Incidence and prevalence of acromegaly in a large US health plan database.

PURPOSE: Incidence and prevalence estimates of acromegaly in the United States (US) are limited. Most existing reports are based on European data sources. The objective of this study was to estimate the annual incidence and prevalence of acromegaly in a large US managed care population, overall and stratified by age, sex, and geographic region, using data from 2008 to 2012. METHODS: Using administrative claims data, commercial health plan enrollees were identified with acromegaly if they had two or more medical claims with an acromegaly diagnosis code (ICD-9-CM: 253.0×) or one medical claim with an acromegaly diagnosis code in combination with one other claim for a pituitary tumor or pituitary procedure. The first date for an acromegaly-related claim set the index year. Incidence rates for each year were calculated by dividing the number of new acromegaly cases by the calculated person-time at risk. Annual prevalence estimates were calculated by dividing the number with any evidence of acromegaly by the total number of health plan enrollees enrolled for at least 1 day during each calendar year. Incidence and prevalence estimates were stratified by age (0-17, 18-44, 45-64, 65+ years), sex (male, female), and US geographic region of the health plan (Midwest, Northeast, South, West). RESULTS: Overall annual incidence rates of acromegaly were relatively constant across 2008-2012 with ~11 cases per million person-years (PMPY). Rates increased with age, ranging from 3-8 cases PMPY among children aged 0-17 years old to 9-18 cases PMPY among adults aged 65 and older. Females had 12 cases PMPY on average compared to 10 cases PMPY among men. On average, the Midwest had the lowest incidence rates (7 cases PMPY) compared to the Northeast, South and West (14, 12, and 10 cases PMPY, respectively). The overall annual prevalence of acromegaly was relatively constant across the 5 years from 2008 to 2012 with approximately 78 cases per million each year. Annual prevalence estimates increased with age, ranging from 29-37 cases per million among children aged 0-17 years old to 148-182 cases per million among adults aged 65 years and older. Males and females were similarly affected; each with approximately 77 cases per million each year. The Northeast and South had the highest prevalence estimates (92 and 89 cases per million, respectively); while the estimates for the West and Midwest were lower (65 and 57 cases per million, respectively) each year. CONCLUSION: This study examined 5 years of recent data to estimate the incidence and prevalence of acromegaly in a large geographically-diverse managed care population. The incidence rates were higher on average than published rates outside the US (11 vs. 3.3 PMPY), but prevalence estimates were consistent with previous reports. Incidence and prevalence both increased by age, did not differ for males and females, and varied slightly by US geographic region. The age and sex distribution of the selected population matched the known epidemiology of the disease. Using a claims-based approach, this analysis only captured acromegaly cases with an acromegaly-related medical claim. As a result, these estimates may underestimate the incidence and prevalence of acromegaly in US commercial health plans as they did not include individuals who were undiagnosed, in remission, undertreated, or not monitored during the study period. At the same time, these estimates may be viewed as an upper bound on the incidence of acromegaly in the US as the estimates did not include individuals who were in other health plans or uninsured during the study period. Additional evaluations are needed to identify the full extent of acromegaly in the US.

Algorithm development and the clinical and economic burden of Cushing's disease in a large US health plan database.

PURPOSE: This study aimed to develop an algorithm to identify patients with CD, and quantify the clinical and economic burden that patients with CD face compared to CD-free controls. METHODS: A retrospective cohort study of CD patients was conducted in a large US commercial health plan database between 1/1/2007 and 12/31/2011. A control group with no evidence of CD during the same time was matched 1:3 based on demographics. Comorbidity rates were compared using Poisson and health care costs were compared using robust variance estimation. RESULTS: A case-finding algorithm identified 877 CD patients, who were matched to 2631 CD-free controls. The age and sex distribution of the selected population matched the known epidemiology of CD. CD patients were found to have comorbidity rates that were two to five times higher and health care costs that were four to seven times higher than CD-free controls. CONCLUSION: An algorithm based on eight pituitary conditions and procedures appeared to identify CD patients in a claims database without a unique diagnosis code. Young CD patients had high rates of comorbidities that are more commonly observed in an older population (e.g., diabetes, hypertension, and cardiovascular disease). Observed health care costs were also high for CD patients compared to CD-free controls, but may have been even higher if the sample had included healthier controls with no health care use as well. Earlier diagnosis, improved surgery success rates, and better treatments may all help to reduce the chronic comorbidity and high health care costs associated with CD.

Retrospective analysis of variation in heavy menstrual bleeding treatments by age and underlying cause.

OBJECTIVE: To describe treatment patterns associated with heavy menstrual bleeding (HMB) in US practice. STUDY DESIGN: A retrospective claims-based analysis of organic (ICD-9 codes 218.x, 621.0, 622.7, 219.x, and bleeding disorders) or idiopathic (no underlying condition identified) HMB treatment patterns among newly diagnosed, commercially insured women who were enrolled in a large US health plan. First HMB claim (index date; ICD-9-CM 626.2 and 627.0), second HMB claim within 180 days of index date, and continuous enrollment ≥6 months prior to (pre-index period) and 18 months following (post-index period) index date were required. RESULTS: The database included 13,579 organic and 21,362 idiopathic HMB patients. More organic HMB patients received only one treatment type (64% vs 58%; p < 0.001) or two treatments types (14% vs 11%; p < 0.001) compared to idiopathic HMB patients. During the 18 month post-index period, fewer organic HMB patients had no observed treatment compared to idiopathic HMB patients (21% vs 31%; p < 0.001). The idiopathic cohort had significantly higher rates (p < 0.001) of medication use and endometrial ablation, whereas the organic HMB cohort had a higher rate of hysterectomy (p < 0.001). Women <35 years were more frequently prescribed medical treatments (p ≤ 0.037), while women aged >35 years utilized significantly more surgical approaches (p < 0.001). CONCLUSIONS: Among organic and idiopathic HMB patients, considerable variation was observed in the medications and procedures used to treat HMB. Current treatment pattern awareness may improve HMB management. Future research is needed to understand factors that influence women's treatment choices (including newer medications LNG-IUS and tranexamic acid) and age in relation to child-bearing preference.

Real-world comorbidities and treatment patterns of patients with acromegaly in two large US health plan databases.

Acromegaly is a rare, chronic, and debilitating disease that results from excessive growth hormone production. Clinically, this disease is associated with enlargement of soft tissue, excessive skeletal growth, and increased risk of cardiovascular disease. Acromegaly is often diagnosed late, when a wide range of comorbidities may already be present. First-line therapy for acromegaly is typically surgery; but a number of highly-specific pharmacological agents have recently enabled a more aggressive medical management of acromegaly. Since surgical cure of acromegaly is low for macroadenomas, medical control of active acromegaly is an important component of treatment. There are no published US data currently available regarding real-world rates of comorbidities and treatment patterns among patients with acromegaly. This retrospective study examined the comorbidities and treatment patterns of 949 health plan enrollees, who had acromegaly diagnosis and/or procedure codes in an administrative claims database from July 1, 2002 through June 30, 2010. Acromegaly was associated with high rates of hypertension and diabetes along with a number of other comorbidities. The incidence of comorbidities was highest among patients with acromegaly-related treatment, which may have resulted, in part, from inadequate disease management and/or poor disease control. Unexpectedly, 55% of patients identified with acromegaly received no treatment for acromegaly (i.e., surgery, radiotherapy, and medication) and only 28% received a medication treatment during the observation period. However, some patients may have received a curative surgery prior to the observation period, which may have reduced the use of other acromegaly-related treatments during the study period. Of those treated with medications, the most common first medications were octreotide, cabergoline, and bromocriptine. Given the high incidence of serious comorbidities associated with active acromegaly, earlier diagnosis and treatment, along with appropriate follow-up care, may potentially avoid the life-long consequences of uncontrolled disease.

Medical cost associated with prediabetes.

In this article, we estimate national health care resource use and medical costs in 2007 associated with prediabetes (PD), defined as either fasting plasma glucose between 100 and 125 or oral glucose tolerance test between 140 and 200. We use Poisson regression with medical claims for an adult population continuously insured between 2004 and 2006 to analyze patterns of health care resource use by PD status. Combining rate ratios that reflect health care use patterns with national PD prevalence rates from the National Health and Nutrition Examination Survey, we calculate etiological fractions to estimate the portion of national health resource use associated with PD. The findings suggest that PD is associated with statistically higher rates of ambulatory visits for hypertension; endocrine, metabolic, and renal complications; and general medical conditions. PD is associated with a slight increase in visit rates for neurological symptoms, peripheral vascular disease, and cardiovascular disease, but the increase is not statistically significant. There is no indication that PD is associated with an increase in emergency visits and inpatient days. Extrapolating these patterns to the 57 million adults with PD in 2007 suggests that national annual medical costs of PD exceed $25 billion, or an additional $443 for each adult with PD. PD is associated with excessive use of ambulatory services for comorbidities known to be related to diabetes. Our findings strengthen the business case for lifestyle interventions to prevent diabetes by adding additional economic benefits that potentially can be achieved by preventing or delaying PD.

Neoadjuvant percutaneous 4-hydroxytamoxifen decreases breast tumoral cell proliferation: a prospective controlled randomized study comparing three doses of 4-hydroxytamoxifen gel to oral tamoxifen.

PURPOSE: Two chemoprevention randomized studies using tamoxifen showed drug efficacy; however, adverse effects such as hot flushes, endometrial cancer, and above all, thromboembolism, remain a problem. 4 hydroxytamoxifen (4-OHT) is a very active metabolite of tamoxifen. This randomized study was designed to analyze if 4-OHT gel, administered percutaneously on the breast skin, can inhibit the proliferation of malignant breast cells to the same extent as orally administered tamoxifen. PATIENTS AND METHODS: Fifty-five postmenopausal women with an invasive estrogen receptor-positive breast cancer were randomly assigned to receive (for 2 to 3 weeks) either 4-OHT gel (0.5, 1, or 2 mg/d) or oral tamoxifen (20 mg/d) or no treatment. Response was evaluated using proliferation markers (Ki-67, proliferating cell nuclear antigen) and apoptosis markers in tissue samples obtained by Tru-cut biopsy before treatment, and at surgery after treatment. RESULTS: Administration of 4-OHT gel resulted in reductions in tumor tissue proliferation indexes (Ki-67 and PCNA), with approximate equivalence between the 1.0 mg/d or 2.0 mg/d 4-OHT dose, and oral tamoxifen, but had no effect on apoptotic markers. Plasma levels of 4-OHT were consistently higher in the oral tamoxifen group than in the gel groups. No dose-related pattern was shown for estrogen or progesterone receptor levels, and topical 4-OHT gel appeared to be generally well tolerated. Hot flushes are as common in the two higher gel doses as with tamoxifen. CONCLUSION: Percutaneous 4-OHT gel has a local impact on tumor proliferation. It could be tested in future prospective trials of chemoprevention or ductal carcinoma in situ adjuvant hormonotherapy.