Spanish Consensus on the Management of Chronic Rhinosinusitis With Nasal Polyps (POLIposis NAsal/POLINA 2.0).

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly prevalent and burdensome disease for both individuals and health systems. Its management involves many specialties, including otorhinolaryngology, allergology, pulmonology, primary care, pharmacy, and pediatrics. A multidisciplinary approach and the participation of the patient in decision-making are essential, both for diagnosis and for therapy. The authors of the consensus aim to translate current knowledge into an easy-to-read practical guide and emphasize those aspects requiring further discussion or with unmet needs owing to the lack of appropriate scientific evidence. An iterative approach for the development of an evidence-based systematic review with recommendations was followed using a standard quality assessment approach (Scottish Intercollegiate Guidelines Network [SIGN] and National Institute for Health and Care Excellence [NICE]). The guideline was critically evaluated using the Appraisal of Guidelines for Research and Evaluation (AGREE II) and Recommendation Excellence (AGREE REX) instruments. Consequently, POLINA has been considered a high-quality guideline by an independent agency. The POLINA consensus provides new definitions of control, therapeutic management (including surgery and evaluation of severity), indications for use of biologics, and response. Finally, this guideline focuses on unmet research needs in CRSwNP.

Spanish Consensus on the Management of Chronic Rhinosinusitis With Nasal Polyps (POLIposis NAsal/POLINA 2.0)

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly prevalent and burdensome disease for both individuals and health systems. Its management involves many specialties, including otorhinolaryngology, allergology, pulmonology, primary care, pharmacy, and pediatrics. A multidisciplinary approach and the participation of the patient in decision-making are essential, both for diagnosis and for therapy. The authors of the consensus aim to translate current knowledge into an easy-to-read practical guide and emphasize those aspects requiring further discussion or with unmet needs owing to the lack of appropriate scientific evidence. An iterative approach for the development of an evidence-based systematic review with recommendations was followed using a standard quality assessment approach (Scottish Intercollegiate Guidelines Network [SIGN] and National Institute for Health and Care Excellence [NICE]). The guideline was critically evaluated using the Appraisal of Guidelines for Research and Evaluation (AGREE II) and Recommendation Excellence (AGREE REX) instruments. Consequently, POLINA has been considered a high-quality guideline by an independent agency. The POLINA consensus provides new definitions of control, therapeutic management (including surgery and evaluation of severity), indications for use of biologics, and response. Finally, this guideline focuses on unmet research needs in CRSwNP (AU)

La rinosinusitis crónica con pólipos nasales (RSCcPN) es una enfermedad de alta prevalencia y onerosa para las personas y los sistemas de salud cuyo manejo involucra a muchas especialidades: otorrinolaringología, alergología, neumología, atención primaria, farmacia y pediatría. El abordaje multidisciplinar y la participación del paciente en la toma de decisiones son fundamentales, tanto para el diagnóstico como para la estrategia terapéutica. Los autores del consenso pretenden traducir los conocimientos actuales en una guía práctica de fácil lectura y enfatizar aquellos aspectos en los que todavía hay discusión o necesidades no cubiertas por falta de evidencia científica adecuada. Se utilizó un enfoque iterativo para el desarrollo de una revisión sistemática basada en evidencia con recomendaciones, utilizando un esquema de evaluación de calidad estándar (Scottish Intercollegiate Guidelines Network -SIGN- y National Institute for Health and Care Excellence -NICE-), y una evaluación crítica de la directriz se ha llevado a cabo a través del instrumento Evaluación de Directrices para la Investigación y Evaluación (AGREE II) y Recomendación de Excelencia (AGREE REX). Con base en lo anterior, la guía POLINA ha sido considerada una guía de buena calidad por una agencia independiente El consenso POLINA aporta nuevos esquemas para la definición de control, manejo terapéutico incluyendo evaluación de gravedad, indicaciones de la cirugía y del uso de biológicos, y la respuesta al tratamiento. Finalmente, esta guía se enfoca en las necesidades de investigación insatisfechas en la RSCcPN (AU)

Correlation between thrombus regression and recurrent venous thromboembolism. Examining venographic and clinical effects of low-molecular-weight heparins: a meta-analysis.

We analyzed the correlation between thrombus regression on control venography performed after discontinuation of heparin therapy and recurrent venous thromboembolism (VTE) detected during clinical follow-up in randomized trials comparing low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) in patients with deep vein thrombosis (DVT). Data were abstracted from MEDLINE, conference abstracts and reference lists of previous reviews. Randomized, controlled trials comparing LMWH and UFH for the treatment of DVT using a combined venographic and clinical assessment and with at least 2 months of follow-up were selected. The proportions of patients with thrombus regression on control venography performed soon after discontinuation of heparin therapy and recurrent VTE at 2-6 months were independently collected by two researchers. Thirteen studies met the inclusion criteria. There was a strong inverse correlation between thrombus regression and recurrent VTE (r =- 0.70; P =0.008). The venographic effect varied between the different LMWHs (P = 0.013). A very strong correlation was found when the results were pooled by the type of LMWH used (r = - 0.84; P=0.037). No influence of the dose interval used on the venographic effect (P=0.156) or on recurrent VTE (P=0.218) was shown. The lack of thrombus regression in venography, performed soon after heparin discontinuation, was correlated with clinical recurrence. Non-invasive imaging techniques should be relevant to identify non-responders and to assess the optimal duration of initial heparin treatment in daily clinical practice.

Economic impact of an electronic alert system to prevent venous thromboembolism in hospitalised patients.

OBJECTIVES: The prevention of venous thromboembolism (VTE) is a priority for improved safety in hospitalised patients. Worldwide, there is growing concern over the undersuse of appropriate thromboprophylaxis. Computerised decision support improves the implementation of thromboprophylaxis and reduces inpatient VTE. However, an economic assessment of this approach has not yet been performed. OBJECTIVES: To evaluate the economic impact of an electronic alert (e-alert) system to prevent VTE in hospitalised patients over a 4year period. PATIENTS/METHODS: All hospitalised patients at a single institution during the first semesters of 2005-2009 (n=32280) were included. All cases of VTE developed during hospitalisation were followed and direct costs of diagnosis and management collected. RESULTS: E-alerts achieved a sustained reduction of the incidence of in-hospital VTE, OR 0.50 (95% CI, 0.29-0.84), the impact being especially significant in medical patients, OR 0.44 (95% CI, 0.22-0.86). No increase in prophylaxis-related bleeding was observed. In our setting, the mean direct cost (during hospitalisation and after discharge) of an in-hospital VTE episode is €7058. Direct costs per single hospitalised patient were reduced after e-alerts from €21.6 to €11.8, while the increased use of thromboprophylaxis and the development of e-alerts meant €3 and €0.35 per patient, respectively. Thus, the implementation of e-alerts led to a net cost saving of €6.5 per hospitalised patient. Should all hospitalised patients in Spain be considered, total yearly savings would approach €30million. CONCLUSIONS: E-alerts are useful and cost-effective tools for thromboprophylaxis strategy in hospitalised patients. Fewer thromboembolic complications and lower costs are achieved by its implementation.

Optimal dosing of bemiparin as prophylaxis against venous thromboembolism in surgery for cancer: an audit of practice.

AIMS: Low-molecular-weight heparins are drugs of first choice for thromboprophylaxis in cancer surgery. We sought to determine the optimal use of bemiparin in cancer surgery in standard clinical practice. PATIENTS AND METHODS: A retrospective, multicentre audit on the use of bemiparin in patients undergoing cancer surgery and given prophylaxis with bemiparin was undertaken. Surgeons' assessment of venous thromboembolic (VTE) risk (moderate or high) was compared to the criteria of current Consensus Guidelines for VTE management. We assessed the incidence of documented symptomatic VTE, bleeding events, thrombocytopenia, deaths and total events related to VTE or bemiparin prophylaxis (i.e. bleeding, thrombocytopenia). The potential economic impact of postoperative vs. preoperative bemiparin was also analysed. RESULTS: Clinical records from 197 patients from 5 Spanish centres were checked. Prophylaxis was started postoperatively in 45 patients (22.8%). According to the surgeons' criteria, 73 (37.1%) patients were at high VTE risk and received bemiparin 3500 IU/d. However, according to the criteria of current Guidelines, 189 (95.9%) patients were at high risk of VTE (heterogeneity P-value<0.0001). Three (1.5%) patients, all of them receiving bemiparin 2500 IU/d, developed a symptomatic confirmed VTE. There were 4 major and 5 minor bleeding events during bemiparin prophylaxis. A lower incidence of bleeding (2.2% vs. 5.3%; P=0.48) and total events (2.2% vs. 9.9%; P=0.11) was seen with bemiparin started postoperatively as compared to preoperative bemiparin. Bleeding rates did not significantly differ between patients given low or high bemiparin prophylactic doses (4.0% vs. 5.5%; P=0.72). Two patients died due to cardio-respiratory failure and sepsis, respectively. Postoperative bemiparin provided net cost savings of 909 euro per patient compared to preoperative start of prophylaxis due to shorter hospital stays (9 vs. 11 days) and lower incidence of complications in the postoperative bemiparin group. CONCLUSIONS: Many cancer patients are still poorly assessed for risk of VTE. Bemiparin 3500 IU/d is associated with a lower incidence of VTE without significant increase in complications as compared with bemiparin 2500 IU/d. Postoperative bemiparin prophylaxis seems to be as effective and safer than preoperative start of prophylaxis. Further prospective clinical studies are needed to fully address this issue.

Low-molecular-weight heparin, bemiparin, in the outpatient treatment and secondary prophylaxis of venous thromboembolism in standard clinical practice: the ESFERA Study.

The objective of this study is to assess the clinical and economic outcomes associated with outpatient treatment and secondary prophylaxis of acute venous thromboembolism (VTE) with a low-molecular-weight heparin, bemiparin. This study was designed as an open-label, multicentre, prospective, cohort study in standard clinical practice. Sixty-three investigators from 54 Spanish centres participated in the study. Five hundred eighty-three patients (434 outpatients and 149 inpatients) with acute VTE were followed up for 98 days (median). Outcome measures were costs and adverse events during initial VTE treatment with bemiparin (outpatient vs. inpatient cohorts) and long-term treatment [bemiparin (BEM) vs. vitamin K antagonists (VKA) cohorts]. Mean total costs per patient were lower in the outpatient cohort as compared with those in the inpatient cohort (1206 vs. 5191 euros; difference = -3985 euros; p < 0.001), with similar rates of adverse events (5.1 outpatient vs. 7.4% inpatient; p = 0.196) over 98 days. Mean total costs per patient were similar in the BEM/BEM and BEM/VKA cohorts (3616 vs. 3831 euros; difference = -215 euros; p = 0.412), but patients on long-term bemiparin treatment had lower rates of major bleeding (0.4 vs. 1.7%; p = 0.047), minor bleeding (1.8 vs. 6%; p = 0.032) and total adverse events (2.9 vs. 9.5%; p = 0.007) than patients in the BEM/VKA cohort. Outpatient management of VTE with bemiparin in selected patients resulted in significant cost-savings compared to inpatient treatment, while maintaining effectiveness and safety. Bemiparin may be a safer and cost-neutral alternative to VKA for long-term treatment of VTE.

Acute liver injury associated with the use of ebrotidine, a new H2-receptor antagonist.

BACKGROUND/AIM: Ebrotidine is a new H2-receptor antagonist marketed in Spain in early 1997 and withdrawn in July 1998. We report 11 cases of acute liver injury related to ebrotidine and submitted to a Regional Registry of Hepatotoxicity between June 1997 and August 1998. METHODS: In all cases a structured protocol was used to ascertain the role of ebrotidine and to exclude other causes (viral, immunologic, metabolic) of liver injury. RESULTS: All patients showed clinical symptoms of acute hepatitis, with a marked increase in aminotransferase activities (ALT values ranging from 15 to 91 times the upper limit of normal). Total bilirubin values were also greatly increased (mean 16 mg/dl), and the liver injury was defined as hepatocellular. Features of hypersensitivity were absent. Liver biopsy was done in three patients. Histopathological examination revealed mainly centrozonal necrosis (two cases) or massive necrosis (one patient). Withdrawal of the drug was followed by a gradual improvement in liver dysfunction, except in one patient who developed fulminant hepatic failure and died. There was a positive response to rechallenge in one patient after an inadvertent drug administration. CONCLUSION: Ebrotidine therapy seems to be associated with severe acute liver injury, and therefore its benefit/risk ratio is unfavorable. The relative rareness and unpredictability of the injury, the lack of dose-relationship and the absence of hallmarks of drug allergy are suggestive of an idiosyncratic metabolic mechanism.