Association between duration of anticoagulant thromboprophylaxis and revision rate in primary total hip arthroplasty: a Danish and Norwegian nationwide cohort study.

BACKGROUND AND PURPOSE: There are concerns that bleeding following primary total hip arthroplasty (THA) contributes to prolonged wound drainage and prosthetic joint infection (PJI). We examined whether short (1-5 days), medium (6-14 days), and extended (≥ 15 days) duration of thromboprophylaxis is associated with the 5-year revision rate after THA due to osteoarthritis. PATIENTS AND METHODS: We performed a cohort study based on data from hip arthroplasty and administrative registries in Denmark and Norway (2008-2014). The outcome was revision surgery due to PJI, aseptic loosening or any cause, and patient mortality. Adjusted cause-specific hazard ratios (HRs) were analyzed with Cox regression analyses. RESULTS: Among 50,482 THA patients, 8,333 received short, 17,009 received medium, and 25,140 received extended thromboprophylaxis. The HRs for revision due to PJI within 5 years were 1.0 (95%CI 0.7-1.3) and 1.1 (CI 0.9-1.3) for short and extended vs. medium treatment, whereas HR for extended vs. medium prophylaxis was 1.5 (CI 1.2-2.0) within 3 months. The HRs for revision due to aseptic loosening within 5 years were 1.0 (CI 0.7-1.4) and 1.1 (CI 0.9-1.4) for short and extended vs. medium treatment. The HRs for any revision within 5 years were 0.9 (CI 0.8-1.1) and 0.9 (CI 0.8-1.0) for short and extended vs. medium treatment. Extended vs. medium prophylaxis was associated with a decreased 0-3 month mortality. The absolute differences at 5 years were ≤ 1%. CONCLUSION: Our data suggests no association between duration of anticoagulant thromboprophylaxis and revision rate within 5 years of primary THA. The extended thromboprophylaxis might be associated with early increased revision rate due to PJI but also with lower mortality; however, the clinical relevance of this finding requires further research.

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.

Prediction of Early Periprosthetic Joint Infection After Total Hip Arthroplasty.

Purpose: To develop a parsimonious risk prediction model for periprosthetic joint infection (PJI) within 90 days after total hip arthroplasty (THA). Patients and Methods: We used logistic LASSO regression with bootstrap ranking to develop a risk prediction model for PJI within 90 days based on a Swedish cohort of 88,830 patients with elective THA 2008-2015. The model was externally validated on a Danish cohort with 18,854 patients. Results: Incidence of PJI was 2.45% in Sweden and 2.17% in Denmark. A model with the underlying diagnosis for THA, body mass index (BMI), American Society for Anesthesiologists (ASA) class, sex, age, and the presence of five defined comorbidities had an area under the curve (AUC) of 0.68 (95% CI: 0.66 to 0.69) in Sweden and 0.66 (95% CI: 0.64 to 0.69) in Denmark. This was superior to traditional models based on ASA class, Charlson, Elixhauser, or the Rx Risk V comorbidity indices. Internal calibration was good for predicted probabilities up to 10%. Conclusion: A new PJI prediction model based on easily accessible data available before THA was developed and externally validated. The model had superior discriminatory ability compared to ASA class alone or more complex comorbidity indices and had good calibration. We provide a web-based calculator (https://erikbulow.shinyapps.io/thamortpred/) to facilitate shared decision making by patients and surgeons.

Prognostic value of myocardial perfusion imaging after first-line coronary computed tomography angiography: A multi-center cohort study.

PURPOSE: Further diagnostic testing may be required after a coronary computed tomography angiography (CTA) showing suspected coronary stenosis. Whether myocardial perfusion imaging (MPI) provides further prognostic information post-CTA remains debated. We evaluated the prognosis for patients completing CTA stratified for post-CTA diagnostic work-up using real-world data. METHODS: We identified all patients in our uptake area with angina symptoms undergoing first-time CTA over a 10-year period. Follow-up time was a median of 3.7 years [1.9-5.8]. The primary endpoint was a composite of myocardial infarction or death. The secondary endpoint was late revascularization. RESULTS: During the study period 53,351 patients underwent CTA. Of these, 24% were referred for further down-stream testing, 3,547 (7%) to MPI and 9,135 (17%) to invasive coronary angiography (ICA). The primary and secondary endpoints occurred in 2,026 (3.8%) and 954 (1.8%) patients. Patient-characteristic-adjusted hazard ratios for the primary and secondary endpoint using patients with a normal CTA as reference were 1.37 (1.21-1.55) and 2.50 (1.93-3.23) for patient treated medically, 1.68 (1.39-2.03) and 6.13 (4.58-8.21) for patients referred to MPI and 1.94 (1.69-2.23) and 9.18 (7.16-11.78) for patients referred for ICA, respectively. Adjusted analysis with stratification for disease severity at CTA showed similar hazard ratios for patients treated medically after CTA and patients referred for MPI and treated medically after the MPI. CONCLUSION: In patients completing coronary CTA, second-line MPI testing seems to identify patients at low risk of future events. MPI seems to have the potential to act as gatekeeper for ICA after coronary CTA.

Ranitidine and Risk of Bladder and Kidney Cancer: A Population-Based Cohort Study.

BACKGROUND: In 2019, ranitidine was withdrawn due to high levels of N-nitrosodimethylamine, a probable human carcinogen. The risk of bladder and kidney cancer in ranitidine users, however, remains unclear. METHODS: In a Danish nationwide cohort study, we included adults (18 years or older) without previous cancer, who between 1996 and 2008 redeemed at least two prescriptions for ranitidine and, as two separate comparison cohorts, patients with at least two prescriptions for other H2-receptor antagonists (H2-blockers), or proton pump inhibitors (PPI). Follow-up for bladder or kidney cancer started at date of the second prescription and continued to date of cancer, death, emigration, or December 31, 2018, whichever occurred first. We used propensity scores for ranitidine use to compute stabilized inverse probability of treatment (sIPT) weights and used Cox regression to compute crude and weighted HRs. RESULTS: We identified 31,393 initiators of ranitidine, 65,384 initiating other H2-blockers, and 509,849 initiating PPI. Compared with other H2-blockers, the crude HR for bladder cancer was 1.33 [95% confidence interval (CI): 1.15-1.55], but sIPT weighting attenuated this to 1.11 (95% CI: 0.95-1.29). Compared with PPI initiators, the weighted HR was 1.24 (95% CI: 1.04-1.48). For kidney cancer, the weighted HR was 0.89 (95% CI: 0.72-1.10) compared with users of H2-blockers and 0.87 (95% CI: 0.67-1.13) compared with users of PPI. CONCLUSIONS: Our findings did not suggest a substantial increase in bladder or kidney cancer occurrence in ranitidine users. IMPACT: These findings are reassuring for previous ranitidine users.

Reduction of Myocardial Infarction and All-Cause Mortality Associated to Statins in Patients Without Obstructive CAD.

OBJECTIVES: The aim of this work was to evaluate the prognostic impact of statin therapy in symptomatic patients without obstructive CAD. BACKGROUND: Information on the prognostic impact of post-coronary computed tomographic angiography (CTA) statin use in patients with no or nonobstructive coronary artery disease (CAD) is sparse. METHODS: Patients undergoing CTA with suspected CAD in western Denmark from 2008 to 2017 with <50% coronary stenoses were identified. Information on post-CTA use of statin therapy and cardiovascular events were obtained from national registries. RESULTS: The study included 33,552 patients, median aged 56 years, 58% female, with no (n = 19,669) or nonobstructive (n = 13,883) CAD and a median follow-up of 3.5 years. The absolute risk of the combined end point of myocardial infarction (MI) or all-cause mortality was directly associated with the CAD burden with an event rate/1,000 patient-years of 4.13 (95% CI: 3.69-4.61) in no, 7.74 (95% CI: 6.88-8.71) in mild (coronary artery calcium score [CACS] 0-99), 13.72 (95% CI: 11.61-16.23) in moderate (CACS 100-399), and 32.47 (95% CI: 26.25-40.16) in severe (CACS ≥400) nonobstructive CAD. Statin therapy was associated with a multivariable adjusted HR for MI and death of 0.52 (95% CI: 0.36-0.75) in no, 0.44 (95% CI: 0.32-0.62) in mild, 0.51 (95% CI: 0.34-0.75) in moderate, and 0.52 (95% CI: 0.32-0.86) in severe nonobstructive CAD. The estimated numbers needed to treat to prevent the primary end point were 92 (95% CI: 61-182) in no, 36 (95% CI: 26-58) in mild, 24 (95% CI: 15-61) in moderate, and 13 (95% CI: 7-86) in severe nonobstructive CAD. Residual confounding may persist, but not to an extent explaining all of the observed risk reduction associated with statin treatment. CONCLUSIONS: The risk of MI and all-cause mortality in patients without obstructive CAD is directly associated with the CAD burden. Statin therapy is associated with a reduction of MI and all-cause death across the spectrum of CAD, however, the absolute benefit of treatment is directionally proportional with the CAD burden.

Use of bisphosphonates in multiple myeloma patients in Denmark, 2005-2015.

PURPOSE: To describe use of bisphosphonates in newly diagnosed multiple myeloma patients in Denmark. METHODS: Using data from the Danish National Multiple Myeloma Registry, we conducted a population-based cohort study. Among patients newly diagnosed with multiple myeloma from 2005 to 2015, we examined use of bisphosphonates at first- and at progression/second-line anti-myeloma treatment overall, by patient characteristics, and myeloma complications. RESULTS: Of 2947 patients starting first-line anti-myeloma treatment, 2207 patients (74.9%) received bisphosphonates. During a median follow-up of 27.6 (quartiles, 10.6-52.5) months, disease progression post-first-line treatment was recorded in 1546 patients, of whom 1065 (68.9%) were treated with bisphosphonates. Altogether, 80.9% of patients with and 37.6% of patients without myeloma bone disease were treated with bisphosphonates at first line and 73.0% and 42.7%, respectively, at progression/second line. Moreover, the proportion of patients treated with bisphosphonates decreased with increasing severity of renal impairment at first and at progression/second-line treatment. CONCLUSION: The proportion of patients treated with bisphosphonates as part of first- and second-line anti-myeloma treatment increased with presence of myeloma bone disease and decreased by presence and severity of renal impairment. Overall, 25% of newly diagnosed multiple myeloma patients had no record of bisphosphonate treatment, potentially indicating an unmet need.

Advanced heart sound analysis as a new prognostic marker in stable coronary artery disease.

Aims: Recent technological advances enable diagnosing of obstructive coronary artery disease (CAD) from heart sound analysis with a high negative predictive value. However, the prognostic impact of this approach remains unknown. To investigate the prognostic value of heart sound analysis as two scores, the Acoustic-score and the CAD-score, in patients with suspected CAD which is treated according to standard of care. Methods and results: Consecutive patients with angina symptoms referred for coronary computed tomography angiography (CTA) were enrolled. The Acoustic-score was developed from eight acoustic CAD-related features. This score was combined with risk factors to generate the CAD-score. A cut-off score >20 was pre-specified for both scores to indicate disease. If coronary CTA raised suspicion of obstructive CAD, patients were referred to invasive angiography and revascularized when indicated. Of 1675 enrolled patients, 1464 (87.4%) were included in this substudy. The combined primary endpoint was all-cause mortality and myocardial infarction (n = 26). Follow-up was 3.1 (2.7-3.4) years. Of patients with primary endpoints, the Acoustic-score was >20 in 25 (96%); the CAD-score was >20 in 22 (85%). In an unadjusted Cox analysis of the primary endpoints, the hazard ratio for scores >20 under current standard clinical care was 12.6 (1.7-93.2) for the Acoustic-score and 5.4 (1.9-15.7) for the CAD-score. The CAD-score contained prognostic information even after adjusting for lipid-lowering therapy initiation, stenosis at CTA, and early revascularization. Conclusion: Heart sound analysis seems to carry prognostic information and may improve initial risk stratification of patients with suspected CAD. Clinicaltrialsorg ID: NCT02264717.

Platelet Count within the Normal Range at Hospital Admission is Associated with Mortality in Patients with Community-Acquired Pneumonia.

BACKGROUND: Apart from their hemostatic role, platelets are immune cells that play a role in fighting infections. The presence of thrombocytopenia and thrombocytosis at hospital admission are predictors of mortality in community-acquired pneumonia patients. We hypothesized that variations in platelet counts within the normal range also may be associated with mortality in these patients. METHODS: The study included all adults in the North and Central Denmark Regions with a first acute hospital admission for community-acquired pneumonia during 2006-2012. We assessed the association between the first platelet count within ± 24 hours of admission (within the normal range of 150 to 400 x 109/L) and 30-day mortality using Cox models. Analyses were adjusted for age, sex, Charlson Comorbidity Index score, hemoglobin level, leukocyte count, and creatinine level at admission. RESULTS: Among the 12,905 study patients, 30-day mortality was 12.4%. The mean platelet count upon admission was 250 × 109/L. Compared with the 250-275 × 109/L category, platelet counts of 151-175 were associated with a lower 30-day mortality (adjusted hazard ratio [aHR]: 0.79, 95% confidence interval [CI]: 0.63-0.99), while higher platelet counts were associated with a higher 30-day mortality (351-375 × 109/L, aHR: 1.34, 95% CI: 1.07-1.68; 376-400× 109/L, aHR: 1.21, 95% CI: 0.94-1.56). CONCLUSION: Platelet counts, even within the normal range, are associated with mortality in adult patients hospitalized for community-acquired pneumonia.

Rheumatoid Arthritis as a Risk Factor for Coronary Artery Calcification and Obstructive Coronary Artery Disease in Patients with Chest Pain: A Registry Based Cross-Sectional Study.

PURPOSE: To examine the occurrence and severity of coronary artery disease (CAD) in patients with rheumatoid arthritis (RA) compared to non-RA patients in a population referred for coronary computed tomography angiography (CTA) due to chest pain. PATIENTS AND METHODS: In this cross-sectional study, 46,210 patients from a national CTA database were included. Patients with RA were stratified on serology, treatment with conventional synthetic or biological disease-modifying antirheumatic drugs (DMARDs), and the need for relapse or flare treatment with intraarticular or -muscular glucocorticoid injections (GCIs). Primary outcomes were coronary artery calcium score (CACS) >0 and CACS ≥400, and secondary outcome was obstructive CAD. Associations between RA and outcomes were examined using logistic regression and results were adjusted for age, sex, cardiovascular risk factors and comorbidities. RESULTS: A total of 395 (0.9%) RA patients were identified. In overall RA, crude odds ratio (OR) for having CACS >0 was 1.48 (1.21-1.82) and 1.52 (1.15-2.01) for CACS ≥400, whereas adjusted ORs were 1.08 (0.86-1.36) and 1.21 (0.89-1.65), respectively. Seropositive RA patients had adjusted OR of 1.16 (0.89-1.50) for CACS >0 and 1.37 (0.98-1.90) for CACS ≥400. Patients who had received ≥1 GCI in the period of 3 years prior to the CTA had an adjusted OR of 1.37 (0.94-2.00) for having CACS >0 and 1.46 (0.92-2.31) for CACS ≥400. CONCLUSION: This is the first large-scale, CTA-based study examining the occurrence and severity of CAD in RA patients with symptoms suggestive of cardiovascular disease. A higher prevalence of coronary artery calcification was found in RA patients. After adjusting for age, sex, cardiovascular risk factors and comorbidities, the tendency was less pronounced. We found a trend for increased coronary calcification in RA patients being seropositive or needing treatment with GCI for a relapse or flare.

Platelet counts of adults upon acute hospital admission to internal medicine units are a predictor of mortality.

The objective of this cohort study was to examine the association between platelet counts upon acute hospitalization and mortality. The study included all adults in North and Central Denmark Regions with a first acute admission to an internal medicine unit during 2006-2012, categorized by first platelet count within +/-24 hours of admission. We assessed the association between platelet count and in-hospital, 30-day, 90-day, and 365-day mortality using age- and sex-adjusted Cox models. We also stratified analyses by presence/absence of comorbidity and performed additional analyses restricted to patients with a primary discharge diagnosis of cardiovascular disease or infection. Among the 274,148 study patients, the 1-year mortality was 12.6%. The association between platelet count and mortality took the form of an asymmetric U-shaped curve. For 30-day mortality, hazard ratios (HRs) were 5.24 (95% CI: 4.60-5.97) for platelet count < 50 × 109/L and 2.50 (95% CI: 2.33-2.69) for platelet count ≥ 500 × 109/L, compared with a normal platelet count (150-400 × 109/L). A slightly increased risk of mortality was observed for platelet counts < 200 × 109/L and ≥ 250 × 109/L. A similar pattern was observed for 30-day, 90-day, and 365-day mortality and in all subgroups except patients with a primary discharge diagnosis of infection. In this case, patients with a platelet count between 150 × 109/L and 199 × 109/L had the lowest mortality. Platelet counts in adults upon acute hospital admission to internal medicine units, including counts within the normal range, are a predictor of mortality.

​Risk of major adverse cardiovascular events among patients with rheumatoid arthritis after initial CT-based diagnosis and treatment.

OBJECTIVE: Rheumatoid arthritis (RA) is a known risk factor for developing coronary artery disease (CAD). The influence of RA on the prognosis after initial CAD diagnosis and treatment is however largely unknown. We examined the risk of major cardiovascular events among RA and non-RA patients with chest pain referred to cardiac CT. METHODS: This was a follow-up study, using data from the Western Denmark Heart Registry, containing data on CT angiography examinations (Cardiac CT). Information on RA diagnosis and covariates were identified through nationwide administrative registers. The primary outcome was a combined outcome including, myocardial infarction, ischaemic or unspecified stroke, coronary artery bypass grafting, percutaneous coronary intervention, and all-cause mortality. Median time until events or censoring was 3.5 years (min/max: 0.0: 9.2). Cox proportional hazard models were used to examine the association between RA/non-RA patients and outcomes. RESULTS: Among 42 257 patients, referred between 2008 and 2016, we identified 358 (0.8%) with RA. An increased risk was seen in RA compared with non-RA (adjusted HR 1.35, 95% CI 0.93 to 1.96). Among patients who had received flare treatment more than once prior to cardiac CT the adjusted HR 1.80 (95% CI 1.08 to 3.00), and among patients with seropositive RA the adjusted HR 1.42 (95% CI 0.93 to 2.16). CONCLUSION: In patients referred to cardiac CT due to chest pain, we found a trend of an association between RA and the combined primary outcome, supporting that RA per se, but in particular seropositive and active RA, may increase the risk of CAD even after initial CAD diagnosis and treatment.

Optimal duration of anticoagulant thromboprophylaxis in total hip arthroplasty: new evidence in 55,540 patients with osteoarthritis from the Nordic Arthroplasty Register Association (NARA) group.

Background and purpose - The recommended optimal duration of the thromboprophylaxis treatment in total hip arthroplasty (THA) patients has been a matter of debate for years. We examined the association between short (1-5 days), standard (6-14 days), and extended (≥ 15 days) duration of thromboprophylaxis, with regards to the risk of venous thromboembolism (VTE), major bleeding, and death in unselected THA patients. Patients and methods - We performed a cohort study using prospectively collected data from the population-based hip arthroplasty registries, prescription databases, and patient administrative registries in Denmark and Norway. We included 55,540 primary THA patients with osteoarthritis Results - The 90-day cumulative incidence of VTE was 1.0% for patients with standard treatment (reference), 1.1% for those with short-term treatment (adjusted hazard ratio [aHR] of 1.1, 95% confidence interval (CI) 0.8-1.5) and 1.0% for those with extended treatment (aHR of 0.9, CI 0.8-1.2). The aHRs for major bleeding were 1.1 (CI 0.8-1.6) for short and 0.8 (CI 0.6-1.1) for extended vs. standard treatment. In addition, patients with short and extended treatment had aHRs for death of 1.2 (CI 0.8-1.8) and 0.8 (CI 0.5-1.1) vs. standard treatment, respectively. Patients who started short treatment postoperatively had an aHR for death of 1.8 (CI 1.1-3.1) and absolute risk difference of 0.2%, whereas patients who started short treatment preoperatively had an aHR for death of 0.5 (CI 0.2-1.2) and absolute risk difference of 0.3% compared with patients who had standard treatment with post- and preoperative start, respectively. Interpretation - In routine clinical practice, we observed no overall clinically relevant difference in the risks of VTE and major bleeding within 90 days of THA with respect to thromboprophylaxis duration. However, our data indicate that short-term thromboprophylaxis started postoperatively is associated with increased 90-day mortality. The significance of these data should be explored further.