Association of In-Hospital Surgical Bleeding Events with Prolonged Hospital Length of Stay, Days Spent in Critical Care, Complications, and Mortality: A Retrospective Cohort Study Among Patients Undergoing Neoplasm-Directed Surgeries in English Hospitals.

PURPOSE: To evaluate the association of in-hospital surgical bleeding events with the outcomes of hospital length of stay (LOS), days spent in critical care, complications, and mortality among patients undergoing neoplasm-directed surgeries in English hospitals. PATIENTS AND METHODS: This is a retrospective cohort study using English hospital discharge data (Hospital Episode Statistics [HES]) linked to electronic health records (Clinical Practice Research Datalink [CPRD]). HES includes information on patient demographics, admission and discharge dates, diagnoses and procedures, days spent in critical care, and discharge status. CPRD includes information on patient demographics, diagnoses and symptoms, drug exposures, vaccination history, and laboratory tests. Patients aged ≥18 years who underwent selected neoplasm-directed surgeries between 1-Jan-2010 and 29-February-2016: hysterectomy, low anterior resection (LAR), lung resection, mastectomy, and prostate surgery were included. The primary independent variable was in-hospital surgical bleeding events identified by diagnosis of haemorrhage and haematoma complicating a procedure or reopening/re-exploration and surgical arrest of postoperative bleeding. Outcomes included LOS, days spent in critical care, in-hospital complications (diagnoses of infections, acute renal failure, vascular events), and in-hospital mortality, identified during surgery through discharge. Multivariable regression was used to examine the adjusted association of bleeding events with outcomes. RESULTS: The study included 26,437 neoplasm-directed surgeries (hysterectomy=6092; LAR=2957; lung=1538; mastectomy=12,806; prostate=3044). Incidence proportions of bleeding events were: hysterectomy=1.9% (95% confidence interval=1.1-2.5%); LAR=3.0% (CI=2.3-3.6%); lung=1.8% (CI=1.1-2.5%); mastectomy=1.6% (CI=1.3-1.8%); prostate=1.0% (CI=0.6-1.3%). In adjusted analyses, bleeding events were associated with: prolonged LOS: 3.1 (CI=1.1-6.3) mastectomy to 5.7 (CI=3.6-8.2) LAR days longer; more days spent in critical care: 0.4 (CI=0.03-0.27) mastectomy to 6.5 (CI=2.5-13.6) hysterectomy days more; and higher incidence proportions of all examined complications; all P<0.05. CONCLUSION: This study quantifies a substantial clinical and healthcare resource utilization burden associated with surgical bleeding among patients undergoing neoplasm-directed surgery in England hospitals.

Impact of bleeding complications on length of stay and critical care utilization in cardiac surgery patients in England.

BACKGROUND: Bleeding is a significant complication in cardiac surgery and is associated with substantial morbidity and mortality. This study evaluated the impact of bleeding on length of stay (LOS) and critical care utilization in a nationwide sample of cardiac surgery patients treated at English hospitals. METHODS: Retrospective, observational cohort study using linked English Hospital Episode Statistics (HES) and Clinical Practice Research Datalink (CPRD) records for a nationwide sample of patients aged ≥18 years who underwent coronary artery bypass graft (CABG), valve repair/replacement, or aortic operations from January 2010 through February 2016. The primary independent variables were in-hospital bleeding complications and reoperation for bleeding before discharge. Generalized linear models were used to quantify the adjusted mean incremental difference [MID] in post-procedure LOS and critical care days associated with bleeding complications, independent of measured baseline characteristics. RESULTS: The study included 7774 cardiac surgery patients (3963 CABG; 2363 valve replacement/repair; 160 aortic procedures; 1288 multiple procedures, primarily CABG+valve). Mean LOS was 10.7d, including a mean of 4.2d in critical care. Incidences of in-hospital bleeding complications and reoperation for bleeding were 6.7 and 0.3%, respectively. Patients with bleeding had longer LOS (MID: 3.1d; p < 0.0001) and spent more days in critical care (MID: 2.4d; p < 0.0001). Reoperation for bleeding was associated with larger increases in LOS (MID = 4.0d; p = 0.002) and days in critical care (MID = 3.2d; p = 0.001). CONCLUSIONS: Among English cardiac surgery patients, in-hospital bleeding complications were associated with substantial increases in healthcare utilization. Increased use of evidence-based strategies to prevent and manage bleeding may reduce the clinical and economic burden associated with bleeding complications in cardiac surgery.

Peg-Interferon Lambda Treatment Induces Robust Innate and Adaptive Immunity in Chronic Hepatitis B Patients.

IFN-lambda (IFNλ) is a member of the type III IFN family and is reported to possess anti-pathogen, anti-cancer, and immunomodulatory properties; however, there are limited data regarding its impact on host immune responses in vivo. We performed longitudinal and comprehensive immunosurveillance to assess the ability of pegylated (peg)-IFNλ to augment antiviral host immunity as part of a clinical trial assessing the efficacy of peg-IFNλ in chronic hepatitis B (CHB) patients. These patients were pretreated with directly acting antiviral therapy (entecavir) for 12 weeks with subsequent addition of peg-IFNλ for up to 32 weeks. In a subgroup of patients, the addition of peg-IFNλ provoked high serum levels of antiviral cytokine IL-18. We also observed the enhancement of natural killer cell polyfunctionality and the recovery of a pan-genotypic HBV-specific CD4+ T cells producing IFN-γ with maintenance of HBV-specific CD8+ T cell antiviral and cytotoxic activities. It was only in these patients that we observed strong virological control with reductions in both viral replication and HBV antigen levels. Here, we show for the first time that in vivo peg-IFNλ displays significant immunostimulatory properties with improvements in the main effectors mediating anti-HBV immunity. Interestingly, the maintenance in HBV-specific CD8+ T cells in the presence of peg-IFNλ is in contrast to previous studies showing that peg-IFNα treatment for CHB results in a detrimental effect on the functionality of this important antiviral T cell compartment. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT01204762.

Two cases of hepatitis B in patients with moderate to severe psoriasis with ustekinumab.

BACKGROUND: Patients with psoriasis who are treated with systemic and biologic therapies may have an increased risk of infections, including hepatitis B virus (HBV). Cytokines that modulate CD4+ T cell subsets, including interleukin (IL)-12 and IL-23, have been suggested to play a role in the pathogenesis of HBV infection. OBJECTIVE: To report the first known cases of acute HBV infection in 2 ustekinumab-treated patients with psoriasis from a phase 3 (PHOENIX 1) and a phase 4 (TRANSIT) study. RESULTS: Both ustekinumab-treated patients generated an immune response toward HBV and experienced typical courses of infection, without progression to chronic HBV infection. CONCLUSION: Continued monitoring of liver-related adverse events in clinical trials, registries, and spontaneous reporting from the postmarketing setting will further contribute to understanding the role of ustekinumab in viral hepatitis.