Economic evaluation of the levonorgestrel-releasing intrauterine system for the treatment of dysfunctional uterine bleeding in Spain

To compare the cost and effectiveness of the levonorgestrel-releasing intrauterine system (LNG-IUS) versus combined oral contraception (COC) and progestogens (PROG) in first-line treatment of dysfunctional uterine bleeding (DUB) in Spain. STUDY DESIGN: A cost-effectiveness and cost-utility analysis of LNG-IUS, COC and PROG was carried out using a Markov model based on clinical data from the literature and expert opinion. The population studied were women with a previous diagnosis of idiopathic heavy menstrual bleeding. The analysis was performed from the National Health System perspective, discounting both costs and future effects at 3%. In addition, a sensitivity analysis (univariate and probabilistic) was conducted. RESULTS: The results show that the greater efficacy of LNG-IUS translates into a gain of 1.92 and 3.89 symptom-free months (SFM) after six months of treatment versus COC and PROG, respectively (which represents an increase of 33% and 60% of symptom-free time). Regarding costs, LNG-IUS produces savings of 174.2-309.95 and 230.54-577.61 versus COC and PROG, respectively, after 6 months-5 years. Apart from cost savings and gains in SFM, quality-adjusted life months (QALM) are also favourable to LNG-IUS in all scenarios, with a range of gains between 1 and 2 QALM compared to COC and PROG. CONCLUSIONS: The results indicate that first-line use of the LNG-IUS is the dominant therapeutic option (less costly and more effective) in comparison with first-line use of COC or PROG for the treatment of DUB in Spain. LNG-IUS as first line is also the option that provides greatest health-related quality of life to patients.

Early transjugular intrahepatic portosystemic shunt in cirrhotic patients with acute variceal bleeding: a systematic review and meta-analysis of controlled trials.

INTRODUCTION: There is conflicting evidence on the benefit of early transjugular intrahepatic portosystemic shunt (TIPSS) on the survival of patients with acute variceal bleeding (AVB). AIM: To assess the effect of early TIPSS on patient prognosis. MATERIALS AND METHODS: We carried out a meta-analysis of trials evaluating early TIPSS in cirrhotic patients with AVB. RESULTS: Four studies were included. Early TIPSS was associated with fewer deaths [odds ratio (OR)=0.38, 95% confidence interval (CI)=0.17-0.83, P=0.02], with moderate heterogeneity between studies (P=0.15, I=44%). Early TIPSS was not significantly associated with fewer deaths among Child-Pugh B patients (OR=0.35, 95% CI=0.10-1.17, P=0.087) nor among Child-Pugh C patients (OR=0.34, 95% CI=0.10-1.11, P=0.074). There was no heterogeneity between studies in the Child-Pugh B analysis (P=0.6, I=0%), but there was a high heterogeneity in the Child-Pugh C analysis (P=0.06, I=60%). Early TIPSS was associated with lower rates of bleeding within 1 year (OR=0.08, 95% CI=0.04-0.17, P<0.001) both among Child-Pugh B patients, (OR=0.15, 95% CI=0.05-0.47, P=0.001) and among Child-Pugh C patients (OR=0.05, 95% CI=0.02-0.15, P<0.001), with no heterogeneity between studies. Early TIPSS was not associated with higher rates of encephalopathy (OR=0.84, 95% CI=0.50-1.42, P=0.5). CONCLUSION: Cirrhotic patients with AVB treated with early TIPSS had lower death rates and lower rates of clinically significant bleeding within 1 year compared with patients treated without early TIPSS. Additional studies are required to identify the potential risk factors leading to a poor prognosis after early TIPSS in patients with AVB and to determine the impact of the degree of liver failure on the patient's prognosis.

Self-expandable metal stents in the treatment of acute esophageal variceal bleeding.

Acute variceal bleeding (AVB) is a life-threatening complication in patients with cirrhosis. Hemostatic therapy of AVB includes early administration of vasoactive drugs that should be combined with endoscopic therapy, preferably banding ligation. However, failure to control bleeding or early rebleed within 5 days still occurs in 15-20% of patients with AVB. In these cases, a second endoscopic therapy may be attempted (mild bleeding in a hemodynamically stable patient) or we can use a balloon tamponade as a bridge to definitive derivative treatment (i.e., a transjugular intrahepatic portosystemic shunt). Esophageal balloon tamponade provides initial control in up to 80% of AVB, but it carries a high risk of major complications, especially in cases of long duration of tamponade (>24 h) and when tubes are inserted by inexperienced staff. Preliminary reports suggest that self-expandable covered esophageal metallic stents effectively control refractory AVB (i.e., ongoing bleeding despite pharmacological and endoscopic therapy or massive bleeding precluding endoscopic therapy) with a low incidence of complications. Thus, covered self-expanding metal stents may represent an alternative to the Sengstaken-Blakemore balloon for the temporary control of bleeding in treatment failures. Further studies are required to determine the role of this new device in AVB.

Early Recurrence and Cerebral Bleeding in Patients With Acute Ischemic Stroke and Atrial Fibrillation: effect of Anticoagulation and Its Timing: the RAF Study.

BACKGROUND AND PURPOSE: The best time for administering anticoagulation therapy in acute cardioembolic stroke remains unclear. This prospective cohort study of patients with acute stroke and atrial fibrillation, evaluated (1) the risk of recurrent ischemic event and severe bleeding; (2) the risk factors for recurrence and bleeding; and (3) the risks of recurrence and bleeding associated with anticoagulant therapy and its starting time after the acute stroke. METHODS: The primary outcome of this multicenter study was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding within 90 days from acute stroke. RESULTS: Of the 1029 patients enrolled, 123 had 128 events (12.6%): 77 (7.6%) ischemic stroke or transient ischemic attack or systemic embolism, 37 (3.6%) symptomatic cerebral bleeding, and 14 (1.4%) major extracranial bleeding. At 90 days, 50% of the patients were either deceased or disabled (modified Rankin score ≥3), and 10.9% were deceased. High CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesion and type of anticoagulant were predictive factors for primary study outcome. At adjusted Cox regression analysis, initiating anticoagulants 4 to 14 days from stroke onset was associated with a significant reduction in primary study outcome, compared with initiating treatment before 4 or after 14 days: hazard ratio 0.53 (95% confidence interval 0.30-0.93). About 7% of the patients treated with oral anticoagulants alone had an outcome event compared with 16.8% and 12.3% of the patients treated with low molecular weight heparins alone or followed by oral anticoagulants, respectively (P=0.003). CONCLUSIONS: Acute stroke in atrial fibrillation patients is associated with high rates of ischemic recurrence and major bleeding at 90 days. This study has observed that high CHA2DS2-VASc score, high National Institutes of Health Stroke Scale, large ischemic lesions, and type of anticoagulant administered each independently led to a greater risk of recurrence and bleedings. Also, data showed that the best time for initiating anticoagulation treatment for secondary stroke prevention is 4 to 14 days from stroke onset. Moreover, patients treated with oral anticoagulants alone had better outcomes compared with patients treated with low molecular weight heparins alone or before oral anticoagulants.

Incidence and consequence of major bleeding in primary percutaneous intervention for ST-elevation myocardial infarction in the era of radial access: an analysis of the international randomized Acute myocardial infarction Treated with primary angioplasty and intravenous enoxaparin Or unfractionated heparin to Lower ischemic and bleeding events at short- and Long-term follow-up trial.

AIMS: The aims of the study are to compare the outcome with and without major bleeding and to identify the independent correlates of major bleeding complications and mortality in patients described in the ATOLL study. METHODS: The ATOLL study included 910 patients randomly assigned to either 0.5 mg/kg intravenous enoxaparin or unfractionated heparin before primary percutaneous coronary intervention. Incidence of major bleeding and ischemic end points was assessed at 1 month, and mortality, at 1 and 6 months. Patients with and without major bleeding complication were compared. A multivariate model of bleeding complications at 1 month and mortality at 6 months was realized. Intention-to-treat and per-protocol analyses were performed. RESULTS: The most frequent bleeding site appears to be the gastrointestinal tract. Age >75 years, cardiac arrest, and the use of insulin or >1 heparin emerged as independent correlates of major bleeding at 1 month. Patients presenting with major bleeding had significantly higher rates of adverse ischemic complications. Mortality at 6 months was higher in bleeders. Major bleeding was found to be one of the independent correlates of 6-month mortality. The addition or mixing of several anticoagulant drugs was an independent factor of major bleeding despite the predominant use of radial access. CONCLUSIONS: This study shows that major bleeding is independently associated with poor outcome, increasing ischemic events, and mortality in primary percutaneous coronary intervention performed mostly with radial access.

Systematic review with meta-analysis: self-expanding metal stents in patients with cirrhosis and severe or refractory oesophageal variceal bleeding.

BACKGROUND: The prognosis of patients with cirrhosis and acute variceal bleeding is very poor when the standard-of-care fails to control bleeding. New treatment modalities are needed in these patients. AIM: To synthesise the available evidence on the efficacy of self-expanding metal stents (SEMS) in patients with cirrhosis and severe or refractory oesophageal variceal bleeding. METHODS: Meta-analysis of trials evaluating SEMS in patients with cirrhosis and severe or refractory oesophageal variceal bleeding. RESULTS: Thirteen studies were included. The pooled estimate rates were 0.40 (95% confidence interval, CI = 0.31-0.49) for death, 0.41 (95% CI = 0.29-0.53) for liver-related death and 0.36 (95% CI = 0.26-0.47) for death at day 30, with low heterogeneity between studies. The pooled estimate rates were 0.12 (95% CI = 0.07-0.21) for mortality related to variceal bleeding, and 0.18 (95% CI = 0.11-0.29) for failure to control bleeding with SEMS, with no or low heterogeneity between studies. The pooled estimate rate were 0.16 (95% CI = 0.04-0.48) for rebleeding after stent removal and 0.28 (95% CI = 0.17-0.43) for stent migration, with high heterogeneity. A significant proportion of patients had access to liver transplantation or to TIPSS [pooled estimate rate 0.10 (95% CI = 0.04-0.21) and 0.26 (95% CI = 0.18-0.36), respectively]. CONCLUSIONS: Fewer than 40% of patients treated with SEMS were dead at 1 month. SEMS can be used as a bridge to TIPSS or to liver transplantation in a significant proportion of patients. Additional studies are required to identify potential risk factors leading to a poor prognosis in patients with acute variceal bleeding in whom the use of SEMS could be considered.

Association between smoking and recurrence of venous thromboembolism and bleeding in elderly patients with past acute venous thromboembolism.

BACKGROUND: While the association between smoking and arterial cardiovascular events has been well established, the association between smoking and venous thromboembolism (VTE) remains controversial. OBJECTIVES: To assess the association between smoking and the risk of recurrent VTE and bleeding in patients who have experienced acute VTE. PATIENTS/METHODS: This study is part of a prospective Swiss multicenter cohort that included patients aged ≥65years with acute VTE. Three groups were defined according to smoking status: never, former and current smokers. The primary outcome was the time to a first symptomatic, objectively confirmed VTE recurrence. Secondary outcomes were the time to a first major and clinically relevant non-major bleeding. Associations between smoking status and outcomes were analysed using proportional hazard models for the subdistribution of a competing risk of death. RESULTS: Among 988 analysed patients, 509 (52%) had never smoked, 403 (41%) were former smokers, and 76 (8%) current smokers. After a median follow-up of 29.6months, we observed a VTE recurrence rate of 4.9 (95% confidence interval [CI] 3.7-6.4) per 100 patient-years for never smokers, 6.6 (95% CI 5.1-8.6) for former smokers, and 5.2 (95% CI 2.6-10.5) for current smokers. Compared to never smokers, we found no association between current smoking and VTE recurrence (adjusted sub-hazard ratio [SHR] 1.05, 95% CI 0.49-2.28), major bleeding (adjusted SHR 0.59, 95% CI 0.25-1.39), and clinically relevant non-major bleeding (adjusted SHR 1.21, 95% CI 0.73-2.02). CONCLUSIONS: In this multicentre prospective cohort study, we found no association between smoking status and VTE recurrence or bleeding in elderly patients with VTE.

Radiological findings of uterine arteriovenous malformation: a case report of an unusual and life-threatening cause of abnormal vaginal bleeding

Uterine arteriovenous malformations may cause life-threatening abnormal genital bleeding in women at childbearing age. Transvaginal Doppler ultrasonography is a widely available, noninvasive and excellent diagnostic method. The authors report the case of a patient with history of gestational trophoblastic disease and multiple curettage procedures who developed uterine arteriovenous malformations, with remission of the lesions after treatment with methotrexate.

Computed tomography angiography in patients with active gastrointestinal bleeding

Abstract Gastrointestinal bleeding represents a common medical emergency, with considerable morbidity and mortality rates, and a prompt diagnosis is essential for a better prognosis. In such a context, endoscopy is the main diagnostic tool; however, in cases where the gastrointestinal hemorrhage is massive, the exact bleeding site might go undetected. In addition, a trained professional is not always present to perform the procedure. In an emergency setting, optical colonoscopy presents limitations connected with the absence of bowel preparation, so most of the small bowel cannot be assessed. Scintigraphy cannot accurately demonstrate the anatomic location of the bleeding and is not available at emergency settings. The use of capsule endoscopy is inappropriate in the acute setting, particularly in the emergency department at night, and is a highly expensive method. Digital angiography, despite its high sensitivity, is invasive, presents catheterization-related risks, in addition to its low availability at emergency settings. On the other hand, computed tomography angiography is fast, widely available and minimally invasive, emerging as a promising method in the diagnostic algorithm of these patients, being capable of determining the location and cause of bleeding with high accuracy. Based on a critical literature review and on their own experience, the authors propose a computed tomography angiography protocol to assess the patient with gastrointestinal bleeding.

In vitro activity of essential oils of Lippia sidoides and Lippia gracilis and their major chemical components against Thielaviopsis paradoxa, causal agent of stem bleeding in coconut palms

Essential oils of Lippia sidoides, Lippia gracilis and their main chemical components were investigated for in vitro control of Thielaviopsis paradoxa. Mycelial growth and a number of pathogen conidia were inhibited by the essential oil of L. sidoides at all concentrations tested (0.2; 0.5; 1.0; 3.0 µL mL-1). L. sidoides oil contained 42.33% thymol and 4.56% carvacrol, while L. gracilis oil contained 10% thymol and 41.7% carvacrol. Mycelial growth and conidial production of T. paradoxa were completely inhibited by thymol at a 0.3 µL m-1 concentration. The results suggest that thymol could potentially be used for controlling coconut stem bleeding.

Complex pulmonary aspergilloma treated by cavernostomy

Objective: To evaluate the effectiveness of cavernostomy in patients with complex fungal balls.Methods: We analyzed the medical records of patients undergoing cavernostomy between January 2005 and May 2013, evaluating: age, gender, preoperative signs and symptoms, predisposing disease, preoperative tests, location of the aspergilloma, etiologic agent, cavernostomy indication, postoperative outcome.Results: Ten patients were male. The mean age was 42.9 years (34-56). The most frequent symptom was repeated pulmonary bleeding. Cavernostomy was proposed for patients at high risk for lung resection. It was performed in 17 patients and all of them had pulmonary tuberculosis sequelae, with cavitations. The indication in all cases was hemoptysis and elimination of phlegm. The cavernostomies were performed in a single surgical procedure. In all 17 patients the cavity was left open after the withdrawal of the mycetoma. In all patients hemoptysis ceased immediately. Operative mortality was 9.5% (1).Conclusion: cavernostomy is an effective treatment alternative in patients at high risk. It may be useful in some patients with complex aspergilloma, irrespective of lung function or bilateral disease. It is technically easy, has low-risk, saves parenchyma, and may be performed in a single operative time.

Benzodiazepines and Cognitive Functioning in Older Adults. With Emphasis on Long-Term Use and Withdrawal

Benzodiazepines (BZD) and benzodiazepine related drugs (RD) are the most commonly used psychotropics among the aged. The use of other psychotropics taken concomitantly with BZD/ RD or their cognitive effects with BZD/RD have not been studied frequently. The aim of this academic thesis was to describe and analyse relationships between the use of BZD/RD alone or concomitantly with antipsychotics, antidepressants, opioids, antiepileptics, opioids and anticholinergics in the aged and their health. Especially, the relationships between long-term use of BZD/RD and cognitive decline were studied. Additionally, the effect of melatonin on BZD/RD withdrawal and the cognitive effects of BZD/RD withdrawal were studied. This study used multiple data sets: the first study (I) was based on clinical data containing aged patients (≥65 years; N=164) admitted to Pori City Hospital due to acute disease. The second data set (Studies II and III) was based on population-based data from the Lieto Study, a clinico-epidemiological longitudinal study carried out among the aged (≥65 years) in the municipality of Lieto. Follow-up data was formed by combining the cohort data collected in 1990-1991 (N=1283) and in 1998-1999 (N=1596) from those who participated in both cohorts (N=617). The third data set (Studies IV and V) was based on the Satauni Study’s data. This study was performed in the City of Pori in 2009-2010. In the RCT part of the Satauni Study, ninety-two long-term users of BZD/RD were withdrawn from their drugs using melatonin against placebo. The change of their cognitive abilities was measured during and after BZD/ RD withdrawal. BZD/RD use was related to worse cognitive and functional abilities, and their use may predict worse cognitive outcomes compared with BZD/RD non-users. Hypnotic use of BZD/RD could be withdrawn with psychosocial support in motivated participants, but melatonin did not improve the withdrawal results compared to those with placebo. Cognitive abilities in psychomotor tests did not show, or showed only modest, improvements for up to six months after BZD/RD withdrawal. This suggests that the cognitive effects of BZD/RD may be longlasting or permanent.