Long-term cancer surveillance: results from the Forteo Patient Registry Surveillance Study.

The Forteo Patient Registry estimated the incidence of osteosarcoma in US patients treated with teriparatide and enrolled in the study between 2009 and 2019. No incident cases of osteosarcoma were identified among patients registered, and the crude incidence rate was 0 (95% confidence interval [CI], 0-10.2) cases per million person-years. PURPOSE: The prospective, voluntary Forteo Patient Registry was established to estimate the incidence of osteosarcoma in patients who have received treatment with teriparatide (Forteo). METHODS: Information on US adults prescribed teriparatide and enrolled in the Forteo Patient Registry 2009-2019 was linked with data from participating state cancer registries annually (2010-2019) to identify incident osteosarcoma cases using a standardized linkage algorithm. Teriparatide exposure was ascertained from self-reported data that included teriparatide initiation and demographics necessary to complete linkage. Osteosarcoma cases diagnosed on or after January 1, 2009, were identified by participating state cancer registries. The crude incidence rate (IR) and standardized incidence ratio (SIR) of observed cases to the expected number of cases adjusted to the background rate (3 per million person-years) and corresponding 95% CIs for the occurrence of osteosarcoma were calculated whereby the cumulative amount of person-time observed was adjusted for mortality. RESULTS: Data for 75,247 enrolled patients (representing 361,763 cumulative person-years) were linked to each of 42 participating state cancer registries (covering 93% of the US population), which included information on 6180 cases of osteosarcoma. No matches with incident cases of osteosarcoma following registry enrollment were found. The crude IR was 0 (95% CI, 0-10.2) cases per million person-years and the SIR was 0 (95% CI, 0-3.0). CONCLUSIONS: The ability to draw conclusions about the incidence of osteosarcoma among patients participating in the registry was limited due to the smaller than expected amount of patient follow-up time and the fact that no cases were identified.

The Forteo Patient Registry linkage to multiple state cancer registries: study design and results from the first 8 years.

The Forteo Patient Registry (FPR) aims to estimate the incidence of osteosarcoma in US patients treated with teriparatide. Enrollment began in 2009 and will continue through 2019, with linkage planned through 2024. To date, no incident cases of osteosarcoma have been identified among patients registered in the FPR. INTRODUCTION: The Forteo Patient Registry (FPR) was established in 2009 to estimate the incidence of osteosarcoma in US patients treated with teriparatide. The objective of this paper is to describe study methods, challenges encountered, and progress to date. METHODS: The FPR is a prospective US registry designed to link data from participants annually with state cancer registries. Patient enrollment is planned for 10 years (2009-2019) and annual linkage with US state cancer registries for 15 years (2010-2024). All US state cancer registries and DC were invited to participate. Patients are recruited using pre-enrollment materials included in teriparatide device packaging, kits, and brochures distributed by health-care providers; a toll-free number; and a study website. A linkage algorithm is used to match data from enrolled participants with cancer registry data. RESULTS: For the eighth annual linkage in 2017, information necessary for linkage with 63,270 patients in the FPR was submitted to each of the 42 participating registries. These patients contributed approximately 242,782 person-years of follow-up. A total of 5268 adult osteosarcoma cases diagnosed since January 1, 2009, were available for linkage from participating state cancer registries. To date, no incident cases of osteosarcoma have been identified among patients registered in the FPR. CONCLUSIONS: Based on the estimated 242,782 person-years of observation as of the eighth annual linkage and projecting current enrollment rate to study end in 2024, it is anticipated that the completed study will be able to detect a fourfold increase in the risk of osteosarcoma if one exists.

Prevalence of lower urinary tract symptoms and prostate enlargement in the primary care setting.

PURPOSE: Men with lower urinary tract symptoms (LUTS) from benign prostatic hyperplasia often do not discuss their symptoms with their primary care physicians (PCPs). The primary objectives of this study were to estimate the prevalence of LUTS, prostate enlargement, and prostate-specific antigen (PSA) > or = 1.5 ng/ml in men visiting their PCP and to assess patients' intent to discuss LUTS with their PCP. METHODS: Men over age 50 presenting for a routine office visit at one of six PCP offices during the 8-week data collection period were invited to participate in this cross-sectional study. Men with prostate cancer, bladder cancer, indwelling urethral catheter or previous pelvic irradiation were excluded. Four hundred and forty-four men were enrolled and completed a self-administered questionnaire [including the International Prostate Symptom Score (IPSS)], provided a blood sample for PSA, and underwent a digital rectal examination (DRE), with the prostate classified as enlarged or non-enlarged by their PCP. RESULTS: Forty-two per cent of men had IPSS > 7; 48% had an enlarged prostate based on DRE and 43% had PSA > or = 1.5 ng/ml. Twenty-nine per cent (n = 129) of men had IPSS > 7 and enlarged prostate or PSA > or = 1.5 ng/ml. Of these men, 33% (n = 42) intended to discuss their symptoms with their PCP. CONCLUSIONS: Although a significant percentage of men in this older population had enlarged prostate and LUTS, only one-third of them intended to discuss their symptoms with their physician. PCPs may need to increase efforts to detect LUTS and enlarged prostate in older men.

Identification of T-cell epitopes in clotting factor IX and lack of tolerance in inbred mice.

Immune responses to the factor IX protein pose problems for hemophilia B patients who develop antibodies against factor IX and for potential future treatment with gene therapy. To better define the response to human factor IX, we analyzed T-cell responses to human factor IX in factor IX knockout mice on BALB/c and C57BL/6 (B6) backgrounds, both strains having CD4+ T cells that proliferate in response to human factor IX. Surprisingly, wild-type mice have similar factor IX-recognizing CD4+ T cells. We defined a dominant CD4+ epitope for each strain (CVETGVKITVVAGEH for BALB/c and LLELDEPLVLNSYVTPIC for B6) that was recognized by both factor IX knockout and wild-type mice. While human factor IX did not cross-react with the mouse homologs of these epitopes, immunization with peptides from murine factor IX stimulated proliferation in factor IX knockout mice and wild-type mice, demonstrating a failure to delete murine factor IX-specific T cells in normal mice.

Evaluation of three circadian rhythm questionnaires with suggestions for an improved measure of morningness.

Circadian rhythms, cyclic fluctuations in many physiological and psychological functions, are thought to influence adjustment to shiftwork. A widely acknowledged individual difference in circadian rhythms, commonly called morningness, indicates preferences associated with morning or evening activities. Various self-report instruments have been developed to measure morningness, although little measurement data have been published for these scales. Because morningness scales are being used to select workers for night shiftwork, psychometric evaluations of these scales are needed. Psychometric assessments of undergraduate responses (N = 501) on three widely used scales indicate internal (interitem) measurement deficiencies in all three. Therefore, a 13-item scale was developed that distills the best items from two of these scales. Relationships between the new composite scale and external criteria are comparable with or stronger than similar relationships between the published scales and external criteria.