Cost-utility of treatments for pulmonary arterial hypertension: a Markov state-transition decision analysis model.

BACKGROUND AND OBJECTIVE: Clinicians must choose between an increasing number of medications for the treatment of pulmonary arterial hypertension (PAH) with different routes of administration, adverse effects, costs and efficacies. We constructed a decision analysis to help inform treatment choices in PAH. METHODS: We created a Markov-type model to evaluate 1-year treatment with bosentan, treprostinil, epoprostenol, inhaled iloprost, sildenafil, sitaxentan and ambrisentan. Transition probabilities were based on observed transitions between WHO functional classes, adjusted by relative risk of improvement in a 6-minute walk test. Utilities were based on reported values for each functional class, adjusted for burden of treatment administration. Costs were estimated from Medicare and Medicaid reimbursement data. Sensitivity analyses evaluated changes in efficacy, utilities and costs. RESULTS: Treatment with sildenafil was less costly and resulted in a greater gain in quality-adjusted life-years (QALYs) compared with other treatments. Treatment with ambrisentan and bosentan resulted in the same gain in QALYs as sildenafil, but at a higher cost. Sensitivity analyses had minimal impact on these results. CONCLUSIONS: Based on this model, sildenafil is a cost-effective treatment for PAH with a low price and a net increase in QALYs. The results from this analysis are a tool to help guide clinicians in deciding which PAH medications to use; however, the final decisions should be individualized because the effectiveness of therapy, resulting utilities and acceptable costs will differ with each patient.

Ghrelin is independently associated with anti-mullerian hormone levels in obese but not non-obese women with polycystic ovary syndrome.

Ghrelin is an endogenous appetite stimulant that may have a role in ovarian function. Women with polycystic ovary syndrome have anovulation and frequently weight management issues; however the associations between ghrelin and hormonal markers in polycystic ovary syndrome have not been well studied. In order to characterize the association between total ghrelin levels and ovarian function and the possible modification of this relationship by obesity, we examined total ghrelin levels and anti-mullerian hormone, total testosterone, and insulin in obese and non-obese women with and without polycystic ovary syndrome. Total ghrelin levels were lower in obese women with polycystic ovary syndrome (n = 45) compared to obese controls (n = 33) (p = 0.005), but similar in non-obese women with polycystic ovary syndrome (n = 20) compared to non-obese controls (n = 21) (p = NS). In the obese polycystic ovary syndrome group, anti-mullerian hormone was associated with ghrelin levels independent of age, insulin, and total testosterone (p = 0.008). There was no association between total ghrelin and anti-mullerian hormone levels in non-obese women with polycystic ovary syndrome, non-obese controls, or obese controls (p = NS). Our results provide evidence for a potential relationship between ghrelin and ovarian function in obese women with polycystic ovary syndrome that was not observed in non-obese women with polycystic ovary syndrome or controls.

Subclinical thyroid dysfunction and hip fracture and bone mineral density in older adults: the cardiovascular health study.

BACKGROUND: Subclinical thyroid dysfunction is common in the elderly, yet its relationship with hip fracture and bone mineral density (BMD) is unclear. OBJECTIVE: We examined the association between endogenous subclinical hyper- and hypothyroidism and hip fracture and BMD in older adults. METHODS: A total of 4936 US individuals 65 years old or older enrolled in the Cardiovascular Health Study and not taking thyroid preparations were included. Analyses of incident hip fracture were performed by thyroid status, over a median follow-up of 12 years. A cross-sectional analysis of thyroid status and BMD was performed in a subset of 1317 participants who had dual-energy x-ray absorptiometry scans. Models were adjusted for risk factors and stratified by sex. RESULTS: No association was found between subclinical hypothyroidism and incident hip fracture compared with euthyroidism, when assessed at a single time point or persisting at two time points, in either women [hazard ratio (HR) 0.91, 95% confidence interval (CI) 0.69-1.20 for a single and HR 0.79, 95% CI 0.52-1.21 for two time points] or men (HR 1.27, 95% CI 0.82-1.95 for a single and HR 1.09, 95% CI 0.57-2.10 for two time points). Likewise, no association was found between subclinical hyperthyroidism and incident hip fracture in either sex (HR 1.11, 95% CI 0.55-2.25 in women and HR 1.78, 95% CI 0.56-5.66 in men). No association was found between subclinical thyroid dysfunction and BMD at the lumbar spine, total hip, or femoral neck sites. CONCLUSIONS: Our data suggest no association between subclinical hypothyroidism or subclinical hyperthyroidism and hip fracture risk or BMD in older men and women. Additional data are needed to improve the precision of estimates for subclinical hyperthyroidism and in men.

Subclinical hypothyroidism, weight change, and body composition in the elderly: the Cardiovascular Health Study.

BACKGROUND: Subclinical hypothyroidism is common in the elderly, yet its relationship with weight and body composition is unclear. OBJECTIVE: We examined the relationship between subclinical hypothyroidism and weight change and body composition in older adults. METHODS: A total of 427 subclinically hypothyroid and 2864 euthyroid U.S. individuals ≥65 years old enrolled in the Cardiovascular Health Study and not taking thyroid preparations were included. Analyses of 6-year weight change were performed, compared by thyroid status. A cross-sectional analysis of thyroid status and body composition was performed in a subset of 1276 participants who had dual-energy x-ray absorptiometry scans. Models were risk factor-adjusted and stratified by sex. RESULTS: Overall, participants lost weight during follow-up (-0.38 kg/y in men, -0.37 kg/y in women). Subclinical hypothyroidism, when assessed at a single time point or persisting over 2 years, was not associated with a difference in weight change compared with euthyroidism. Subclinical hypothyroidism was also not associated with differences in lean mass, fat mass, or percent fat compared with euthyroidism. A TSH level 1 mU/L higher within the euthyroid or subclinical hypothyroid range was associated with a 0.51-kg higher baseline weight in women only (P < .001) but not with weight change in either sex. A 1 ng/dL higher free T4 level was associated with lower baseline weight and 0.32 kg/y greater weight loss in women only (P = .003). Baseline weight and weight change did not differ by T3 levels. CONCLUSIONS: Our data do not support a clinically significant impact of subclinical hypothyroidism on weight status in the elderly.

Clinical review: The human experience with ghrelin administration.

CONTEXT: Ghrelin is an endogenous stimulator of GH and is implicated in a number of physiological processes. Clinical trials have been performed in a variety of patient populations, but there is no comprehensive review of the beneficial and adverse consequences of ghrelin administration to humans. EVIDENCE ACQUISITION: PubMed was utilized, and the reference list of each article was screened. We included 121 published articles in which ghrelin was administered to humans. EVIDENCE SYNTHESIS: Ghrelin has been administered as an infusion or a bolus in a variety of doses to 1850 study participants, including healthy participants and patients with obesity, prior gastrectomy, cancer, pituitary disease, diabetes mellitus, eating disorders, and other conditions. There is strong evidence that ghrelin stimulates appetite and increases circulating GH, ACTH, cortisol, prolactin, and glucose across varied patient populations. There is a paucity of evidence regarding the effects of ghrelin on LH, FSH, TSH, insulin, lipolysis, body composition, cardiac function, pulmonary function, the vasculature, and sleep. Adverse effects occurred in 20% of participants, with a predominance of flushing and gastric rumbles and a mild degree of severity. The few serious adverse events occurred in patients with advanced illness and were not clearly attributable to ghrelin. Route of administration may affect the pattern of adverse effects. CONCLUSIONS: Existing literature supports the short-term safety of ghrelin administration and its efficacy as an appetite stimulant in diverse patient populations. There is some evidence to suggest that ghrelin has wider ranging therapeutic effects, although these areas require further investigation.

Limitations to the 6-minute walk test in interstitial lung disease and pulmonary hypertension in scleroderma.

OBJECTIVE: To determine factors that influence 6-minute walk distance (6MWD) in patients with scleroderma (systemic sclerosis, SSc)-interstitial lung disease (ILD), SSc-pulmonary hypertension (PH), and idiopathic pulmonary fibrosis (IPF). METHODS: We retrospectively evaluated all patients with SSc or IPF who performed a 6-minute walk test (6MWT) at a university hospital between 1999 and 2003. Chi-square, ANOVA, simple linear regression, and backwards elimination multivariable regressions were performed. RESULTS: Forty-eight consecutive IPF patients with 6MWT were compared to 33 patients with SSc-ILD, 13 with SSc-PH, 19 with both SSc-ILD and SSc-PH (SSc-Both), and 15 with SSc without ILD or PH (SSc-Neither). Mean 6MWD did not differ between groups. Limitations to 6MWT trended toward dyspnea in IPF and lower extremity pain in SSc. SSc-Both had dyspnea limitation more than other SSc subgroups (p = 0.017). Percentage predicted forced vital capacity (FVC%) and percentage predicted carbon monoxide diffusing capacity (DLCO%) were more strongly predictive of 6MWD in IPF than in SSc; however, exclusion of SSc subjects with pain limitation improved the predictive value. Significant correlates of 6MWD in multivariable analysis differed between subgroups. CONCLUSION: Pain limitations confound the utility of the 6MWT, particularly in SSc. Pain may cause failure to reach a dyspnea limitation during 6MWT, especially in SSc patients without both ILD and PH. Correlates of 6MWD differ between SSc subgroups and IPF; therefore, the 6MWT distance is not always reflective of the same physiological process. 6MWT interpretation should include consideration of vascular, pulmonary, and musculoskeletal exercise limitations.

The spectrum of scleroderma lung disease.

Pulmonary disease is the most common cause of death in patients with systemic sclerosis. This article discusses the variety of ways the lung is affected in systemic sclerosis. These include pulmonary hypertension, interstitial lung disease and other restrictive disorders, obstructive disease, pleural disease, lung cancer, and aspiration. For each manifestation we outline the current knowledge of etiology, risk factors, diagnosis, treatment, and prognosis. We also discuss the current state of lung transplantation in this population.