Standard Care Cohort Research Articles

789. Evaluation of Bezlotoxumab for Prevention of Recurrent Clostridioides difficile Infection in Patients at High Risk for Recurrence

BackgroundRecurrent Clostridioides difficile infection (rCDI) within 180 days of the index episode is associated with a 33% increase in mortality and, to-date, few treatment options exist to prevent recurrent infection. Bezlotoxumab (BEZ) is a novel therapeutic option for the prevention of rCDI, yet limited data exist regarding its effectiveness in patients at high-risk for recurrence outside of controlled trials. This study aimed to compare BEZ to a historical standard of care (SoC) cohort for the prevention of rCDI in patients at high risk for recurrence.MethodsA multi-center retrospective cohort study of patients within an academic health-system with one or more risk factors for rCDI. Patients received SoC with oral vancomycin (VAN) or fidaxomicin (FDX) from January 2015 to December 2017 or BEZ, in addition to oral SoC, from September 2017 to September 2019. The primary outcome was rCDI within 90 days of completion of oral VAN or FDX. Secondary outcomes included all-cause readmission, all-cause mortality, and safety events at 90 days.ResultsOne-hundred twenty patients received BEZ in addition to SoC (n=47) or SoC alone (n=73). Mean (SD) age was 55 (16) years, mean (SD) number of lifetime CDI was 3 (2) episodes, and 30.8% of patients had severe CDI. Six (12.8%) patients in the BEZ cohort and thirty-one (42.5%) in the SoC cohort experienced rCDI at 90 days [OR (95% CI) = 0.20 (0.07-0.53), p=< 0.01]. Incidence of all-cause mortality (2.1% vs 5.5%, p=0.67) and all-cause readmission (42.6% vs 56.2%, p=0.20) within 90 days were not statistically different between groups. Patient body weight, timing of BEZ administration, CDI severity, nor prior receipt of fecal microbiota transplantation significantly affected BEZ effectiveness. BEZ was well tolerated with one infusion-related reaction. There were no heart failure exacerbations among BEZ recipients and two exacerbations identified from control group.ConclusionIn patients with at least one risk factor for rCDI, BEZ in addition to SoC was associated with lower rates of recurrent infection than SoC alone and may be a reasonable adjunct therapy in high risk patient populations.Disclosures matthew miller, PharmD, Allergan (Speaker’s Bureau)Tetraphase (Speaker’s Bureau)

Impact of a pharmacist-driven recombinant zoster vaccine administration program

ObjectiveTo determine whether a pharmacist-driven recombinant zoster vaccine (RZV) administration pilot program within a human immunodeficiency virus/infectious diseases clinic setting increased the completion of the 2-dose series when compared with standard care. MethodsIn this retrospective cohort study, the patients enrolled in a pharmacist-driven RZV administration pilot program (intervention) were compared with those in provider-directed RZV education (standard care) for completion of the 2-dose vaccine series. ResultsOne hundred nineteen patients were included (standard care [n = 84], intervention intention to treat [ITT, n = 35], and intervention modified ITT [mITT, n = 23]). There was increased completion of the 2-dose vaccine series in the intervention cohort compared with the standard care cohort (ITT 66% and mITT 100% vs. 23%; P < 0.001). ConclusionThe pharmacist-driven RZV administration program resulted in increased completion of the 2-dose series. However, the revenue generated did not justify the cost of a pharmacist salary for the allocated time commitment.

Abstract 17369: Addressing Missed Opportunities for Cardiometabolic Primary Prevention of Veterans Referred for Stress Testing

Introduction: Patients presenting to stress testing have a high prevalence of cardiometabolic risk factors (RF) which are not at guideline supported goals. Referral to stress testing is often a patient’s first presentation to CV care and represents a missed opportunity for delivery of risk reduction strategies. Hypothesis: Implementation of a cardiometabolic prevention initiative for cardiology-naïve patients referred to stress testing will result in improved delivery of guideline-directed prevention care. Methods: A consecutive prospective cohort of patients who underwent stress testing (12/1/2019-1/31/2020) after implementation of a linked cardiometabolic prevention referral for those with low risk stress tests was compared to a retrospective standard of care (SOC) cohort (9/1/2019-10/1/2019) from a single center Veterans Hospital. Outcomes assessed were change in CV risk reduction care at 90 days following stress test. Results: Of 181 patients, 62.5% were naïve to cardiology specialty care, had &gt;1 CV risk factor not meeting guideline goals, 6% had typical angina as presenting symptoms, and greater than 70% of stress tests were normal or low risk. Baseline CV RF were common and failed to reach goals in SOC and intervention cohorts respectively with LDL above goal (40 vs. 33%), stage 1 or greater hypertension (67 vs 81%), Diabetes with HgA1c &gt; 7 (48 vs. 21%), overweight or obese (68 vs. 79%), current tobacco (11 vs. 12%), and elevated mean 10-year ASCVD risk (32 vs.20%). At 90 days, 28% of SOC cohort had intensification of CV prevention care as compared to 76% of intervention cohort (X 2 26.8, p&lt;0.05). Conclusions: A stress testing setting represents a valuable opportunity to deliver cardiometabolic prevention care. Integration of risk reduction strategies is imperative to shift from cardiac disease management to patient centered health promotion.

Real-World Treatment of Pediatric Patients with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia Using Tisagenlecleucel That Is out of Specification for Commercial Release

Introduction Chimeric antigen receptor (CAR) T cell therapy has been extremely efficacious in pediatric patients with multiply relapsed and/or refractory B-cell acute lymphoblastic leukemia (B-ALL) with overall remission rates of 81% by three months post-infusion (Maude et al., N Engl J Med, 2018), and achieved FDA approval for this indication. In order for the product to meet the standards of this approval for commercial release, both the leukapheresis and manufactured products must meet a variety of specific requirements, some of which are more stringent than those in these pivotal clinical trials. The Managed Access Program (MAP) provides access to tisagenlecleucel for patients with B-ALL or diffuse large B-cell lymphoma that is out of specification (OOS) for whom repeat leukapheresis is not feasible. Patients may also receive OOS tisagenlecleucel by applying for a single-patient Investigational New Drug (IND). Previous reports have shown no difference in efficacy or toxicity between patients receiving tisagenlecleucel that meets commercial release specifications and those receiving OOS tisagenlecleucel (Grupp, et al., Blood Abstr 614, 2019; Jaglowski, et al., Blood Abstr 627, 2019). This study seeks to evaluate outcomes in pediatric and young adult patients who received tisagenlecleucel via the MAP or a single-patient IND in our Pediatric Real World CAR Consortium (PRWCC). Methods Retrospective data were abstracted from the PRWCC database of patients with relapsed/refractory B-ALL from fifteen different US institutions who received tisagenlecleucel as an FDA-approved therapy outside the context of a clinical trial. Patients whose cellular product was obtained through the MAP (NCT03601442) or with single patient IND approval due having either a cryopreserved leukapheresis product and/or manufactured tisagenlecleucel that did not meet specifications for commercial release were categorized as MAP/IND and those whose product met all release criteria were categorized as standard of care (SOC). Results Among 185 total infused patients in our database, 24 (13%) received tisagenlecleucel either via the MAP (n=14) or a single patient IND (n=10). Baseline patient and disease characteristics were not significantly different for MAP/IND patients versus the SOC cohorts (Table 1). Median duration of follow-up post-CAR T cell infusion for these infused patients was 342.5 days (range 107-780) versus 318 days (range 6-863) for the SOC cohort (p=0.43). Reasons for products being OOS included cell viability &amp;lt;80% (n=17), total nucleated cell count &amp;lt;2x109 in leukapheresis product (n=3), failed interferon gamma release assay (n=2), cryopreserved leukapheresis product collected &amp;gt;9 months prior (n=1), and determination of residual beads &amp;gt;50 beads/3x106cells (n=1). Overall survival at 6- and 12-months was 96% versus 83% and 85% versus 70% for the MAP/IND versus SOC, respectively. Event-free survival at 6- and 12-months was 65% versus 63% and 55% versus 51%, respectively. Probability of continued remission at 6- and 12-months among patients who achieved a complete remission (CR) at day 28 was 79% versus 75% and 66% versus 63% for the MAP/IND versus SOC, respectively (Figure 1). Comparing toxicities between patients in the MAP/IND versus SOC cohorts, cytokine release syndrome (CRS, any grade) occurred in 46% versus 61%, CRS (&amp;gt;grade 3) in 17% versus 19%, immune effector cell-associated neurotoxicity syndrome (ICANS) in 8% versus 22%, and infectious complications in 54% vs. 37%, respectively (p=ns for all). Conclusions In our retrospective cohort evaluating the use of tisagenlecleucel to treat pediatric and young adult patients with relapsed/refractory B-ALL in the real-world setting, neither the efficacy nor safety of tisagenlecleucel seem to be compromised by use of products OOS for commercial release. Larger studies are needed to further delineate specific cut-offs outside of which either efficacy and/or safety may truly be impacted. Disclosures Phillips: Novartis: Membership on an entity's Board of Directors or advisory committees. Stefanski:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Margossian:Novartis: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Verneris:Novartis: Membership on an entity's Board of Directors or advisory committees; Fate Therapeutics: Consultancy, Current equity holder in publicly-traded company; Bmogen: Consultancy, Current equity holder in publicly-traded company; Uptodate: Consultancy. Myers:Novartis: Consultancy, Honoraria, Other: ELIANA trial Steering Committee, Speakers Bureau. Brown:Janssen: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Jazz: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Qayed:Mesoblast: Consultancy; Novartis: Consultancy. Hermiston:Novartis: Membership on an entity's Board of Directors or advisory committees; Sobi: Membership on an entity's Board of Directors or advisory committees. Satwani:Mesoblast: Consultancy; Takeda: Consultancy. Curran:Novartis: Consultancy, Research Funding; Celgene: Research Funding; Mesoblast: Consultancy. Mackall:Apricity Health: Consultancy, Current equity holder in private company; Lyell Immunopharma: Consultancy, Current equity holder in private company; BMS: Consultancy; Nektar Therapeutics: Consultancy; Allogene: Current equity holder in publicly-traded company; NeoImmune Tech: Consultancy. Laetsch:Novartis: Consultancy, Research Funding; Bayer: Research Funding; Pfizer: Research Funding; Cellectis: Consultancy.

Abstract 369: Secondary Risk Reduction in Patients With Type 2 Diabetes and Cardiovascular Disease: Experience From a Cardiometabolic Center of Excellence

Background: Optimal guideline-directed medical therapy is delivered to only 6.9% of patients with type 2 diabetes (T2D) and cardiovascular disease (CVD) nationally, despite guideline recommendations emphasizing aggressive comprehensive secondary risk reduction. While there are many potential explanations, lack of effective clinical care delivery models is a key contributor. The Haverty Cardiometabolic Center of Excellence at Saint Luke’s Mid America Heart Institute was designed to address this unmet need, by delivering a patient-centric, collaborative model of care which focuses on aggressive and comprehensive secondary risk reduction in patients with T2D and CVD. Patients are managed by a multidisciplinary team comprised of preventative cardiologists, advanced practice providers and nurses cross-trained in T2D and CVD management, certified diabetes educator, dietician, pharmacist, and other professionals, in close coordination with endocrinologists and primary care clinicians. We aimed to determine whether patients receiving care in the Center had experienced better intermediate outcomes with similar patients receiving routine care in conventional settings. Methods: We analyzed data from the initial 60 patients seen in the Center who had at least one follow-up visit, and propensity matched them 1:3 to similar patients with T2D and CVD treated in conventional care settings. Propensity model included age, sex, baseline weight, HbA1c, systolic blood pressure (SBP), history of CVD, and duration between visits. Linear mixed models with a random effect for matched groups was used to compare between-group differences for changes in weight, LDL-C, and HbA1c. Results: At baseline, patients in the Center weighed 241.3 lbs ± 51.0 and had HbA1c 7.4 ± 1.4 and LDL 68.0 ± 27.0 as compared to 245.5 lbs ± 55.3, HbA1c 7.5 ± 1.5, and LDL 79.1 ± 37.1 in controls. Average duration between follow up visits was 138.3 days ± 52.5 in patients seen in the Center and 138.9 days ± 54.7 in controls. Patients seen in the Center had greater degree of weight loss (12.3 lbs vs 3.8 lbs, p &lt;0.001) and reduction in HbA1c (0.5 vs 0.0%, p = 0.04) and LDL-C (-8.4 vs +4.0 mg/dL, p = 0.04) as compared with controls. Patients receiving care at the Center were more likely to be treated with an SGLT-2i (70.0% [42/60] vs 22.8% [41/180], p&lt;0.001) and/or a GLP-1RA (91.7% [55/60] vs 15.6% [28/180], p&lt;0.001) than those in the standard of care cohort. Conclusion: Patients with T2D and CVD, seen in a specialized, comprehensive Cardiometabolic Center experienced higher use of guideline-directed medical therapies and greater reduction in multiple CVD risk factors within ~4 months, as compared to those seen in the conventional setting. Although longer follow up is needed, these preliminary data suggest that such novel clinical care delivery models may improve the implementation of clinical practice guidelines.

Incisional negative pressure wound therapy in bilateral breast reductions patients

Introduction: Incisional negative pressure wound therapy (iNPWT) has been applied to bilateral breast reduction patients and shown a reduction in surgical complications. However, its effects on opioid use and hospitalisation length in this patient group has not been investigated.Methods: In this single surgeon retrospective cohort study, 52 patients who underwent bilateral breast reduction were analysed, with 23 patients in the iNPWT cohort and 29 in the standard-of-care (SOC) wound dressing cohort. Hospitalisation length, postoperative opioid use and surgical site complications were compared between cohorts. Mean (range) follow-up time was 369.15 (77-1329) days.Results: Hospitalisation length in days was significantly less in the iNPWT cohort (1.35) than the SOC cohort (2.03). Total ward opioid use was significantly reduced in the iNPWT cohort (45.50mg) compared to the SOC cohort (62.50mg). Discharge opioid prescription was significantly reduced in the iNPWT cohort (125.50mg) compared to the SOC cohort (230.00mg). The number of surgical site complications was significantly different between the groups (p=0.014).Discussion: This study suggests the use of iNPWT in bilateral breast reduction provides significant benefit through the reduction of hospitalisation, complications and opioid use. Conclusion: This is the first study to provide evidence for iNPWT in bilateral breast reduction in reducing postoperative opioid use and hospitalisation. It supports current literature showing a reduction in surgical site complications using iNPWT in bilateral breast reduction.

Evaluation of Noninvasive Respiratory Volume Monitoring in the PACU of a Low Resource Kenyan Hospital

This research aims to evaluate the use of the noninvasive respiratory volume monitor (RVM) compared to the standard of care (SOC) in the Post-Anesthesia Care Unit (PACU) of Kijabe Hospital, Kenya. The RVM provides real-time measurements for quantitative monitoring of non-intubated patients. Our evaluation was focused on the incidence of postoperative opioid-induced respiratory depression (OIRD). The RVM cohort (N = 50) received quantitative OIRD assessment via the RVM, which included respiratory rate, minute ventilation, and tidal volume. The SOC cohort (N = 46) received qualitative OIRD assessment via patient monitoring with oxygenation measurements (SpO2) and physical examination. All diagnosed cases of OIRD were in the RVM cohort (9/50). In the RVM cohort, participants stayed longer in the PACU and required more frequent airway maneuvers and supplemental oxygen, compared to SOC (all p < 0.05). The SOC cohort may have had fewer diagnoses of OIRD due to the challenging task of distinguishing hypoventilation versus OIRD in the absence of quantitative data. To account for the higher OIRD risk with general anesthesia (GA), a subgroup analysis was performed for only participants who underwent GA, which showed similar results. The use of RVM for respiratory monitoring of OIRD may allow for more proactive care.

Comparison of Daratumumab Plus Bortezomib, Melphalan, and Prednisone (D-VMP) with Standard of Care for Patients from Latin America with Newly Diagnosed Multiple Myeloma (NDMM) Who Were Transplant Ineligible: A Propensity Score Matching Analysis

Comparison of Daratumumab Plus Bortezomib, Melphalan, and Prednisone (D-VMP) with Standard of Care for Patients from Latin America with Newly Diagnosed Multiple Myeloma (NDMM) Who Were Transplant Ineligible: A Propensity Score Matching Analysis

Diagnostic accuracy and temporal impact of ultrasound in patients with dyspnea admitted to the emergency department.

ObjectiveFew studies have prospectively evaluated the diagnostic accuracy and temporal impact of ultrasound in the emergency department (ED) in a randomized manner. In this study, we aimed to perform a randomized, standard therapy controlled evaluation of the diagnostic accuracy and temporal impact of a standardized ultrasound strategy, versus standard care, in patients presenting to the ED with acute dyspnea.MethodsThe patients underwent a standardized ultrasound examination that was blinded to the team caring for the patient. Ultrasound results remained blinded in patients randomized to the treating team but were unblinded in the interventional cohort. Scans were performed by trained emergency physicians. The gold standard diagnosis (GSDx) was determined by two physicians blinded to the ultrasound results. The same two physicians reviewed all data >30 days after the index visit.ResultsFifty-nine randomized patients were enrolled. The mean±standard deviation age was 54.4±11 years, and 37 (62%) were male. The most common GSDx was acute heart failure with reduced ejection fraction in 13 (28.3%) patients and airway diseases such as acute exacerbation of asthma or chronic obstructive pulmonary disease in 10 (21.7%). ED diagnostic accuracy, as compared to the GSDx, was 76% in the ultrasound cohort and 79% in the standard care cohort (P=0.796). Compared with the standard care cohort, the final diagnosis was obtained much faster in the ultrasound cohort (mean±standard deviation: 12±3.2 minutes vs. 270 minutes, P<0.001).ConclusionA standardized ultrasound approach is equally accurate, but enables faster ED diagnosis of acute dyspnea than standard care.

Variations in study outcomes relative to intention-to-treat and per-protocol data analysis techniques in the evaluation of efficacy for treatment of venous leg ulcers with dehydrated human amnion/chorion membrane allograft.

Statistical interpretation of data collected in a randomised controlled trial (RCT) is conducted on the intention‐to‐treat (ITT) and/or the per‐protocol (PP) study populations. ITT analysis is a comparison of treatment groups including all patients as originally allocated after randomisation regardless if treatment was initiated or completed. PP analysis is a comparison of treatment groups including only those patients who completed the treatment as originally allocated, although it is often criticised because of its potential to instil bias. A previous report from an RCT conducted to evaluate the efficacy of dehydrated human amnion/chorion membrane allograft (EpiFix) as an adjunct to standard comprehensive wound therapy consisting of moist dressings and multi‐layer compression in the healing of venous leg ulcers (VLUs) only reported PP study results (n = 109, 52 EpiFix and 57 standard care patients), although there were 128 patients randomised: 64 to the EpiFix group and 64 to the standard care group. Primary study outcome was the incidence of healing at 12 weeks. The purpose of the present study is to report ITT results on all 128 randomised subjects and assess if both ITT and PP data analyses arrive at the same conclusion of the efficacy of EpiFix as a treatment for VLU. Rates of healing for the ITT and PP populations were, respectively, 50% and 60% for those receiving EpiFix and 31% and 35% for those in the standard care cohort. Within both ITT and PP analyses, these differences were statistically significant; P = 0.0473, ITT and P = 0.0128, PP. The Kaplan‐Meier plot of time to heal within 12 weeks for the ITT and PP populations demonstrated a superior wound‐healing trajectory for EpiFix compared with VLUs treated with standard care alone. These data provide clinicians and health policymakers an additional level of assurance regarding the effectiveness of EpiFix.

Modeling long-term health outcomes of patients with cystic fibrosis homozygous for F508del-CFTR treated with lumacaftor/ivacaftor.

Background:Lumacaftor/ivacaftor combination therapy is efficacious and generally safe for patients with cystic fibrosis (CF) homozygous for the F508del-CF transmembrane conductance regulator (CFTR) mutation. However, long-term survival benefits of lumacaftor/ivacaftor (LUM/IVA) cannot yet be quantified. Simulation models can provide predictions about long-term health outcomes. In this study, we aimed to project long-term health outcomes of LUM/IVA plus standard care (SC) in patients with CF homozygous for F508del-CFTR.Methods:This modeling study was an individual patient simulation in US patients aged ⩾6 years with CF, homozygous for F508del-CFTR. The primary outcome was projected survival among (a) a cohort of patients who ever initiated LUM/IVA, accounting for treatment discontinuations, and (b) a cohort of patients who remain on continuous LUM/IVA. Patient characteristics and model parameters were derived from clinical trials: VX14-809-109, VX13-809-011B, TRAFFIC/TRANSPORT, and PROGRESS; published literature; and the US CF Foundation Patient Registry.Results:Lumacaftor/ivacaftor + SC is expected to increase median survival by 6.1 years versus SC alone, accounting for treatment discontinuations. The incremental median predicted survival versus SC assuming initiation of LUM/IVA at ages 6, 12, 18, and 25 years was 17.7, 12.6, 8.0, and 3.8 years, respectively. Assuming lifetime treatment with LUM/IVA, incremental median survival was predicted to be 7.8 years longer in the LUM/IVA + SC cohort. Initiating LUM/IVA at ages 6, 12, 18, and 25 years and assuming lifetime treatment resulted in incremental median predicted survival of 23.4, 18.2, 11.0, and 4.8 years, respectively.Conclusions:Lumacaftor/ivacaftor is projected to increase survival for patients with CF. Initiation at an early age and treatment persistence result in further increments in projected survival.

Chronic Kidney Disease, Queensland (CKD.QLD) Registry: Management of CKD With Telenephrology

IntroductionEnabled by the Chronic Kidney Disease, Queensland (CKD.QLD) Registry, we aim to outline the structure, implementation, and outcomes of telenephrology clinics for the management of patients with chronic kidney disease (CKD) in rural, regional, and remote areas of the Darling Downs region in Queensland, Australia.MethodsThis is an observational registry–based study involving adult patients with CKD, attending specialist clinics, and residing ≥50 km away from Toowoomba Hospital. The telenephrology cohort (TC) included those who had their follow-up appointments via videoconference at local Queensland Health facilities, and the standard care cohort (SCC) included those who continue to have their follow-up in Toowoomba Hospital.ResultsA total of 234 patients with CKD were seen via videoconference clinics between September 1, 2011 and December 31, 2016, representing 22.2% of the CKD registry cohort from Toowoomba Hospital. The baseline characteristics and comorbid profiles of both groups were similar. The Aboriginal population was overrepresented in the TC (22.2% vs. 5.9%). As a group for each visit, the TC traveled 100,000 km less (both ways) to see a specialist physically. During follow-up, 5.1% of patients in the TC were initiated on dialysis whereas 9.9% were initiated on dialysis in the SCC (P = 0.02). There was lower mortality in the TC (11.1% vs. 18.2%; P = 0.02).ConclusionTelenephrology clinics were safe, economical, and efficient for the delivery of specialist care for patients with CKD living at a distance from the main referral hospital. Such care was comparable to standard care delivered at the main hospital but with clear benefits to the patients in terms of reduced travel distance, more independence, and similar outcomes.

Standard of Care Versus Metastases-directed Therapy for PET-detected Nodal Oligorecurrent Prostate Cancer Following Multimodality Treatment: A Multi-institutional Case-control Study

BackgroundMost prostate cancer (PCa) patients with a biochemical failure following primary multimodality treatment (surgery and postoperative radiotherapy) relapse in the nodes. ObjectiveTo perform a matched-case analysis in men with lymph node recurrent PCa comparing standard of care (SOC) with metastasis-directed therapy (MDT). Design, setting, and participantsPCa patients with a prostate-specific antigen (PSA) progression following multimodality treatment were included in this retrospective multi-institutional analysis. InterventionThe SOC cohort (n=1816) received immediate or delayed androgen deprivation therapy administered at PSA progression. The MDT cohort (n=263) received either salvage lymph node dissection (n=166) or stereotactic body radiotherapy (n=97) at PSA progression to a positron emission tomography-detected nodal recurrence. Outcome measurements and statistical analysisThe primary endpoint, cancer-specific survival (CSS), was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards models, and propensity score-matched analyses. Results and limitationsAt a median follow-up of 70 (interquartile range: 48–98) mo, MDT was associated with an improved CSS on univariate (p=0.029) and multivariate analysis (hazard ratio: 0.33, 95% confidence interval [CI]: 0.17–0.64) adjusted for the year of radical prostatectomy (RP), age at RP, PSA at RP, time from RP to PSA progression, Gleason score, surgical margin status, pT- and pN-stage. In total, 659 men were matched (3:1 ratio). The 5-yr CSS was 98.6% (95% CI: 94.3–99.6) and 95.7% (95% CI: 93.2–97.3) for MDT and SOC, respectively (p=0.005, log-rank). The main limitations of our study are its retrospective design and lack of standardization of systemic treatment in the SOC cohort. ConclusionsMDT for nodal oligorecurrent PCa improves CSS as compared with SOC. These retrospective data from a multi-institutional pooled analysis should be considered as hypothesis-generating and inform future randomized trials in this setting. Patient summaryProstate cancer patients experiencing a lymph node recurrence might benefit from local treatments directed at these lymph nodes.

Intra-Articular Tranexamic Acid Injection During the Hip Hemi-Arthroplasty in Elderly Patients: A Retrospective Study.

Introduction:The objective was to evaluate the safety and efficacy of intra-articular injection of tranexamic acid (TXA) in patients between 80 and 100 years of age with femoral neck fracture undergoing hip hemi-arthroplasty (HA).Material and Methods:We conducted a retrospective review to assess perioperative blood loss and transfusion rate after intra-articular injection of TXA during HA. This was a single-center, retrospective, single-surgeon, and standard care cohort study covering the period between January and December 2016. One hundred three consecutive patients undergoing HA under spinal or general anesthesia were included. Fifty-four and 49 patients received and did not receive intra-articular injection of TXA during the HA, respectively. After closing the capsule, 50 mL of a TXA solution at a concentration of 1 g/100 mL of saline was injected into joint capsule. We compared the following outcomes: preoperative hemoglobin (HB) level, postoperative day 1 HB level, postoperative day 3 HB level, the net reduction of HB level by postoperative day 3, transfusion rate, and 30- and 90-day postoperative mortality rates. In addition, we use logistic regression to analyze the factors affecting the transfusion rate.Result:Day 3 postoperative HB level and the net reduction in HB level within 3 days following surgery were 93.22 ± 11.70 g/L and 25.98 ± 6.29 g/L in TXA group, respectively, while were 87.10 ± 10.52 g/L and 35.44±8.61 g/L in no-TXA group. Transfusion rate was 9% (5/54) in TXA group and 24% (12/49) in no-TXA group, respectively. The differences were statistically significant between the both groups. Logistic regression indicated that the topical administration of TXA would reduce the risk for transfusion, while in male diabetes mellitus would increase the risk. There were no significant differences in the deep venous thrombosis, pulmonary embolism, and mortality rates of 30 and 90 days postoperatively (P > .05).Discussion:Because of lower systemic absorption and a higher concentration in the wound, topical use of TXA is safer for elderly patients who may have renal or liver dysfunction. TXA at therapeutic concentration does not affect platelet count, platelet aggregation, or coagulation parameters, and is of value in elderly patients who take antiplatelet drug for secondary prevention of cardiovascular diseases.Conclusion:For patients between 80 and 100 years of age with femoral neck fracture undergoing HA, intra-articular injection of TXA may reduce the perioperative blood loss and transfusion rate without increasing risk of thrombosis.

Impact of pharmacist management of pain, agitation, and delirium in the intensive care unit through participation in multidisciplinary bundle rounds.

A two-phase program to increase pharmacist involvement in management of pain, agitation and delirium (PAD) at a large community teaching hospital is described. Florida Orlando Hospital implemented a two-phase initiative to decrease intensive care unit (ICU) length of stay (LOS), ventilator use, sedative use, and hospital expenditures while advancing pharmacists' scope of practice. Phase 1 of the initiative involved a pilot project to evaluate pharmacist management of sedative therapy for mechanically ventilated patients. Using a newly developed PAD order set, a pharmacist performed daily sedation management in a cohort of patients; relative to physician-managed standard care, pharmacist-directed sedation management resulted in fewer hours of patient exposure to continuous sedation, with an overall 46% reduction in continuous infusions of sedatives and reductions in both ICU and total hospital LOS, resulting in estimated savings of $1.2 million in direct hospital costs and $183,216 in drug costs. In phase 2 of the project, an expanded group of pharmacists collaborated with interprofessional teams to manage PAD using an integrated "ABCDE bundle" to promote early mobility and weaning from sedatives and analgesics. A retrospective comparison of data on a cohort of medical ICU patients managed using the ABCDE bundle approach (n = 436) and a standard-care cohort (n = 499) demonstrated improvements in several outcomes, including mean ventilator days per patient, ICU LOS, and mortality. The provision of proactive critical care pharmacist services directed at PAD management is an innovative approach to fostering interprofessional collaboration and optimizing clinical outcomes.

Dynamics of Telomere Length Reflect the Clonal Suppression Seen with the Telomerase Inhibitor Imetelstat in Patients with Essential Thrombocythemia

Dynamics of Telomere Length Reflect the Clonal Suppression Seen with the Telomerase Inhibitor Imetelstat in Patients with Essential Thrombocythemia

Coronary CT angiography versus standard of care strategies to evaluate patients with potential coronary artery disease; effect on long term clinical outcomes

Background: Previous studies have shown that computed tomography coronary angiography (CTA) in patients with suspected coronary artery disease (CAD) predicts short term adverse events. However, there is no current data on whether identifying atherosclerosis on CTA impacts outcomes. We performed a case–control study to assess whether information from CTA can improve outcomes. Methods: 4244 symptomatic patients (mean age 58 ± 9, 62.5% male) without known CAD who underwent CTA (n = 2538) to rule out CAD were matched to 1706 patients who underwent standard of care in an academic cardiology clinic. Patients were propensity-matched by gender, age, ethnicity, CAD risk factors and follow-up duration. The primary outcome measure was all-cause mortality. Multivariable Cox proportional hazards models incorporated age, gender and traditional risk factors for coronary disease as well as pre-test probability of CAD. Results: There were no significant differences in age, gender, conventional risk factors between groups (p > 0.05). During a mean follow up of 80 ± 11 months, the overall death rate was 6.3% (270 deaths). Death rate was significantly lower in CTA group (n = 106, 4.2%) as compared to the control group (n = 184, 10.8%, p = 0.001). Event free survival was 95.8% and 89.2% in CTA and standard of care groups, respectively. Risk-adjusted hazard ratio of death were 2.5 (95%CI: 1.6–6.7, p = 0.003) in standard of care cohort as compared to CTA group. Multivariate analysis demonstrated that undergoing coronary CTA resulted in a risk reduction of 32%, p = 0·0001. Conclusions: Improved knowledge of atherosclerosis or increased anti-atherosclerotic therapies among those undergoing CTA may have contributed to improved survival. Our results provide evidence of potential benefit from scanning for atherosclerosis with CTA in symptomatic patients. Large randomized trials are warranted.

Management of primary metastatic breast cancer in elderly patients—An international comparison of oncogeriatric versus standard care

An oncogeriatric approach may affect management of elderly patients with breast cancer. However, little is known about oncogeriatric care in the metastatic setting. Therefore, we performed an international comparison of management of elderly patients with primary metastatic disease who were treated in two different care settings. Patients who were ≥70years at diagnosis of primary metastatic disease were eligible. The first cohort comprised a population-based cohort of 104 patients (Comprehensive Cancer Center West, The Netherlands), who all received standard care. The second cohort comprised a hospital-based cohort of 42 patients (H. Lee Moffitt Cancer Center, Florida, United States), who all received oncogeriatric care. No large differences in patient and tumor characteristics were observed between both cohorts. Most patients in the standard care cohort received systemic therapy as primary therapy, whereas most patients in the oncogeriatric cohort received a combination of systemic and local therapy. Patients in the standard care cohort received fewer lines of treatment (mean number of treatments 2.1 vs. 3.6, p<0.001), and particularly received less breast surgery, chemotherapy, and trastuzumab. Three-year overall mortality was 71% (95% CI: 61-83%) as compared to 58% (95% CI: 42-75%) among patients in the oncogeriatric care cohort (multivariable HR: 1.59 [95% CI: 0.88-2.87], p=0.125). In primary metastatic breast cancer, oncogeriatric care intensifies treatment and might improve survival in elderly patients. Future studies on a larger scale should investigate the potential for improved survival, and whether this is accompanied by a better (preservation of) quality of life and functional status.

The Angio-Seal™ femoral closure device allows immediate ambulation after coronary angiography and percutaneous coronary intervention

To test the safety of immediate mobilisation of patients undergoing coronary angiography and percutaneous coronary intervention (PCI) closed with Angio-Seal™ -a femoral vascular closure device. First, a randomised controlled trial of immediate mobilisation vs. delayed ambulation was performed followed by a prospective validation registry to test the obtained results in a real-world situation. The randomised trial comprised 300 patients; the validation registry comprised 1,097 patients. Primary endpoints were complications defined as: small haematoma <5 cm and/or minor bleeding/oozing from the puncture site, haematomas ≥ 5 cm, bleeding needing transfusion, bleeding needing surgical attention, pseudoaneurysm and vasovagal reaction. In the randomised trial, overall complications were similar in both groups (16.0%vs.18.8%; p=0.53). Small haematomas/small bleedings/oozing were the most frequent (12.2% vs.15.3; p=0.44). There were no bleedings needing transfusion or surgical attention, and no pseudoaneurysms occurred. The prospective registry showed similar results. In the standard-care cohort, complications were similar to those in the implementation cohort (9.6% vs.11.3%; p=0.41), mainly consisting of small haematomas/minor bleedings/oozing (6.1% vs.7.3%; p=0.49). No bleedings needed transfusion or surgical attention. Pseudoaneurysms occurred in 1 (0.34%) vs. 3 (0.37%; p=0.94) and vasovagal reactions in three (1.0%) vs. four (0.5%; p=0.33) patients. It was possible to mobilise 87% of patients in the implementation cohort. In patients undergoing coronary angiography or PCI, the use of immediate mobilisation after Angio-Seal™ deployment is safe. With routine use of a femoral vascular closure device, approximately 87% of patients are suitable for immediate mobilisation.

Getting the Grip on Nonspecific Treatment Effects: Emesis in Patients Randomized to Acupuncture or Sham Compared to Patients Receiving Standard Care

BackgroundIt is not known whether or not delivering acupuncture triggers mechanisms cited as placebo and if acupuncture or sham reduces radiotherapy-induced emesis more than standard care.Methodology/Principal FindingsCancer patients receiving radiotherapy over abdominal/pelvic regions were randomized to verum (penetrating) acupuncture (n = 109; 99 provided data) in the alleged antiemetic acupuncture point PC6 or sham acupuncture (n = 106; 101 provided data) performed with a telescopic non-penetrating needle at a sham point 2–3 times/week during the whole radiotherapy period. The acupuncture cohort was compared to a reference cohort receiving standard care (n = 62; 62 provided data). The occurrence of emesis in each group was compared after a mean dose of 27 Gray. Nausea and vomiting were experienced during the preceding week by 37 and 8% in the verum acupuncture group, 38 and 7% in the sham acupuncture group and 63 and 15% in the standard care group, respectively. The lower occurrence of nausea in the acupuncture cohort (verum and sham) compared to patients receiving standard care (37% versus 63%, relative risk (RR) 0.6, 95 % confidence interval (CI) 0.5–0.8) was also true after adjustment for potential confounding factors for nausea (RR 0.8, CI 0.6 to 0.9). Nausea intensity was lower in the acupuncture cohort (78% no nausea, 13% a little, 8% moderate, 1% much) compared to the standard care cohort (52% no nausea, 32% a little, 15% moderate, 2% much) (p = 0.002). The acupuncture cohort expected antiemetic effects from their treatment (95%). Patients who expected nausea had increased risk for nausea compared to patients who expected low risk for nausea (RR 1.6; Cl 1.2–2.4).Conclusions/SignificancePatients treated with verum or sham acupuncture experienced less nausea and vomiting compared to patients receiving standard care, possibly through a general care effect or due to the high level of patient expectancy.Trial Registration ClinicalTrials.gov NCT00621660