Establishing the Cost-Effectiveness of New Pharmaceuticals under Conditions of Uncertainty—When Is There Sufficient Evidence?

Decisions about which health-care interventions represent adequate value to collectively funded health-care systems are as widespread as they are unavoidable. In the case of new pharmaceuticals, many countries now require formal cost-effectiveness analysis to inform this decision-making process. This requires evidence on parameters associated with health-related utilities, treatment effects, resource use, and costs, for which data from available regulatory trials are invariably absent or highly uncertain. This uncertainty results from a number of factors including the predominance of intermediate end points in the clinical evidence-base and the limited period of follow-up of patients in clinical studies. Despite these imperfections in the evidence base, decisions about whether new pharmaceuticals are sufficiently cost-effective for reimbursement cannot be side-stepped. Data limitations do, however, require the use of rigorous analytical methods to support decision making. Probabilistic decision models and value of information analysis offer a means of structuring decision problems, synthesizing all available data, characterizing the uncertainty in the decision, quantifying the cost of uncertainty, and establishing the expected value of perfect information. This analytical framework is important because it addresses two fundamental questions about new pharmaceuticals. First, is the product expected to be cost-effective on the basis of existing evidence? Second, is additional research concerning the product itself cost-effective? In addressing these questions, the analytical framework can establish when sufficient evidence exists to sustain a claim for a new pharmaceutical to be cost-effective.     

Association analysis of genes in the renin‐angiotensin system with subclinical cardiovascular disease in families with Type 2 diabetes mellitus: The Diabetes Heart Study

Aims Cardiovascular disease (CVD) is a major complication of Type 2 diabetes mellitus. The renin‐angiotensin system (RAS) and nitric oxide production are both important regulators of vascular function and blood pressure. Genes encoding proteins involved in these pathways are candidates for a contribution to CVD in diabetic patients. We have investigated variants of the angiotensinogen (AGT), angiotensin converting enzyme (ACE), angiotensin type 1 receptor (AT1R) and endothelial nitric oxide synthase (NOS3) genes for association with subclinical measures of CVD in families with Type 2 diabetes mellitus (T2DM). Methods Atherosclerosis was measured by carotid intima‐media thickness and calcification of the carotid and coronary arteries in 620 European Americans and 117 African Americans in the Diabetes Heart Study. Because of the role of these systems in blood pressure regulation, blood pressure was also investigated. Results Compelling evidence of association was not detected with any of the SNPs with any outcome measures after adjustments for covariates despite sufficient power to detect relatively small differences in traits for specific genotype combinations. Conclusions Genetic variation of the RAS and NOS3 genes do not appear to strongly influence subclinical cardiovascular disease or blood pressure in this diabetic population.     

Development of the Qualeffo–31, an osteoporosis-specific quality-of-life questionnaire

Introduction Vertebral deformities are a common consequence of osteoporosis and are known to decrease quality of life. The Qualeffo–41 is a quality-of-life questionnaire especially developed for measuring quality of life in patients with vertebral deformities. It consists of 41 questions arranged in five domains: pain, physical function, social function, general health perception, and mental function. The objectives of this study were: (1) to develop a shorter version of the Qualeffo–41 by removing redundant questions; and (2) to investigate the scale characteristics, reliability, and validity of this shorter version. Methods The study was performed using data from the Qualeffo validation study and the Multiple Outcomes of Raloxifene Evaluation (MORE) study. The analyses were performed in patients with vertebral deformities (n=579). Factor analysis on polychoric correlations and an item response theory (IRT) model, i.e., the generalized partial credit model (GPCM), were used to create a shorter version of Qualeffo–41. Using GPCM, scoring weights were computed for all items. Results Three items were removed from the data set because of too many missing values. Factor analysis identified three instead of five domains: (1) pain, (2) physical function, and (3) mental function. Five items had factor loadings <0.4 and were not included in the GPCM. After excluding several items, the domains pain (four items), physical function (18 items), and mental function (nine items) showed a good, reasonable, and excellent fit, respectively. This indicates that the mental function domain and the pain domain are more unidimensional than the physical function domain. All three domains showed a very high correlation (r ≥0.95) with the corresponding domains of the Qualeffo–41. Conclusions Qualeffo–31 was developed, consisting of three domains with a reasonable to excellent fit to the GPCM. Although the fit to the GPCM supports the construct validity of the Qualeffo–31, validation in a new study should be performed before using it in practice.     

运用市场手段实现医药自然分开的理论探讨

回顾了韩国、我国台湾和大陆实行医药分开改革的过程,认为我国以往的相关改革陷入了“管制”的思维误区。认为通过制度设计,创造医疗机构门诊处方自由流动的环境,依靠市场竞争形成处方流向结构多元化,可以实现医药自然分开状态。提出了“医药自然分开”、“处方流向结构”和“处方分散度”等新概念。     

Linear atrophoderma of Moulin together with leuconychia: a case report

Linear atrophoderma of Moulin has a distinctive disease pattern characterized by hyperpigmented atrophoderma and was described originally in 1992. It follows the line of Blaschko, and occurs without preceding inflammation, subsequent induration or scleroderma. The lesions usually develop during childhood or adolescence, and the prognosis is good. The diagnosis is made clinically and histopathologically. In our 18-year-old male patient, there were atrophic plaques unilaterally located on the trunk and arm, and white discoloration on all finger nails. Histopathological examination revealed epidermal atrophy together with disruption of collagen fibres.     

Reviewing the definition of "elderly"

Conventionally, "elderly" has been defined as a chronological age of 65 years old or older, while those from 65 through 74 years old are referred to as "early elderly" and those over 75 years old as "late elderly." However, the evidence on which this definition is based is unknown. We have attempted to review the definition of elderly by analyzing data from long-term longitudinal epidemiological studies, and clinical and pathological studies that have been accumulated at the Tokyo Metropolitan Geriatric Hospital and the Tokyo Metropolitan Institute of Gerontology. Our recommendation might be a starting point in developing a strategy for a successful society by reviewing the definition of elderly based on comprehensive evidence in all aspects of social, cultural and medical sciences.     

The effects of altering time delays of coupled pacing during acute atrial fibrillation

BACKGROUND: Coupled pacing (CP), which consists of delivering a premature electrical stimulation to the heart after the effective refractory period of ventricular activation, is a novel method for controlling ventricular rate during atrial fibrillation (AF). It also has been established that CP improves pump function by enhancing external cardiac work and myocardial efficiency. OBJECTIVE: The purpose of the present study was to determine if two time delays for CP (short and long) would result in similar improvements in ventricular function. METHODS: In a canine model, we applied CP at two time delays (CP-S and CP-L) during two stages: sinus rhythm (SR) and acute AF. The cardiac responses to CP during SR served as the nontachycardic and nondepressed control. During both rhythms, we shortened the coupling interval until we obtained maximal contractility, designated CP-S. Next, we increased the delay until we started to see a measurable secondary contraction (left ventricular pressure development of approximately 20 mmHg). These longer delays were designated CP-L. RESULTS: Our results showed that the ventricular rate of intrinsic activation (VRIA) remained decreased despite prolongation of the time delay of CP during both AF and SR. Also, both delays of CP increased left ventricular systolic pressure (LVSP) and dLVP/dt, which are indices of myocardial contractility. In contrast, CP increased external cardiac work only during AF. Prolonging this time delay did not markedly decrease the improvement in external cardiac work. Myocardial O(2) consumption (MVO(2)) did not significantly change as the result of CP during either SR or AF. Finally, myocardial efficiency improved during AF as the result of CP at both time delays. CONCLUSIONS: In conclusion, shorter time delays for CP increased contractile strength during both SR and AF. However, extending the time delay of CP had minimal effects on diminishing the improved ventricular pump function and energetics that resulted from CP during AF. Thus, the maximal enhancement of myocardial contractility via CP-S was not needed to maintain the improved ventricular function during acute AF when CP is applied.     

单亲大学生心理健康状况及心理问题的教育对策研究

目的针对单亲大学生心理健康问题提供有效的教育对策．方法针对大学新生开展16PF调查并发现单亲大学生的心理问题。结果本次测查共测量被试8302人，删除部分无效量表．实际有效数据为7742人，问卷有效率为93．27％．以一般情况问卷中“是否是单亲家庭子女”回答“是”的．作为单亲大学生的认定标准，检出单亲家庭子女555人，占总人数的7．17%，其中男生占40．0％．女生60．0％．17．5％的单亲出现各种心理问题．调查表明．单亲家庭子女与非单亲家庭子女相比，在乐群性和怀疑性两个因子有显着区别。事实上也表现为与正常大学生心理健康状况的显着差异。结论单亲大学生心理问题表现为：自卑心理、怀旧心理、逆反心理、猜疑心理等等。教育对策：加强社会教育系统、学校教育系统、家庭教育对单亲大学生心理的干预与影响，同时．单亲大学生遗要加强心理健康的自我教育．以多元系统帮助他们形成健全人格。     

胃癌术后残胃无力(附17例分析)

目的:探讨胃癌术后残胃无力的诊治及预防。方法:对1998年~2004年间284例胃癌术后出现的17(6%)例残胃无力患者进行回顾性研究。结果:残胃无力发生于术后6~15天,症状持续10~21天。经消化道造影确诊,用非手术方法治疗后症状全部消失。结论:消化道造影是可靠的诊断方法,非手术方法治疗效果肯定。