Follow-up intervals in patients with Cushing's disease: recommendations from a panel of experienced pituitary clinicians.

PURPOSE: Follow-up guidelines are needed to assess quality of care and to ensure best long-term outcomes for patients with Cushing's disease (CD). The purpose of this study was to assess agreement by experts on recommended follow-up intervals for CD patients at different phases in their treatment course. METHODS: The RAND/UCLA modified Delphi process was used to assess expert consensus. Eleven clinicians who regularly manage CD patients rated 79 hypothetical patient scenarios before and after ("second round") an in-person panel discussion to clarify definitions. Scenarios described CD patients at various time points after treatment. For each scenario, panelists recommended follow-up intervals in weeks. Panel consensus was assigned as follows: "agreement" if no more than two responses were outside a 2 week window around the median response; "disagreement" if more than two responses were outside a 2 week window around the median response. Recommendations were developed based on second round results. RESULTS: Panel agreement was 65.9% before and 88.6% after the in-person discussion. The panel recommended follow-up within 8 weeks for patients in remission on glucocorticoid replacement and within 1 year of surgery; within 4 weeks for patients with uncontrolled persistent or recurrent disease; within 8-24 weeks in post-radiotherapy patients controlled on medical therapy; and within 24 weeks in asymptomatic patients with stable plasma ACTH concentrations after bilateral adrenalectomy. CONCLUSIONS: With a high level of consensus using the Delphi process, panelists recommended regular follow-up in most patient scenarios for this chronic condition. These recommendations may be useful for assessment of CD care both in research and clinical practice.

BIOCHEMICAL CONTROL DURING LONG-TERM FOLLOW-UP OF 230 ADULT PATIENTS WITH CUSHING DISEASE: A MULTICENTER RETROSPECTIVE STUDY.

OBJECTIVE: Cushing disease (CD) results from excessive exposure to glucocorticoids caused by an adrenocorticotropic hormone-secreting pituitary tumor. Inadequately treated CD is associated with significant morbidity and elevated mortality. Multicenter data on CD patients treated in routine clinical practice are needed to assess treatment outcomes in this rare disorder. The study purpose was to describe the burden of illness and treatment outcomes for CD patients. METHODS: Eight pituitary centers in four U.S. regions participated in this multicenter retrospective chart review study. Subjects were CD patients diagnosed at ≥18 years of age within the past 20 years. Descriptive statistical analyses were conducted to examine presenting signs, symptoms, comorbidities, and treatment outcomes. RESULTS: Of 230 patients, 79% were female (median age at diagnosis, 39 years; range, 18 to 78 years). Length of follow-up was 0 to 27.5 years (median, 1.9 years). Pituitary adenomas were 0 to 51 mm. The most common presenting comorbidities included hypertension (67.3%), polycystic ovary syndrome (43.5%), and hyperlipidemia (41.5%). Biochemical control was achieved with initial pituitary surgery in 41.4% patients (91 of 220), not achieved in 50.0% of patients (110 of 220), and undetermined in 8.6% of patients (19 of 220). At the end of follow-up, control had been achieved with a variety of treatment methods in 49.1% of patients (110 of 224), not achieved in 29.9% of patients (67 of 224), and undetermined in 21.0% of patients (47 of 224). CONCLUSION: Despite multiple treatments, at the end of follow-up, biochemical control was still not achieved in up to 30% of patients. These multicenter data demonstrate that in routine clinical practice, initial and long-term control is not achieved in a substantial number of patients with CD. ABBREVIATIONS: BLA = bilateral adrenalectomy CD = Cushing disease CS = Cushing syndrome eCRF = electronic case report form MRI = magnetic resonance imaging PCOS = polycystic ovary syndrome.

The impact of genomic testing on the recommendation for radiation therapy in patients with ductal carcinoma in situ: A prospective clinical utility assessment of the 12-gene DCIS score™ result.

BACKGROUND AND OBJECTIVES: Twenty percent of breast cancers are ductal carcinoma in situ (DCIS), with 15-60% having a local recurrence (LR) after surgery. Radiotherapy reduces LR by 50% but has not impacted survival. The validated Oncotype DX(®) 12-gene assay (DCIS Score) provides individualized 10-year LR estimates. This is the first study to assess whether DCIS Score impacts physicians' recommendations for radiation. METHODS: Ten sites enrolled women (9/2012-2/2014) with DCIS eligible for breast-conserving therapy, excluding patients with invasive carcinoma and planned mastectomy. Prospective data collected included clinicopathologic factors, DCIS Score assay, and treatment recommendation before and after the assay result was known. RESULTS: In 115 patients (median age: 61 years; 74.8% postmenopausal), median DCIS size was 8 mm; 20% were nuclear grade 1, 46.1% grade 2; 64.4% reported necrosis. 86.1% were ER+, 79.1% PR+ (immunohistochemistry assay). Median DCIS Score: 29 (range: 0-85). Pre-assay, 73% (95%CI: 64.0-80.9%) had radiotherapy recommendations vs. 59.1% (95%CI: 49.6-68.2%) post-assay (P= 0.008). Physicians rated DCIS Score as the most impactful factor in planning treatment. CONCLUSIONS: The radiotherapy recommendation changed from pre-assay to post-assay 31.3% (95%CI: 23.0-40.6%) of the time--a clinically significant change. This study supports the clinical utility of the DCIS Score and indicates that the test provides additional, individualized information on LR risk.

Validation of an ICD-9-based claims algorithm for identifying patients with chronic idiopathic/spontaneous urticaria.

BACKGROUND: There is no specific International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code for chronic idiopathic urticaria or spontaneous urticaria (CIU/CSU), a skin condition characterized by hives and angioedema lasting at least 6 weeks with no known cause. OBJECTIVE: To validate an ICD-9-CM-based algorithm for identification of patients with CIU/CSU and thus facilitate claims-based research. METHODS: Patient records were reviewed at 4 US practices. Patients included in the study were from a random sample of those identified by their physician as having CIU/CSU or because they met the following diagnosis-based algorithm: (1) at least 2 outpatient ICD-9-CM diagnosis codes 708.1, 708.8, or 708.9 at least 6 weeks apart or (2) 1 outpatient diagnosis of 708.1, 708.8, or 708.9 and 1 diagnosis of 995.1 at least 6 weeks apart. Data collected included ICD-9-CM codes, diagnoses of urticaria and allergy-related conditions, and medication use. Sensitivity and positive predictive value were calculated. The study was approved by the Western Institutional Review Board. RESULTS: One hundred forty-nine patient records were reviewed (mean age 41.1 years; 73.8% were women; 69.1% were white): 115 were identified with the diagnosis-based algorithm, 90 were patients with "known CIU/CSU", and 56 were in the 2 groups. The mean duration of CIU/CSU was 2.9 to 3.1 years. The 2 cohorts most frequently had diagnoses of idiopathic urticaria, unspecified urticaria, and other specified urticaria. The diagnosis-based algorithm had a positive predictive value of 90.4% and a sensitivity of 71.1%. CONCLUSION: The high positive predictive value suggests that patients identified using the algorithm are highly likely to have CIU/CSU. The 71.1% sensitivity suggests that most patients with CIU/CSU will be identified. The validation statistics support the use of the diagnosis-based algorithm in claims-based research, although future studies could refine the algorithm further.

Dairy products do not lead to alterations in body weight or fat mass in young women in a 1-y intervention.

BACKGROUND: Previous results suggested that increased intake of dairy calcium is associated with reduced weight and fat mass. OBJECTIVE: The purpose of this study was to determine whether long-term increases in consumption of dairy calcium alter body weight and fat mass in young, healthy women. DESIGN: We used a randomized, 1-y intervention for dairy calcium. Subjects were 155 young (aged 18-30 y), healthy, normal-weight women with intake of dietary calcium < 800 mg/d and energy intake

Effect of 1-year dairy product intervention on fat mass in young women: 6-month follow-up.

OBJECTIVE: Previous results from this laboratory suggest that a 1-year dairy intake intervention in young women does not alter fat mass. The objective of this study was to determine the impact of the 1-year dairy intervention 6 months after completion of the intervention. RESEARCH METHODS AND PROCEDURES: Previously, normal-weight young women (n = 154) were randomized to one of three calcium intake groups: control (<800 mg/d), medium dairy (1000 to 1100 mg/d), or high dairy (1300 to 1400 mg/d) for a 1-year trial (n = 135 completed). In the current study, 51 women were assessed 6 months after completion of the intervention trial. Body compositions (body fat, lean mass) were measured using DXA. Self-report questionnaires were utilized to measure activity and dietary intake (kilocalories, calcium). RESULTS: The high-dairy group (n = 19) maintained an elevated calcium intake (1027 +/- 380 mg/d) at 18 months compared with the control group (n = 18, 818 +/- 292; p = 0.02). Mean calcium intake over the 18 months predicted a negative change in fat mass (p = 0.04) when baseline BMI was controlled in regression analysis (model R(2) = 0.11). 25-Hydroxyvitamin D levels were correlated with fat mass at each time-point (baseline, r = -0.41, p = 0.003; 12 months, r = -0.42, p = 0.002; 18 months, r = -0.32, p = 0.02) but did not predict changes in fat mass. DISCUSSION: Dietary calcium intake over 18 months predicted a negative change in body fat mass. Thus, increased dietary calcium intakes through dairy products may prevent fat mass accumulation in young, healthy, normal-weight women.