Invited Commentary: Achieving Post-Bypass Hemostasis in Young Children: At What Cost?

Young children requiring bypass often develop coagulopathy resulting in major postoperative blood loss. Increased post-bypass bleeding and donor exposures are independently associated with adverse outcomes. When transfusion of hemostatic blood products fails to reduce bleeding to an acceptable level, rescue therapies including prothrombin complex concentrates (PCCs), and/or recombinant activated factor VII are being given "off-label" with increasing frequency. A number of studies attempting to determine the safety and efficacy of PCCs in neonates and young children are being published. These studies are most commonly retrospective, observational, performed in a single center with varying doses, indications for, and timing of administration in a small number of patients with varying results. The results of these individual studies are questionable and are not to be generalized to other center's patients. Because factor VIII inhibitor bypassing activity (FEIBA) contains the activated form of factor VII and factor X there are concerns regarding the potential for thrombotic events in a population with a known risk of postoperative thromboembolism. Currently, there is no validated assay with which to measure the efficacy of FEIBA in vivo to determine dose titration. Well-designed multicenter randomized control trials are needed to determine the optimal dose and risk-benefit of PCCs after pediatric cardiac surgery. Until such data are available the decision to give a procoagulant to neonates and young children after bypass needs to be made when the consequences of blood loss and replacement pose more risk than the risk of thrombotic complications from the drug.

Cost-effectiveness of Fibrinogen Concentrate vs Cryoprecipitate for Treating Acquired Hypofibrinogenemia in Bleeding Adult Cardiac Surgical Patients.

Importance: Excessive bleeding requiring fibrinogen replacement is a serious complication of cardiac surgery. However, the relative cost-effectiveness of the 2 available therapies-fibrinogen concentrate and cryoprecipitate-is unknown. Objective: To determine cost-effectiveness of fibrinogen concentrate vs cryoprecipitate for managing active bleeding in adult patients who underwent cardiac surgery. Design, Setting, and Participants: A within-trial economic evaluation of the Fibrinogen Replenishment in Surgery (FIBERS) randomized clinical trial (February 2017 to November 2018) that took place at 4 hospitals based in Ontario, Canada, hospitals examined all in-hospital resource utilization costs and allogeneic blood product (ABP) transfusion costs incurred within 28 days of surgery. Participants included a subset of 495 adult patients from the FIBERS trial who underwent cardiac surgery and developed active bleeding and acquired hypofibrinogenemia requiring fibrinogen replacement. Interventions: Fibrinogen concentrate (4 g per dose) or cryoprecipitate (10 units per dose) randomized (1:1) up to 24 hours postcardiopulmonary bypass. Main Outcomes and Measures: Effectiveness outcomes included number of ABPs administered within 24 hours and 7 days of cardiopulmonary bypass. ABP transfusion (7-day) and in-hospital resource utilization (28-day) costs were evaluated and a multivariable net benefit regression model built for the full sample and predefined subgroups. Results: Patient level costs for 495 patients were evaluated (mean [SD] age 59.2 [15.4] years and 69.3% male.) Consistent with FIBERS, ABP transfusions and adverse events were similar in both treatment groups. Median (IQR) total 7-day ABP cost was CAD $2280 (US dollars [USD] $1697) (CAD $930 [USD $692]-CAD $4970 [USD $3701]) in the fibrinogen concentrate group and CAD $2770 (USD $1690) (IQR, CAD $1140 [USD $849]-CAD $5000 [USD $3723]) in the cryoprecipitate group. Median (interquartile range) total 28-day cost was CAD $38 180 (USD $28 431) $(IQR, CAD $26 350 [USD $19 622]-CAD $65 080 [USD $48 463]) in the fibrinogen concentrate group and CAD $38 790 (USD $28 886) (IQR, CAD $26 180 [USD $19 495]-CAD $70 380 [USD $52 409]) in the cryoprecipitate group. After exclusion of patients who were critically ill before surgery (11%) due to substantial variability in costs, the incremental net benefit of fibrinogen concentrate vs cryoprecipitate was positive (probability of being cost-effective 86% and 97% at $0 and CAD $2000 (USD $1489) willingness-to-pay, respectively). Net benefit was highly uncertain for nonelective and patients with critical illness. Conclusions and Relevance: Fibrinogen concentrate is cost-effective when compared with cryoprecipitate in most bleeding adult patients who underwent cardiac surgery with acquired hypofibrinogenemia requiring fibrinogen replacement. The generalizability of these findings outside the Canadian health system needs to be verified.

Eltrombopag para purpura trombocitopénica inmune / Eltrombopag for immune thrombocytopenic purpura

DESCRIPCIÓN DEL PROBLEMA DE SALUD PURPURA TROMBOCITOPÉNICA INMUNE: La trombocitopenia inmune primaria o púrpura trombocitopénica idiopática (PTI) es una condición autoinmune usualmente benigna caracterizada por el aumento de la destrucción plaquetaria y la subóptima producción plaquetaria. Está definida como la presencia de plaquetas disminuidas y ausencia de otras causas de trombocitopenia. Esta condición se considera poco frecuente con una incidencia estimada anual entre 50-100 casos por millón de personas a nivel mundial (5 -10 x 100,000). Las manifestaciones clínicas de la PTI son variables, y puede ir desde casos asintomáticos, hasta sangrado de las mucosas, o incluso hemorragias desde cualquier sitio corporal. Para llegar al diagnóstico de PTI se debe cumplir los siguientes criterios: Trombocitopenia (recuento plaquetario menor a 100 x 109/L); ausencia de enfermedad infecciosa aguda concomitante (mononucleosis, hepatitis, etc.); y ausencia de patología sistémica de base (lupus eritematoso sistémico, síndrome de inmunodeficiencia adquirido, linfoma, entre otras). En caso de que la PTI se asocie a alguna patología reconocible será secundaria a dicha enfermedad (5, 6). Nueve por ciento de los pacientes adultos puede tener una remisión espontánea (por lo general en los primeros 3-6 meses tras el diagnostico) y entre un 3 - 15% desarrollará una enfermedad autoinmune sistémica en los siguientes años. El riesgo de hemorragia se encuentra asociado a recuentos de plaquetas inferiores a 30 x 109/I y es mayor en pacientes de edad avanzada. El objetivo del tratamiento es inducir el aumento plaquetario y reducir el riesgo de sangrado. Son plausibles de tratamiento aquellos pacientes con recuentos plaquetários ¬¬¬¬ menor ou igual a 30 x 109/L. TRATAMIENTO ACTUAL/ COMPARADOR: El comparador es considerado como el procedimiento con mayor probabilidad de ser reemplazado en la práctica clínica de la intervención solicitada Eltrombopag, para lo cual el comparador actual son los mejores cuidados de soporte en tercera línea. METODOLOGÍA: Se realizó una búsqueda en las principales bases de datos bibliográficas Pubmed: (Criterios de búsqueda y términos MeSH) Se filtró la búsqueda a Estudios Clínicos fase III, controlados randomizados, Revisiones Sistemáticas, Metaanálisis, Guías de Práctica Clínica, además se limitó la búsqueda estudios en humanos. También se realizó búsqueda manual en otras bases de datos bibliográficas (Cochrane, NIH, TRIP DATABASE), en buscadores genéricos de internet, agencias de evaluación de tecnologías sanitarias y financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas, meta-análisis, estudios clínicos aleatorizados y controlados, guías de práctica clínica, evaluaciones de tecnología sanitaria, evaluaciones económicas y políticas de cobertura de otros sistemas de salud. CONCLUSIONES: Eficacia: Eltrombopag ha demostrado ser eficaz incrementando los recuentos de plaquetas en pacientes diagnosticados de PTI refractarios a otros tratamientos tanto en los estudios pivótales como en estudios de extensión, pero este resultado se ha estudiado frente a placebo y aun no existen estudios que lo comparen frente a otros tratamientos activos. Además, Ninguno de los estudios incluyó la supervivencia general, por tanto, no es posible confirmar si los agonistas de receptores de TPO ayudan a prolongar la vida. El efecto de Eltrombopag sobre la incidencia de sangrado no está claro. Se ha estudiado de cómo una variable secundaria y de forma ambigua ya que no se ha estimado según la gravedad del sangrado. Por lo anterior Eltrombopag solo se recomienda como una opción para el tratamiento de la trombocitopenia idiopática crónica en adultos si la condición es refractaria a los tratamientos activos y terapias de rescate y se tiene enfermedad severa con un alto riesgo de sangrado que necesita frecuentes terapias de rescate. Seguridad: En cuanto a la seguridad, el tratamiento con Eltrombopag no presentó diferencias significativas en la frecuencia de eventos adversos severos y totales, incluso con una ligera ventaja respecto a placebo por lo que se considera con un perfil de seguridad aceptable. Los resultados de calidad de vida no fueron concordantes entre los estudios Conveniencia: Eltrombopag posee mejor adecuación dada su administración por vía oral, pero presenta potenciales interacciones con otros fármacos de uso habitual. Respecto al manejo, la fase inicial de ajuste de dosis requiere un estrecho seguimiento de los pacientes, para aumento o disminución de esta respecto a la respuesta plaquetaria. Costo: El tratamiento con Eltrombopag presenta un importante impacto económico para el hospital por lo que se deberían seleccionar los pacientes que más se beneficiarían del tratamiento.

Real-world economic and clinical outcomes associated with current hemostatic matrix use in spinal surgery.

Aim: Bleeding during spine surgery is controlled using topical hemostatic agents. Studies have reported outcomes between Surgiflo® and Floseal, the most widely used flowable hemostatic matrices, but have not included the latest Surgiflo formulation which is more adherent to the bleeding surface than prior formulations. Materials & methods: A propensity score-matched analysis was conducted using the Premier Healthcare Database to compare economic and clinical outcomes of adults undergoing inpatient spinal surgery between 2013 and 2018 receiving current Surgiflo or Floseal. Results: This retrospective study included 28,910 patients in each group and found comparable outcomes for bleeding events, overall transfusion rate, inpatient mortality and readmissions between Surgiflo and Floseal. Surgiflo was associated with $430 (USD) lower hospitalization costs, shorter length of stay and shorter operating room time than Floseal.

Topical hemostatic agents such as Surgiflo^® and Floseal are used during invasive surgery to manage bleeding. We compared outcomes of spine surgeries that used either of two most frequently used topical hemostatic agents, Surgiflo or Floseal. This is the largest retrospective study presenting economic and clinical outcomes of patients receiving Surgiflo versus Floseal during spine surgery using the latest product formulations. The study suggests that clinical outcomes are comparable between Surgiflo and Floseal groups and that Surgiflo is associated with lower hospitalization costs, slightly shorter hospital stay and shorter operating room time among patients undergoing spine surgery.

Thrombosis risk assessment in patients with congenital thrombophilia during COVID - 19 infection.

BACKGROUND: Coagulation dysfunction represents a serious complication in patients during the COVID-19 infection, while fulminant thrombotic complications emerge as critical issues in individuals with severe COVID-19. In addition to a severe clinical presentation, comorbidities and age significantly contribute to the development of thrombotic complications in this disease. However, there is very little data on association of congenital thrombophilia and thrombotic events in the setting of COVID-19. Our study aimed to evaluate the risk of COVID-19 associated thrombosis in patients with congenital thrombophilia. METHODS: This prospective, case-control study included patients with confirmed COVID-19 infection, followed 6 months post-confirmation. The final outcome was a symptomatic thrombotic event. In total, 90 COVID-19 patients, 30 with known congenital thrombophilia and 60 patients without thrombophilia within the period July 2020-November 2021, were included in the study. Evaluation of hemostatic parameters including FVIII activity and D-dimer was performed for all patients at 1 month, 3 months and 6 months post-COVID-19 diagnosis. RESULTS: Symptomatic thrombotic events were observed in 7 out of 30 (23 %) COVID-19 patients with thrombophilia, and 12 out of 60 (20 %) without thrombophilia, P = 0.715. In addition, the two patient groups had comparable localization of thrombotic events, time to thrombotic event, effect of antithrombotic treatment and changes in FVIII activity, while D-dimer level were significantly increased in patients without thrombophilia. CONCLUSION: Our findings suggest that patients with congenital thrombophilia, irrespective of their age, a mild clinical picture and absence of comorbidities, should receive anticoagulant prophylaxis, adjusted based on the specific genetic defect.

The important impact of dental care on haemostatic treatment burden in patients with mild haemophilia.

BACKGROUND: Mild haemophilia (MH) is mainly characterized by haemorrhages secondary to surgery/invasive procedures or trauma. Haemostatic treatment in MH ranges from on demand to short prophylaxis according to the type of bleeding events and the basal clotting factor level. Oral surgery and dental extractions can represent a frequent haemostatic challenge in MH requiring appropriate treatment. However, only few studies on limited numbers of patients are available in the literature regarding the implications of dental management in patients with MH. OBJECTIVES: The purpose of the study was to evaluate the impact of dental care on the burden of haemostatic treatment in patients affected by MH. METHODS: We conducted a retrospective multicentre study evaluating adult patients with MH regularly examined at the Haemophilia Treatment Centres (HTCs) of the Saint-Luc University Hospital, Brussels (Belgium) and of Paolo Giaccone Hospital, Palermo (Italy). The population consisted of 107 male patients with MH, with a mean age of 39 years (range 18-81 years). RESULTS: The majority of patients (86/107, 79%) needed at least one treatment within the study period, and 44% (38/86) of them received haemostatic therapy for dental care. Haemostatic therapy in our study varied from antifibrinolytic therapy alone and perioperative factor replacement to the absence of treatment at all. The great majority of oral interventions (27/42, 64%) were managed with clotting factor concentrate. CONCLUSION: This study demonstrates that dental care currently represents a major reason for haemostatic treatments in patients with MH. Maintaining good oral health appears as a priority to minimize avoidable replacement therapy and optimize resources.

Dynamic use of fibrinogen under viscoelastic assessment results in reduced need for plasma and diminished overall transfusion requirements in severe trauma.

BACKGROUND: Despite advances in trauma management, half of trauma deaths occur secondary to bleeding. Currently, hemostatic resuscitation strategies consist of empirical transfusion of blood products in a predefined fixed ratio (1:1:1) to both treat hemorrhagic shock and correct trauma-induced coagulopathy. At our hospital, the implementation of a resuscitation protocol guided by viscoelastic hemostatic assays (VHAs) with rotational thromboelastometry has resulted in a goal-directed approach. The objective of the study is twofold, first to analyze changes in transfusion practices overtime and second to identify the impact of these changes on coagulation parameters and clinical outcomes. We hypothesized that progressive VHA implementation results in a higher administration of fibrinogen concentrate (FC) and lower use of blood products transfusion, especially plasma. METHODS: A total of 135 severe trauma patients (January 2008 to July 2019), all requiring and initial assessment for high risk of trauma-induced coagulopathy based on high-energy injury mechanism, severity of bleeding and hemodynamic instability were included. After 2011 when we first modified the transfusion protocol, a progressive change in transfusional management occurred over time. Three treatment groups were established, reflecting different stages in the evolution of our strategy: plasma (P, n = 28), plasma and FC (PF, n = 64) and only FC (F, n = 42). RESULTS: There were no significant differences in baseline characteristics among groups. Progressive implementation of rotational thromboelastometry resulted in increased use of FC over time ( p < 0.001). Regression analysis showed that group F had a significant reduction in transfusion of packed red blood cells ( p = 0.005), plasma ( p < 0.001), and platelets ( p = 0.011). Regarding outcomes, F patients had less pneumonia ( p = 0.019) and multiorgan failure ( p < 0.001), without significant differences for other outcomes. Likewise, overall mortality was not significantly different. However, further analysis comparing specific mortality due only to massive hemorrhage in the F group versus all patients receiving plasma, it was significantly lower ( p = 0.037). CONCLUSION: Implementing a VHA-based algorithm resulted in a plasma-free strategy with higher use of FC and a significant reduction of packed red blood cells transfused. In addition, we observed an improvement in outcomes without an increase in thrombotic complications. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Health care costs and resource utilization among commercially insured adult patients with hemophilia A managed with FVIII prophylaxis in the United States.

BACKGROUND: Standard of care for patients with severe hemophilia A (HA) is life-long prophylaxis with factor VIII (FVIII) concentrate or other hemostatic agents. Published literature highlights a wide range of treatment costs for patients with HA. OBJECTIVE: To estimate average annual health care costs and resource utilization for a cross-section of adult patients managed with FVIII concentrate prophylaxis using recent data from a large US commercial claims database. METHODS: Adult males with 1 or more claim with HA diagnosis, continuous commercial plan enrollment, and 4 or more FVIII prescription dispenses during 12 months were identified from IBM MarketScan Research Database from January 2013 to September 2019, excluding those with FVIII inhibitors, an HIV/AIDS diagnosis, or diagnosis and treatment for hepatitis B or C. Patients were classified as using FVIII prophylaxis if they met any of the following definitions: (1) 6 or more FVIII dispenses, (2) a gap of 60 days or less between dispenses, and (3) at least 273 days supply in the 12-month period. Additionally, subgroups of patients meeting each individual definition were examined, with some patients included in all 3 subgroups. RESULTS: The overall cohort included 411 patients who met 1 or more of the 3 definitions, with a mean age of 28.9 years. Subgroups of 401, 325, and 237 patients met the first, second, and third FVIII prophylaxis definitions, respectively. Per-patient mean (SD) annual all-cause health care costs were $654,571 ($380,762) in the overall cohort and ranged from $650,065 ($382,196) to $759,661 ($387,040) among subgroups. Cost of FVIII concentrate accounted for more than 96% of total costs in the overall cohort and in each subgroup. Cost of FVIII in the overall cohort varied according to type of concentrate, with the highest among patients who were treated with both standard and extended half-life (SHL and EHL) FVIII ($784,945), followed by EHL FVIII only ($708,928), SHL FVIII only ($647,800), and plasma-derived FVIII ($535,614). The most common treatment type was SHL FVIII only (45.7% of all patients). In the overall cohort, the majority had 1 or more outpatient visits (94.9%), while emergency department visits, hospital admissions, and home health visits occurred less frequently (27.0%, 7.1%, and 7.1%, respectively). CONCLUSIONS: Commercially insured patients with HA incur substantial all-cause annual health care costs, with FVIII concentrate accounting for a majority of costs. DISCLOSURES: This study was funded by BioMarin Pharmaceutical Inc, which was involved in the protocol development, analysis plan development, data interpretation, manuscript preparation, and publication decisions. All authors contributed to protocol development, analysis plan development, data interpretation, and manuscript development and maintained control over the final content. Thornburg has received professional fees from BioMarin Pharmaceutical, CSL Behring, Genentech, Novo Nordisk, Sanofi Genzyme, HEMA Biologics, and Spark Therapeutics and institutional research funding from BioMarin Pharmaceutical, Novo Nordisk, and Sanofi Genzyme. Adamski, Cook, and Sendhil are employees of Analysis Group, a consulting company that was contracted by BioMarin Pharmaceutical to conduct this study and develop the manuscript. Vembusubramanian is a former employee of Analysis Group. Hinds, Chen, and Sammon are employees and shareholders of BioMarin Pharmaceutical. Solari is a former employee of BioMarin Pharmaceutical. Garrison has received consulting fees from BioMarin Pharmaceutical and Analysis Group. Croteau has received professional fees from BioMarin Pharmaceutical, Bayer, CSL Behring, HEMA Biologics, and Pfizer and institutional research funding from Novo Nordisk and Spark Therapeutics.

Impact of an active hemostatic product treatment approach on bleeding-related complications and hospital costs among inpatient surgeries in the United States.

AIMS: To examine the impact of active only (A) vs. combined passive and active (PA) hemostatic products on bleeding-related complications and costs among inpatient surgeries. MATERIALS AND METHODS: This retrospective analysis of the US Premier Hospital Database included patients who had an inpatient procedure within a specialty of interest (cardiac, vascular, noncardiac thoracic, solid organ, general, reproductive organ, knee/hip replacement, spinal, or neurosurgery) that utilized a hemostatic product from January 1, 2017 to December 31, 2018. Patients were directly matched 1:1 on surgery code, age categories, and Charlson Comorbidity Index score categories into A or PA cohorts. Unadjusted and adjusted rates of bleeding-related complications, length of stay (LOS) and total hospital costs were compared between cohorts. RESULTS: A total of 5,934 cardiac, 7,986 vascular, 2,042 noncardiac thoracic, 8,260 solid organ, 9,502 general, 4,616 reproductive organ, 2,758 knee/hip replacement, 42,648 spinal, and 10,716 neuro surgeries were included. Higher unadjusted rates of bleeding-related complications and greater LOS and total hospital costs were observed in the PA cohort vs A cohort across all specialties. The adjusted odds of bleeding complications were significantly higher in solid organ, general, knee/hip replacement, reproductive organ, and spinal surgery (OR range = 1.17-2.48, all p <.01), while incremental costs per hospitalization associated with PA (vs A) controlling for covariates were higher across all specialties (ratio range = 1.04-1.22, all p <.05). LIMITATIONS: This analysis focused on patients who had a single surgery during the hospital encounter; results may not be generalizable to patients undergoing multiple surgeries. CONCLUSIONS: The use of A hemostatic products was associated with significantly lower rates of bleeding-related complications and total hospital costs compared to PA hemostatic products. A treatment approach which considers bleeding-related factors including severity, risk and variability based on surgery type may provide guidance in choosing the optimal hemostatic product to improve surgical outcomes and costs.

Systematic review of hemostatic agents used in vascular surgery.

BACKGROUND: Hemostatic agents are routinely used in vascular surgery to complement proper suture techniques and decrease the risk of perioperative bleeding. A relative lack of comparative research studies have left surgeons with the option of choosing hemostatic agents based on their personal experience. The present review has highlighted the efficacy and safety of hemostatic agents and categorized them according to their primary mechanism of action and cost. METHODS: A systematic search strategy encompassing hemostatic agent products was deployed in the PubMed database. Single-center and multicenter, randomized, controlled trials with >10 patients were included in the present study. RESULTS: We reviewed 12 studies on the efficacy and safety of hemostatic agents compared with manual compression or other hemostatic agents. Using the time to hemostasis as the primary end point, all studies had found hemostatic agents to be significantly more efficient than manual compression. Likewise, adhesives (high pressure sealants) and dual agents (containing biologically active and absorbable components) were found to be more efficient, but costlier, than agents with either biologically active or absorbable components only. Agents with porcine or bovine constituents were found to trigger anaphylactic reactions in rare cases. Additionally, the absence of fibrin stabilizing factor XIII in a brand of fibrin sealant was speculated to reduce the affinity of the fibrin sealant for the expanded polytetrafluoroethylene graft. The cost of agents varied greatly depending on their active ingredient. CONCLUSIONS: Hemostatic agents appear to be highly effective at decreasing the risk of bleeding during surgical procedures. Although some hemostatic agents were demonstrated to achieve hemostasis faster than others, most are able to control bleeding within <10 minutes. Based on the limited data, the least expensive agents might suffice for limited suture lines used in routine procedures.

Clinical and economic impact of oxidized regenerated cellulose for surgeries in a Chinese tertiary care hospital.

Aim: To assess the impact of oxidized regenerated cellulose (ORC) on blood transfusion and hospital costs associated with surgeries. Patients & methods: This retrospective cohort study selected ten surgeries to create propensity-score matching groups to compare ORC versus nonORC (conventional hemostatic techniques such as manual pressure, ligature and electrocautery). Results: NonORC was associated with both higher blood transfusion volume and higher hospital costs than ORC in endoscopic transnasal sphenoidal surgery, nonskull base craniotomy, hepatectomy, cholangiotomy, gastrectomy and lumbar surgery. However, nonORC was associated with better outcomes than ORC in open colorectal surgery, mammectomy and hip arthroplasty surgery. Conclusion: When compared with conventional hemostatic technique, using ORC could impact blood transfusion and hospital costs differently by surgical settings.

Hemostatic agent use during partial nephrectomy: trends, outcomes, and associated costs.

PURPOSE: To evaluate the ability of hemostatic agents (HA) to limit bleeding complications following partial nephrectomy (PN) and determine HA usage and costs as well as factors associated with post-operative bleeding complications. METHODS: The records of 429 PN performed for kidney cancers were reviewed for clinical, pathologic, and perioperative variables. Surgical approach, HA use, and HA expenditure were determined. Bleeding complications and management to 90 days after PN were annotated. Wilcoxon rank-sum and two-sample t tests identified factors associated with HA use. Univariate and limited multivariate logistic regression determined variables associated with bleeding complications. RESULTS: Use of HA was associated with longer OR duration, longer ischemia time, higher EBL, and method of PN (OPN and LPN > RPN) (all p values < 0.001). On bivariate analysis, while multiple factors were associated with bleeding complications, neither HA use (p = 0.924) nor the number of HA used (two agents vs one p = 0.712; three agents vs. one p = 0.606) were. A multivariable model noted that increasing RENAL score (p = 0.013) and surgical approach (OPN vs. RPN [p = 0.009] and LPN vs. RPN (p = 0.002]) were independently associated with bleeding complications, while HA use was not (p = 0.294). During the 16 years of analysis, a total of $77,687 USD was spent on HA. Average annual HA expenditure was $4855 USD with the peak being in 2010 where expense was $14,086. Mean annual costs for HA use were greater for OPN vs RAPN starting in 2013 (p = 0.02) CONCLUSIONS: The use of HA during PN was not associated with lower rates of bleeding complications. Therefore, judicious use in a case-specific manner is requisite to limit potentially unnecessary operative cost.

The Effect of Carbazochrome Sodium Sulfonate in Patients with Colonic Diverticular Bleeding: Propensity Score Matching Analyses Using a Nationwide Inpatient Database.

Objective Carbazochrome sodium sulfonate (CSS) has been routinely used to treat bleeding; however, no study has examined the effect of CSS for gastrointestinal bleeding. Therefore, we aimed to investigate the effect of CSS for colonic diverticular bleeding. Methods We performed a nationwide observational study using the Japanese Diagnosis Procedure Combination inpatient database. We identified patients who were admitted for diverticular bleeding from July 2010 to March 2018. Patients who received CSS on the day of admission were defined as the CSS group, and those not receiving CSS were defined as the control group. The primary outcome was in-hospital mortality. Secondary outcomes were length of stay, total costs, and blood transfusion within 7 days of admission. Propensity score matching analyses were performed to compare outcomes between the two groups. Results A total of 59,965 patients met our eligibility criteria. Of these, 14,437 (24%) patients received CSS on the day of admission. One-to-one propensity score matching created 14,379 matched pairs. There was no significant difference in the in-hospital mortality between the CSS and control groups (0.6% vs. 0.5%, respectively; odds ratio: 0.96; 95% confidence interval: 0.72-1.29). The length of stay was longer in the CSS group than in the control group (11.4 vs. 11.0 days, respectively; difference: 0.44; 95% confidence interval: 0.14-0.73). There were no significant differences in the total costs or the proportion of patients receiving blood transfusion between the groups. Conclusions CSS may not reduce in-hospital mortality, length of stay, total costs, or the need for blood transfusion in patients with colonic diverticular bleeding.

Renal transplant biopsy complications: assessment of risk factors and potential of desmopressin to decrease risk of hemorrhage.

BACKGROUND: Renal transplant biopsies are essential in nephrology; however, they are invasive and complications can occur. PURPOSE: To explore the risk of transplant kidney biopsy (TxB) complications in relation to possible preventive effects of desmopressin prophylaxis. MATERIAL AND METHODS: A total of 515 consecutive TxB (375 patients, median age 53 years) were analyzed. In 252 TxB, the Resistive Index (RI) was measured right before the biopsy. A total of 282 patients had serum creatinine >150 µmol/L. In one of the six hospitals 39/282 patients consecutively received desmopressin (dose 0.3 µg/kg subcutaneously) as prophylaxis within 1 h before the biopsy. Fisher's exact and χ2 test were used (odds ratio [OR], 95% confidence interval [CI]). Univariate and multiple binary logistic regression analyses were performed. A two-sided P value <0.05 was considered significant. RESULTS: RI ≥ 0.8 was a risk factor for major TxB complications (OR 4.2, 95% CI 1.13-15.76). The risk for minor complications decreased with mean arterial blood pressure (MAP) (97.9 vs. 89.5 mmHg, OR 0.97, 95% CI 0.95-0.997). In a multiple regression analysis for overall biopsy complications, the risk remained increased for patients with RI ≥ 0.8 (OR 4.45, 95% CI 1.32-15.04). No patients (0/39) with desmopressin prophylaxis had a major complication versus 8/243 in the other group. In patients with serum creatinine >150 µmol/L, those with a higher MAP had more overall TxB complications (104.5 vs. 98.2 mmHg, OR 1.05, 95% CI 1.004-1.1). CONCLUSION: RI ≥ 0.8 was a risk factor for major and overall complications and a lower MAP for minor biopsy complications. Desmopressin prophylaxis showed yet no verified benefit as prophylaxis in TxB.

Topical Hemostatic Agents in Gynecologic Surgery for Benign Indications.

Since a variety of procoagulant products, collectively called hemostatic agents, became available to surgeons in the mid-20th century, their use has increased across multiple specialties, including gynecology. Congruent with past research on the causes of regional variation in the practice of medicine, available evidence suggests that a central predictor for use of these products is physician preference rather than documented clinical necessity. Use of these products adds risks and avoidable cost. This article seeks to highlight specific gynecologic circumstances in which evidence and surgical judgment supports hemostatic agent use and other settings in which use should be reconsidered.

Over-the-scope clips are cost-effective in recurrent peptic ulcer bleeding.

Background: A recent prospective randomised controlled trial ('STING') showed superiority of over-the-scope clips compared to standard treatment in recurrent peptic ulcer bleeding. Cost-effectiveness studies on haemostasis with over-the-scope clips have not been reported so far. Objective: The aim of this study was to investigate whether the higher efficacy of the over-the-scope clips treatment outweighs the higher costs of the device compared to standard clips. Methods: For the analysis, the study population of the STING trial was used. Costs for the hospital stay in total as well as treatment-related costs were obtained. The average cost-effectiveness ratio, representing the mean costs per designated outcome, and the incremental cost-effectiveness ratio, expressing the additional costs of a new treatment strategy per difference in outcome were calculated. The designated outcome was defined as successful haemostasis without rebleeding within seven days, which was the primary endpoint of the STING trial. Average cost-effectiveness ratio and incremental cost-effectiveness ratio were calculated for total costs of the hospital stay as well as the haemostasis treatment alone. The cost-effectiveness analysis is taken from the perspective of the care provider.Results: Total costs and treatment-related costs per patient were 13,007.07 € in the standard group vs 12,808.56 € in the over-the-scope clip group (p = 0.812) and 2084.98 € vs 1984.71 € respectively (p = 0.663). The difference was not statistically significant. Total costs per successful haemostasis (average cost-effectiveness ratio) were 30,677.05 € vs 15,104.43 € and 4917.41 € vs 2340.46 € for the haemostasis treatment. The additional costs per successful haemostasis with over-the-scope clip treatment (incremental cost-effectiveness ratio) is -468.18 € for the whole treatment and -236.49€ for the haemostasis treatment. Conclusions: Over-the-scope clip treatment is cost-effective in recurrent peptic ulcer bleeding.

Retrospective Assessment of Desmopressin Effectiveness and Safety in Patients With Antiplatelet-Associated Intracranial Hemorrhage.

OBJECTIVE: Current international guidelines offer a conditional recommendation to consider a single dose of IV desmopressin (DDAVP) for antiplatelet-associated intracranial hemorrhage based on low-quality evidence. We provide the first comparative assessment analyzing DDAVP effectiveness and safety in antiplatelet-associated intracranial hemorrhage. DESIGN: Retrospective chart review. SETTING: Single tertiary care academic medical center. PATIENTS: Adult patients taking at least one antiplatelet agent based on presenting history and documented evidence of intracranial hemorrhage on cerebral CT scan were included. Patients were excluded for the following reasons: repeat cerebral CT scan not performed within the first 24 hours, noncomparative repeat cerebral CT scan, chronic anticoagulation, administration of fibrinolytic medications, concurrent ischemic stroke, and neurosurgical intervention. In total, 124 patients were included, 55 received DDAVP and 69 did not. INTERVENTIONS: DDAVP treatment at recognition of antiplatelet-associated intracranial hemorrhage versus nontreatment. MEASUREMENTS AND MAIN RESULTS: Primary effectiveness outcome was intracranial hemorrhage expansion greater than or equal to 3 mL during the first 24 hospital hours. Primary safety outcomes were the largest absolute decrease from baseline serum sodium during the first 3 treatment days and new-onset thrombotic events during the first 7 days. DDAVP was associated with 88% decreased likelihood of intracranial hemorrhage expansion during the first 24 hours ([+] DDAVP, 10.9% vs [-] DDAVP, 36.2%; p = 0.002; odds ratio [95% CI], 0.22 [0.08-0.57]). Largest median absolute decrease from baseline serum sodium ([+] DDAVP, 0 mEq/L [0-5 mEq/L] vs [-] DDAVP, 0 mEq/L [0-2 mEq/L]; p = 0.089) and thrombotic events ([+] DDAVP, 7.3% vs [-] DDAVP, 1.4%; p = 0.170; odds ratio [95% CI], 5.33 [0.58-49.16]) were similar between groups. CONCLUSIONS: DDAVP was associated with a decreased likelihood of intracranial hemorrhage expansion during the first 24 hours. DDAVP administration did not significantly affect serum sodium and thrombotic events during the study period.

Using flowable gelatin in anterior cervical spine surgery in real-world practice: a retrospective cohort study.

AIM: To assess the clinical and economic impact of flowable gelatin hemostatic matrix (FGHM) in anterior cervical spine surgery (ACSS). PATIENTS & METHODS: A total of 451 patients with performed ACSS were included to compare FGHM with conventional hemostatic methods for clinical and cost outcomes using propensity score matching method. RESULTS: The comparisons of the matched 125 pairs observed that FGHM was associated with significantly lower blood transfusion volume (11.2 vs 36.3 ml; p = 0.039), shorter postsurgery hospital stay length (3.7 vs 4.7 days; p = 0.002), shorter operation time (103.5 vs 117.7 min; p = 0.004), lower drainage placement rate (51.2 vs 89.6%; p < 0.001) and also lower total hospital costs (median ¥64,717 vs ¥65,064; p = 0.035). CONCLUSION: Use of FGHM in ACSS improved perioperative outcomes without increasing hospital costs.

Comparison of the medical costs and effects of large traumatic eardrum perforations treatment.

OBJECTIVE: We investigated the medical costs and effects of ofloxacin drops (OFLX), gelatin sponge patches, spontaneous healing, and endoscopic myringoplasty on healing in large tympanic membrane perforations (TMPs). METHODS: In total, 100 patients with large traumatic TMPs involving >50% of the eardrum were randomly assigned to OFLX, gelatin sponge, spontaneous healing, or endoscopic myringoplasty treatment groups. Medical costs, closure times, and closure rates were compared among groups at 6 months. RESULTS: The closure rates in the OFLX, gelatin sponge, spontaneous healing, and endoscopic myringoplasty groups were 95.7%, 82.6%, 58.3%, and 91.7%, respectively (P = 0.05). The mean closure time was 13.73 ±â€¯6.14 days in the OFLX group, 15.89 ±â€¯4.95 days in the gelatin sponge group, 48.36 ±â€¯10.37 days in the spontaneous healing group, and 12 days in the endoscopic myringoplasty group (P < 0.001). The mean medical costs in US dollars were $15.53 ±â€¯3.15, $103.64 ±â€¯111.58, $11.17 ±â€¯1.33, and $715.90 in the OFLX, gelatin sponge, spontaneous healing, and endoscopic myringoplasty groups, respectively (P < 0.001). CONCLUSION: Although the gelatin sponge and myringoplasty treatments significantly shortened the closure time compared with spontaneous healing, the gelatin sponge patch did not significantly improve the closure rate, and the medical cost of myringoplasty was significantly higher than that of the other treatments. In contrast, OFLX significantly shortened closure time and had a higher closure rate than spontaneous healing, and the medical costs were lower than those of the gelatin sponge and myringoplasty procedures.