratio ranging from 1.5 to 2.4 between age categories). After 5 years, no significant differences in the risk of revision were seen between the groups. Infection and aseptic loosening were the most common causes of revision in both groups, but TKA instability was a more frequent indication for revision in the PTFA group. In both groups, the revision rates were higher with younger age and extended duration of primary surgery. Interpretation - We found an increased risk of early and medium-term revision of TKAs inserted due to previous fractures in the distal femur and/or proximal tibia. Predictors of revision such as age <50 years and extended duration of primary surgery were identified, and revision due to instability occurred more frequently in TKAs performed due to previous fractures.

Comorbidities in Patients With Anterior Cruciate Ligament Reconstruction Compared With Matched Controls Without Anterior Cruciate Ligament Injury From Danish Registries.

PURPOSE: To describe and compare comorbidity among anterior cruciate ligament (ACL)-reconstructed patients and a gender- and age-matched group without ACL injury. Furthermore, we sought to evaluate the impact of comorbid diseases on the risk of ACL revision surgery. METHODS: This case-control study included 13,443 unilateral primary ACL-reconstructed patients from the Danish Knee Ligament Reconstruction Register matched on gender and age with a comparison group without ACL injury. Information on medical comorbid conditions was obtained from the Danish National Registry of Patients. The prevalence of all comorbid conditions was described for ACL-reconstructed patients and the comparison group in terms of (1) the Charlson Comorbidity Index (CCI); (2) International Classification of Diseases, Tenth Revision disease chapters; and (3) more common chronic diseases in a younger population. Finally, we assessed the risk of ACL revision surgery according to the more common chronic diseases in a younger population, using Cox regression analysis. RESULTS: Although we found a large variety of diseases present among ACL-reconstructed patients, the percentage of patients with a CCI equal to 0 was high in both groups. ACL-reconstructed patients generally had a slightly lower prevalence of almost all International Classification of Diseases, Tenth Revision-classified comorbid disease groups compared with the comparison group without ACL injury. As expected, the prevalence of most diseases increased slightly with rising age. Furthermore, we found that having back pain or diseases of the back did alter the risk of revision surgery. CONCLUSIONS: ACL-reconstructed patients are found to be generally healthy individuals with a low prevalence of serious and chronic diseases compared with an age- and gender-matched control group from the general population. A large variety of diseases are present in the ACL-reconstructed group but with very low prevalence rates and low CCIs, indicating that the severity of their illness is limited. LEVEL OF EVIDENCE: Level III, case-control study.

The "true" incidence of surgically treated deep prosthetic joint infection after 32,896 primary total hip arthroplasties: a prospective cohort study.

BACKGROUND AND PURPOSE: It has been suggested that the risk of prosthetic joint infection (PJI) in patients with total hip arthroplasty (THA) may be underestimated if based only on arthroplasty registry data. We therefore wanted to estimate the "true" incidence of PJI in THA using several data sources. PATIENTS AND METHODS: We searched the Danish Hip Arthroplasty Register (DHR) for primary THAs performed between 2005 and 2011. Using the DHR and the Danish National Register of Patients (NRP), we identified first revisions for any reason and those that were due to PJI. PJIs were also identified using an algorithm incorporating data from microbiological, prescription, and clinical biochemistry databases and clinical findings from the medical records. We calculated cumulative incidence with 95% confidence interval. RESULTS: 32,896 primary THAs were identified. Of these, 1,546 had first-time revisions reported to the DHR and/or the NRP. For the DHR only, the 1- and 5-year cumulative incidences of PJI were 0.51% (0.44-0.59) and 0.64% (0.51-0.79). For the NRP only, the 1- and 5-year cumulative incidences of PJI were 0.48% (0.41-0.56) and 0.57% (0.45-0.71). The corresponding 1- and 5-year cumulative incidences estimated with the algorithm were 0.86% (0.77-0.97) and 1.03% (0.87-1.22). The incidences of PJI based on the DHR and the NRP were consistently 40% lower than those estimated using the algorithm covering several data sources. INTERPRETATION: Using several available data sources, the "true" incidence of PJI following primary THA was estimated to be approximately 40% higher than previously reported by national registries alone.

Effect of an exercise intervention targeting hip strengthening in patients undergoing revision total hip replacement-A study protocol for a multicenter randomized controlled trial.

BACKGROUND: Limited evidence exists regarding the effectiveness of pain relief and functional improvement in patients undergoing revision total hip replacement (THR). Furthermore, there are no clinical guidelines or consensus on optimal rehabilitation after revision THR. PURPOSE: The primary aim of this study was to compare the effectiveness of an exercise intervention targeting hip strengthening with standard community-based rehabilitation in patients undergoing revision THR. METHODS: This multicenter randomized controlled assessor-blinded trial will be conducted at eight hospitals and multiple municipality rehabilitation centers in Denmark. A total of 84 patients undergoing revision THR are estimated to be allocated to either an exercise intervention targeting hip strengthening (NEMEX-STR) or standard community-based rehabilitation (Usual care). Recruitment was initiated in November 2022 and is expected to be completed by June 2024. The primary outcome is change in functional performance measured by the 30 s chair stand test, from baseline to 4 months after the start of intervention. Secondary outcomes include hip disability and osteoarthritis outcome score; 40 m fast-paced walk test; 9-step timed stair climb test; leg extensor muscle power; global perceived effect; and adverse events. Other outcomes include The International Physical Activity Questionnaires, pain intensity, and European quality of life-5 dimensions. An intention-to-treat approach will be used for analyzing changes in primary and secondary outcome measures. The trial was approved by the Central Denmark Region Committees on Health Research Ethics (Journal No 1-10-72-134-22) and registered on the Central Denmark Regions' internal list of research projects (Journal No 1-16-02-285-22). DISCUSSION: To our knowledge, this study is the first to explore different rehabilitation programs after revision THR through a randomized controlled trial. The results will provide clinically relevant evidence for optimal rehabilitation after revision THR for improving functional performance, physical function, and quality of life, with great importance for patients, relatives, physiotherapists, and decision-makers. CLINICALTRIAL: GOV: NCT05657054.

Major comorbid diseases as predictors of infection in the first month after hip fracture surgery: a population-based cohort study in 92,239 patients.

PURPOSE: Comorbidity level is a predictor of infection in the first 30 days after hip fracture surgery. However, the roles of individual comorbid diseases as predictors of infection remain unclear. We investigated individual major comorbid diseases as predictors of infection after hip fracture surgery. METHODS: We obtained Danish population-based medical registry data for patients undergoing hip fracture surgery (2004-2018). Information was obtained on 27 comorbidities, included in various comorbidity indices, 5 years before surgery. The primary outcome was any hospital-treated infection within 30 days after surgery. Cumulative incidence of infection was calculated by considering death as competing risk. We used logistic regression to compute mutually adjusted odds ratios with 95% confidence interval for infection. RESULTS: Of 92,239 patients with hip fracture, 71% were women, and the median age was 83 years. The most prevalent comorbidities were hypertension (23%), heart arrhythmia (15%), and cerebrovascular disease (14%). The 30-day incidence of infection was 15% and 12% among the total cohort and among patients with no record of comorbidities, respectively. Infection incidence was highest among patients with renal disease (24%), depression/anxiety (23%), and chronic pulmonary disease (23%), and lowest among patients with metastatic solid tumor (15%). Adjusted odds ratios of infection ranged from 0.94 [0.80-1.10] for metastatic solid tumor to 1.77 [1.63-1.92] for renal disease. CONCLUSION: Most comorbid diseases were predictors of infection after surgery for hip fracture. Awareness of patients' comorbidity profiles might help clinicians initiate preventive measures or inform patients of their expected risk.

Development and validation of a clinical prediction model for 90-day venous thromboembolism risk following total hip and total knee arthroplasty: a multinational study.

BACKGROUND: The risk of venous thromboembolism (VTE) following total hip arthroplasty (THA) and total knee arthroplasty (TKA) is 1.0% to 1.5%, despite uniform thromboprophylaxis. OBJECTIVES: To develop and validate a prediction model for 90-day VTE risk. METHODS: A multinational cohort study was performed. For model development, records were used from the Oxford Royal College of General Practitioners Research and Surveillance Centre linked to Hospital Episode Statistics and Office of National Statistics UK routine data. For external validation, data were used from the Danish Hip and Knee Arthroplasty Registry, the National Patient Registry, and the National Prescription Registry. Binary multivariable logistic regression techniques were used for development. RESULTS: In the UK data set, 64 032 THA/TKA procedures were performed and 1.4% developed VTE. The prediction model consisted of age, body mass index, sex, cystitis within 1 year before surgery, history of phlebitis, history of VTE, presence of varicose veins, presence of asthma, history of transient ischemic attack, history of myocardial infarction, presence of hypertension and THA or TKA. The area under the curve of the model was 0.65 (95% CI, 0.63-0.67). Furthermore, 36 169 procedures were performed in the Danish cohort, of whom 1.0% developed VTE. Here, the area under the curve was 0.64 (95% CI, 0.61-0.67). The calibration slope was 0.92 in the validation study and 1.00 in the development study. CONCLUSION: This clinical prediction model for 90-day VTE risk following THA and TKA performed well in both development and validation data. This model can be used to estimate an individual's risk for VTE following THA/TKA.

Evaluating the comparability of osteoporosis treatments using propensity score and negative control outcome methods in UK and Denmark electronic health record databases.

Evidence on the comparative effectiveness of osteoporosis treatments is heterogeneous. This may be attributed to different populations and clinical practice, but also to differing methodologies ensuring comparability of treatment groups before treatment effect estimation and the amount of residual confounding by indication. This study assessed the comparability of denosumab vs oral bisphosphonate (OBP) groups using propensity score (PS) methods and negative control outcome (NCO) analysis. A total of 280 288 women aged ≥50 years initiating denosumab or OBP in 2011-2018 were included from the UK Clinical Practice Research Datalink (CPRD) and the Danish National Registries (DNR). Balance of observed covariates was assessed using absolute standardised mean difference (ASMD) before and after PS weighting, matching, and stratification, with ASMD >0.1 indicating imbalance. Residual confounding was assessed using NCOs with ≥100 events. Hazard ratio (HR) and 95% confidence interval (CI) between treatment and NCO was estimated using Cox models. Presence of residual confounding was evaluated with two approaches1: >5% of NCOs with 95% CI excluding 1,2 >5% of NCOs with an upper CI <0.75 or lower CI >1.3. The number of imbalanced covariates before adjustment (CPRD 22/87; DNR 18/83) decreased, with 2-11% imbalance remaining after weighting, matching or stratification. Using approach 1, residual confounding was present for all PS methods in both databases (≥8% of NCOs), except for stratification in DNR (3.8%). Using approach 2, residual confounding was present in CPRD with PS matching (5.3%) and stratification (6.4%), but not with weighting (4.3%). Within DNR, no NCOs had HR estimates with upper or lower CI limits beyond the specified bounds indicating residual confounding for any PS method. Achievement of covariate balance and determination of residual bias were dependent upon several factors including the population under study, PS method, prevalence of NCO, and the threshold indicating residual confounding.

Treatment groups in clinical practice may not be comparable as patient characteristics differ according to the need for the prescribed medication, known as confounding. We assessed comparability of two common osteoporosis treatments, denosumab and oral bisphosphonate, in 280 288 postmenopausal women using electronic health records from UK Clinical Practice Research Datalink (CPRD) and Danish National Registries (DNR). We evaluated comparability of recorded patient characteristics with three propensity score (PS) methods, matching, stratification, and weighting. We assessed residual confounding from unrecorded patient characteristics via negative control outcomes (NCO), events known not to be associated with treatment such as delirium. We found that achieving comparability of osteoporosis treatment groups depended on the study population, PS method, and definition of residual confounding. Weighting and stratification performed the best in DNR and CPRD, respectively. Using a stricter threshold based on statistical significance for the NCO suggested the treatment groups were not comparable, except for PS stratification in DNR. Applying clinically significant thresholds of treatment effect size showed comparability using weighting in CPRD and all PS methods in DNR. Studies should consider more than one PS method to test robustness and identify the largest number of NCO to give the greatest flexibility in detecting residual confounding.

Increased risk of revision after anteromedial compared with transtibial drilling of the femoral tunnel during primary anterior cruciate ligament reconstruction: results from the Danish Knee Ligament Reconstruction Register.

PURPOSE: The goal was to study revision rates and clinical outcome after anterior cruciate ligament (ACL) reconstruction using the anteromedial (AM) technique versus the transtibial (TT) technique for femoral drill hole placement. METHODS: A total of 9,239 primary ACL reconstruction procedures were registered in the Danish Knee Ligament Reconstruction Register between January 2007 and December 2010. The failure of the 2 different femoral drilling techniques was determined using revision ACL reconstruction as the primary endpoint. As secondary endpoints, we used the pivot-shift test and instrumented objective test as well as patient-reported outcome, registered in the Danish Knee Ligament Reconstruction Register. Relative risks (RRs) with 95% confidence intervals (CI) were calculated. RESULTS: We identified 1,945 AM and 6,430 TT primary ACL procedures. The cumulative revision rates for ACL reconstruction after 4 years with the AM and TT techniques were 5.16% (95% CI: 3.61%, 7.34%) and 3.20% (95% CI: 2.51%, 4.08%), respectively. The adjusted overall RR for revision ACL surgery in the AM group was 2.04 (95% CI: 1.39, 2.99), compared with the TT group. Use of the AM technique increased from 13% of all operations in 2007 to 40% in 2010. AM technique was further associated with increased RRs of positive pivot shift of 2.86 (95% CI: 2.40, 3.41) and sagittal instability of 3.70 (95% CI: 3.09, 4.43), compared with the TT technique. CONCLUSIONS: This study found an increased risk of revision ACL surgery when using the AM technique for femoral drill hole placement, compared with the TT technique, in the crude data as well as the stratified and adjusted data. Our finding could be explained by technical failures resulting from introduction of a new and more complex procedure or by the hypothesis put forward in prior studies that compared with a nonanatomic graft placement, a greater force is carried by the anatomic ACL reconstruction and, hence, there is a concomitant higher risk of ACL rupture. LEVEL OF EVIDENCE: Level II, prospective comparative study.

Association of anticholinergic drug use with postoperative mortality among patients with hip fracture. A nationwide cohort study.

PURPOSE: Anticholinergic (AC) drugs are associated with various determinantal outcomes. Data regarding the effect of AC drugs on mortality among geriatric hip fracture patients are limited and inconsistent. METHODS: Using Danish health registries, we identified 31,443 patients aged ≥65 years undergoing hip fracture surgery. AC burden was assessed 90 days before surgery by the Anticholinergic Cognitive Burden (ACB) score and number of AC drugs. Logistic and Cox regression producing odds ratios (OR) and hazard ratios (HR) for 30- and 365- day mortality, adjusting for age, sex, and comorbidities were computed. RESULTS: AC drugs were redeemed by 42% of patients. The 30-day mortality increased from 7% for patients with ACB score of 0 to 16% for patients with ACB score of ≥5, corresponding to an adjusted OR 2.5 (CI: 2.0-3.1). The equivalent adjusted HR for 365-mortality was 1.9 (CI: 1.6-2.1). Using count of AC drugs as exposure we found a stepwise increase in ORs and HRs with increased number of AC drugs; Compared to non-users, adjusted ORs for 30-days mortality were 1.6 (CI: 1.4-1.7), 1.9 (CI: 1.7-2.1), and 2.3 (CI: 1.9-2.7) for users of 1, 2 and 3+ AC drugs. HRs for 365-day mortality were 1.4 (CI: 1.3-1.5), 1.6 (CI: 1.5-1.7) and 1.8 (CI: 1.7-2.0). CONCLUSION: Use of AC drugs was associated with increased 30-day and 365-day mortality among older adults with hip fracture. Simply counting the number of AC drugs may be a clinically relevant and easy AC risk assessment tool. Continued effort to reduce AC drug-use is relevant.

Effect of single versus multiple prophylactic antibiotic doses on prosthetic joint infections following primary total hip arthroplasty in patients with osteoarthritis at public and private hospitals in Denmark: protocol for a nationwide cross-over, cluster randomised, non-inferiority trial [The Pro-Hip-Quality Trial].

INTRODUCTION: A feared complication after total hip arthroplasty (THA) is prosthetic joint infection (PJI), associated with high morbidity and mortality. Prophylactic antibiotics can reduce the risk of PJI. However, there is no consensus on the dosages and current recommendations are based on a low evidence level. The objective is to compare the effect of a single versus multiple doses of prophylactic antibiotics administered within 24 hours on PJI. METHODS AND ANALYSIS: The study is designed as a cross-over, cluster randomised, non-inferiority trial. All clinical centres use both antibiotic practices (1 year of each intervention). All Danish orthopaedic surgery departments will be involved: Based on quality databases, 2-year cohorts of approximately 20 000 primary THAs conducted at 39 public and private hospitals, will be included. INCLUSION CRITERIA: age ≥18 years, all indications for THA except patients operated due to acute or sequelae from proximal femoral or pelvic fractures or bone tumour or metastasis. The primary outcome is PJI within 90 days after primary THA. Secondary outcomes include (1) serious adverse events, (2) potential PJI, (3) length of hospitalisation stay, (4) cardiovascular events, (5) hospital-treated infections, (6) community-based antibiotic use, (7) opioid use and (8) use of acetaminophen and non-steroidal anti-inflammatory drugs. All outcome measures will be extracted from national databases. Analyses will be based on the intention-to-treat population. Non-inferiority will be shown if the upper limit of the two-sided 95% CI for the OR is less than 1.32 for the single dose as compared with multiple doses. The results will establish best practice on antibiotic prophylaxis dosages in the future. ETHICS AND DISSEMINATION: This study has been approved by Committees on Health Research Ethics for The Capital Region of Denmark (21069108) and The Danish Medicines Agency (2021091723). All results will be presented in peer-reviewed medical journals and international conferences. TRIAL REGISTRATION NUMBER: NCT05530551.