Epidemiology and Treatment of New-Onset and Established Rheumatoid Arthritis in an Insured US Population.

OBJECTIVE: To investigate the epidemiology and treatment of rheumatoid arthritis (RA) in a population broadly representative of employed adults in the US, using a retrospective cohort design. METHODS: Incident and prevalent RA cohorts were defined from a sample of 4.66 million adults with complete followup data from the period of January 2005 through September 2008 in the Pharmetrics medical claims database. Demographics, comorbidity, and medical therapies were summarized using descriptive statistics. RESULTS: Median duration in the database was 5.7 years. Age- and sex-adjusted incidence in 2006 was 0.71 per 1,000 persons at risk (n = 3,992) and prevalence in 2005 was 0.63% (n = 30,530). Within 12 months after diagnosis, 65%, 64%, and 20% of the incident cohort had been prescribed corticosteroids, nonbiologic disease-modifying antirheumatic drugs (DMARDs), and tumor necrosis factor (TNF) inhibitors, respectively. Median time to first anti-TNF prescription was 6 months; 31% switched to a second drug and 15% to a third. An aggressive subcohort (11% of incident patients) received more DMARDs (83%) and TNF inhibitors (43%), and was more likely to switch. Twenty-eight percent of incident patients received only symptomatic therapy over a minimum of 1.75 years of followup; these patients were older with more comorbidities and contraindications to methotrexate. CONCLUSION: In this insured population-based cohort, only two-thirds of newly diagnosed RA patients were prescribed a DMARD in year 1 and 28% received no antirheumatic therapy. Although limited by lack of clinical information and by left-censoring, administrative databases capture clinical practice and suggest that gaps exist in treatment options available to a significant number of patients.

Benign prostatic hyperplasia: racial differences in treatment patterns and prostate cancer prevalence.

OBJECTIVE: • To compare prostate cancer, prostate-related surgery and acute urinary retention rates, as well as associated healthcare resource use over 11 years in African American and Caucasian men with benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: • The BPH-related medical and surgical charges and events were determined for 398 African American men and 1656 Caucasian men followed for a mean of 10.2 years within a health maintenance organization. • Racial differences in clinical outcomes were evaluated using time-to-event analysis, stratifying results by baseline prostate-specific antigen (PSA) values. RESULTS: • Risk of a prostate cancer diagnosis was 2.2 times greater in African American than Caucasian men (95% CI 1.48-3.35, P < 0.001) in analyses adjusting for serum PSA level. • Although African Americans were more likely to receive medical therapy for symptoms of BPH than Caucasians (43.5% vs 37.2%, respectively; P= 0.029), there were no clinically meaningful differences with respect to subsequent acute urinary retention or BPH-related surgery between them, or BPH-related medical charges (US $407 vs US $405 per month). CONCLUSION: • As evidenced by this analysis of 'real-world' clinical practice, African Americans with BPH have a much greater risk of developing prostate cancer than similar Caucasian men highlighting the need for education and early detection in this population.

Risk factors for nonfatal pulmonary embolism in a Japanese population: A hospital-based case-control study.

Risk factors for pulmonary embolism (PE) have been identified among populations in Western countries but have not been well characterized in Japan. A hospital-based case-control design employed cases with PE, which diagnosed by standard imaging techniques; controls were individuals drawn by systematic random sampling from the hospital admission register. A total of 100 (38 males and 62 females) and 199 controls were identified. Patients with PE were younger (56.5 vs 60.9 years) and more likely to be female. The odds ratio ([OR] adjusted for other factors) and 95% confidence interval (CI) for risk of PE was elevated for the following: female gender, prolonged immobilization, history of prior venous thromboembolism (VTE), lower extremity varicose veins, body mass index (BMI) > or = 25 kg/m( 2), extremity paralysis, and gout/hyperuricemia. Inherited thrombophilia was found in 14 patients with PE (14%). Risk factors for PE in Japan are comparable in magnitude to those in Western countries; only one third of PE cases had received VTE prophylaxis.

Changes in prostate volume in Japanese patients with benign prostatic hyperplasia: association with other urological measures and risk of surgical intervention.

OBJECTIVES: To evaluate changes in prostate volume (PV) and its association with selected urological measures and risk of surgical intervention in Japanese men with benign prostatic hyperplasia (BPH). METHODS: The medical records of all consecutive urologist-diagnosed BPH patients of >or=40 years old who attended any of four urology clinics in Japan during January 2004-June 2006 were reviewed. Both cross-sectional and longitudinal data were captured to analyze baseline correlations among urological measures, to evaluate the longitudinal changes in PV and selected urological measures, and to examine the predictors of surgical intervention. RESULTS: The follow-up period was 2.8 years. Mean PV and mean prostate-specific antigen (PSA) of 1331 eligible patients were 34.0 mL and 4.0 ng/mL, respectively. Both measures increased directly with age. Baseline PV correlated with residual urine volume (r = 0.18, P < 0.05) and PSA (r = 0.41, P < 0.001). Among 319 patients who had more than one PV measurement, PV increased in 51% of patients, remained the same in 28% and decreased in 21%. Use of alpha-blockers at baseline and during follow up was not associated with PV change. Patients who had a PV >or=30 mL, a severe International Prostate Symptom Score and a PSA level >or=1.5 ng/mL at baseline, were more likely to have surgical intervention during the follow-up period. CONCLUSIONS: Predictors generated in this study may help to identify a subset of BPH patients at high risk of surgical intervention.

Change in International Prostate Symptom Score, prostrate-specific antigen and prostate volume in patients with benign prostatic hyperplasia followed longitudinally.

OBJECTIVE: The natural history of benign prostatic hyperplasia (BPH) in Japan resembles Western studies in that symptoms worsen, improve or stabilize in equal proportions of patients. We sought to determine if this pattern persisted in men seeking care at a urology referral center and if worsening of symptoms was due to increase in prostate volume (PV). METHODS: We reviewed the records of all BPH patients who attended the Urology Clinic of Sapporo Medical University Hospital, during December 2003 and June 2004 with the inclusion criterion that they have at least two PV and lower urinary tract symptoms measurements using the International Prostate Symptom Score (IPSS). Patients who had prostate cancer or who underwent hormone therapy or prostate surgery between the two visits were excluded. Correlation (Spearman's rank) was used to assess interrelationships among variables at baseline and follow up; the strength of association between change in IPSS and change in PV were modeled by multiple linear regression. RESULTS: Sixty-seven patients were eligible. Baseline PV correlated with residual urine volume (r = 0.37, P < 0.05) and prostate-specific antigen (PSA; r = 0.65, P < 0.001) but not IPSS (r =-0.16). PV increased in 46 (70%) men, remained the same in 10 and decreased in 11; in the former group, the mean prostate enlargement generally increased as baseline PV increased. In multiple linear regression models that included baseline IPSS, correlation between change in IPSS and change in PV was 0.47 (P = 0.05) based on 25 patients with measures at concurrent visits. Change in PV was also correlated with change in quality of life score (0.46, P = 0.02) but not with change in PSA (r = 0.38, P = 0.07, maximum flow rate (-0.24) or residual urine volume (-0.06). CONCLUSIONS: IPSS were not correlated with any laboratory measure of urinary function at baseline; however, change in IPSS was associated with change in PV. PV was also moderately correlated to PSA levels and residual urine volume at baseline.

Adverse events from systemic therapies for psoriasis are common in clinical practice.

BACKGROUND: Patients with moderate-to-severe psoriasis frequently require systemic treatment and these medications may be associated with adverse effects. Little is known about the frequency of these events when systemic agents are used in true clinical practice. OBJECTIVE: To determine the frequency of adverse events associated with various systemic psoriasis therapies. METHODS: A retrospective chart review of 753 patients treated in an academic dermatology practice was performed to identify the frequency of adverse events. Poisson regression was used to estimate the odds of significant events for each systemic therapy; UVB-treated patients served as a control population. RESULTS: Methotrexate seemed to be the most prescribed medication. Adverse events were noted with all forms of systemic psoriasis therapy. The highest event rate was seen with oral retinoids, though most of these were considered minor (64%). Cyclosporine had the highest significant adverse event rate (0.9 events/patient). For 'significant' adverse events, oral agents had an adjusted odds ratio>6 compared to standard UVB therapy. The highest risk was for cyclosporine (OR = 20.3); however, the estimate was imprecise (95% confidence interval [4.3, 96.6]). CONCLUSIONS: Traditional psoriasis therapies are associated with significant adverse events in some patients despite toxicity-sparing approaches such as combination therapy. Clinicians need to be aware of screening for adverse events in order to best ensure the safety of their patients and to maximize the efficacy of a given agent. There is still a need for the development of safe and effective treatments for patients with moderate-to-severe psoriasis.

Hypereosinophilic syndrome: an update.

Hypereosinophilic syndrome (HES) is a rare disorder that is characterized by persistent and marked eosinophilia combined with organ system dysfunction. HES has substantial clinical heterogeneity but can be fatal without treatment, especially in patients who present with a myelodysplastic variant of the disorder. Although the pathophysiology of HES is poorly defined, dysregulation of cytokines (interleukin 5 [IL-5], IL-3, granulocyte-macrophage colony-stimulating factor [GM-CSF]) responsible for the maturation of eosinophils is a primary feature. Of these cytokines, IL-5 appears to have the greatest role in the regulation of eosinophil maturation. There is no Food and Drug Administration-approved treatment for HES as yet; current strategies are designed to lower blood eosinophils and attempt to limit end-organ damage. Historically, corticosteroids and cytotoxic agents have been the mainstays of therapy, with biological response modifiers such as interferon-alpha also effective in some patients. However, despite improvements in survival, available agents have significant limitations in terms of efficacy, tolerability, and long-term toxicity. More recently, new agents directed at specific targets in the pathogenesis of HES have been developed. These include imatinib mesylate, a tyrosine kinase inhibitor, and more recently, mepolizumab, an anti-IL-5 monoclonal antibody. In a small case series of patients, these agents have been shown to produce hematological and clinical responses in patients with HES, although they may be effective in different subsets of patients. These targeted therapies have the potential to improve clinical outcomes and to further the understanding the pathophysiology of this difficult-to-treat condition.

Changes in the freezing protocol for human zygotes alter embryonic development and pregnancy rates.

OBJECTIVE: To determine the effect of various freezing protocols on postthaw development and pregnancy rates resulting from transfer of human zygotes. DESIGN: Prospective study. SETTING: Tertiary care center. PATIENT(S): Couples undergoing assisted reproductive technology (ART) procedures who wished to have their excess zygotes cryopreserved. INTERVENTION(S): We cryopreserved zygotes with one of three protocols. MAIN OUTCOME MEASURE(S): Post-thaw survival and development of the zygotes as well as pregnancy rate after transfer of these zygotes. RESULT(S): A 3-minute hold time after seeding, followed by a final preplunging temperature of -180 degrees C, resulted in a clinical pregnancy rate of 28.6%. In contrast, a 15-minute postseed hold time and a -30 degrees C final chamber temperature resulted in a 37.3% clinical pregnancy rate. When we combined the protocols to provide a 15-minute postseed holding time and a -180 degrees C before plunging into liquid nitrogen, we achieved a 69.6% clinical pregnancy rate. CONCLUSION(S): By increasing the postseeding hold time and decreasing the temperature of the freezing chamber before plunging the zygotes into liquid nitrogen, significant improvements can be made in postthaw development and pregnancy rates.

The comorbid state of psoriasis patients in a university dermatology practice.

BACKGROUND: Psoriasis treatment is frequently complicated by the various types and severities of disease as well as the large number of therapies available. Another critical consideration in treatment planning is the presence of comorbid diseases. PURPOSE: The purpose of this study was to evaluate the relative prevalence of major comorbid disease states in patients with psoriasis and to identify significant predictors of these concurrent diseases in such patients. METHODS: A retrospective chart review of 753 patients from an academic dermatology practice was performed. The patients were identified by ICD-9 code for psoriasis in billing records of patients seen between 1997 and 2000. Data on comorbidities were compiled from review of electronic chart notes from all physician visits in the university practice. RESULTS: Comorbid diagnoses were listed in 551 out of 753 (73%) charts. As would be expected, hypertension, dyslipidaemia, diabetes and heart disease were the most common comorbidities; renal failure and hepatitis were least likely. Hepatitis was associated with use of systemic therapies (odds ratio = 2.19) and non-white race. When compared with national prevalence estimates, psoriasis patients had increased heart disease, hypertension, diabetes and emphysema; however, these findings must be interpreted with some caution. CONCLUSIONS: Comorbid diseases are common in psoriasis patients and should be taken into account during treatment planning and surveillance; they may pose unique challenges in caring for patients with psoriasis, particularly those requiring systemic therapy.

Conclusions about the effects on fertilization of time from aspiration to incubation and blood in the aspirate depend on the use of appropriate statistical techniques.

OBJECTIVE: To examine the effects of exposure to blood and time from aspiration to incubation on oocyte fertilization. DESIGN: Retrospective, cohort study. SETTING: Hospital-based IVF practice. PATIENT(S): Eighty-two women undergoing IVF procedures. INTERVENTION(S): Patients received a standard gonadotropin protocol or a microdose flare protocol. MAIN OUTCOMES MEASURE(S): Logistic regression was used to estimate odds of nonfertilization, adjusting for maternal age, time from aspiration to incubation, presence of blood in the aspirate, and a time-by-blood interaction. Two statistical methods were used: an analysis that assumed oocytes were independent and an analysis that adjusted for the lack of independence of oocytes within mothers (i.e., cluster-correlated data). RESULT(S): The 82 women contributed 1093 oocytes. In a model with blood dicotomized as present or absent, and with time elapsed and maternal age categorized into quartiles, both time and maternal age were statistically significant when conventional logistic regression was used. In analyses that accounted for clustering within mother, retrieval-to-incubation times more than 4 minutes were associated with an increased risk of nonfertilization, but age and blood were not; there was no evidence of an interaction between time elapsed and blood. CONCLUSION(S): If appropriate statistics are applied, retrieval-to-incubation times more than 4 minutes are associated with increased risk of nonfertilization.

Clinical process improvement: reduction of pneumothorax and mortality in high-risk preterm infants.

OBJECTIVE: To develop multidisciplinary clinical process improvement methods using evidence-based medicine to decrease the incidence of pneumothorax in a NICU. STUDY DESIGN: All inborn infants <28 weeks' gestation (n=79) served as the historical baseline group. A prospective protocol, using evidence-based medicine and a rapid-cycle, multidisciplinary clinical process improvement method, was designed to measure changes in the incidence of pneumothorax in subsequent infants of similar gestational ages. RESULTS: Sixty consecutive inborn infants <28 weeks' gestational age comprised the study group. In comparison to the historical control group, there was a significant reduction in the incidence of pneumothorax (from 26.6% to 10%, p=0.018) and in mortality (36.7% to 15%, p=0.007) without adversely affecting any other measured outcome variable. CONCLUSIONS: Introduction of multidisciplinary clinical process improvement methods can significantly decrease the incidence of adverse outcomes in neonatal intensive care units.

Effect of topotecan infusion duration on hematologic toxicity in recurrent ovarian carcinoma.

In an open-label, multicenter, nonrandomized, counterbalanced study, we investigated the tolerability and antitumor profile of a 10-min infusion duration of topotecan. A total of 12 patients with evaluable recurrent ovarian cancer were enrolled into the study and treated with 1.5 mg/m2/d topotecan for 5 d of a 21-d course by either a 10-, 30-, or 120-min intravenous infusion. Patients were evaluated for tolerability and tumor response. The primary toxicity associated with topotecan was noncumulative myelosuppression. All 12 patients experienced grade 3/4 neutropenia. Grade 3/4 thrombocytopenia, leukopenia, and anemia were reported in five (42%), two (17%), and two (17%) patients, respectively. Likewise, the majority of courses were associated with hematologic toxicity, with grade 3/4 neutropenia, thrombocytopenia, leukopenia, and anemia reported in 97%, 19%, 6%, and 6% of courses, respectively. The infusion duration had little impact on the myelotoxicity profile of topotecan. The mean nadir levels for all hematologic parameters were similar for all infusion durations, and myelosuppression was reversible and returned to near-preinfusion levels prior to administering the subsequent course, irrespective of infusion duration. A complete response was obtained by three (25%) patients, and five (42%) patients achieved stable disease; therefore, 67% of patients obtained clinical benefit. The results of this study demonstrate that topotecan administered over a 10-min interval has a comparable tolerability and safety profile compared with a 30-min infusion. A 10-min infusion may result in greater patient convenience and a reduction in the consumption of healthcare resources.