Psychometric validation of the SF-36® Health Survey in ulcerative colitis: results from a systematic literature review.

PURPOSE: To conduct a systematic literature review of the reliability, construct validity, and responsiveness of the SF-36® Health Survey (SF-36) in patients with ulcerative colitis (UC). METHODS: We performed a systematic search of electronic medical databases to identify published peer-reviewed studies which reported scores from the eight scales and/or two summary measures of the SF-36 collected from adult patients with UC. Study findings relevant to reliability, construct validity, and responsiveness were reviewed. RESULTS: Data were extracted and summarized from 43 articles meeting inclusion criteria. Convergent validity was supported by findings that 83% (197/236) of correlations between SF-36 scales and measures of disease symptoms, disease activity, and functioning exceeded the prespecified threshold (r ≥ |0.40|). Known-groups validity was supported by findings of clinically meaningful differences in SF-36 scores between subgroups of patients when classified by disease activity (i.e., active versus inactive), symptom status, and comorbidity status. Responsiveness was supported by findings of clinically meaningful changes in SF-36 scores following treatment in non-comparative trials, and by meaningfully larger improvements in SF-36 scores in treatment arms relative to controls in randomized controlled trials. The sole study of SF-36 reliability found evidence supporting internal consistency (Cronbach's α ≥ 0.70) for all SF-36 scales and test-retest reliability (intraclass correlation coefficient ≥0.70) for six of eight scales. CONCLUSIONS: Evidence from this systematic literature review indicates that the SF-36 is reliable, valid, and responsive when used with UC patients, supporting the inclusion of the SF-36 as an endpoint in clinical trials for this patient population.

Ulcerative Colitis Treatment Patterns and Cost of Care.

OBJECTIVES: To examine treatment patterns, dosing, health care resource utilization, and cost of tumor necrosis factor inhibitors (TNFi), adalimumab (ADA) and infliximab (IFX), among patients enrolled in US Humana insurance plans who have been diagnosed with ulcerative colitis (UC). METHODS: This retrospective cohort study identified the first pharmacy or medical claim for ADA or IFX (from January 1, 2007, to December 31, 2014) in patients with continuous enrollment for 6 months or more preindex and 12 months or more postindex, with one or more UC diagnosis claim 6 months pre- or postindex. TNFi discontinuation was defined as a therapy gap of 56 days or more for ADA and 112 days or more for IFX. TNFi switch was defined as nonindex TNFi initiation. Health care resource utilization and costs were characterized quarterly according to treatment patterns. RESULTS: The study population comprised 295 patients: mean age 50.9 years, 50.5% females, and 61.7% in southern United States. At the index date, 17% of patients received ADA and 83% received IFX. Treatment discontinuation was observed in 52% of ADA and 45% of IFX users through 12 months postindex (mean time 19 and 22 weeks, respectively). Among discontinuers, 46% of ADA and 68% of IFX users did not restart/switch TNFi. ADA and IFX showed mean times to switch of 18 and 30 weeks, respectively. TNFi discontinuers had the lowest mean quarterly total health care cost ($3,935) versus patients who initiated/switched TNFi ($15,004). Nevertheless, discontinuers had higher UC-related hospitalization versus patients receiving therapy. CONCLUSIONS: Approximately half of ADA and IFX users discontinued, with approximately half of discontinuers not restarting/switching therapies. Further investigation of treatment patterns and outcomes after TNFi discontinuation is required.

The effect of thyroid dysfunction on N-terminal pro-B-type natriuretic peptide concentrations.

BACKGROUND: B-type natriuretic peptides and N-terminal pro-B-type natriuretic peptides (NT-proBNP) have been suggested as being useful for the diagnosis of congestive heart failure. We have shown previously that changes in thyroid function are associated with changes in concentrations of other low molecular weight molecules. Therefore, the aim of this study was to assess whether similar changes occurred with NT-proBNP concentrations following treatment of thyroid dysfunction. METHODS: Seventeen patients (12 female, 5 male, age range 24-77 years) with newly diagnosed hypothyroidism and 21 patients (16 female, 5 male, age range 21-66 years) with newly diagnosed hyperthyroidism had NT-proBNP measured at baseline and when they subsequently became euthyroid. RESULTS: NT-proBNP levels were not significantly different in the hyperthyroid group from the hypothyroid, either before (P = 0.706) or after treatment to euthyroidism (P = 0.170). The hypothyroid group showed a rise in NT-proBNP after treatment (P < 0.001). There was a marginally significant fall in the NT-proBNP levels in the hyperthyroid group (P = 0.05). However, these changes were within the expected wide range of biological variability of NT-proBNP shown in earlier studies. CONCLUSIONS: Hypothyroidism alters NT-proBNP concentrations, but the magnitude of this effect may be lost in the wide biological variability of natriuretic peptides and this statistically significant finding is not likely to be of clinical relevance.

The effect of soy phytoestrogen supplementation on thyroid status and cardiovascular risk markers in patients with subclinical hypothyroidism: a randomized, double-blind, crossover study.

CONTEXT: There is concern whether soy phytoestrogens may affect thyroid function. If true, soy phytoestrogens may be expected to have a greater impact in subjects with subclinical hypothyroidism. OBJECTIVE: The primary aim was to determine the effect of soy phytoestrogen supplementation on thyroid function, with a secondary aim of assessing the effects on cardiovascular risk indices in patients with subclinical hypothyroidism. DESIGN AND SETTING: We conducted a randomized, double-blind, crossover study in a tertiary care setting. PARTICIPANTS: Sixty patients with subclinical hypothyroidism participated in the study. INTERVENTION: Patients were randomly assigned to either low-dose phytoestrogen (30 g soy protein with 2 mg phytoestrogens, representative of a Western diet) or high-dose phytoestrogen (30 g soy protein with 16 mg phytoestrogens, representative of a vegetarian diet) supplementation for 8 wk, then crossed over after an 8-wk washout period. MAIN OUTCOME MEASURES: The primary outcome was progression to overt hypothyroidism, with secondary outcome measures of blood pressure, insulin resistance, lipids, and highly sensitive C-reactive protein (hsCRP). RESULTS: Six female patients in the study progressed into overt hypothyroidism with a standardized rate ratio of 3.6 (95% confidence interval, 1.9, 6.2) after 16-mg phytoestrogen supplementation. Both systolic and diastolic blood pressure decreased with 16 mg phytoestrogens, whereas systolic pressure alone decreased with 2 mg phytoestrogens. Insulin resistance (homeostasis model assessment of insulin resistance, 3.5 ± 0.09 vs. 2.6 ± 0.08; P < 0.02) and hsCRP (4.9 ± 0.04 vs. 3.9 ± 0.03; P < 0.01) decreased with 16 mg phytoestrogens. Lipid profile remained unchanged. CONCLUSION: There is a 3-fold increased risk of developing overt hypothyroidism with dietary supplementation of 16 mg soy phytoestrogens with subclinical hypothyroidism. However, 16-mg soy phytoestrogen supplementation significantly reduces the insulin resistance, hsCRP, and blood pressure in these patients.

Effect of dopamine agonists on prolactinomas and normal pituitary assessed by dynamic contrast enhanced magnetic resonance imaging (DCE-MRI).

CONTEXT: Dopamine agonists (DA) may act on prolactinoma size and secretion through additional effects on adenoma vascularity that can be visualized using dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). OBJECTIVE: We hypothesized that DAs may exert their effect through a change in tumour functional vascularity leading to a reduction of prolactin (PRL) levels and tumour size. SUBJECTS AND METHODS: To investigate this, 23 subjects were studied comprising five with macroprolactinomas, 11 with microprolactinomas, seven with non-lesion hyperprolactinemia and 15 normal volunteers (including five females on oral contraceptive pills). Patients with macroprolactinomas were treated with cabergoline 4 mg weekly and microprolactinomas were treated with quinagolide 75 microg daily for the duration of study. DCE-MRI was performed immediately pre-treatment and at 3-4 days, 1 and 3-4 months after treatment. Normal volunteers took three 75 microg quinagolide doses and were scanned pre-treatment and at 3 days. Data were analysed using the Brix model, producing a measure of vascular permeability and leakage space. RESULTS: PRL levels were significantly reduced in all patients and volunteers. Vascular parameters decreased significantly for four of five macroprolactinomas and all microprolactinomas which were maintained during the treatment period (p < 0.01). No changes were seen in normal volunteers or non-lesion hyperprolactinemia. One of five macroprolactinomas showed no change in either permeability or tumour size. CONCLUSION: Functional prolactinoma vascularity differs from non-lesion hyperprolactinemic pituitary and normal pituitary, and is responsive to DA therapy. The reduction in vascular parameters precedes shrinkage in macroprolactinomas, and if not seen within days of treatment may indicate DA resistance requiring early surgery.