Effects of accelerated versus standard care surgery on the risk of acute kidney injury in patients with a hip fracture : A substudy protocol of the hip fracture Accelerated surgical TreaTment and Care tracK (HIP ATTACK) international randomised controlled trial

Introduction Inflammation, dehydration, hypotension and bleeding may all contribute to the development of acute kidney injury (AKI). Accelerated surgery after a hip fracture can decrease the exposure time to such contributors and may reduce the risk of AKI. Methods and analysis Hip fracture Accelerated surgical TreaTment And Care tracK (HIP ATTACK) is a multicentre, international, parallel-group randomised controlled trial (RCT). Patients who suffer a hip fracture are randomly allocated to either accelerated medical assessment and surgical repair with a goal of surgery within 6 hours of diagnosis or standard care where a repair typically occurs 24 to 48 hours after diagnosis. The primary outcome of this substudy is the development of AKI within 7 days of randomisation. We anticipate at least 1998 patients will participate in this substudy. Ethics and dissemination We obtained ethics approval for additional serum creatinine recordings in consecutive patients enrolled at 70 participating centres. All patients provide consent before randomisation. We anticipate reporting substudy results by 2021. Trial registration number NCT02027896; Pre-results

Effects of accelerated versus standard care surgery on the risk of acute kidney injury in patients with a hip fracture : a substudy protocol of the hip fracture Accelerated surgical TreaTment And Care tracK (HIP ATTACK) international randomised controlled trial

Introduction Inflammation, dehydration, hypotension and bleeding may all contribute to the development of acute kidney injury (AKI). Accelerated surgery after a hip fracture can decrease the exposure time to such contributors and may reduce the risk of AKI. Methods and analysis Hip fracture Accelerated surgical TreaTment And Care tracK (HIP ATTACK) is a multicentre, international, parallel-group randomised controlled trial (RCT). Patients who suffer a hip fracture are randomly allocated to either accelerated medical assessment and surgical repair with a goal of surgery within 6 hours of diagnosis or standard care where a repair typically occurs 24 to 48 hours after diagnosis. The primary outcome of this substudy is the development of AKI within 7 days of randomisation. We anticipate at least 1998 patients will participate in this substudy. Ethics and dissemination We obtained ethics approval for additional serum creatinine recordings in consecutive patients enrolled at 70 participating centres. All patients provide consent before randomisation. We anticipate reporting substudy results by 2021. Trial registration number NCT02027896; Pre-results

Rationale and design of the hip fracture accelerated surgical treatment and care track (hip attack) trial : A protocol for an international randomised controlled trial evaluating early surgery for hip fracture patients

Introduction Annually, millions of adults suffer hip fractures. The mortality rate post a hip fracture is 7%-10% at 30 days and 10%-20% at 90 days. Observational data suggest that early surgery can improve these outcomes in hip fracture patients. We designed a clinical trial - HIP fracture Accelerated surgical TreaTment And Care tracK (HIP ATTACK) to determine the effect of accelerated surgery compared with standard care on the 90-day risk of all-cause mortality and major perioperative complications. Methods and analysis HIP ATTACK is a multicentre, international, parallel group randomised controlled trial (RCT) that will include patients ≥45 years of age and diagnosed with a hip fracture from a low-energy mechanism requiring surgery. Patients are randomised to accelerated medical assessment and surgical repair (goal within 6 h) or standard care. The co-primary outcomes are (1) all-cause mortality and (2) a composite of major perioperative complications (ie, mortality and non-fatal myocardial infarction, pulmonary embolism, pneumonia, sepsis, stroke, and life-threatening and major bleeding) at 90 days after randomisation. All patients will be followed up for a period of 1 year. We will enrol 3000 patients. Ethics and dissemination All centres had ethics approval before randomising patients. Written informed consent is required for all patients before randomisation. HIP ATTACK is the first large international trial designed to examine whether accelerated surgery can improve outcomes in patients with a hip fracture. The dissemination plan includes publishing the results in a policy-influencing journal, conference presentations, engagement of influential medical organisations, and providing public awareness through multimedia resources. Trial registration number NCT02027896; Pre-results

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Maintenance of efficacy following tofacitinib dose reduction in patients with ulcerative colitis in stable remission

Background Tofacitinib is an oral, small-molecule JAK inhibitor approved in several countries for the treatment of ulcerative colitis (UC). Safety and efficacy of tofacitinib 5 and 10 mg twice daily (BID) were evaluated in 2 Phase 3 induction studies (OCTAVE Induction 1 and 2, NCT01465763 and NCT01458951), a 52-week, Phase 3 maintenance study (OCTAVE Sustain, NCT01458574), and an ongoing open-label, long-term extension (OLE) study (NCT01470612). Here, we assess maintenance of remission following tofacitinib dose reduction from 10 mg BID in OCTAVE Sustain to 5 mg BID in the OLE study, and explore potential predictors of successful dose reduction. Methods Patients in remission (total Mayo score ≤2 with no individual subscore &gt;1, rectal bleeding subscore 0) at Wk52 of OCTAVE Sustain (central read) received tofacitinib 5 mg BID in the OLE study. We present remission rates (local read; as observed and with non-responder imputation) with tofacitinib 5 mg BID in the OLE study (as of 10 November 2017) among patients who achieved remission with tofacitinib 10 mg BID in OCTAVE Sustain, and evaluate characteristics of these patients, stratified by whether they subsequently maintained remission (local read; as observed) with 5 mg BID at Month (M)12 of the OLE study. Results Of 76 patients treated with tofacitinib 10 mg BID who were in remission at Wk52 of OCTAVE Sustain and received 5 mg BID in the OLE study, 82% and 76% (as observed) were in remission at M12 and M24 of the OLE study, respectively (table). Patient characteristics by remission status at M12 of the OLE study are shown (table). Alternatively, by duration of remission in OCTAVE Sustain: among patients in remission at baseline (BL), Wk24 and Wk52 of OCTAVE Sustain (remission ≥12 months pre-dose reduction), 91% (21/23) maintained remission at M12 of the OLE study, vs. 82% (18/22) who were not in remission at OCTAVE Sustain BL but in remission at both Wk24 and Wk52 (remission 6–&lt;12 months pre-dose reduction), and 71% (15/21) who were in remission at Wk52 but not Wk24, regardless of BL status (remission &lt;6 months pre-dose reduction). Conclusions In this post-hoc analysis, most patients with UC who achieved remission with tofacitinib 10 mg BID in OCTAVE Sustain and reduced to 5 mg BID in the OLE study maintained remission through M24 of the OLE study. Despite small pt numbers, maintenance of remission after dose reduction was numerically more likely for patients in remission for ≥6 months than for those in remission for &lt;6 months prior to reduction. Further studies are needed to evaluate flexible dosing of tofacitinib in patients with UC.</p

Maintenance of efficacy following tofacitinib dose reduction in patients with ulcerative colitis in stable remission

Background Tofacitinib is an oral, small-molecule JAK inhibitor approved in several countries for the treatment of ulcerative colitis (UC). Safety and efficacy of tofacitinib 5 and 10 mg twice daily (BID) were evaluated in 2 Phase 3 induction studies (OCTAVE Induction 1 and 2, NCT01465763 and NCT01458951), a 52-week, Phase 3 maintenance study (OCTAVE Sustain, NCT01458574), and an ongoing open-label, long-term extension (OLE) study (NCT01470612). Here, we assess maintenance of remission following tofacitinib dose reduction from 10 mg BID in OCTAVE Sustain to 5 mg BID in the OLE study, and explore potential predictors of successful dose reduction. Methods Patients in remission (total Mayo score ≤2 with no individual subscore >1, rectal bleeding subscore 0) at Wk52 of OCTAVE Sustain (central read) received tofacitinib 5 mg BID in the OLE study. We present remission rates (local read; as observed and with non-responder imputation) with tofacitinib 5 mg BID in the OLE study (as of 10 November 2017) among patients who achieved remission with tofacitinib 10 mg BID in OCTAVE Sustain, and evaluate characteristics of these patients, stratified by whether they subsequently maintained remission (local read; as observed) with 5 mg BID at Month (M)12 of the OLE study. Results Of 76 patients treated with tofacitinib 10 mg BID who were in remission at Wk52 of OCTAVE Sustain and received 5 mg BID in the OLE study, 82% and 76% (as observed) were in remission at M12 and M24 of the OLE study, respectively (table). Patient characteristics by remission status at M12 of the OLE study are shown (table). Alternatively, by duration of remission in OCTAVE Sustain: among patients in remission at baseline (BL), Wk24 and Wk52 of OCTAVE Sustain (remission ≥12 months pre-dose reduction), 91% (21/23) maintained remission at M12 of the OLE study, vs. 82% (18/22) who were not in remission at OCTAVE Sustain BL but in remission at both Wk24 and Wk52 (remission 6– Conclusions In this post-hoc analysis, most patients with UC who achieved remission with tofacitinib 10 mg BID in OCTAVE Sustain and reduced to 5 mg BID in the OLE study maintained remission through M24 of the OLE study. Despite small pt numbers, maintenance of remission after dose reduction was numerically more likely for patients in remission for ≥6 months than for those in remission for <6 months prior to reduction. Further studies are needed to evaluate flexible dosing of tofacitinib in patients with UC.</p