Pharmacoeconomic aspects of treatment of acute myocardial infarction with thrombolytic agents

Thrombolytic therapy reduces early mortality, preserves left ventricular function and improves long term prognosis of acute myocardial infarction. However it is relatively expensive and increasing use will have considerable financial consequences. With competing demand for health resources, information on economic evaluation of this revolutionary therapeutic modality is much needed. Economic evaluation of thrombolytic therapy of acute myocardial infarction entails the assessment of all resources consumed (costs) directly and indirectly in relation to the administration of thrombolytic drugs, versus the beneficial effects (outcome) on health preservation of the patients. To save 1 year of life, the costs of thrombolytic therapy using intravenous streptokinase, alteplase (recombinant tissue plasminogen activator; rt-PA) or anistreplase (anisoylated plasminogen streptokinase activator complex) under standard restricted indication criteria, vary from 1000 pounds British sterling to 1700 pounds British sterling in the UK, SEK3090 to 9660 in Scandinavia and $US35 000 to 800 000 in the US, depending on time delay in starting treatment after pain onset, size of infarct, thrombolytic agents used, study methodology, lists of clinical events considered in cost counting and the discount rate. Cost-utility analyses revealed that the costs of thrombolytic treatment are similar to those of many other treatments for cardiac or other diseases, but methods for evaluating quality of life and utility require further refinement and validation. Economic assessments confirm that thrombolytic treatment of the elderly ( greater than 70 years) is as cost-effective as treatment of younger patients and that both early and late thrombolytic therapy (given 6 to 12 hours after infarction) are beneficial and cost-effective. There are major logistical problems with prehospital thrombolysis, which despite great initial enthusiasm, is unlikely to be cost-effective in saving lives unless savings in time are greater than 1 hour. Cost-effectiveness/utility value of one drug determined from one study cannot be directly compared with that found in other studies using different drugs. More direct prospective comparative trials will be needed in respect of relative benefits and costs with different agents and adjunctive therapies.     

溶血栓药物在急性脑梗死中的应用进展

脑梗死是导致人类致残和死亡的主要疾病之一,在发生脑梗死的超急性期,积极给予溶栓治疗,开通闭塞的血管,恢复缺血区的再灌注是治疗的关键。目前只有重组组织型纤溶酶原激活剂(rt-PA)被FDA批准应用于急性脑梗死的溶栓治疗,其他的许多药物如瑞替普酶,替奈普酶,去氨普酶、安克洛酶等在脑梗死治疗应用方面正在探索中。本文将针对上述几种主要的溶血栓药物及其已经开展的相关临床研究进行论述。     

Antithrombotic trials in acute ischaemic stroke: a selective review

Stroke is a common cause of morbidity and mortality throughout the US and the world. Given the highly disabling nature of this disease, it is important to provide acute therapy when indicated to improve individual outcomes. Recombinant tissue plasminogen activator (rt-PA) is, at present, the only approved drug for the treatment of acute strokes due to cerebral ischaemia. It can be given intravenously within a 3-h window of the onset of neurological deficits. Intra-arterial administration of rt-PA within a 6-h window is performed at several academic centres in patients with middle cerebral and other intracranial artery occlusions based on results of a randomised clinical trial. Other thrombolytic agents are being studied in randomised trials. Although acute therapy of ischaemic stroke has received much attention since the approval of rt-PA, only a small percentage of individuals actually receive rt-PA. This article will review the main thrombolytic agents and the trials performed thus far, as well as examine some important ongoing trials. How administration of acute thrombolytic therapy may evolve in the future will also be addressed.     

Echinocandins in the treatment of candidaemia and invasive candidiasis: clinical and economic perspectives

Candidaemia and invasive candidiasis (IC) complicate modern medical therapy, contributing to high morbidity and mortality. Managing candidiasis is costly, with an additional healthcare expenditure of nearly US$300 million annually. Recent consensus guidelines have suggested the use of newer antifungal agents, such as echinocandins, for the treatment of candidaemia and IC owing to promising clinical outcomes compared with older-generation antifungal agents, but at higher drug acquisition and administration costs. Comprehensive cost-effectiveness data for echinocandins in treating candidaemia and IC remain relatively scant, underlining the need for more studies to incorporate robust economic analyses into clinical decisions. Assessment of the cost efficiencies of these expensive antifungal agents is essential for maximising health outcomes within the constraints of healthcare resources. This review will explore the epidemiology of candidaemia and IC in the context of clinical and economic aspects of the antifungal agents used to treat IC, especially the echinocandins. Standardising the outcome measure, methodology and reporting of results used in economic studies is central to ensure validity and comparability of the findings. Future studies comparing the economic advantages of all available antifungal treatment options and in the context of new diagnostic tools for fungal infections are anticipated.     

The role of cost-effectiveness analysis in the era of pharmacogenomics

The broad availability of genetic information and technologies heralds an era when practitioners will utilise genomic testing to individualise patients' care. Pharmacogenomics uses a spectrum of approaches to explore the association of genetic variation with drug efficacy or toxicity. Investigators have described a broad array of genetic polymorphisms that confer inter-individual differences in drug response. Pharmacogenomics offers the potential to improve drug effectiveness, reduce adverse drug reactions and provide cost-effective care. However, it has had little impact on current clinical practice and the economic implications of pharmacogenomics remain unclear. Assessing the incremental cost effectiveness of a pharmacogenomic strategy involves examination of factors associated with the genotype of interest, the genomic test, the disease state and the treatment. A pharmacogenomic strategy is likely to be cost effective when: (i) the polymorphism under consideration is prevalent in the population and has a high degree of penetrance; (ii) genetic testing is highly sensitive and specific, and less costly alternative tests that could be used to individualise therapy are not readily available; (iii) the disease state involves outcomes with significant morbidity or mortality if left untreated; and (iv) the treatment involves significant outcomes and/or costs that can be impacted by genotype-individualised therapy. We foresee pharmacogenomic applications being particularly relevant for drugs: with a narrow therapeutic index or a high degree of variability in inter-individual response; where there are limitations in current methods for monitoring their adverse effects and treatment responses; and where there are few alternative treatment options. Because of the characteristics of chemotherapeutic agents and the severity of clinical outcomes in cancer, oncology appears to be one of the most appropriate disease areas for the application of pharmacogenomics. We have developed a framework which can assist researchers, pharmacists, physicians, and policy makers in evaluating the implications of specific strategies, and identifying when formal cost-effectiveness analyses should be conducted to quantitatively evaluate the benefits of pharmacogenomics.     

影响急性缺血性脑卒中溶栓治疗预后的因素

溶栓治疗是改善急性缺血性脑卒中患者临床预后的有效治疗方法 ,但同时有再灌注损伤、症状性颅内出血、血管再闭塞等并发症,且起病至溶栓治疗时间、神经功能缺损程度、患者年龄、溶栓药物剂量、高血压、糖尿病、抗血小板药物等因素均可能增加溶栓并发症的发生及影响临床预后,在临床应用时应充分考虑影响预后的各种因素,以此指导溶栓治疗。现将临床常见影响溶栓治疗预后的因素进行综述。     

Clinical pharmacy, pharmaceutical care, and the quality of drug therapy

BACKGROUND: Because of concerns about patient safety and the quality of health care in America, in particular about drug therapy, pharmacists have unprecedented opportunities to increase their value and significance. When defining clinical pharmacy and pharmaceutical care, pharmacists long ago recognized the need to improve the safety and effectiveness of drug therapy. OBJECTIVE: To describe how clinical pharmacy and pharmaceutical care, closely related concepts, can contribute to a strategy for improving the quality of drug therapy. DESIGN: Commentary and review of selected publications. CONCLUSION: Pharmacists can improve the quality of drug therapy by improving the organizational structures through which drug therapy is provided, specifically by creating medications use systems and by regularly evaluating their performance. As envisaged by the Institute of Medicine, these systems must be patient centered, cooperative, and interprofessional. To maximize pharmacists' participation in such systems, pharmaceutical education should include courses in medications use systems as necessary counterparts to courses in pharmacotherapeutics. Clinical functions must be organized around patient need and directed at outcomes. Clinical practice should constitute the mainstream practice of pharmacy rather than an "optional" specialty. Pharmaceutical care describes the original purpose of clinical pharmacy, when it was understood as a professional practice rather than a health science. It describes a way that clinical pharmacy, especially specialists and subspecialists, could coordinate their work more effectively. The concept of clinical pharmacy adds essential clarity about the process component of pharmacists' participation in, and strengthens the academic basis of, pharmaceutical care. The clinical, humanitarian, and economic case for preventing drug-related morbidity is strong, and pharmacy has much to offer. It is, again, time to work together as a profession to plan our common future.     

Clinical monograph for drug formulary review: systemic agents for psoriasis/psoriatic arthritis

BACKGROUND: Significant advances in the pharmacologic treatment of psoriasis, most notably the introduction of the biologic agents efalizumab and alefacept, have occurred recently. In addition, another biologic agent, etanercept, was recently approved for the treatment of psoriasis and psoriatic arthritis, thus adding to the list of biologic agents approved for the treatment of these disease states. A review was conducted by the Drug Information Service of a pharmacy benefits manager (PBM) to determine the relative merits and place in therapy of commonly used systemic agents for the treatment of psoriasis and psoriatic arthritis. OBJECTIVE: To provide readers with a comprehensive clinical monograph on psoriasis and psoriatic arthritis agents, written with a managed care perspective, as used in actual drug formulary decision making by a PBM. METHODS: The drug formulary of this PBM is designed to provide health plans with an evidence-based review of drugs, therapeutic classes, and disease states with a managed care focus. For each therapeutic class or disease review, an extensive and thorough literature search of MEDLINE is conducted for efficacy, safety, effectiveness, and humanistic and economic data. Drug/disease-state databases (UpToDate online, MICROMEDEX), U.S. Food and Drug Administration clinical reviews, key Internet sites, medical/pharmacy-related news sites, clinical guidelines, and AMCP dossiers are also reviewed. Formulary drug monographs produced by the Drug Information Service of the PBM include a critical analysis and summary of disease-oriented and patient-oriented clinical outcomes, effectiveness, and humanistic data. Additional data considered and included in the formulary review process are clinical attributes, patent expirations/generic competition, off-label or pending indications, and pharmacoeconomic data. RESULTS: The biologic agents do not appear to be as efficacious as traditional systemic therapies but are associated with fewer long-term toxicities that often limit treatment duration with traditional systemic agents. Although no head-to-head comparisons between alefacept and efalizumab exist, efalizumab appears to offer slightly higher efficacy rates, while alefacept has a longer duration of action. Etanercept at the higher approved dose appears more efficacious compared with efalizumab or alefacept for the treatment of psoriasis, and it is the only biologic currently approved for the treatment of psoriatic arthritis. Efalizumab and alefacept are generally well tolerated, but rebound flare of psoriasis is associated with efalizumab, thus requiring continuous treatment to avoid a flare in disease. Efalizumab and etanercept can be self-administered by the patient, while alefacept and infliximab require administration by a health care professional. CONCLUSIONS: Systemic therapy is reserved for patients with moderate-to-severe psoriasis or patients with psoriatic arthritis. The biologic agents are not as efficacious as traditional therapies but, due to better tolerability, are gaining acceptance in the treatment of psoriasis and psoriatic arthritis. The biologic agents differ in efficacy rates and are generally well tolerated. Clinical attributes, overall efficacy, and economic costs associated with the biologic agents will be significant factors in selecting agents for the treatment of psoriasis and psoriatic arthritis.     

儿科临床药师参与1例病毒性脑炎并发细菌真菌感染药物治疗案例分析

目的:探讨临床药师在儿科药物治疗中的作用。方法:描述患儿病程发展和药物治疗及转归情况,分析病毒性脑炎的初始治疗方案、呼吸机相关肺炎的抗感染治疗及持续静脉给药的药学监护要点。结果:通过临床药师在患儿癫痫持续状态、细菌真菌感染治疗过程中提供的合理用药建议,有利于有效评估和处置治疗过程中出现的药品不良反应。结论:儿科临床药师参与医疗团队,协助医师确定、调整药物治疗方案,可及时处理药品不良反应,有利于提升药物治疗效果。     

Current issues in the management of hypertension

Major trials evaluating antihypertensive therapy are reviewed, and the current issues surrounding the choice of therapy in mild and isolated systolic hypertension are discussed. Several major trials have shown that patients with mild hypertension benefit from therapy. These results have prompted widespread use of antihypertensive agents; however, there are still no clear guidelines on when drug therapy should be initiated. Only the Hypertension Detection and Follow-up Program has shown significant decreases in coronary heart disease (CHD) related deaths. Thiazide diuretics are recommended as agents of first choice in the stepped-care approach to the management of uncomplicated mild to moderate hypertension. The Multiple Risk Factor Intervention Trial evaluated the effects of modifying several cardiovascular risk factors in more than 12,000 high-risk men. It failed to document significant differences in CHD-related mortality in patients who received special care as compared with those who received usual care. Concerns have been raised about the contribution of antihypertensive therapy, particularly diuretics, to the lack of differences in therapeutic outcomes. There is renewed interest in lipid alterations secondary to antihypertensive agents and the effect of diuretic-induced hypokalemia. Antihypertensive therapy should be instituted with an individualized assessment of the potential benefits of therapy relative to the short- and long-term risks of treatment.     

Cost effectiveness of three drugs for the treatment of S. aureus infections in Nigeria

Background Resistance of microorganisms to existing antimicrobial agents threatens the effective utilization of available resources in sub-Saharan Africa. Cost-effective utilization of antibacterial agents is essential in effective health care delivery in Nigeria. Objectives To determine the most cost effective antibacterial agent in the treatment of S. aureus infections in Lagos metropolis. Setting The study was carried out in a teaching hospital, a specialist hospital, a referral center and two private hospitals. Methods Cost effectiveness analysis of ciprofloxacin, cefuroxime and gentamicin identified to be most effective agent against 463 clinical isolates of S. aureus obtained from the five hospitals was carried out on the basis of societal, health care and third party perspectives using 'decision table" as an analytical model. Criteria considered in the model included degree of efficacy of the agents, adherence tendencies and tolerability. Both direct (cost of drugs, diagnosis/monitoring, personnel and transportation) and indirect (loss of productivity) costs were evaluated. Main outcome measures These include economic outcome as total therapy cost, clinical outcomes as extent of antibacterial effectiveness obtained from degree of antibacterial efficacy, a proxy measurement of cure rates, and adherence tendency. Humanistic outcome was also measured as tolerability prorated from literature reported degree of adverse drug reactions events, risk of infection and pains from drug administration. Results Ciprofloxacin tablet is a dominant option and much more cost-effective than either cefuroxime or gentamicin in the treatment of S. aureus in Lagos. Regardless of the perspective of analysis, ciprofloxacin has the least cost effectiveness ratio of NGN4214.66 ($28.09), NGN2392.63 ($16.00) and NGN2048.66 ($13.65) from societal, health care and third party payer perspectives, respectively. Sensitivity analysis by increasing the effectiveness index of gentamicin injection-the least cost effective option to the value for the most cost effective option did not change the results. Conclusion Ciprofloxacin should be used as first-line-treatment of S aureus in Lagos as it will lead to significant cost savings in the treatment of S. aureus infections.     

Evaluating the economic consequences of early antidepressant treatment discontinuation: a comparison between controlled-release and immediate-release paroxetine

INTRODUCTION: Early antidepressant discontinuation has been linked to significant clinical and economic consequences. Clinical practice guidelines suggest that treatment should last for at least 3 to 9 months into the continuation phase; however, 30% of patients discontinue therapy within 30 days, and over 40% discontinue therapy within 90 days of initiation, primarily due to adverse events. Clinical trials have shown that controlled-release (CR) paroxetine has a favorable tolerability profile when compared to immediate-release (IR) paroxetine, which may result in lower discontinuation rates and improved economic outcomes. This is the first study to directly compare treatment discontinuation rates and health care expenditures of a CR selective serotonin reuptake inhibitors with its IR counterpart. METHODS: This matched retrospective study used claims from a national managed care database to assess differences in discontinuation rates and health care expenditures between paroxetine CR and IR for treating depression and/or anxiety. Discontinuation was assessed by survival analysis, and health care expenditure was assessed using average monthly medical and pharmacy charges. RESULTS: There were 1275 paroxetine CR patients and 2550 paroxetine IR patients matched in the analysis. At 90 days, 62% of paroxetine CR patients continued therapy versus 56% of paroxetine IR patients. At 180 days, 51% of paroxetine CR patients continued therapy versus 42% of paroxetine IR patients. When evaluating all medical charges, paroxetine CR patients incurred US 119 dollars less per month than paroxetine IR patients (P = 0.054). CONCLUSIONS: Patients receiving paroxetine CR remained on therapy longer than patients on paroxetine IR, which resulted in lower total monthly medical costs for patients receiving paroxetine CR. Differences in costs were primarily driven by reduction in hospitalization expenditures.     

抗癫痫药的药物经济学研究进展

癫痫为慢性发作性疾病,需长期坚持药物治疗,抗癫痫药物治疗是癫痫治疗的主要手段,并取得了良好临床疗效.治疗过程中,在保证疗效的前提下,同时如何尽可能地为病人节省费用是一大难题,故经济因素也常常影响抗癫痫药的选择.随着新型抗癫痫药物在临床中的广泛应用,为选择治疗药物提供优良备选方案和应用思路.本文旨在对抗癫痫药物进行药物经济学评价,为临床合理用药提供参考.     

Pathophysiology and treatment of deep-vein thrombosis and pulmonary embolism

The pathophysiology of deep-vein thrombosis (DVT) and pulmonary embolism (PE) is briefly discussed, and the efficacy, dosage and administration, laboratory monitoring, and adverse effects of thrombolytic agents, heparin, and warfarin are reviewed. Acute therapy of DVT and PE is usually initiated with intravenous heparin; however, thrombolytic agents such as streptokinase and urokinase may be preferred in patients with massive PE or severe DVT when clot lysis rather than clot stabilization is deemed necessary. For DVT or PE, an intravenous loading dose of streptokinase or urokinase is given, followed by a continuous infusion of the drug. Therapy with streptokinase is continued for 24 hours in patients with PE and for 72 hours in those with DVT; urokinase is continued for 12 hours in patients with PE. Monitoring of blood coagulation tests during thrombolytic therapy is recommended primarily for ensuring that a lytic state is achieved. Intravenous heparin is preferred for acute treatment of DVT or PE; controversy exists regarding whether administration by continuous infusion or intermittent bolus injection is superior. Heparin dosage is usually adjusted to maintain the activated partial-thromboplastin time (APTT) ratio between 1.5 and 2.5; however, the ideal therapeutic range has never been firmly established. After acute treatment with heparin, most patients should continue to receive either warfarin or subcutaneous heparin for several months to prevent recurrent thromboembolism. Bleeding is the major adverse effect of thrombolytic agents and anticoagulants. The risk of bleeding with heparin and warfarin therapy increases with excessive prolongation of the APTT and prothrombin time (PT), respectively. Future clinical trials should further define the role of thrombolytic agents in the treatment of DVT and PE and the efficacy of less-intense warfarin therapy for pulmonary embolism or arterial thromboembolic events.     

Outcome assessment of pain: functional status measures and quality of life as therapeutic endpoints

These studies and others will provide tools for cancer treatment centers to integrate pain management into comprehensive care strategies. Pharmacists in all health care settings where the cancer patient with pain is being treated should take leadership roles in the improvement of therapeutic outcomes. This leadership is essential, because drug therapy remains the mainstay of palliation.     

Treatments for behavioural disorders in neurodegenerative diseases: drug development strategies

Neuropsychiatric symptoms and behavioural alterations are common in neurodegenerative diseases, and effective treatment of these changes represents an important unmet public health need. Imaging, neuropathological, neurotransmitter and molecular genetic studies increasingly identify specific mechanisms that mediate behavioural changes in neurodegenerative disorders and provide a platform for seeking effective therapeutic interventions. Measuring behavioural outcomes in clinical trials of antidementia agents represents an important means of evaluating treatment effectiveness, and clinical trial methodologies and behavioural instrumentation are evolving to facilitate drug development in this important therapeutic target area.     

A short term cost-effectiveness model for oral antidiabetic medicines in Europe

A short term (6-month) cost-effectiveness model has been developed to simulate current medical practice and disease progression in patients with type 2 (non-insulin-dependent) diabetes mellitus uncontrolled by diet and exercise. The model is based on decision-analytical techniques and includes probabilities of switching between treatments, the reason for the switch and the most common switch options. Effectiveness and economic measures are the 2 main outcomes. In order to assess effectiveness, we use symptom-free days with acceptable control (SFDACs), which represent each day of treatment without adverse events or symptoms, and with acceptable control of glucose and lipids. For the economic evaluation, only incremental costs incurred directly by a health insurance system are considered. This model should prove useful in the evaluation of new oral antidiabetic agents, since the short term aim of antidiabetic therapy is to provide adequate control in the absence of adverse effects and symptoms (a prerequisite for successful long term treatment). Furthermore, short term analysis provides data for comparing initial investment in drug therapy with potential savings over a longer treatment period.     

顽固性心绞痛治疗进展

顽固性心绞痛是指传统的抗心绞痛药物均无效 ,又不适合做冠状动脉内介入治疗和冠脉搭桥术的心绞痛。新的药物治疗 (新的抗血小板药物、低分子肝素、溶栓药物、抗心肌缺血的代谢疗法 )、神经刺激、增强的体外反搏、激光血管重建术、基因治疗、经皮穿刺心肌静脉动脉化、心脏移植代表了目前顽固性心绞痛治疗上的新的探索     

Impact of Parkinson's disease and its pharmacologic treatment on quality of life and economic outcomes.

The impact of Parkinson's disease (PD) and its pharmacologic treatment on health-related quality of life (HRQL) and economic outcomes is reviewed. PD is a chronic and progressive neurologic disorder characterized by specific motor deficits resulting from the degeneration of dopaminergic neurons in the substantia nigra. The cardinal symptoms are tremor, rigidity, bradykinesia, and loss of postural reflexes. PD markedly reduces HRQL and places an economic burden on society of up to $25 billion per year. Patients' inability to move freely and to perform everyday tasks restricts their independence and leads to increased reliance on caregivers and assistive devices. Emotional and psychosocial well-being is also negatively affected. As the disease progresses, the response to levodopa typically decreases and various motor complications develop; these are difficult to treat and result in further declines in HRQL. The economic costs of PD include both direct health care costs (for drugs, physician services, and hospitalization) and indirect costs (for lost worker productivity). Economic analyses of PD and its treatments can help guide effective allocation of health care resources. Various antiparkinsonian agents and formulations, such as extended-release levodopa-carbidopa and pramipexole, have been found to be cost-effective relative to other agents. The newest antiparkinsonian drugs, cathechol-O-methyltransferase inhibitors, also have the potential to improve HRQL and economic outcomes, although more study is needed to confirm this. The total impact of PD and its treatment can be fully appreciated only when HRQL and economic outcomes, in addition to clinical outcomes, are examined.     

A Case for Enhanced Linkage of Substance Abusers to Primary Medical Care

Abstract

Alcohol and drug abuse continue to be problems of major significance throughout the United States. Although experts have advocated linking substance abusers with primary medical care to help achieve both individual and public health goals, few successful and generalizable methods for linkage have been developed. Specific potential benefits for such linkage include HIV testing and initiation of therapy, treatment of tuberculosis and sexually transmitted diseases, appropriate immunizations, cervical cancer screening, promotion of healthy behaviors regarding sexual and drug practices, and encouragement of cessation of substance use. Distributive or decentralized models linking patients receiving addiction treatment to existing primary medical care services need evaluation, as they may be more generalizable and cost-effective compared with on-site integrated programs. Health care providers and policy makers need to explore innovative approaches to bring substance abusers into a medical care system in a way that will provide continuity, comprehensiveness, and prevention so as to improve health care utilization patterns and reap benefits of improved addiction, behavioral, and health outcomes.