Alternative decision analysis modeling in the economic evaluation of tumor necrosis factor inhibitors for rheumatoid arthritis

OBJECTIVES: To provide a review of the studies that use decision models in the economic evaluation of tumor necrosis factor (TNF) inhibitors in rheumatoid arthritis (RA) and to address some important issues surrounding the choice of such modeling techniques in these economic evaluations. METHODS: A systematic literature search was conducted by 1 author from the literature published from January 1996 to March 2005 through Medline, Embase, and Cochrane library databases. RESULTS: The review yielded 29 studies that used decision models. Only 10 studies used a decision model in the economic analysis of the TNF inhibitors and were included in the final review. Decision model types included the following in the review articles: decision tree (2), Markov model (7), and discrete event simulation (1). These models vary in complexity and their choice depends on the course of disease, the impact of treatment, and the available data. CONCLUSIONS: Based on the results derived from alternative modeling techniques, it is safe to say that all methods can provide useful information with regard to economic evaluations of TNF inhibitors. Even though different modeling techniques provide an appropriate representation of available data, their results should be interpreted contingent on the input data, assumptions, sensitivity analyses, and other alternative scenario analyses. RELEVANCE: The transparency in the models will encourage end users such as policymakers and prescribers to make informed judgments regarding the appropriateness of the methods and the validity of the results.     

Endoscopic full-thickness plication for the treatment of gastroesophageal reflux disease: A randomized, sham-controlled trial

BACKGROUND & AIMS: The aim of this study was to determine the effectiveness of endoscopic full-thickness plication for the treatment of gastroesophageal reflux disease (GERD) in comparison with a sham procedure. METHODS: Patients with symptomatic GERD requiring maintenance proton pump inhibitor (PPI) therapy were entered into a randomized, single-blind, prospective, multicenter trial. Seventy-eight patients were randomly assigned to undergo endoscopic full-thickness restructuring of the gastric cardia with transmural suture. Eighty-one patients underwent a sham procedure. Group assignments were revealed following the 3-month evaluation. The primary end point was > or =50% improvement in GERD health-related quality of life (HRQL) score. Secondary end points included medication use and esophageal acid exposure. RESULTS: By intention-to-treat analysis, at 3 months, the proportion of patients achieving > or =50% improvement in GERD-HRQL score was significantly greater in the active group (56%) compared with the sham group (18.5%; P < .001). Complete cessation of PPI therapy was higher among patients in the active group than in the sham group by intention-to-treat analysis (50% vs 24%; P = .002). The percent reduction in median percent time pH < 4 was significantly improved within the active group versus baseline (7 vs 10, 18%, P < .001) but not in the sham group (10 vs 9, -3%, P = .686). Between-group analysis revealed the active therapy to be superior to the sham in improving median percent time pH < 4 (P = .010). There were no perforations or deaths. CONCLUSIONS: Endoscopic full-thickness plication more effectively reduces GERD symptoms, PPI use, and esophageal acid exposure than a sham procedure.     

Clinical effectiveness of neuraminidase inhibitors—oseltamivir,zanamivir, laninamivir,and peramivir—for treatment of influenza A(H3N2) and A(H1N1)pdm09 infection: an observational study in the 2010–2011 influenza season in Japan

The clinical effectiveness of the newly released neuraminidase inhibitors (NAIs) laninamivir and peramivir has not been sufficiently evaluated in influenza-infected patients in clinical and practical settings. In this study, we analyzed the clinical data of 211 patients infected with influenza A virus subtype H3N2 (A(H3N2)) and 45 patients infected with influenza A virus subtype H1N1pdm (A(H1N1)pdm09) who received the NAIs oseltamivir, zanamivir, laninamivir, or peramivir during the 2010-2011 influenza season. The duration of fever from the first dose of the NAI to fever alleviation to <37.5 °C was evaluated as an indicator of the clinical effectiveness of the NAIs in the influenza-infected patients. For the A(H3N2)-infected patients, Kaplan–Meier analysis showed the peramivir treatment group had the fastest time of fever alleviation to <37.5 °C (median 17.0 h, 95 % confidence interval [CI] 7.2–26.8 h) of the four treatment groups. No significant difference was found in the time to fever alleviation among the other antivirals, oseltamivir, zanamivir, and laninamivir. Results of multivariate analysis, using a Cox proportional-hazards model (hazard ratio 3.321) adjusted for the factors age, sex, body weight, vaccination status, time from onset to the clinic visit, and body temperature showed significantly faster fever alleviation in the peramivir treatment group compared with the oseltamivir treatment group. For the A(H1N1)pdm09-infected patients, only the oseltamivir and zanamivir treatment groups were compared, and no significant difference in time to alleviation of fever was observed between the two groups. Based on a cycling probe real-time polymerase chain reaction (PCR) assay, none of the A(H1N1)pdm09 strains in this study had the H275Y mutation conferring oseltamivir resistance. Further evaluation of the clinical effectiveness of the newly released NAIs for influenza-infected patients, including those infected with A(H1N1)pdm09, is needed.     

Use of selective serotonin reuptake inhibitors and sleep disturbances in community-dwelling older women

OBJECTIVES: To determine the association between use of selective serotonin reuptake inhibitors (SSRIs) and objective measures of sleep disturbances in older community-dwelling women, including women without evidence of depression. DESIGN: Cross-sectional study. SETTING: Four U.S. clinical centers. PARTICIPANTS: Two thousand eight hundred fifty-three women aged 71 and older (2,630 nonusers of antidepressants and 223 taking SSRIs alone, not in combination with other antidepressants). MEASUREMENTS: Medication use, assessed using an interviewer-administered questionnaire with verification of use from medication containers and computerized dictionary used to categorize type of medication; evidence of depression assessed using self-report or a score of 6 or higher on the Geriatric Depression Scale; and sleep parameters measured using a wrist actigraph, with data collected for an average of four consecutive 24-hour periods. RESULTS: Of the overall cohort of 2,853 women and of 2,337 women without evidence of depression, sleep disturbances were more common in women taking SSRIs than in those not taking antidepressants. After excluding women with evidence of depression and adjusting for multiple potential confounders, women taking SSRIs were more likely to have a sleep duration of 5 hours or less (multivariate odds ratio (MOR)=2.15, 95% confidence interval (CI)=1.04-4.47), sleep efficiency less than 70% (MOR=2.37, 95% CI=1.32-4.25), sleep latency of 1 hour or more (MOR=3.99, 95% CI=2.29-6.96) and eight or more long wake episodes (MOR=1.75, 95% CI=0.99-3.10). CONCLUSION: SSRI use by older women, including those without evidence of depression, is associated with a greater likelihood of sleep disturbances, including poorer sleep efficiency, longer sleep latency, and sleep fragmentation, manifested by multiple long wake episodes. These results add to the uncertainty regarding risks and benefits of SSRI use in aged populations.     

Paradoxical rebound platelet activation after painkillers cessation: missing risk for vascular events?

Background

Several reliable reports strongly indicate that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase-2 (COX-2) inhibitors is associated with an increased risk of cardiovascular events. Considering the key role of platelets in coronary atherosclerosis and the fact that antiplatelet therapy with aspirin (and more recently, clopidogrel) has been associated with reduced vascular mortality, we sought to determine the effect of therapy and withdrawal of NSAIDs and COX-2 inhibitors on platelet activity.

Methods

Platelet characteristics from 34 aspirin-naive volunteers who were receiving NSAIDs and COX-2 inhibitors were compared with 138 drug-free controls. Platelets were assessed twice at baseline (at least 1 month of NSAIDs and COX-2 inhibitors) and after a 14-day washout. We used adenosine diphosphate-induced conventional aggregometry, the point-of-care Ultegra analyzer (Ultegra Accumetrics, San Diego, Calif), and whole blood flow cytometry.

Results

Platelet activity during therapy with NSAIDs and COX-2 inhibitors was similar and unremarkable between groups. However, there was a highly significant increase of platelet activity as assessed by conventional aggregometry (P = .0003), Ultegra analyzer readings (P = .03), and expression of GPIIb/IIIa (P = .02), P-selectin (P = .03), and platelet endothelial cell adhesion molecule-1 (P = .001) after withdrawal from NSAIDs and COX-2 inhibitors.

Conclusions

These data suggest that drug cessation, rather than continuous therapy with NSAIDs and COX-2 inhibitors, may be associated with rebound platelet activation, which may predispose one to a higher risk of vascular events. This hypothesis requires intensive testing in crossover randomized studies and may justify more aggressive antiplatelet regimens in patients after discontinuation of therapy with NSAIDs and COX-2 inhibitors.     

Tadalafil in the treatment of erectile dysfunction; an overview of the clinical evidence

Prevalence and severity of erectile dysfunction (ED) increase with aging and are often associated with illnesses, like diabetes mellitus, heart disease, and hypertension, pathologically characterized by endothelial dysfunction and whose prevalence increases with age. The assumption that ED is mainly a neurovascular disease is supported by the evidence that specific phosphodiesterase type 5 (PDE5) inhibition produces an efficient erection in a wide range of ages and conditions. The availability of specific PDE5 inhibitors has enabled the development of effective treatment strategies, in this contest, tadalafil may be considered as the least “typical” PDE5 inhibitor. In clinical trials, tadalafil significantly enhanced, in patients of different ages, all efficacy outcomes across disease etiologies and severities. With an effectiveness lasting up to 36h, tadalafil allows patients to choose when to have sexual activities without the need to time it, showing positive feedback in terms of quality of life related to the treatment. Headache and dyspepsia were the most frequent side-effects of tadalafil, followed by back pain, nasal congestion, myalgia, and flushing, but the impact that long time action could have on effectiveness and safety is not yet entirely defined. The aim of this article is to critically review the available evidence from the tadalafil clinical research program and give the physician a rational approach for intervention in the treatment of ED and related diseases.     

Sildenafil in the treatment of erectile dysfunction: an overview of the clinical evidence

Erectile dysfunction (ED) is a highly prevalent disease associated with aging as well as with several risk factors including hypertension, heart disease, obesity, dyslipidemia, diabetes, hypogonadism, drugs-related, and pelvic surgery. Many of these factors are components of the metabolic syndrome, a multiplex risk factor for cardiovascular disease (CVD). ED shares common risk factors with CVD. Endothelial dysfunction seems to be the early underlying pathophysiology across both conditions. The efficacy, tolerability and cardiovascular safety of sildenafil has been evaluated in numerous large, randomized, double-blind, placebo-controlled clinical studies in the broad population of men with ED including men with several co-morbid conditions. Sildenafil is effective in several specific patient populations including the difficult-to-treat subpopulations such as diabetes mellitus and after radical prostatectomy. It is associated with rapid onset of action – within 14 minutes for some men – and an extended duration of action for up to 12 hours. Sildenafil improves quality of life and satisfaction for treated men and is well tolerated with a favorable safety profile. New data suggest that sildenafil has beneficial effects in several chronic conditions. It has been approved for the treatment of idiopathic pulmonary hypertension. Numerous articles have suggested that it improves endothelial function and a possible role on premature ejaculation or treatment of lower urinary tract symptoms has been suggested.     

用诺和锐和诺和灵R持续皮下输注治疗2型糖尿病的疗效对比

目的　比较速效胰岛素类似物 (诺和锐 )和短效人胰岛素 (诺和灵R)用外置的胰岛素泵持续皮下输注 (CSⅡ )治疗 2型糖尿病 (T2DM )的疗效。　方法　该研究为持续 2 4周随机、开放、交叉实验 ,2 9例T2DM患者 ,随机分为诺和锐组和诺和灵R组 ,诺和锐为餐前即刻输注 ,诺和灵R为餐前 30min输注 ,12周治疗后两组交换用药。观察两种不同治疗方式患者糖化血红蛋白 (HbA1c)、8个时点 (3餐前后、睡前、凌晨 2点 )血糖、低血糖及胰岛素泵的安全性的差异。　结果　接受诺和锐治疗组的患者HbA1c指标好于诺和灵R组 (P <0 0 1)。 8个时点血糖检测显示诺和锐组三餐后及睡前血糖水平均低于诺和灵R组 (P <0 0 1～ 0 0 5 )。两组患者胰岛素用量、低血糖发生率及胰岛素泵的安全性均无差异。　结论　诺和锐与诺和灵R均可安全有效的降低血糖及HbA1c ,诺和锐用于CSⅡ控制餐后血糖更具优点。     

纤溶酶原激活物抑制剂与一氧化氮在老年人不稳定型心绞痛发病中的临床意义

目的　探讨纤溶酶原激活物抑制剂 (PAI 1)与一氧化氮 (NO)在老年冠心病不稳定型心绞痛患者发病中的临床意义。　方法　测定 172例老年冠心病不稳定型心绞痛患者血清PAI 1与NO水平 ,并与 16 5例健康对照者比较。　结果　不稳定型心绞痛组的PAI 1水平〔(6 8 2 6± 13 5 3)μg/L〕明显高于对照组〔(37 71± 7 39) μg/L,P <0 0 5〕 ;NO的水平〔(75 2 8± 12 31) μmol/L〕则显著低于对照组〔(12 5 36± 2 5 36 ) μmol/L〕 ,两组比较差异有显著性 (P <0 0 5 )。　 结论　老年人不稳定型心绞痛的发病与血清PAI 1的水平升高和NO的水平降低可能有关。