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Objective: Heart failure (HF) is an impactful complication of type 2 diabetes mellitus (T2DM). We aimed to develop and validate a risk score for hospitalization for HF (HHF) incorporating biomarkers and clinical factor(s) in patients with T2DM.Research Design and Methods: We derived a risk score for HHF using clinical data, high-sensitivity troponin T (hsTnT), and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) from 6,106 placebo-treated patients with T2DM in SAVOR-TIMI 53 (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53). Candidate variables were assessed using Cox regression. The strongest indicators of HHF risk were included in the score using integer weights. The score was externally validated in 7,251 placebo-treated patients in DECLARE-TIMI 58 (Dapagliflozin Effect on CardiovascuLAR Events-Thrombolysis in Myocardial Infarction 58). The effect of dapagliflozin on HHF was assessed by risk category in DECLARE-TIMI 58.Results: The strongest indicators of HHF risk were NT-proBNP, prior HF, and hsTnT (each P < 0.001). A risk score using these three variables identified a gradient of HHF risk (P-trend <0.001) in the derivation and validation cohorts, with C-indices of 0.87 (95% CI, 0.84-0.89) and 0.84 (0.81-0.86), respectively. Whereas there was no significant effect of dapagliflozin versus placebo on HHF in the low-risk group (hazard ratio [HR] 0.98 [95% CI 0.50-1.92]), dapagliflozin significantly reduced HHF in the intermediate-, high-, and very-high-risk groups (HR 0.64 [0.43-0.95], 0.63 [0.43-0.94], and 0.72 [0.54-0.96], respectively). Correspondingly, absolute risk reductions (95% CI) increased across these latter 3 groups: 1.0% (0.0-1.9), 3.0% (0.7-5.3), and 4.4% (-0.2 to 8.9) (P-trend <0.001).Conclusions: We developed and validated a risk score for HHF in T2DM that incorporated NT-proBNP, prior HF, and hsTnT. The risk score identifies patients at higher risk of HHF who derive greater absolute benefit from dapagliflozin. [ABSTRACT FROM AUTHOR]

Aims PEGASUS-TIMI 54 demonstrated that long-term dual antiplatelet therapy (DAPT) with aspirin and ticagrelor reduced the risk of major adverse cardiovascular events (MACE), with an acceptable increase in bleeding, in patients with prior myocardial infarction (MI). While much of the discussion around prolonged DAPT has been focused on stented patients, patients with prior MI without prior coronary stenting comprise a clinically important subgroup. Methods and results This was a pre-specified analysis from PEGASUS-TIMI 54, which randomized 21 162 patients with prior MI (1–3 years) and additional high-risk features to ticagrelor 60 mg, 90 mg, or placebo twice daily in addition to aspirin. A total of 4199 patients had no history of coronary stenting at baseline. The primary efficacy outcome (MACE) was the composite of cardiovascular death, MI, or stroke. Patients without history of coronary stenting had higher baseline risk of MACE [13.2% vs. 8.0%, adjusted hazard ratio (HR) 1.41, 95% confidence interval (CI) 1.15–1.73, in the placebo arm]. The relative risk reduction in MACE with ticagrelor (pooled doses) was similar in patients without (HR 0.82, 95% CI 0.68–0.99) and with prior stenting (HR 0.85, 95% CI 0.75–0.96; P for interaction = 0.76). Conclusion Long-term ticagrelor reduces thrombotic events in patients with prior MI regardless of whether they had prior coronary stenting. These data highlight the benefits of DAPT in prevention of spontaneous atherothrombotic events and indicate that long-term ticagrelor may be considered in high-risk patients with prior MI even if they have not been treated with stenting. ClinicalTrials.gov Identifier NCT01225562. Open in new tab Download slide Open in new tab Download slide [ABSTRACT FROM AUTHOR]

Bone impaction grafting is a biologically and mechanically appealing option in acetabular revision surgery, allowing restitution of the bone stock and restoration of the biomechanics. We analysed differences in proximal migration of the revision acetabular components when bone impaction grafting is used together with a cemented or an uncemented cup.~Background~Background~43 patients (47 hips), revised due to acetabular loosening and judged to have less than 50% host bone-implant contact were included. The hips were randomised to either an uncemented (n = 20) or a cemented (n = 27) revision cup. Radiostereometry and radiography was performed postoperatively, at 3 and 6 months, 1, 2, 3, 5, 7, 10 and 13 and 17 years postoperatively. Clinical follow-up was performed at 1, 2 and 5 years postoperatively and thereafter at the same interval as in the radiographic follow-up.~Patients and Methods~Methods~There were no differences in the base line demographic data between the 2 groups. At the last follow-up (17 years) 14 hips (10 cemented, 4 uncemented) had been re-revised due to loosening. 3 additional cups (1 uncemented and 2 cemented) were radiographically loose. There was a higher early proximal migration in the cemented cups.~Results~Results~Cups operated on with cement showed a higher early migration measured with RSA and also a higher number of late revisions. The reason for this is not known, but factors such as inclusion of cases with severe bone defects, use of smaller bone chips and issues related to the impaction technique might have had various degrees of influence.~Discussion~Conclusions [ABSTRACT FROM AUTHOR]

Introduction: Cardiovascular outcome trials (CVOTs) are essential to explore the long term cardiovascular effects of medicines, and since 2008 it is also mandatory for all new antidiabetic drugs, targeting T2DM, to demonstrate CV no harm. Since CVOTs normally recruit thousands of patients and are running for many years, trial design is extra important since an incorrect estimate of the expected event rate can generate unwelcome costs and delays. Hypothesis: In this work, we investigate the prevalence and rate of over optimistic event rate estimation when designing outcomes trials and its potential impact on chance of successful trials. Methods: In this systematic review, we compare predicted event rate, extracted from earliest available study protocol, to reported event rate, from main publication in NEJM or Lancet, in all CVOTs with at least 1000 subjects published between start of 2010 and end of 2016. A linear regression model was used estimate relation between predicted and observed event rate. A model weighted on planned follow-up (patient years) as well as sensitivity analyses on several covariates were also performed. Logistic regression was used to test covariate influence on likelihood of trial success. Results: Out of 2205 articles, 173 trials were identified and 78 were eligible for the analysis. On average, the observed event rate was 14 percent lower (slope=0.86, p<0.0001) than what was originally predicted in the study protocol. In the model weighted on planned patient years, the overestimation was 24 percent. Publication year, journal, Industry or non-industry sponsor, active comparator or primary endpoint (MACE, MACE+ or other) did not affect the predictability. Thirty of the 78 trials (38 percent) met their primary objective. Most variables did not influence likelihood of success, but non-inferiority trials were more likely to succeed than superiority studies, 76.9% vs 30.8%, respectively. Conclusions: In CVOTs reported during 2010-2016, the estimation of event rate in general was significantly over-optimistic. The consequences of such mispredictions normally result in prolonged study duration, increased sample size or a decreased power. To decrease the risk when investments are made in CVOTs, the identification of highly relevant source data is critical. [ABSTRACT FROM AUTHOR]

Debridement, antibiotics, and implant retention (DAIR) is a surgical treatment for periprosthetic joint infection (PJI). DAIR is a desirable treatment option from an economic and patient perspective, if successful. The aim of this observational study was to compare the rates of success, defined as no additional reoperations due to PJI, between DAIR with exchange of modular components and DAIR without exchange in patients who had first-time PJI after primary total hip arthroplasty (THA)., Methods: Patients with PJI at the site of a primary THA who were treated with DAIR in Sweden between January 1, 2009, and December 31, 2016, were identified in the Swedish Hip Arthroplasty Register. Supplementary questionnaires were sent to orthopaedic departments for additional variables of interest related to PJI. The primary end point was another reoperation due to PJI within 2 years after the first-time DAIR. DAIR with exchange was compared with DAIR without exchange using Kaplan-Meier survival analysis and Cox regression analysis., Results: A total of 575 patients treated with DAIR for a first-time PJI at the site of a primary THA were analyzed; 364 underwent component exchange and 211 did not. The exchange of components was associated with a lower rate of reoperations due to PJI after DAIR (28.0%) compared with non-exchange (44.1%). The Kaplan-Meier implant survival estimate for exchange was 71.4% (95% confidence interval [CI] = 66.9% to 76.3%) compared with 55.5% (95% CI = 49.1% to 62.7%) for non-exchange. With the analysis adjusted for confounders, DAIR with exchange was associated with a significantly decreased risk of another reoperation due to PJI compared with non-exchange (hazard ratio [HR] = 0.51 [95% CI = 0.38 to 0.68])., Conclusions: In patients with a first-time PJI at the site of a primary THA, DAIR with exchange of modular components was superior to non-exchange DAIR. Surgeons should strive to exchange components when they perform DAIR, but there is a need to further identify how DAIR best should be practiced and which patients benefit from it., Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: This research was funded by regional research grants (ALFGBG-719961) and the Doktor Felix Neubergh Foundation. On the Disclosure of Potential Conflicts of Interest forms, which are provided with the online version of the article, one or more of the authors checked “yes” to indicate that the author had a relevant financial relationship in the biomedical arena outside the submitted work (http://links.lww.com/JBJSOA/A230)., (Copyright © 2020 The Authors. Published by The Journal of Bone and Joint Surgery, Incorporated. All rights reserved.)

Aims: In PEGASUS-TIMI 54, ticagrelor significantly reduced the risk of the composite of major adverse cardiovascular (CV) events by 15-16% in stable patients with a prior myocardial infarction (MI) 1-3 years earlier. We report the efficacy and safety in the subpopulation recommended for treatment in the European (EU) label, i.e. treatment with 60 mg b.i.d. initiated up to 2 years from the MI, or within 1 year after stopping previous adenosine diphosphate receptor inhibitor treatment., Methods and Results: Of the 21 162 patients enrolled in PEGASUS-TIMI 54, 10 779 patients were included in the primary analysis for this study, randomized to ticagrelor 60 mg (n = 5388) or matching placebo (n = 5391). The cumulative proportions of patients with events at 36 months were calculated by the Kaplan-Meier (KM) method. The composite of CV death, MI, or stroke occurred less frequently in the ticagrelor group (7.9% KM rate vs. 9.6%), hazard ratio (HR) 0.80 [95% confidence interval (CI) 0.70-0.91; P = 0.001]. Ticagrelor also reduced the risk of all-cause mortality, HR 0.80 (0.67-0.96; P = 0.018). Thrombolysis in myocardial infarction major bleeding was more frequent in the ticagrelor group 2.5% vs. 1.1%; HR 2.36 (1.65-3.39; P < 0.001). The corresponding HR for fatal or intracranial bleeding was 1.17 (0.68-2.01; P = 0.58)., Conclusion: In PEGASUS-TIMI 54, treatment with ticagrelor 60 mg as recommended in the EU label, was associated with a relative risk reduction of 20% in CV death, MI, or stroke. Thrombolysis in myocardial infarction major bleeding was increased, but fatal or intracranial bleeding was similar to placebo. There appears to be a favourable benefit-risk ratio for long-term ticagrelor 60 mg in this population., Clinical Trial Registration: http://www.clinicaltrials.gov NCT01225562., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)