Premedication prior to PEG-asparaginase is cost-effective in pediatric patients with acute lymphoblastic leukemia.

BACKGROUND: PEG-asparaginase is critical in pediatric acute lymphoblastic leukemia (ALL) therapy but is highly immunogenic. Severe allergic reactions lead to substitution of further PEG-asparaginase with Erwinia. Erwinia is associated with more frequent dosing, increased expense, and limited availability. Premedication may reduce rates of allergic reactions. PROCEDURES: This Markov model evaluated the cost-effectiveness of three strategies: premedication plus therapeutic drug monitoring (TDM), TDM alone, and no premedication or TDM. We modeled two scenarios: a standard-risk (SR) B-ALL patient receiving two asparaginase doses and a high-risk (HR) patient receiving seven asparaginase doses. The model incorporated costs of asparaginase, premedication, TDM and clinic visits, and lost parental wages associated with each additional Erwinia dose. We incorporated a five-year time horizon with a societal perspective. Outcomes were Erwinia substitutions avoided and differences in quality-adjusted life years (QALYs). Probabilistic and one-way sensitivity analyses evaluated model uncertainty. RESULTS: In both scenarios, premedication was the least costly strategy. In SR and HR scenarios, premedication with monitoring resulted in 8% and 7% fewer changes to Erwinia compared with monitoring alone and 3% and 2% fewer changes compared with no premedication/monitoring, respectively. Premedication resulted in the most QALYs gained in the SR patients. Individual variation of model inputs did not change premedication/monitoring favorability for either scenario. In probabilistic sensitivity analyses, premedication/monitoring was favored in >87% of iterations in both scenarios. CONCLUSION: Compared with other strategies, premedication use and asparaginase level monitoring in children with B-ALL is potentially cost-saving.

A cost-utility analysis of dabigatran, enoxaparin, and usual care for venous thromboprophylaxis after hip or knee replacement surgery in Thailand.

To analyze the cost-utility of oral dabigatran etexilate, enoxaparin sodium injection, and no intervention for venous thromboembolism (VTE) prophylaxis after total hip or knee replacement (THR/TKR) surgery among Thai patients. A cost-utility analysis using a decision tree model was conducted using societal and healthcare payers' perspectives to simulate relevant costs and health outcomes covering a 3-month time horizon. Costs were adjusted to year 2014. The willingness-to-pay threshold of THB 160,000 (USD 4926) was used. One-way sensitivity and probabilistic sensitivity analyses using a Monte Carlo simulation were performed. Compared with no VTE prophylaxis, dabigatran and enoxaparin after THR and TKR surgery incurred higher costs and increased quality adjusted life years (QALYs). However, their incremental cost-effectiveness ratios were high above the willingness to pay. Compared with enoxaparin, dabigatran for THR/TKR lowered VTE complications but increased bleeding cases; dabigatran was cost-saving by reducing the costs [by THB 3809.96 (USD 117.30) for THR] and producing more QALYs gained (by 0.00013 for THR). Dabigatran (vs. enoxaparin) had a 98 % likelihood of being cost effective. Dabigatran is cost-saving compared to enoxaparin for VTE prophylaxis after THR or TKR under the Thai context. However, both medications are not cost-effective compared to no thromboprophylaxis.

Cost-effectiveness analysis of pharmacokinetic-driven prophylaxis vs. standard prophylaxis in patients with severe haemophilia A.

: The objective of this study was to assess the cost-effectiveness of pharmacokinetic-driven prophylaxis in severe haemophilia A patients. A microsimulation model was developed to evaluate the cost-effectiveness of pharmacokinetic-driven prophylaxis vs. standard prophylaxis and estimate cost, annual joint bleed rate (AJBR), and incremental cost-effectiveness ratio over a 1-year time horizon for a hypothetical population of 10 000 severe haemophilia A patients. A dose of 30 IU/kg per 48 h was assumed for standard prophylaxis. Pharmacokinetic prophylaxis was individually adjusted to maintain trough levels at least 1 and 5 IU/dl or less. AJBR was estimated on the relationship between factor VIII (FVIII) levels and bleeding rate reported in the literature. Sensitivity analyses were performed to assess the stability of the model and the reliability of results. The FVIII dose was reduced in the 27.8% of patients with a trough level more than 5 IU/dl on standard prophylaxis, with a negligible impact on AJBR (+0.1 bleed/year). The FVIII dose was increased in the 10.6% of patients with trough levels less than 1 IU/dl on standard prophylaxis, with a significant reduction of AJBR (-1.9 bleeds/year). On average, overall, pharmacokinetic-driven prophylaxis was shown to decrease the AJBR from 1.012 to 0.845 with a slight reduction of the infusion dose of 0.36 IU/kg, with total saving of 5 197&OV0556; per patient-year. Pharmacokinetic-driven prophylaxis was preferable (i.e. more effective and less costly) compared with standard prophylaxis, with savings of 31 205&OV0556; per bleed avoided. Pharmacokinetic-driven prophylaxis, accounting for patients' individual pharmacokinetic variability, appears to be a promising strategy to improve outcomes with efficient use of available resources in severe haemophilia A patients.

Cost-effectiveness of prophylactic granulocyte colony-stimulating factor for febrile neutropenia in breast cancer patients receiving FEC-D.

5-fluorouracil, epirubicin, cyclophosphamide â†’ docetaxel (FEC-D) has been associated with higher-than-expected rates of febrile neutropenia (FN) that meet the current guideline threshold of 20 % for primary prophylaxis (PP) with granulocyte colony-stimulating factor (G-CSF). We examined the cost-effectiveness of FEC-D with varying strategies of G-CSF prophylaxis from the perspective of the public payer in Ontario, Canada. A state-transition model was developed to compare three strategies: FEC-D with secondary prophylaxis (SP) only, PP starting with the first cycle of D, and PP starting with the first cycle of FEC. Analysis was conducted for a hypothetical cohort of 50-year-old early-stage breast cancer patients undergoing adjuvant chemotherapy, at a 10-year horizon. Results were expressed in quality-adjusted life-years (QALYs) and 2013 Canadian dollars. Costs and benefits were discounted at 5 %. Event rates, costs, and utilities were derived from the literature. One-way and probabilistic sensitivity analyses were conducted. Using filgrastim, the incremental cost-effectiveness ratios (ICERs) for starting PP with the first cycle of D and starting PP with the first cycle of FEC, compared to using SP only, were $57,886/QALY and $116,186/QALY, respectively. With pegfilgrastim, the ICERs for the same strategies were $90,735/QALY and $149,483/QALY. Compared to using filgrastim SP only, starting PP with D had a 24 % chance of being cost-effective at a willingness-to-pay (WTP) threshold of $50,000/QALY, and a 99 % chance at a WTP threshold of $100,000/QALY. Results were sensitive to FN-related parameters, such as the risk of FN per cycle with D and the associated mortality, but were robust to uncertainty in parameters related to breast cancer, such as the utilities and hazard of relapse. FEC-D with PP starting with the first cycle of D is most likely to be cost-effective, especially with increased risk of FN and mortality from FN.

Demanda al servicio de urgencias de profilaxis para infecciones de transmisión sexual tras prácticas sexuales de riesgo / Sexual risk behavior and demand for prophylaxis for sexually transmitted diseases

Objetivos: Analizar las características de las consultas a urgencias en demanda de profilaxis para las infecciones de transmisión sexual (ITS) tras una práctica sexual de riesgo. Método: Durante 6 meses se han revisado las demandas de profilaxis atendidas en el servicio de urgencias tras una práctica sexual de riesgo. Se utilizaron como variables datos epidemiológicos, tipo de práctica, motivo de consulta, tratamiento profiláctico y coste económico. Resultados: Se han incluido 189 pacientes con una edad media de 32,5 (8,3) años. De ellos, 162 eran hombres (85,7%). El 67,2% eran españoles. Ciento trece casos (59,8%)eran hombres que tuvieron sexo con otros hombres (HSH), con pareja VIH positiva(30,7%) o de estatus serológico desconocido (61,9%). Usaron preservativo el 49,7%de pacientes, pero consultaron por su rotura o pérdida el 45,5%. La penetración anal, activa o pasiva, fue la práctica sexual más frecuente (53,4%). El 85,2% recibió tratamiento profiláctico para el VIH con antirretrovirales durante 28 días, el 77,2% recibió también profilaxis antibiótica para otras ITS y un 22,8% inició inmunización para virus hepatotropos. El coste medio de la visita y de la profilaxis administrada o prescrita en urgencias fue de 858 (275) euros por paciente. Conclusiones: La práctica sexual de riesgo como motivo de consulta a urgencias es frecuente, principalmente entre un hombre que practica sexo con otro hombre. La mayoría de pacientes acude por una rotura del preservativo, pero casi la mitad no lo usan a pesar de desconocer el estado serológico de la pareja o ser ésta portadora del VIH. La consulta a urgencias y el tratamiento farmacológico generan un coste económico elevado (AU)

Objective: To analyze the characteristics of patients coming to the emergency room seeking postexposure prophylaxis for sexually transmitted diseases (STDs) after high-risk sex. Methods: Over a 6-month period, emergency requests for postexposure STD prophylaxis were reviewed. We recorded epidemiologic variables, type of sexual risk behavior, reason for coming to the emergency room, STD prophylaxis prescribed, and cost. Results: A total of 189 patients with a mean (SD) age of 32.5 (8.3) years were included; 162 (85.7%) were men and67.2% were Spanish. One hundred thirteen (59.8%) were men who had sex with men; the partner was seropositive for human immunodeficiency virus (HIV) in 30.7% of the cases or of unknown serostatus in 61.9%. Condoms were used by49.7%, but 45.5% reported breakage. The most frequent practice was anal penetration (active or passive) (53.4%).Twenty-eight days of preventive HIV antiretroviral therapy was prescribed for 85.2%; 77.2% also received prophylactic antibiotics for other STDs, and 22.8% started immunization against hepatropic viruses. The mean cost per visit and preventive treatment administered or prescribed in the emergency department was €858 (€275).Conclusions: Sexual risk behavior is a frequent reason for emergency department visits, particularly among men who have sex with men. A large proportion of patients come because a condom has broken, but nearly half do not use a condom even when they do not know the serostatus of the partner or know the partner is seropositive for HIV. Emergency care and pharmacologic treatment for these patients are costly (AU)

New anticoagulants as thromboprophylaxis after total hip or knee replacement.

OBJECTIVES: Due to a high risk of thromboembolism in patients undergoing major orthopedic surgery, it has become standard practice to give thromboprophylactic treatment. We assessed the relative efficacy and cost-effectiveness of two new oral anticoagulants, rivaroxaban and dabigatran, relative to subcutaneous enoxaparin for the prevention of thromboembolism after total hip replacement (THR) and total knee replacement surgery (TKR). METHODS: We conducted a systematic review of the literature to assess efficacy and safety, and evaluated quality of documentation using GRADE. Cost-effectiveness was assessed by developing a decision model. The model combined two modules; a decision tree for the short-term prophylaxis and a Markov model for the long-term complications and survival gain. RESULTS: For rivaroxaban compared with enoxaparin, we found statistically significant decreases in deep vein thrombosis, but also a trend toward increased risk of major bleeding. For mortality and pulmonary embolism there were no statistically significant differences between the treatments. We did not find statistically significant differences between dabigatran and enoxaparin for our efficacy and safety outcomes. Assuming a willingness to pay of EUR62,500 per QALY, rivaroxaban following THR had a probability of 38 percent, and enoxaparin following TKR had a probability of 34 percent of being cost-effective. Clinical efficacy had the greatest impact on decision uncertainty. CONCLUSIONS: Dabigatran and rivaroxaban are comparable with enoxaparin following THR and TKR regarding the efficacy and safety outcomes. However, there is great uncertainty regarding which strategy is the most cost-effective. More research on clinical efficacy of rivaroxaban and dabigatran is likely to change our results.

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.

[Cost-effectiveness analysis of pre-seasonal medication for cedar pollinosis in Japan].

Pre-seasonal medication is recommended for cases of cedar pollinosis that are expected to manifest severe symptoms during the season, according to the standard clinical guideline in Japan. This study aims to appraise the value for money of additional costs that accompany the choice of pre-seasonal medication from payer's perspective. Based on the 12 reports of controlled clinical trials with Symptom Score (SS) and Medication Score (MS) comparing pre-seasonal medication with intra-seasonal symptomatic medication, 15 incremental cost-effectiveness ratios (ICERs) and 4 integrated ICERs of each group of targeted agents are estimated. Incremental effects are estimated by reading SS charts, and incremental costs are estimated by reading MS charts and using National Health Insurance Medical Fee Schedule and National Health Insurance Drug Price Standard. Estimated ICERs range from ¥322,195 per quality-adjusted life-year (QALY) to ¥57,088,063 per QALY. Integrated ICERs are: ¥1,128,286 per QALY for 2nd generation histamine H(1) receptor antagonists, ¥2,248,018 per QALY for leukotriene receptor antagonists, ¥2,692,911 per QALY for prostaglandin D(2) and thromboxane A(2) receptor antagonists, ¥1,150,943 per QALY for Th2 cytokine suppressors, and ¥1,291,341 per QALY for all agents. Pre-seasonal medication for cedar pollinosis is cost-effective regardless of the choice of the prophylactic agent among 2nd generation histamine H(1) receptor antagonists, leukotriene receptor antagonists, prostaglandin D(2) and thromboxane A(2) receptor antagonists, or Th2 cytokine suppressors, taking the suggested threshold of ¥5,000,000 per 1 QALY gain in Japan. The use of 2nd generation histamine H(1) receptor antagonists and Th2 cytokine suppressors are found more favourable.

Clinical and economic outcomes with appropriate or partial prophylaxis.

INTRODUCTION: Despite the existence of evidence-based guidelines for venous thromboembolism (VTE) prevention, prophylaxis is often inappropriately prescribed. This study compared the efficacy, safety, and cost of appropriate (ACCP-recommended) prophylaxis with partial prophylaxis (not completely conforming to ACCP guidelines) in patients at-risk of VTE receiving enoxaparin or unfractionated heparin. METHODS: The MarketScan((R)) Hospital Drug Database from Thomson Reuters (January 2004-March 2007), was queried for medical and surgical patients at high risk of VTE, aged > or =40years, and with a hospital stay > or =6days. Univariate and multivariate analyses compared hospital-acquired VTE events, adverse events, and hospital costs between appropriate or partial prophylaxis discharges. RESULTS: Of the 21,001 discharge records included, appropriate prophylaxis was received by 5136 (24.5%) patients. Compared with partial prophylaxis, appropriate prophylaxis was associated with significantly lower incidences of hospital-acquired pulmonary embolism (0.9% vs 0.5%; adjusted odds ratio [OR] 0.55, 95% confidence intervals [CI] 0.35-0.87, P=0.010), and bleeding events (10.7% vs 5.1%; adjusted OR 0.57, 95% CI 0.50-0.66, P<0.001). Total costs per discharge were lower for appropriate prophylaxis ($17,386+/-12,004) than partial prophylaxis ($23,823+/-19,783) with an adjusted mean difference of $6370 in favor of appropriate prophylaxis (P<0.001). CONCLUSION: This retrospective study suggests that ACCP-guideline recommended appropriate prophylaxis reduces hospital-acquired pulmonary embolism and bleeding events in patients at-risk of VTE and is cost-saving when total direct medical costs are considered. The substantial US clinical and economic VTE burden may, therefore, be reduced by improving prophylaxis adherence with guideline recommendations.

Uninterrupted warfarin for periprocedural anticoagulation in catheter ablation of typical atrial flutter: a safe and cost-effective strategy.

INTRODUCTION: Many patients undergoing catheter ablation of atrial flutter (AFL) require periprocedural anticoagulation. We compared a strategy of conversion to low molecular weight heparin (LMWH) periprocedure to uninterrupted warfarinization in a nonrandomized, case-controlled study. METHODS: One hundred and one consecutive patients requiring periprocedural anticoagulation for catheter ablation of typical AFL were studied. The first 51 patients underwent conversion to LMWH (enoxaparin 1 mg/kg bd) with a warfarin pause (LMWH group), the subsequent 50 continued with uninterrupted oral anticoagulation (Warfarin group). Primary endpoint was a composite of major and minor bleeding complications and groin symptoms. RESULTS: Fewer patients in the Warfarin group reached the primary endpoint (36.0% vs 56.8%, P = 0.013). Four patients in the LMWH group but no patient in the Warfarin group required hospital admission for bleeding-related complications. Cost analysis showed mean cost per patient of anticoagulation with LMWH to be pounds sterling 100.9 (95% CI 94.46-107.30) compared to pounds sterling 10.23 (4.49-15.97) in the Warfarin group (P < 0.0001). Transesophageal echocardiography (TEE) was performed prior to ablation in 11 patients in the Warfarin group and in 3 patients in the LMWH (P = 0.019). When TEE costs were included, costs were pounds sterling 125.00 ($188.25) (96.80-153.60) for the LMWH strategy and pounds sterling 108.5 ($163.40) (54.92-162.1) for the Warfarin group (P < 0.0001). CONCLUSIONS: Catheter ablation of typical AFL without interruption of warfarin appears safer and more cost-effective than periprocedural conversion to LMWH. It could be used as a routine anticoagulation strategy for the ablation of right-sided arrhythmias.

[Effect of preliminary medication on oxaliplatin hypersensitivity].

Oxaliplatin therapy is a standard treatment for advanced colorectal cancer, and oxaliplatin hypersensitivity is one of its side effects that should be particularly considered. In the present study, we observed a decrease in the incidence of oxaliplatin hypersensitivity since the introduction of preliminary medication involving the administration of escalated doses of steroids and the use of antihistamine agents. From the medical economics perspective, although the costs of the preliminary medication were generated, those for the treatment of oxaliplatin hypersensitivity, which were higher than the total cost of the preliminary medication, needed to be generated for all patients. Introduction of preliminary medication decreased the overall cost, since the medication decreased the incidence of hypersensitivity. Therefore, preliminary medication was recognized to be effective from the perspective of medical economics. The preliminary medication we introduced contributed to a safe, cost-effective, and high-quality treatment for advanced colorectal cancer by preventing oxaliplatin hypersensitivity.

[Evaluation of short-time premedication with d-chlorpheniramine maleate injection for paclitaxel-induced hypersensitivity reaction].

Paclitaxel(referred to hereinafter as PTX )is used in ovarian cancer, non-small cell lung cancer, breast cancer, gastric cancer, and endometrial cancer with positive treatment result reports. However, severe allergic reactions such as decreases in blood pressure and impaired breathing occur with relatively high frequency. For the prevention of such allergic reactions, administration of a premedication composed of the three components, dexamethasone sodium phosphate injection, diphenhydramine hydrochloride tablet, and ranitidine hydrochloride injection solution(or injectable famodine), is advised in the appended documentation. Administration is difficult because, among these three components, only diphenhydramine hydrochloride is administered orally and thus must be provided through the internal medicine department. Particularly when this combined dosage is administered as outpatient chemotherapy, the doctor must prescribe diphenhydramine hydrochloride tablets, and the patient must not forget to bring them on the day in which chemotherapy is administered. Also, checks by the medical staff such as pharmacists and nurses are required, complicating the administration of this therapy further. Taking this situation into consideration, our hospital uses a short-time premedication method wherein d-Chlorpheniramine Maleate injections are substituted for diphenhydramine hydrochloride tablets, and the time required for premedication is reduced to 15 minutes. This study investigated the allergic reaction ratio to consider the safety and usefulness of the short-time premedication method used at our hospital. The chemotherapy regimens conducted for the subject patients were 9 cases of PTX+CBDCA, 6 cases of biweekly- PTX, and 5 cases of weekly-PTX. A total of 67 PTX injections were given, 15 of them being first-time administrations. The ratio of allergic/hypersensitivity reactions was 10.0%(2 cases in 20). The short-time premedication method using d-Chlorpheniramine Maleate injections did not display a significant difference from the conventional method used for prevention of allergic and hypersensitivity reactions. Also, since this method of medication proves useful for is easy for the patient, reduces treatment time, is safe, economical, and helps reduce the workload of doctors, pharmacists, and nurses.

Recommendations for reporting economic evaluations of haemophilia prophylaxis: a nominal groups consensus statement on behalf of the Economics Expert Working Group of The International Prophylaxis Study Group.

BACKGROUND: The need for clearly reported studies evaluating the cost of prophylaxis and its overall outcomes has been recommended from previous literature. OBJECTIVES: To establish minimal ''core standards'' that can be followed when conducting and reporting economic evaluations of hemophilia prophylaxis. METHODS: Ten members of the IPSG Economic Analysis Working Group participated in a consensus process using the Nominal Groups Technique (NGT). The following topics relating to the economic analysis of prophylaxis studies were addressed; Whose perspective should be taken? Which is the best methodological approach? Is micro- or macro-costing the best costing strategy? What information must be presented about costs and outcomes in order to facilitate local and international interpretation? RESULTS: The group suggests studies on the economic impact of prophylaxis should be viewed from a societal perspective and be reported using a Cost Utility Analysis (CUA) (with consideration of also reporting Cost Benefit Analysis [CBA]). All costs that exceed $500 should be used to measure the costs of prophylaxis (macro strategy) including items such as clotting factor costs, hospitalizations, surgical procedures, productivity loss and number of days lost from school or work. Generic and disease specific quality of lífe and utility measures should be used to report the outcomes of the study. CONCLUSIONS: The IPSG has suggested minimal core standards to be applied to the reporting of economic evaluations of hemophilia prophylaxis. Standardized reporting will facilitate the comparison of studies and will allow for more rational policy decisions and treatment choices.

Cost-effectiveness of respiratory syncytial virus prophylaxis with palivizumab.

BACKGROUND: A monoclonal antibody, palivizumab, directed against respiratory syncytial virus (RSV) has been shown to decrease hospitalisation rates. Because of its expense, the cost-effectiveness of this agent should be determined for high-risk groups. AIM: To determine characteristics of RSV infection in Townsville and the economic feasibility of palivizumab immunoprophylaxis in high-risk groups. METHODS: Cases of RSV-positive bronchiolitis were retrospectively identified. Cases were grouped according to recognised risk factors. The hypothetical costs of palivizumab immunoprophylaxis for infants at risk were calculated. RESULTS: The rate of hospitalisation with RSV-positive lower respiratory tract infection was 22 per 1000 live births but increased to 50 per 1000 among Indigenous babies born weighing <2500 g. The cost of preventing an admission in each of the identified high-risk groups, based on drug costs alone, ranged from AD 69,861 to AD 88,547. CONCLUSION: Palivizumab was not cost-effective in the prophylaxis of RSV in the high-risk group of infants tested here.

Surgery for hemophilia in developing countries.

Surgical interventions in patients with hemophilia (PWH) in the developing world are difficult in the setting of limited availability of factor concentrates. Although the adequacy of international guidelines for factor concentrate prophylaxis for PWH undergoing surgery has been established, frequently it is not practical in the developing world. These recommendations were not established based on large clinical trials and fail to define the safe lower limit of factor concentrate prophylaxis for surgery. The need to define these lower limits is essential in the developing world so that the limited resources may be used optimally for the cohort of PWH. There are limited data from the developing world with regard to PWH undergoing surgical procedures. In this article, we outline experience from our institution, a tertiary referral center for hemophilia care in India. We trace the basis on which our current factor concentrate prophylaxis regimen (which is lower than that recommended internationally) was established. In our experience our low-dose protocols are effective, reduce factor consumption by one third, and are not associated with a significantly increased risk of delayed hemorrhage. We hope that this experience will form a framework on which guidelines can be established for developing countries.

A randomised controlled trial of microwave endometrial ablation without endometrial preparation in the outpatient setting: patient acceptability, treatment outcome and costs.

OBJECTIVE: To compare outpatient microwave endometrial ablation (MEA) in the postmenstrual phase to standard MEA treatment after drug preparation in a day case theatre environment. DESIGN: A randomised controlled trial. SETTING: A large United Kingdom teaching hospital. POPULATION: Two hundred and ten women complaining of excessive menstrual loss. METHODS: Two hundred and ten women with excessive menstrual loss were randomised. Ninety-seven women were treated as outpatients in the immediate post-menstrual phase and 100 were treated in an operating theatre after hormonal preparation. All procedures were commenced under local anaesthesia with or without conscious sedation. Analysis was by modified intention to treat. MAIN OUTCOME MEASURES: Primary outcome measures were satisfaction with treatment (measured at one year) and acceptability of treatment (measured at two weeks). Secondary outcome measures were menstrual outcome and financial cost. RESULTS: Significantly more women found treatment post-menses acceptable; 86 (89.5%) versus 76 (76.0%) [difference in proportions 13.6%, 95% CI (3.0%, 23.9%)]. Similar numbers in each arm were totally or generally satisfied with the treatment, 86 (92.5%) versus 84 (88.4%) [difference in proportions 4.1%, 95% CI (-4.7%, 12.9%)] while amenorrhoea rates at one year were comparable, 52 (55.9%) versus 60 (61.9%). [difference in proportions -5.9%, 95% CI (-19.8%, 7.6%)]. The mean health service costs were 124 pounds (95% CI 86-194 pounds) lower for the patients in the post-menses group. CONCLUSION: MEA performed under local anaesthesia (with or without conscious sedation) in the post-menstrual phase achieves high levels of satisfaction is very acceptable to patients and results in significantly reduced health service costs. Importantly menstrual outcomes are not affected by omission of drug preparation. There is now good evidence to support the use of MEA, without drug endometrial preparation, in the outpatient setting.

Pharmacologic prophylaxis for postoperative atrial tachyarrhythmia in general thoracic surgery: evidence from randomized clinical trials.

BACKGROUND: Atrial tachyarrhythmia is the most common complication after general thoracic surgery and is associated with significant morbidity, longer hospital stay, and higher costs. We sought to determine whether the use of antiarrhythmic medications is associated with a reduced rate of postoperative atrial tachyarrhythmia. METHODS: MEDLINE, EMBASE, Cochrane Database of clinical trials (1980-2003), and reference lists of relevant articles were searched for randomized controlled trials with placebo control, general thoracic patients, and noncombined and prophylactic use of the medications. Search, data abstraction, and analyses were performed and confirmed by at least 2 authors. A fixed-effects model was used to perform meta-analyses. RESULTS: There were 11 unique trials (total n = 1294) that met the inclusion criteria. Calcium-channel blockers and beta-blockers reduced the risk of atrial tachyarrhythmia in 4 and 2 trials, respectively (relative risk of 0.50 and 95% confidence interval of 0.34-0.73; relative risk of 0.40 and 95% confidence interval of 0.17-0.95, respectively). However, beta-blockers tended to increase the risk of pulmonary edema (relative risk, 2.15; 95% confidence interval, 0.74-6.23). Magnesium tested in one unblinded trial also reduced the risk of atrial tachyarrhythmia (relative risk, 0.4; 95% confidence interval, 0.21-0.78). On the other hand, digitalis preparations were found to be harmful because they increased the risk of atrial tachyarrhythmia in 3 trials (relative risk, 1.51; 95% confidence interval, 1.00-2.28). Finally, 2 other medications, flecainide and amiodarone, were each tested in a single small trial, and their effects were associated with great uncertainty. CONCLUSIONS: Calcium-channel blockers and beta-blockers are effective in reducing postoperative atrial tachyarrhythmia. The use of these medications should be individualized, and possible adverse events of beta-blockers should be taken into account. Randomized clinical trials do not support the use of digitalis in general thoracic surgery. The value of magnesium as a supplement to a main prophylactic regimen should be explored.

[Surgery in patients with bleeding disorders--expensive treatment for a small group of patients]. / Kirurgi ved alvorlig blødersykdom--kostbar behandling til en liten pasientgruppe.

BACKGROUND: During surgical procedures, patients with bleeding disorders have a major risk of bleeding complications. To reduce the risk of bleeding it is necessary to provide pre-, peri- and postoperative antihaemorrhagic therapy. In less severe bleeding disorders, pharmacologic treatment may be sufficient, but in patients with severe bleeding disorders there is always a need for clotting factor concentrates. MATERIALS AND METHODS: This study includes all patients with bleeding disorders admitted to Rikshospitalet University Hospital between 1997 and 2003 for surgical procedures during which therapy with clotting factor concentrates was mandatory. RESULTS AND INTERPRETATION: Over the study period, 135 patients underwent a total of 255 different surgical procedures. In 47% of the patients there was a causal relationship between the need for surgery and the bleeding disorder. Our results show that patients with severe bleeding disorders, including patients with inhibitors, can be treated safely provided that the patients receive adequate treatment with clotting factor concentrates. However, substitution therapy with clotting factor concentrates is very expensive. Cost related to substitution therapy is the main determinant of how many patients with severe bleeding disorders can undergo elective surgery in our hospital each year.