Disease Control, Health Resource Use, Healthcare Costs, and Predictors in Gout Patients in the United States, the United Kingdom, Germany, and France: A Retrospective Analysis.

INTRODUCTION: The present study aimed to assess disease control, health resource utilization (HRU), and healthcare costs, and their predictors in gout patients across the USA, UK, Germany, and France. METHODS: Data were extracted from the PharMetrics Plus (USA), Clinical Practice Research Datalink-Hospital Episode Statistics (UK), and Disease Analyzer databases (Germany and France) for adult gout patients over a 3-year period: 2009-2011 (all dates +1 year for France). Patients had "prevalent established gout" (i.e., were treated with urate-lowering therapy [ULT] or eligible for ULT based on American College of Rheumatology guidelines) in the preindex panel-year, with January 1 of the second study year as the study index date. Assessments of disease control (uncontrolled gout definition: ≥1 serum urate (sUA) elevation or ≥2 flares; analysis limited to the subpopulation with sUA) data, HRU, and costs were in the second post-index panel-year, while potential predictors (demographics and gout treatment characteristics) were identified in the first post-index panel-year. RESULTS: Treatment rates were high (>70% with chronic urate-lowering treatment in all countries but France), while between 31.3% (France) and 62.9% (USA) of patients remained uncontrolled. Predictors of control included female gender and high adherence. In Germany, the UK, and France, lack of disease control predicted increased gout-attributed costs and increased HRU, both gout-attributed (also in the USA) and non-gout-attributed. CONCLUSION: Gout management remains suboptimal, as many patients remain uncontrolled despite using urate-lowering treatment. Effective and convenient treatment options are needed to improve disease control and minimize additional HRU and costs. FUNDING: AstraZeneca.

Comorbidity Burden in Trial-Aligned Patients with Established Gout in Germany, UK, US, and France: a Retrospective Analysis.

INTRODUCTION: Patients with gout have numerous comorbidities. We aimed to estimate the prevalence and incidence rates of renal and cardiovascular morbidities in trial-aligned patients with established gout in Germany (DE), the United Kingdom (UK), the United States (US), and France (FR). METHODS: This longitudinal cohort study used retrospective data from IMS Disease Analyzer™ (DE, FR), Clinical Practice Research Datalink-Hospital Episode Statistics (UK), and IMS' PharMetrics Plus database linked with outpatient laboratory results (US). Included patients were ≥18 years at index date (January 1, 2010; all dates +1 year for FR), with continuous enrollment during the pre-index year, had "prevalent established gout" determined by data in the pre-index year, and ≥1 documented visit after index date; additional inclusion/exclusion criteria were aligned with recent gout clinical trials. Look-back for comorbidity prevalence extended to January 1, 2003 (US: January 1, 2009). Follow-up for incidence extended from index date to at most March 26, 2013 (FR: May 31, 2014). Events of interest were identified by diagnostic codes and/or laboratory data. RESULTS: The trial-aligned cohorts included 35,118 (DE), 24,607 (UK), 121,591 (US), and 17,338 (FR) patients. Among renal conditions, baseline diagnosis of chronic kidney disease/renal failure was most prevalent in the UK followed by DE; abnormal serum creatinine was most prevalent in the UK. Hypertension was the most prevalent cardiovascular diagnosis in all countries, followed by ischemic heart disease (IHD) and myocardial infarction. Incidence rates (per 100 patient-years) for new/worsening renal impairment ranged from 1.67 (DE) to 4.34 (US) and for nephrolithiasis diagnosis from 0.31 (FR) to 3.79 (US). The incidence rates for hypertension diagnosis were highest among cardiovascular-related events, ranging from 3.23 (UK) to 20.27 (US), followed by IHD. CONCLUSIONS: Patients with established gout such as those included in gout trials have a high burden of established morbidity and new diagnoses of morbid events. Consideration of comorbidities, which greatly exacerbate disease burden, is important in gout management. FUNDING: AstraZeneca.

Association of lower urinary tract symptoms and the metabolic syndrome: results from the Boston area community health survey.

PURPOSE: In this study we investigated the relationship between lower urinary tract symptoms as defined by the American Urological Association symptom index and the metabolic syndrome, and determined the relationship between individual symptoms comprising the American Urological Association symptom index and the metabolic syndrome. MATERIALS AND METHODS: The Boston Area Community Health Survey used a 2-stage cluster design to recruit a random sample of 2,301 men 30 to 79 years old. Analyses were conducted on 1,899 men who provided blood samples. Urological symptoms comprising the American Urological Association symptom index were included in the analysis. The metabolic syndrome was defined using a modification of the Adult Treatment Panel III guidelines. The association between lower urinary tract symptoms and the metabolic syndrome was assessed using odds ratios and 95% confidence intervals estimated using logistic regression models. RESULTS: Increased odds of the metabolic syndrome were observed in men with mild to severe symptoms (American Urological Association symptom index 2 to 35) compared to those with an American Urological Association symptom index score of 0 or 1 (multivariate OR 1.68, 95% CI 1.21-2.35). A statistically significant association was observed between the metabolic syndrome and a voiding symptom score of 5 or greater (multivariate adjusted OR 1.73, 95% CI 1.06-2.80) but not for a storage symptom score of 4 or greater (multivariate adjusted OR 0.94, 95% CI 0.66-1.33). Increased odds of the metabolic syndrome were observed even with mild symptoms, primarily for incomplete emptying, intermittency and nocturia. These associations were observed primarily in younger men (younger than 60 years) and were null in older men (60 years old or older). CONCLUSIONS: The observed association between urological symptoms and the metabolic syndrome provides further evidence of common underlying factors between lower urinary tract symptoms and chronic conditions outside the urinary tract.

Association of lower urinary tract symptoms and the metabolic syndrome: results from the Boston Area Community Health Survey.

PURPOSE: In this study we investigated the relationship between lower urinary tract symptoms as defined by the American Urological Association symptom index and the metabolic syndrome, and determined the relationship between individual symptoms comprising the American Urological Association symptom index and the metabolic syndrome. MATERIALS AND METHODS: The Boston Area Community Health Survey used a 2-stage cluster design to recruit a random sample of 2,301 men 30 to 79 years old. Analyses were conducted on 1,899 men who provided blood samples. Urological symptoms comprising the American Urological Association symptom index were included in the analysis. The metabolic syndrome was defined using a modification of the Adult Treatment Panel III guidelines. The association between lower urinary tract symptoms and the metabolic syndrome was assessed using odds ratios and 95% confidence intervals estimated using logistic regression models. RESULTS: Increased odds of the metabolic syndrome were observed in men with mild to severe symptoms (American Urological Association symptom index 2 to 35) compared to those with an American Urological Association symptom index score of 0 or 1 (multivariate OR 1.68, 95% CI 1.21-2.35). A statistically significant association was observed between the metabolic syndrome and a voiding symptom score of 5 or greater (multivariate adjusted OR 1.73, 95% CI 1.06-2.80) but not for a storage symptom score of 4 or greater (multivariate adjusted OR 0.94, 95% CI 0.66-1.33). Increased odds of the metabolic syndrome were observed even with mild symptoms, primarily for incomplete emptying, intermittency and nocturia. These associations were observed primarily in younger men (younger than 60 years) and were null in older men (60 years old or older). CONCLUSIONS: The observed association between urological symptoms and the metabolic syndrome provides further evidence of common underlying factors between lower urinary tract symptoms and chronic conditions outside the urinary tract.

Association of C-reactive protein and lower urinary tract symptoms in men and women: results from Boston Area Community Health survey.

OBJECTIVES: To determine whether an association exists between C-reactive protein (CRP) levels and lower urinary tract symptoms (LUTS) as assessed by the American Urological Association Symptom Index (AUA-SI) among both men and women, and to determine the association of CRP levels with the individual urologic symptoms comprising the AUA-SI among both men and women. METHODS: The Boston Area Community Health survey used a multistage stratified design to recruit a random sample of 5502 adults aged 30-79 years. Blood samples were obtained from 3752 participants. The analyses were conducted on 1898 men and 1854 women with complete data on CRP levels. Overall LUTS was defined as an AUA-SI of >or=8 (moderate to severe LUTS). The urologic symptoms comprising the AUA-SI were included in the analysis as reports of fairly often to almost always vs non/rarely/a few times. RESULTS: A statistically significant association was observed between the CRP levels and overall LUTS among both men and women. The pattern of associations between the individual symptoms and CRP levels varied by sex. Nocturia and straining were associated with greater CRP levels among men, and incomplete emptying and weak stream were associated with greater CRP levels among women. CONCLUSIONS: The results of this study have demonstrated an association between CRP levels and LUTS in both men and women. The dose-response relationship between increased CRP levels and an increased odds of LUTS supports the hypothesized role of inflammatory processes in the etiology of LUTS.

The burden of lower urinary tract symptoms: evaluating the effect of LUTS on health-related quality of life, anxiety and depression: EpiLUTS.

OBJECTIVE: To evaluate the impact of lower urinary tract symptoms (LUTS) on urinary-specific health-related quality of life (HRQL), generic health indices, depression and anxiety in a population-representative sample of men and women, as research has linked LUTS with reduced HRQL and depression, but little is known about the effects of individual LUTS on HRQL, depression and anxiety. SUBJECTS AND METHODS: A cross-sectional population-representative survey was conducted via the Internet in the USA, the UK and Sweden. Participants rated the frequency and symptom-specific bother of individual LUTS and condition-specific HRQL, generic health status, anxiety and depression. Descriptive statistics were used to evaluate outcome differences by International Continence Society LUTS subgroups; logistic regressions were used to determine associations of LUTS and perception of bladder problems, anxiety and depression. RESULTS: The overall survey response rate was 59.2%; 30 000 subjects (14 139 men and 15 861 women) participated. Men and women with LUTS in the all LUTS subgroup (storage, voiding and postmicturition) reported the lowest levels of HRQL and highest levels of anxiety and depression, with 35.9% of men and 53.3% of women meeting self-reported screening criteria for clinical anxiety (Hospital Anxiety and Depression Scale, HADS, Anxiety > or =8), and 29.8% of men and 37.6% of women meeting self-reported criteria for clinical depression (HADS Depression > or =8). In both men and women, storage symptoms were significantly associated with greater perceived bladder impact, whereas voiding symptoms were not. Significant predictors of anxiety included nocturia, urgency, stress urinary incontinence, leaking during sexual activity, weak stream and split stream in women; and nocturia, urgency, incomplete emptying and bladder pain in men. For depression, weak stream, urgency and stress urinary incontinence were significant for women, and perceived frequency and incomplete emptying were significant for men. CONCLUSION: The negative effect of LUTS is apparent across several domains of HRQL and on overall perception of bladder problems, general health status and mental health. The high level of psychiatric morbidity in patients with multiple LUTS has important implications for treatment and highlights the need for further research to pinpoint specific mechanisms underlying this association.

The overlap of storage, voiding and postmicturition symptoms and implications for treatment seeking in the USA, UK and Sweden: EpiLUTS.

OBJECTIVE: To assess the (i) the overlap between voiding, storage, and postmicturition symptoms; and (ii) the relative effect of bother and implications for treatment seeking within these symptom groups, using data from the EpiLUTS study. SUBJECTS AND METHODS: This cross-sectional population-representative survey was conducted via the Internet in the USA, the UK and Sweden. Participants were asked to rate the frequency and symptom-specific bother of individual LUTS. Descriptive statistics were used to examine differences in International Continence Society LUTS subgroups. Logistc regressions were used with treatment seeking as the dependent variable and the bother of individual symptoms as predictors. RESULTS: The survey response rate was 59%. The sample included 30,000 participants (14,139 men and 15,861 women); 71% of men and 75% of women reported at least one LUTS, and about half reported LUTS from more than one symptom group. Rates of bother were greatest for those who reported multiple storage, voiding and postmicturition LUTS (men 83%, women 89%). Less than a third of participants with LUTS from all three groups reported seeking treatment. Consistent correlates of treatment seeking across genders included bother due to weak stream, incomplete emptying, perceived daytime frequency, nocturia and urgency. There were also significant associations for several types of incontinence, most commonly stress incontinence in women and leaking during sexual activity in men. Despite high rates of symptom overlap and symptom-specific bother, few participants sought treatment for LUTS. CONCLUSION: Common conditions such as BPH and OAB are treatable, and clinicians should proactively ask patients about urinary symptoms. Given the many types of LUTS that patients experience, it is imperative that clinicians assess all LUTS to ensure that appropriate treatments are prescribed.

Risk factors and comorbid conditions associated with lower urinary tract symptoms: EpiLUTS.

OBJECTIVE: To explore the risk factors and comorbid conditions associated with subgroups of lower urinary tract symptoms (LUTS) in men and women aged > or =40 years in three countries, using data from the EpiLUTS study, as LUTS are common amongst men and women and increase in prevalence with age. SUBJECTS AND METHODS: This cross-sectional, population-representative survey was conducted via the Internet in the USA, the UK and Sweden. Participants were asked to rate how often they experienced individual LUTS during the past 4 weeks on a 5-point Likert scale. Eight LUTS subgroups were created. Descriptive statistics and logistic regressions within each LUTS subgroup were used to assess the data. RESULTS: The survey response rate was 59%. The final sample was 30,000 (men and women). The voiding + storage + postmicturition (VSPM) group reported the highest rates of comorbid conditions for both men and women, and the fewest were reported in the no/minimal LUTS and the postmicturition-only groups. Increasing age was associated with increasing LUTS in men, but not in women. Comorbid conditions significantly associated with the VSPM group were arthritis, asthma, chronic anxiety, depression, diabetes (men only), heart disease, irritable bowel syndrome, neurological conditions, recurrent urinary tract infection, and sleep disorders. Risk factors, such as body mass index, exercise level and smoking, played less of a role, except for childhood nocturnal enuresis, which was significantly associated with most LUTS subgroups. CONCLUSION: In this large population study, many comorbid conditions and risk factors were significantly associated with LUTS among both men and women. Further longitudinal investigations of the associations noted here would help physicians to understand the pathophysiology of LUTS and comorbid conditions, and provide clinical guidelines for patient management of comorbid conditions sharing common pathophysiological pathways.

The impact of lower urinary tract symptoms on male sexual health: EpiLUTS.

OBJECTIVE: To evaluate the association between International Continence Society categories of lower urinary tract symptoms (LUTS; storage, voiding, and postmicturition) and individual LUTS (associated with decreased sexual activity and sexual satisfaction in men) with erectile dysfunction (ED), ejaculatory dysfunction (EjD) and premature ejaculation (PE). SUBJECTS AND METHODS: The impact of LUTS on men's sexual health was captured as part of a cross-sectional epidemiological study to assess the prevalence LUTS among men and women aged > or =40 years in the USA, the UK and Sweden. RESULTS: The analysis included 11 834 men with a mean age of 56.1 years, 71% of whom reported being currently sexually active. The primary reason for not being sexually active was no partner (35%), followed by personal health (23%) and no desire (23%). Of the men, 26% had mild to severe ED, 7% had EjD, and 16% PE. Men with multiple LUTS had more severe ED and more frequent EjD and PE. Logistic regression analysis showed that greater age, hypertension, diabetes, depression, urgency with fear of leaking, and leaking during sexual activity were significantly associated with ED. The results were similar in the logistic regression analysis for EjD, whereas being younger and the absence of prostatitis were significantly associated with PE, as were the presence of terminal dribble, incomplete emptying, and split stream. CONCLUSION: LUTS are associated with common sexual dysfunctions in men. The results of this study highlight the importance of assessing the sexual health of men presenting with LUTS.

Lower urinary tract symptoms and sexual health: the role of gender, lifestyle and medical comorbidities.

OBJECTIVE: To investigate the association between urological symptoms and self-reported measures of sexual activity, desire and function in large representative samples of men and women in the Boston Area Community Health (BACH) survey. SUBJECTS AND METHODS: The BACH survey is a racially and ethnically diverse random sample of 5503 community-dwelling residents aged 30-79 years, of Boston, MA, USA. Urological symptoms and sexual function were assessed in men and women at baseline using validated self-report measures, i.e. the International Prostate Symptom Score (IPSS), International Index of Erectile Function, and Female Sexual Function Index. Bivariate and multivariate analyses were conducted to assess the degree of association of sexual function measures with LUTS and other common urological problems in men and women in the BACH sample, controlling for the effects of age, medical comorbidities, and lifestyle factors. RESULTS: Urological symptoms were associated with a significant decrease in sexual activity and function in both men and women. Women were more likely to report low sexual desire than men. Low sexual desire was associated with depression, nocturia and prostatitis in men. Erectile dysfunction in men was significantly associated with LUTS, nocturia and prostatitis in bivariate associations, and with prostatitis in multivariate analyses, controlling for the effects of diabetes and other comorbidities. In the multivariate analysis in women, sexual dysfunction was primarily associated with depression and inversely with alcohol use. CONCLUSION: Sexual activity and function were diminished in both men and women with urological symptoms, although women reported more sexual problems overall than men, and the profile of risk factors and comorbidities was different across genders.

Implications of recent epidemiology studies for the clinical management of lower urinary tract symptoms.

Lower urinary tract symptoms (LUTS) include storage, voiding, and postmicturition symptoms, and occur commonly in both men and women. Findings from two recent epidemiological studies, the Epidemiology of LUTS study and the Boston Area Community Health survey, further extend the understanding of the prevalence of individual LUTS, the overlap of LUTS in men and women, the associations of LUTS with other comorbid conditions, the impact of LUTS on health-related quality of life (HRQL), and the relationships between frequency and bother of LUTS and treatment-seeking behaviour. Examining the clinical implications of these findings might provide directions to physicians for managing their patients with LUTS. For example, common findings of separate patient groups spanning a spectrum from those with typically one urinary symptom of mild to moderate severity to those with multiple more severe LUTS and frequent comorbidities might further encourage the diagnosis and treatment of comorbid conditions as a standard part of the management of patients with LUTS. Likewise, understanding that the impact of LUTS on HRQL and the degree of bother, rather than the frequency of LUTS, are significant drivers for treatment seeking might aid in assisting patients to make decisions about treatment.

The prevalence of lower urinary tract symptoms (LUTS) in the USA, the UK and Sweden: results from the Epidemiology of LUTS (EpiLUTS) study.

OBJECTIVE: To estimate and compare the prevalence and associated bother of lower urinary tract symptoms (LUTS) in the general populations of the USA, UK and Sweden using current International Continence Society (ICS) definitions, as no previous population-based studies evaluating the prevalence of LUTS in the USA, using the 2002 ICS definitions, have been conducted. SUBJECTS AND METHODS: This cross-sectional, population-representative survey was conducted via the Internet in the USA, the UK and Sweden. Members of Internet-based panels were randomly selected to receive an e-mailed invitation to participate. If interested, respondents selected a link to an informed consent page, followed by the survey. Participants were asked to rate how often they experienced individual LUTS during the previous 4 weeks, on a five-point Likert scale, and, if experienced, how much the symptom bothered them. Descriptive statistics were used to summarize and present the data. RESULTS: Responses rates for the USA, the UK and Sweden were 59.6%, 60.6% and 52.3%, respectively, with a final sample of 30,000 (USA 20,000; UK 7500; Sweden 2500). The mean age (range) of the participants was 56.6 (40-99) years; the mean percentages for race were 82.9% white, 6.7% black, 6.0% Hispanic and 4.4% Asian/other. The prevalence of LUTS was defined by two symptom frequency thresholds, i.e. at least 'sometimes' and at least 'often' for all LUTS except incontinence, where frequency thresholds were at least 'a few times per month' and at least 'a few times per week'. The prevalence of at least one LUTS at least 'sometimes' was 72.3% for men and 76.3% for women, and 47.9% and 52.5% for at least 'often' for men and women, respectively. For most LUTS, at least half of the participants were bothered 'somewhat' or more using a frequency threshold of at least 'sometimes'. For a threshold of at least 'often', 'somewhat' or more bother was reported by > or =70% of participants except for terminal dribble in men and split stream in women. CONCLUSION: In this large population study of three countries, LUTS are highly prevalent among men and women aged >40 years. In general, LUTS experienced 'often' or more are bothersome to most people.

Urological symptom clusters and health-related quality-of-life: results from the Boston Area Community Health Survey.

OBJECTIVE To determine whether urological symptom clusters, as identified in previous studies, were associated with health-related quality-of-life (HRQoL) and use of healthcare. SUBJECTS AND METHODS The Boston Area Community Health Survey is a population-based epidemiological study of 2301 male and 3201 female residents of Boston, MA, USA, aged 30-79 years. Baseline data collected from 2002 to 2005 were used in this analysis. Data on 14 urological symptoms were used for the cluster analysis, and five derived symptom clusters among men and four among women were used in multivariate linear regression models (adjusted for age group, race/ethnicity, and comorbidity) to determine their association with physical (PCS-12) and mental health component scores (MCS-12) calculated from the Medical Outcomes Study 12-item Short Form Survey. RESULTS For both men and women, being in the most symptomatic cluster was associated with decrements in the PCS-12 score (men, cluster 5, -10.42; women, cluster 4, -9.80; both P < 0.001) and the MCS-12 score (men, cluster 5, -9.35; women, cluster 4, -6.24; both P < 0.001) compared with the asymptomatic groups. Both men and women in these most symptomatic clusters appeared to have adequate access to healthcare. CONCLUSION For men and women, those with the most urological symptoms reported poorer HRQoL in two domains after adjusting for age and comorbidity, and despite adequate access to care.

Association of urological symptoms and chronic illness in men and women: contributions of symptom severity and duration--results from the BACH Survey.

PURPOSE: We investigated the association between lower urinary tract symptoms and chronic illness, such as heart disease, diabetes, hypertension and depression, in men and women. In addition, we determined whether a dose-response relationship exists in the association between the severity and duration of urological symptoms and major chronic illnesses. MATERIALS AND METHODS: The Boston Area Community Health Survey used a multistage stratified design to recruit a random sample of 5,503 adults who were 30 to 79 years old. Urological symptoms in the American Urological Association symptom index were included in analysis. RESULTS: Statistically significant associations that were consistent by gender were observed between depression and all urological symptoms. Nocturia of any degree of severity or duration was associated with heart disease in men and with diabetes in women. In men a dose-response relationship was observed for the association of symptom severity and/or the duration of urinary intermittency and frequency with heart disease, and for the association of urinary urgency with diabetes. In women a history of heart disease was associated with a weak stream and straining, while a history of hypertension was associated with urgency and a weak stream. CONCLUSIONS: Results indicate a dose-response relationship in the association of the severity and duration of urological symptoms with major chronic illnesses. An association between urinary symptoms and depression was observed in men and women. In contrast, the association between lower urinary tract symptoms and heart disease, diabetes or hypertension varied by gender, suggesting different mechanisms of association in men and women.

Beyond the cluster: methodological and clinical implications in the Boston Area Community Health survey and EPIC studies.

OBJECTIVE: To test the replicability and robustness of findings about urological symptoms in men and women, classified using an objective statistical method, cluster analysis, by planned sensitivity analyses conducted within and across two large, epidemiological studies of lower urinary tract symptoms. METHODS: Sensitivity analyses were used to assess the effects of: (i) the number of urological symptoms included in the cluster analysis; (ii) the use of ordinal vs dichotomous scaling of responses; (iii) the type of cluster analysis used (hierarchical vs non-hierarchical; random vs nonrandom seeds); and (iv) the distance metric (median difference vs root mean square) of the resulting clusters. These sensitivity analyses were conducted independently in each of the two studies, with results systematically compared using Cramer's V statistic. Contingency tables were also used to assess the frequency of transitions or change in classification from one method to another. RESULTS: There were marked similarities in the cluster profiles in men and women across the two studies. For both men and women, the largest clusters consisted of low-frequency, single-symptom profiles, with urinary frequency and urgency symptoms reported by both genders. There was a multiple, mixed and highly symptomatic cluster profile in both genders in the Boston Area Community Health (BACH) and EPIC studies. The sensitivity analyses showed stability across both BACH and EPIC studies, and varying cluster methods and solutions (Cramer's V, 0.37-0.93). CONCLUSION: Sensitivity analyses show that cluster profiles are quite robust from EPIC to BACH, and that gender profiles within studies are relatively consistent across the methods and variables examined. Further studies are needed to investigate the mechanisms of action and clinical management implications of these findings.