Non-infectious Adverse Events Research Articles

Non-infectious adverse events of transperineal prostate biopsies performed under local anaesthesia.

To report non-infectious adverse events associated with transperineal prostate biopsy (TPBx) performed under local anaesthesia (LA) in an outpatient setting. This study reports secondary outcomes from the Norwegian arm of the prospective NORAPP study (ClinicalTrials.gov identifier NCT04146142) and included all patients referred for prostate biopsy from November 2019 to February 2021. Transperineal magnetic resonance imaging-transrectal ultrasonography fusion TPBx were taken using 40 mL 1% lidocaine with 4 mL of 8.4% sodium bicarbonate placed in the perineal skin, under the prostatic apex, in the m. levator ani bilaterally, and along the path of the needle. Follow-up using patient-reported questionnaires was done immediately after TPBx, and after 2 weeks and 2 months. Pain was reported using a visual analogue scale (VAS) during placement of the LA, and during and after TPBx. Haematuria and acute urinary retention (AUR) rates were recorded. We included 402 patients, and the response rate was 99.8% (401/402). The median (interquartile range [IQR]) age was 69 (63-74) years, the prostate volume was 40 (27-58) mL, the prostate-specific antigen level was 7.0 (4.5-11) ng/mL, and the number of biopsy cores taken was 8 (6-10). The median (IQR) VAS pain score was 1 (1-2) during placement of LA, 1 (0-2) during TPBx, and 0 (0-0) after TPBx. Haematuria and AUR rates were 64% (95% confidence interval [CI] 60-69%) and 0.5% (95% CI 0.1-1.8%), respectively. No patients were hospitalised or required after the TPBx surgical intervention. Transperineal prostate biopsies can be performed under LA with limited discomfort to the patient and few post-TPBx adverse events.

Low Disease Burden Pre-CAR-T Cell Therapy for Children and AYA with B-ALL Is Associated with an Impaired Outcome When Obtained through Intensification of the Bridging Therapy

Rationale. The role of bridging therapy, i.e., treatment between apheresis and lymphodepletion (LD) preceding tisagenlecleucel (tisa-cel) infusion for relapsed/refractory B cell acute lymphoblastic leukemia (R/R BCP-ALL) is still unclear. We report a retrospective study on our experience on 81 children, adolescents, and young adults with R/R BCP-ALL who underwent apheresis with an intent to receive tisa-cel infusion, between March 2016 and October 2020. Methods. Bridging therapy intensity was classified into two intensity groups. A high intensity bridging (HIB) regimen, used in 23 patients (pts), was defined as the use of more than 4 intravenous anti-leukemic drugs per week and/or the need of secondary intensification of bridging therapy, the latter being the case in 19 pts (83%). A low-intensity bridging (LIB), in general a combination of vincristine, steroids +/-asparaginase, was used in 58 pts. The aim of the study was to evaluate the impact of HIB versus LIB on tisa-cel efficacy. Factors associated with a failure to infuse tisa-cel were also explored. Results. Patients had a median age of 15 years (range: 1-19). Tisa-cel indication was a primary refractory disease for 5 pts (6%), a first post-allo-HSCT relapse for 47 pts (58%) and a second relapse or more for 29 pts (36%). Patients who received a HIB therapy were more likely to have high-risk genetic features (39% vs 12%, p= .01) and/or a primary refractory disease (17% vs 2%, p=.02). Grade 3+ non-infectious and infectious adverse events during bridging therapy were also more likely in this group, albeit in a non-statistically significant way (35% vs 16 %, p= .07 and 52% vs 34 %, p= .21; respectively). Nine patients (11%) were not infused (disease progression: 3 pts; toxicity: 5 pts (sinusoidal obstruction syndrome: 1 pt, encephalopathy: 2 pts, fungal infection; 1 pt, hemoptysis: 1 pt); and CD19 negativation: 1 pt). A high pre-apheresis tumor burden ( p=.01), the occurrence ( p=.01), and the number of grade ≥ 3 adverse events during bridging period ( p<.01) were associated with a higher risk of tisa-cel non-infusion, while HIB was not ( p=.73). The 72 remaining patients (89%) finally received tisa-cel infusion, 52 (64%) after a LIB therapy and 20 (25%) after a HIB therapy. Despite a comparable BM disease burden at apheresis between the LIB and the HIB groups, patients presenting a high disease burden prior to LD (bone marrow (BM) blasts > 50%) were more frequent in the HIB group ( p< .01). When compared to patients who received a LIB, patients treated with a HIB had a worst, albeit non-statistically different cumulative incidence of relapse (CIR) (SHR 1.94, 95% CI [0.95-3.91], p=.07), an inferior 18-month event-free survival (EFS) (26.9% vs 54.1%; p=.02) and a lower 18-month overall survival (OS) (50.9% vs 88.8%; p<.01). Considering a threshold at 50% BM blasts, patients who presented a high disease burden prior to LD had poorer early response rates (D28 minimal residual disease (MRD) negativity: 85% vs 69%, p< .01), a higher, albeit non-statistically different CIR (SHR 2.27, 95% CI [0.98-5.27], p=.06), an inferior 18-month EFS (26.9% vs 51.3%; p=.02) and a lower 18-month OS (22.6% vs 91.5%; p<.01). We then asked if the bridge intensity, aimed at achieving a low disease burden before LD, could influence patient outcomes. Median percentages of BM blast infiltration were similar after LIB (0%) and HIB therapy (1%, p=.87) in patients with ≤50% BM blast at LD. In these patients, a prior HIB regimen was associated with a higher rate of detectable MRD at D28 (40% vs 8%, p=.02), an inferior 18-month EFS (18.0% vs 57.5%; p=.02) and a higher, albeit non-statistically different CIR (SHR 2.05, 95%CI [0.87-4.88], p=.1). The 18-month OS did not differ between groups (74.0% vs 94.6%; p=.15), suggesting that these patients may respond to further lines of treatment after relapse. The outcome of patients presenting a low disease burden at LD after a HIB regimen was thus similar to those with a high disease burden at LD. Conclusion. This study confirms the prognostic value of a high disease burden pre-LD but also reveals that a low disease burden prior tisa-cel therapy is associated with an impaired outcome when obtained through intensification of the bridging therapy. Additional post-tisa-cel therapies should be considered in this group of patients.

Long Washout Periods Between Biologics for Inflammatory Bowel Disease Clinical Trials Are Unnecessary: A Canadian Retrospective Cohort Study.

To assess the safety of early vs late biologic switch in patients with inflammatory bowel disease. In this retrospective study, we included patients with inflammatory bowel disease who underwent biologic switch between January 2014 and July 2022 at a tertiary center. The primary outcome was any infection by 6 months. There was no statistically significant difference between patients who had early biologic switch (≤30 days, n = 51) and late switch (>30 days, n = 77) in either infectious or noninfectious adverse events by 6 and 12 months. Early biologic switch is safe. A prolonged washout period between 2 biologics is unnecessary.

MP44-16 NON-INFECTIOUS ADVERSE EVENTS OF TRANSPERINEAL PROSTATE BIOPSIES PERFORMED UNDER LOCAL ANESTHESIA IN AN OUTPATIENT SETTING: RESULTS FROM THE NORAPP STUDY

You have accessJournal of UrologyCME1 Apr 2023MP44-16 NON-INFECTIOUS ADVERSE EVENTS OF TRANSPERINEAL PROSTATE BIOPSIES PERFORMED UNDER LOCAL ANESTHESIA IN AN OUTPATIENT SETTING: RESULTS FROM THE NORAPP STUDY Maciej Jacewicz, Erik Rud, and Eduard Baco Maciej JacewiczMaciej Jacewicz More articles by this author , Erik RudErik Rud More articles by this author , and Eduard BacoEduard Baco More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003290.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The aim of our study was to examine the feasibility and adverse events of transperineal prostate biopsies (TPBx) performed under local anesthesia (LA) in an outpatient setting. METHODS: Patients with suspicion of prostate cancer were included in this randomized clinical trial. Primary endpoint was examining the role of antibiotic prophylaxis in TPBx. Secondary endpoints were pain during and after the procedure (VAS), hematuria, hematospermia and acute urinary retention (AUR). Patients with a high risk of infection were excluded. Free-hand MRI-TRUS fusion TPBx, using the Koelis Trinity device, were performed in an outpatient setting under LA. 40 ml of 1% Lidocaine and 4 ml Sodium Bicarbonate was injected in the perineal skin, under the prostatic apex, in levator ani bilaterally and along the path of the needle under TRUS guidance. Target biopsies were performed in patients with PIRADS ≥3 on MRI, systematic biopsies were performed in biopsy naïve and MRI negative patients. VAS was reported immediately after biopsy, followup regarding non-infectious adverse events was after 2 weeks and 2 months. Correlation was analyzed using Pearson coefficient. RESULTS: We included 402 patients. Median age was 69 years (IQR 63-74, range: 38-86), PSA 7.0 ng/ml (IQR 4.5-11) and prostate volume (PV) 40 ml (IQR 27-58). Median number of cores was 8 (IQR 6-10). Response rate to the questionnaire was 100% (401/402). Median VAS during the placement of LA was 1 (IQR: 1-2, range 0-8) and VAS during biopsy 1 (IQR:1-2, range: 0-8). Additional LA was required by 10% (40/401). There was a weak correlation between age and VAS during placement of LA (r: -0.293, p: <0.001), age and VAS during biopsy (r: -0.243 p:<0.001) and number of cores and VAS during biopsy (r:0.137, p=0.006). There was no correlation between VAS and PV. Median post-procedural VAS was 0 (IQR: 0-0, range 0-5), 2% (9/401) used analgesics after the procedure. Hematuria was present in 64% (258/401), median duration was 3 days (IQR:2-7, range 1-35). There was a weak correlation between number of cores and hematuria (r:0.180, p:<0.001. Hematospermia was present in 54% (197/366) of patients, median duration was 14 days (IQR:7-21, range 1-49). AUR occurred in two patients (0.5%, 95% CI:0.1-1.8). One suffered a clot retention resolved by single time catheterization, the other was treated with a permanent catheter for a week. CONCLUSIONS: Transperineal prostate biopsies under LA can safely be performed in an outpatient setting with limited discomfort to the patient and few non-infectious adverse events. Source of Funding: Oslo University Hospital © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e618 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Maciej Jacewicz More articles by this author Erik Rud More articles by this author Eduard Baco More articles by this author Expand All Advertisement PDF downloadLoading ...

ARTHRITIS AND ARTHRALGIA AS EXTRAINTESTINAL MANIFESTATIONS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE TREATED WITH VEDOLIZUMAB: A META-ANALYSIS

Vedolizumab is a humanized gut selective drug that specifically targets α4β7 integrin and has been used successfully in the treatment of Inflammatory Bowel Disease (IBD). Although Vedolizumab is an effective treatment for IBD and acts specifically on the gastrointestinal system, some studies have reported extraintestinal manifestations as adverse events. One of the most frequently reported non-infectious adverse events is articular manifestations. However, it is difficult to know for sure whether the joint symptoms are due to the vedolizumab adverse event or due to extraintestinal symptoms of the disease itself.

Non-infectious adverse events of transperineal prostate biopsies performed under local anesthesia in an outpatient setting – results from the NORAPP study – a randomized clinical trial

Non-infectious adverse events of transperineal prostate biopsies performed under local anesthesia in an outpatient setting – results from the NORAPP study – a randomized clinical trial

ARTHRITIS AND ARTHRALGIA AS EXTRAINTESTINAL MANIFESTATIONS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE TREATED WITH VEDOLIZUMAB: A META-ANALYSIS

Abstract BACKGROUND Vedolizumab is a humanized gut selective drug that specifically targets α4β7 integrin and has been used successfully in the treatment of Inflammatory Bowel Disease (IBD). Although Vedolizumab is an effective treatment for IBD and acts specifically on the gastrointestinal system, some studies have reported extraintestinal manifestations as adverse events. One of the most frequently reported non-infectious adverse events is articular manifestations. However, it is difficult to know for sure whether the joint symptoms are due to the vedolizumab adverse event or due to extraintestinal symptoms of the disease itself. AIMS This systematic review and meta-analysis aimed to assess the incidence of extraintestinal manifestations in patients receiving Vedolizumab and to investigate whether these adverse events are indeed drug-related. METHODS Pubmed, Cochrane, and Scopus were searched for randomized clinical trials reporting the incidence of articular events in patients with Crohn’s Disease or Ulcerative Colitis who were treated with Vedolizumab. The considered outcomes were new-onset or worsening of pre-existing joint manifestations. We used Revman to calculate the pooled incidence of the reported outcomes and their corresponding 95% confidence intervals (95% CI). RESULTS The search strategy yielded 4.206 articles. After removal of duplicates and screening of results, 4 randomized studies met the inclusion criteria (Figure 1). A total of 2.466 patients with moderately to severe IBD were included. Of those, 1822 were randomized to intervention group, with Vedolizumab administration, and 644 to placebo. In the intervention group, 232 patients developed arthritis or arthralgia of any kind, versus 66 patients of placebo group (95% CI 0.7%-1.3%; Figure 2). Of those patients, 73,8% and 33% had prior treatment with anti-TNF and immunomodulators, respectively. 63% and 15% also had prior anti-TNF and immunomodulators previous failure, respectively. CONCLUSION The meta-analysis presented above shows a result without statistical significance to say that vedolizumab is responsible for the manifestations previously described. Therefore, it is necessary to hypothesize that the new onset of worsening arthritis and arthralgia may be associated with the course of the disease itself, the body's response to the drugs or the exclusion of corticosteroids or anti-TNF from concomitant treatment with Vedolizumab. More studies with larger samples are needed, especially randomized clinical trials comparing Anti-TNF, corticosteroids and immunomodulators to assess the incidence of joint manifestations and even other rheumatologic manifestations in patients with Inflammatory Bowel Disease.

The Real-World Effectiveness and Safety of Ustekinumab in the Treatment of Crohn's Disease: Results From the SUCCESS Consortium.

We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD). This study used a retrospective, multicenter, multinational consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions were assessed using time-to-event analysis, and clinical predictors were assessed by using multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation. A total of 1,113 patients (51.8% female, 90% prior antitumor necrosis factor exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naive patients achieved significantly higher rates of clinical and endoscopic remissions at 63% and 55%, respectively. On multivariable analyses, prior antitumor necrosis factor (hazard ratio, 0.72; 95% confidence interval, 0.49-0.99) and vedolizumab exposure (hazard ratio, 0.65; 95% confidence interval, 0.48-0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77 of 102 (75%) underwent dose optimization, and 44 of 77 (57%) achieved clinical response. An additional 152 of 681 patients (22.3%) were dose-optimized because of primary nonresponse incomplete response to UST, of whom 40.1% (61 of 152) responded. Serious infections occurred in 3.4% of patients while other noninfectious adverse events (lymphoma [n = 1], arthralgia [n = 6], rash [n = 6], headache [n = 3], hepatitis [n = 3], hair loss [n = 3], neuropathy [n = 1], and vasculitis [n = 1]) occurred in 2.4% of patients. UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in biologic-naive patients, and dose escalation may recapture clinical response.

Healthcare-Associated Adverse Events in Alternate Level of Care Patients Awaiting Long-Term Care in Hospital.

Introduction: A growing number of Canadian older adults are designated alternate level of care (ALC) and await placement into long-term care (LTC) while admitted to hospital. This creates infrastructural challenges by using resources allocated for acute care during disproportionately long hospital stays. For ALC patients, hospital environments maladapted to their needs impart risk of healthcare-associated adverse events. Methods: In this retrospective descriptive study, we examined healthcare-associated adverse events in 156 ALC patients, 65 years old and older, awaiting long-term care while admitted to two hospitals in London, Ontario in 2015–2018. We recorded incidence of infections and antimicrobial days prescribed. We recorded incidence of non-infectious adverse events including delirium, falls, venothrombotic events, and pressure ulcers. We used a restricted cubic spline model to characterize adverse events as a function of length of stay. Results: Patients waited an average of 56 ALC days (ranging from 6 to 333 days) before LTC placement, with seven deaths occurring prior to placement. We recorded 362 total adverse events accrued over 8668 ALC days: 94 infections and 268 non-infectious adverse events. The most common hospital-acquired infections were urinary-tract infections and respiratory infections. The most common non-infectious adverse events were delirium and falls. A total of 620 antimicrobial days were prescribed for infections. Conclusions: ALC patients incur a meaningful and predictable number of adverse events during their stay in acute care. The incidence of these adverse events should be used to educate stakeholders on risks of ALC stay and to advocate for strategies to minimize ALC days.

Noninfectious transfusion-associated adverse events

Noninfectious transfusion-associated adverse events

Cost-effectiveness and budget impact of whole blood pathogen reduction in Ghana.

Despite the promise of pathogen reduction for reducing transfusion-associated adverse events in sub-Saharan Africa, no health-economic assessment is publicly available. We developed a mathematical risk reduction model to estimate the impact of nationwide whole blood pathogen reduction in Ghana on the incidence of six infectious and one non-infectious transfusion-associated adverse events. We estimated the lifetime direct healthcare costs and disability-adjusted life years lost for each adverse event. For HIV, HCV, and HBV, we simulated disease progression using Markov models, accounting for the likelihood and timing of clinical detection and treatment. We performed probabilistic and univariate sensitivity analysis. Adding whole blood pathogen reduction to Ghana's blood safety portfolio would avert an estimated 19,898 (11,948-27,353) adverse events and 38,491 (16,444-67,118) disability-adjusted life years annually, primarily by averting sepsis (49%) and malaria (31%) infections. One year of pathogen reduction would cost an estimated $8,037,191 ($6,381,946-$9,880,760) and eliminate $8,656,389 ($4,462,614-$13,469,448) in direct healthcare spending on transfusion-associated adverse events. We estimate a 58% probability that the addition of pathogen reduction would reduce overall direct healthcare spending. Findings were most sensitive to uncertainty in the probability that a bacterially contaminated blood donation causes sepsis. Whole blood pathogen reduction would substantially reduce the burden of known transfusion-associated adverse events in Ghana and may reduce overall healthcare spending. Additional benefits not captured by this analysis may include averting secondary transmission of infectious diseases, reducing non-medical costs, and averting new or re-emerging transfusion-transmitted infections.

Bendamustine and Rituximab As Initial Therapy in Indolent Non-Hodgkin's Lymphoma and Mantle Cell Lymphoma in a Canadian Population; Highly Effective with Frequent Infections

Indolent non-Hodgkin's lymphoma (iNHL) and mantle cell lymphoma (MCL) represent a diverse group of treatable but incurable B-cell lymphoid malignancies. Since 2013, bendamustine and rituximab (BR) followed by maintenance rituximab (MR) became standard upfront therapy for patients with treatment naïve iNHL and transplant ineligible MCL at CancerCare Manitoba, a tertiary referral center in the province of Manitoba, Canada. The aim of this retrospective study is to describe efficacy of BR, outside of a clinical trial, with a focus on toxicity.Manitoba provincial oncology drug program database was used to identify patients. Treatment naïve iNHL and transplant-ineligible MCL patients treated with BR were included. Chronic lymphocytic leukemia, transformed and aggressive B-cell lymphoma patients were excluded. Patient and disease characteristics including response evaluation, dates of relapse, death and hematologic and non-hematologic toxicities were collected. Statistical analysis was completed using univariable Cox regression.A total of 187 patients were identified, diagnosed between 1994-2016 (median 2014). At diagnosis, the median age was 65 years (range 41-91); 36% (68/187) of patients were > 70 years old. Follicular lymphoma (FL) was the most common histology [63.4% (97/187); n=54 grade 1-2, n= 31 grade 3A, n=12 unknown grade] followed by 16% (30/187) marginal zone lymphoma, 13% (25/187) Waldenström macroglobulinemia, 12% (22/187) MCL, 2% (3/187) small lymphocytic lymphoma and 5% (10/187) low grade unclassifiable. Median FLIPI score was 2 (range 0-5) and median MIPI score was 5 (range 3-10). 83% (156/187) of patients had Ann Arbor stage III/IV, and 60% (107/178) had extra-nodal disease.Median follow-up from initiation of BR was 21 months (range 0-45). 81% (152/187) of patients completed six cycles of BR (range 1 to 6). Following treatment, 162 patients were evaluable for response; overall response rate (ORR) was 95% [52% (n=84) CR, 43% (n=69) PR]. Most (n=135) received at least one dose of MR (range 1-12). Of the 67 patients with post MR evaluations, the CR rate increased to 84% (n=56). During follow up, 10% (19/187) of patients relapsed, median time to relapse was 14 months (range 3-31). Of these, 7 had FL (n=5 grade 1-2, n=2 grade 3A). Death (all cause) occurred in 9% (17/187) of patients. Median PFS and OS have not been reached within the follow-up period.Infections (all grades) were reported in 62% (116/187) of patients with a total of 251 events. Infections were primarily respiratory (55%, 138/251), fever (7%, 17/251) and of the urinary tract (6%, 16/251). Febrile neutropenia events occurred in 3% (5/187) of patients. Non-infectious adverse events (all grades) were reported in 75% (140/187) of patients with a total of 217 events. Fatigue (25%, 54/217), infusion reaction (14%, 31/217), nausea (12%, 25/217) and diarrhea (7%, 16/217) were the most common. Rash was reported in 26% (48/217) of total events.Severe neutropenia occurred in 22% (41/187 patients) of which 5% (n=10) had grade 3 and 17% (n=31) had grade 4. This resulted in a 1-year cumulative incidence of severe neutropenia during BR therapy of 19.7%. Starting after BR completion, there was a 1-year cumulative incidence of neutropenia of 6.9% (Figure 1). Increasing age significantly correlated with risk of neutropenia [p=0.026, HR 1.46, 95% CI (1.05-2.03)]. The 1-year cumulative incidence of respiratory and non-respiratory infections during BR therapy was 35.7% and 39.7%, respectively.Our real world data of unselected patients (including FL, grade 3A) show that BR is associated with high ORR, similar to the published literature. For those evaluable for post-MR response, CR rate improved compared to post BR assessment. Grade 4 neutropenia was higher than previously reported with older age being a statistically significant risk factor for neutropenia. Risk of neutropenia and infection persisted beyond six months following BR but use of MR could have contributed. Our study show that BR followed by MR is effective for unselected patients with iNHL and transplant ineligible MCL. However, we found higher rates of adverse events than previously reported. Respiratory infection was particularly common and further investigation regarding etiology and benefit of immunizations in this patient population should be explored. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Association of Rituximab Use With Adverse Events in Children, Adolescents, and Young Adults

Rituximab is among the most frequently used immunotherapies in pediatrics. Few studies have reported long-term adverse events associated with its use for children. To describe the use of rituximab and to assess whether its use is associated with short- or long-term adverse events, infections, or time to immune reconstitution in a diverse group of young people. This retrospective cohort study included 468 patients aged younger than 21 years who received rituximab for diverse indications between October 1, 2010, and December 31, 2017, at Texas Children's Hospital, a large pediatric referral hospital. Patterns of adverse events, infections, and immune recovery are described. Data analyses were conducted from December 2019 to June 2020. One or more doses of rituximab. Adverse drug events (eg, anaphylaxis), incidence of mild and severe infections, and time to recovery of B lymphocyte subset counts and immunoglobulin levels. Survival models and logistic regression analyses and were used to identify associated risk factors of infectious and noninfectious adverse drug events. We identified 468 patients receiving at least 1 dose of rituximab. The total follow-up time was 11 713 person-months. Of the 468 patients, 293 (62.6%) were female, the median (interquartile range) age at receipt of dose was 14.3 (9.9-16.8) years, and 209 (44.7%) were self-reported White Hispanic. Adverse events associated with rituximab infusion occurred in 72 patients (15.4%), and anaphylaxis occurred in 17 patients (3.6%). Long-term adverse events, such as prolonged neutropenia and leukoencephalopathy, were absent. Infections occurred in 224 patients (47.9%); 84 patients (17.9%) had severe infections, and 3 patients (0.6%) had lethal infections. Concurrent use of intravenous chemotherapy, treatment of systemic lupus erythematosus, neutropenia, and use of intravenous immunoglobulin were associated with increased risk of infection. Among 135 patients (28.8%) followed up to B cell count recovery, CD19+ or CD20+ cell numbers normalized in a median of 9.0 months (interquartile range, 5.9-14.4 months) following rituximab use; 48 of 95 patients (51%) evaluated beyond a year had low-for-age B cell counts. Recovery of CD27+ memory B cell number occurred in a median of 15.7 months (interquartile range, 6.0-22.7 months). Among patients with normal baseline values, low immunoglobulin G (IgG) levels developed in 67 of 289 patients (23.2%) and low IgM levels in 118 of 255 patients (40.8%); of these patients evaluated beyond 12 months from rituximab, 16 of 117 (13.7%) had persistently low IgG and 37 (33.9%) of 109 had persistently low IgM. Rituximab is well tolerated among young people and is associated with few serious adverse events, but infections are common, corresponding to a prolonged period of B cell count recovery often lasting for longer than a year. Further examination of strategies to prevent infections following rituximab should be pursued.

Hematopoietic stem cell transplantation in systemic sclerosis: Yes!! BUT. . .

Systemic sclerosis is a chronic multisystem, autoimmune disease with high mortality, and to date, has no effective approved therapy. For patients with the most severe forms of systemic sclerosis, autologous hematopoietic stem cell therapy has been proven to be effective, as demonstrated by three randomized controlled clinical trials and at least two registry studies. In the controlled studies, autologous hematopoietic stem cell therapy was shown to improve mortality, skin involvement, quality-of-life, and function compared with patients treated with intravenous cyclophosphamide. There is significant transplant-related mortality associated with autologous hematopoietic stem cell therapy, as well as infectious and noninfectious serious adverse events, including cardiac and renal compromise. Although the results of autologous hematopoietic stem cell therapy clinical trials to date are highly encouraging, a number of important unanswered questions remain. These include the following: What is the optimal transplant regimen; can the spectrum of systemic sclerosis patients who respond to autologous hematopoietic stem cell therapy be expanded; how can disease relapse following autologous hematopoietic stem cell therapy be predicted and managed; can treatment-related toxicity and mortality be mitigated; can response or toxicity be predicted; and finally, is there a place for allogeneic stem cell transplants in systemic sclerosis? Systemic sclerosis is an autoimmune disease with multiple immunological, vascular, and fibrotic abnormalities. Immunosuppressive therapy is frequently used, but to date its efficacy has been generally modest. Stem cell transplantation is the most potent immunosuppressive therapy currently available, and as discussed below, may have an important role in the management of systemic sclerosis.

Eventos adversos relacionados ao cateter venoso central em pacientes internados em um hospital de ensino

O objetivo do estudo é descrever os eventos adversos relacionados ao uso de Cateter Venoso Central (CVC). Trata-se de um estudo observacional descritivo, longitudinal e prospectivo, realizado com 81 pacientes, adultos e pediátricos, que utilizaram CVC durante sua internação, por mais de 48 horas, no período de junho a novembro de 2017 em um hospital público de ensino de médio porte, do estado de Sergipe, Brasil. Após aprovação do Comitê de Ética em Pesquisa, os dados foram coletados por meio de um formulário de busca ativa, conforme as informações contidas no prontuário do paciente. Foram monitorados 104 CVC, com média de 1,3 por paciente, tempo médio de permanência 11 dias (DP=8). A maior taxa de incidência de eventos adversos ocorreu na UTI (39,4%). A média de idade foi 52 anos (DP ± 19), predominando o sexo feminino (56,7%). A incidência acumulada global de eventos adversos foi 40,7%, com densidade de incidência de 26,1 por 1000 CVC-dia. A frequência dos eventos adversos infecciosos (48,5%) foi semelhante à dos eventos adversos não infecciosos (51,5%), destacando-se entre os infecciosos a infecção de sítio de inserção (ISI – CVC) (39,9%) e, dentre os eventos não infecciosos, a perda de cateter (24,2%). Foram registrados 11 óbitos, sendo que 27,3% desenvolveu eventos adversos durante o período de observação. Evidenciou-se que a infecção de sítio de inserção (ISIC-VC) foi o principal evento adverso identificado neste estudo, majoritariamente em indivíduos internados na UTI e do sexo feminino.

Refining Blood Products Utilization: Every One (unit) Matters

INTRODUCTION Appropriate restriction of blood transfusion is important to reduce harm to patients and cost to society. Current research shows that every RBC transfused unit increases 30-day mortality (odd ratio = 1.32), composite morbidity (odd ratio =1.23), pneumonia (odd ratio = 1.24) and sepsis/shock (odd ratio = 1.29) of 95% Confidence Interval. Literature shows that it is feasible to significantly reduce healthcare costs and potential transfusion-related harm by minimizing blood transfusion orders. This will help improve transfusion quality, minimize administrative cost, and maximize patient safety. We examined the extent of adherence to the American Association of Blood Banks (AABB) transfusion guidelines by reviewing blood transfusions orders that were fulfilled throughout the year of 2018, and the potential effect of quality improvement intervention. OBJECTIVES The objective of this research is to restrict blood transfusion products through the implementation of an automated process that accords with current guidelines. The process entails modifying the current interface at the VA Palm Beach and effectively create an embedded clinical decision-making system that includes appropriate logistics to guide the appropriateness of blood transfusion orders. The interface promises interactive pop-up dialogue that engages users with a set of rules to assess transfusion indication and guide its appropriateness. The proposed intervention provides safer evidence-based transfusion, reduced risk of non-infectious adverse events and infectious agents, and decreased demand on limited blood supplies. METHODS This is a retrospective analysis of transfused patients in year 2018 .The data was retrieved from an electronic medical record database, which included patient gender, age, comorbidities, mean baseline hemoglobin, pre- and post- transfusion hemoglobin, hemodynamics status, complications, active bleeding, history of cardiac disease, ordering division, and number of units transfused. Patients were randomly selected from January to August 2018 (n=204). Roughly 302 PRBC units were transfused, averaging 1.4 units per person. Insignificant life-threatening complications were reported. The Average pre-transfusion hemoglobin was 7.6, and post-transfusion hemoglobin was 9.3. 54% received 2 units, whereas 46% received 1 unit. INTERVENTIONS We propose a two-tier auditing system, based on a low and high priority, which reflects the timeline to address non-compliant transfusion orders. Low priority orders are evaluated during the periodic meeting of the transfusion committee, and high priority orders are addressed within a few hours of the transfusion order. All transfusion orders of Hg &gt; 7-8 g/dL are flagged with low priority, whereas those with Hg&gt; 8g/dl and/or with orders exceeding one unit are flagged with high priority. The intervention includes: Identify the key Stakeholders and seek appropriate approvals, modify the existing interface to comply with AABB transfusion guidelines, establish a cultural change of blood management, "Every One (unit) Matters", educate our staff, physicians, residents, and students, through didactic channels on guidelines, and present case reports on patient safety. RESULTS The system was embedded with a logging mechanism to record non-compliant order requests, collect pre and post intervention data, audit transfusion records, restrict transfusions to 1 unit per order. Each unit is treated as a unique clinical decision, and each patient is evaluated for symptoms upon every transfusion. The interface also includes a logistics serving as a clinical decision tool and as an advisory delineating transfusion indication. Each transfusion order placed that doesn't meet requirements is reviewed retrospectively and is considered a fall out and flagged for chart review. Cases are escalated to the medical review committee, based on auditing priority, and the ordering physician is contacted accordingly. CONCLUSION Each unit blood transfused is associated with incrementally increased risk for adverse outcomes. Improvement of the overall transfusion rate is a key component to the success of this project. Our future directions are to engage and earn the confidence of all divisions, as well as change the existing culture in order to promote evidence-based medicine and safer practices in a cost-effective manner. Disclosures No relevant conflicts of interest to declare.

Fast CMV and EBV Reactivations after Ruxolitinib for Graft-Versus-Host Disease Treatment

Introduction: Corticosteroid-refractory graft-versus-host disease (GVHD) remains a serious complication of hematopoietic stem cell transplantation (HSCT) with high morbidity and mortality rates. Unfortunately, no standard therapy exists for this setting. Ruxolitinib (ruxo), an oral selective Janus-associated kinase (JAK) inhibitor, achieved good results for corticoresistant acute and chronic GVHD in preclinical and clinical studies, with 80% overall response rates. Recent studies showed an increased risk of infections in patients treated with ruxo, especially Epstein-Barr virus (EBV) and cytomegalovirus (CMV) reactivations. Patients and methods: In order to assess the efficacy and the safety of ruxo, we reviewed here the outcome of 57 patients who received ruxo for corticosteroid-refractory GVHD (in case of digestive tract involvement or in the absence of available ongoing clinical trials) or as a steroids-sparing medication. EBV and CMV reactivation risks were also assessed in the 137 consecutive patients received HSCT between January 1, 2012 and December 31, 2017 and who presented acute or chonic GVHD (57 of whom received ruxo). For this purpose, each reactivation were analyzed separately as a competing risk with death in a cause specific Cox model of survival after the first GVHD occurrence and the onset of ruxo therapy was coded as time dependent covariate. Results: The median age of 57 patients with ruxo was 55 years (range, 49 to 61). Indication for HSCT was acute myeloid leukemia for 25% patients, lymphoma for 30%, acute lymphoblastic leukemia for 11%, myeloproliferative neoplasm for 14% and myelodysplastic syndrome for 7%. Only 9% of this patients received ruxo before HSCT. Unrelated donor was used for 60% patients and main source of hematopoietic stem cells was peripheral stem cells (93%). T cell depletion with polyclonal anti-thymocyte globulin was performed for 89% of patients. Conditioning with high doses cyclophosphamide was used for 21% patients. A lymphopenia &lt;1G/L persisted at day 100 for 42/51 patients evaluated. In these 57 patients, ruxo was given for 62 episode of GVHD (acute: 21 [which 95% for an acute grade III-IV GVHD]; chronic: 36; overlap syndrome: 5). Response rates to ruxo were 48% for acute GVHD, 60% for overlap syndrom and 58% for chronic GVHD. The overall GVHD related-death rate was 33% (19% for acute GVHD and 14% for chronic GVHD). Our median follow-up was 30 months (range, 9 to 42) after HSCT. Main non-infectious adverse events were cytopenias (17/57) and hepatic cytolysis (6/57) leading to discontinuation or tapering of ruxo in 12 patients. EBV reactivation (&gt; 4 log or increasing viral charge of 0.5 log) occurred in 19 patients after ruxo with a 6-weeks cumulative incidence (6WCuI) of 22% (95CI [95% confidence interval]: 15-34). It was the first reactivation in 13 patients. CMV reactivation (&gt; 3 log) occurred in 8 patients after ruxo with a 6WCuI of 4% (95CI: 7-25). It was the first reactivation in 3 patients (Figure 1). The distribution of first reactivation before ruxo and in the remaining 80 patients is shown in Table 1. Thus, 6WCuI of first EBV and CMV reactivation after the first episode of GVHD was 24% (95CI: 19-31) and 20% (95CI: 15-25) respectively. Finally, onset of ruxo coded as time dependent covariates retained a significant adverse prognostic value for the competing risks of death and first episode of EBV reactivation (HR [Hazard Ratio]: 2,657, p&lt;0,05) as well as first episode of CMV reactivation (HR: 1,747, p&lt;0,05) after first episode of GVHD. Discussion /Conclusion: Ruxo initiation coded as a time-dependent covariate was significantly associated with the overall risk of viral reactivation after the first episode of GVHD and the viral reactivations incidences after ruxo were similar with the incidence of reactivation at the onset of GVHD. Thus, it might be linked to the immuno-compromised state induced by both HSCT and GVHD. Furthermore, as we used ruxo for serious gastro intestinal GVHD, we could have selected patients with a more severe GVHD, requiring multiple immunosuppressive therapy, worsening immune reconstitution. To our knowledge it is the first study to assess the competing risk of CMV and EBV reactivation during ruxo treatment for GVHD. Given its effectiveness in corticoresistant GVHD, ruxo use must not be limited by the fear of viral reactivation at the light of our data, conditioned upon a close monitoring of viral loads in the first weeks. Disclosures No relevant conflicts of interest to declare.

Adverse events in patients with ankylosing spondylitis treated with TNF inhibitors: a cross-sectional study

Background Although TNF inhibitors are well established in ankylosing spondylitis treatment, the majority of studies on TNF inhibitors safety have been performed in rheumatoid arthritis patients. Meanwhile, it seems that TNF inhibitors in ankylosing spondylitis may present a better safety profile than we thought. Objective The aim of our study was to retrospectively investigate the occurrence of adverse events in ankylosing spondylitis patients treated with TNF inhibitors. Setting A single referral center in Poland. Methods Detailed medical history of ankylosing spondylitis patients was obtained during the interview with the patient and by reviewing electronic medical records. Patients treated with TNF inhibitors and patients without TNF inhibitors treatment were compared. Main outcome measure The incidence of adverse events during the 3 months period before the interview. Results A total of 150 patients, 103 in the treatment group and 47 in the control group, were included in the study. There were no differences in the incidence of adverse events, serious adverse events, infections and opportunistic infections between both groups. However, in the treatment group, noninfectious adverse events were significantly less frequent than in control group (RR 0.39, 95% CI 0.23–0.66), with abdominal pain as the most common noninfectious adverse event (RR 0.20, 95% CI 0.07–0.63). The differences in incidence rates of specific infections were not significant, except acute infectious diarrhea which also was less frequent in patients treated with TNF inhibitors (RR 0.17, 95% CI 0.03–0.85). The female gender was significantly associated with any adverse event occurrence (OR 2.36, 95% CI 1.15–4.83). Conclusion TNF inhibitors show a good safety profile in ankylosing spondylitis patients.

Association of 30-Day Mortality With Oral Step-Down vs Continued Intravenous Therapy in Patients Hospitalized With Enterobacteriaceae Bacteremia

Conversion to oral therapy for Enterobacteriaceae bacteremia has the potential to improve the quality of life of patients by improving mobility, eliminating catheter-associated discomfort, decreasing the risk for noninfectious and infectious catheter-associated adverse events, and decreasing health care costs. To compare the association of 30-day mortality with early oral step-down therapy vs continued parenteral therapy for the treatment of Enterobacteriaceae bloodstream infections. This retrospective multicenter cohort study included a 1:1 propensity score-matched cohort of 4967 unique patients hospitalized with monomicrobial Enterobacteriaceae bloodstream infection at 3 academic medical centers from January 1, 2008, through December 31, 2014. Eligibility criteria included appropriate source control measures, appropriate clinical response by day 5, active antibiotic therapy from day 1 until discontinuation of therapy, availability of an active oral antibiotic option, and ability to consume other oral medications or feeding. Statistical analysis was performed from March 2, 2018, to June 2, 2018. Oral step-down therapy within the first 5 days of treatment of Enterobacteriaceae bacteremia. The main outcome was 30-day all-cause mortality. Of the 2161 eligible patients, 1185 (54.8%) were male and 1075 (49.7%) were white; the median (interquartile range [IQR]) age was 59 (48-68) years. One-to-one propensity-score matching yielded 1478 patients, with 739 in each study arm. Sources of bacteremia included urine (594 patients [40.2%]), gastrointestinal tract (297 [20.1%]), central line-associated (272 [18.4%]), pulmonary (58 [3.9%]), and skin and soft tissue (41 [2.8%]). There were 97 (13.1%) deaths in the oral step-down group and 99 (13.4%) in the intravenous (IV) group within 30 days (hazard ratio [HR], 1.03; 95% CI, 0.82-1.30). There were no differences in recurrence of bacteremia within 30 days between the groups (IV, 6 [0.8%]; oral, 4 [0.5%]; HR, 0.82 [0.33-2.01]). Patients transitioned to oral step-down therapy were discharged from the hospital an average of 2 days (IQR, 1-6) sooner than patients who continued to receive IV therapy (5 days [IQR, 3-8 days] vs 7 days [IQR, 4-14 days]; P < .001). In this study, 30-day mortality was not different among hospitalized patients who received oral step-down vs continued parenteral therapy for the treatment of Enterobacteriaceae bloodstream infections. The findings suggest that transitioning to oral step-down therapy may be an effective treatment approach for patients with Enterobacteriaceae bacteremia who have received source control and demonstrated an appropriate clinical response. Early transition to oral step-down therapy may be associated with a decrease in the duration of hospital stay for patients with Enterobacteriaceae bloodstream infections.

2105. Electronic Records of Daily Subglottic Suctioning Predict Infectious and Non-infectious Adverse Ventilator-Associated Events During Critical Care

BackgroundMechanical ventilation is a life-sustaining therapy for critically ill patients, but is associated with increased hospital costs and risk for significant complications with poor outcomes. Adverse ventilator-associated events (VAEs) can be broadly divided into infectious (infectious ventilator-associated complication (IVAC) or ventilator-associated pneumonia (VAP)) and non-infectious (ventilator-associated complication (VAC)) types. We sought to identify factors that predict both types, and factors that discriminate risk for infectious vs. noninfectious VAE, using electronic medical record (EMR) data available prior to index event.MethodsWe evaluated 90 consecutive adverse VAEs in the medical intensive care unit of an academic medical center (January 1, 2013–June 30, 2016) to determine prior patient and care factors that discriminate risk for incident VAE. VAE were defined by surveillance criteria from the CDC. Patient and care data were extracted via the EMR.ResultsA generalized linear mixed effects model found an increase of 1.1 (95% CI 0.53–1.7) subglottic suction events per day (SS/day) on the day before VAE diagnosis, relative to the 4 prior days. Of the 90 VAE included in the study, 41 were infectious (IVAC or VAP), and 49 were labeled ventilator-associated condition (VAC). In the IVAC/VAP group, mean SS/day was 8.0 on the day of VAE diagnosis, 7.5 one day prior, and 6.2 two days prior, compared with 6.6, 6.4, and 5.5 SS/day in the VAC group. Change in antibiotic prescription (87.8% (36) of patients in the IVAC/VAP group vs. 46.9% (23) in the VAC group) (P = 0.023) and acute liver injury (mean AST and ALT 52.9 and 43.6 3 days before IVAC/VAP vs. 1,035.4 and 523.9 before VAC) also differed between the groups (P = 0.0095 and 0.0025).ConclusionIncreased daily subglottic suctioning predicts both non-infectious and infectious VAE, but the observed increase is greater prior to IVAC/VAP. Change in antibiotic prescription and acute liver injury also discriminated IVAC/VAP from non-infectious VAE in this small cohort.Disclosures All authors: No reported disclosures.