Cluster analysis and lower urinary tract symptoms in men: findings from the Boston Area Community Health Survey

OBJECTIVES

To classify lower urinary tract symptoms (LUTS) in a large, representative sample of men in the USA by means of cluster analysis and to investigate risk factors and comorbidities associated with the resulting cluster patterns.

SUBJECTS AND METHODS

A combination of hierarchical and non‐hierarchical cluster methods was used to assign men with LUTS in the Boston Area Community Health (BACH) study to symptom‐based categories or clusters. Of the 2301 men in the BACH study, those reporting one or more of 14 common LUTS (1592 men) were included in the analysis. The prevalence and frequency of symptoms in each cluster was assessed, in addition to the demographic, lifestyle risk factors, comorbidities, quality of life, and interference with activities of daily living associated with each cluster. We used anova methods for assessing cluster effects on continuous variables, and cross‐classification and chi‐square tests for categorical measures. Internal validity of the cluster solution was tested by means of a split‐half replication, and external validity by comparison with previously published data.

RESULTS

Five clusters were identified among symptomatic men. About half of the symptomatic men were assigned to Cluster 1, which included individuals with a low prevalence and frequency of urological symptoms and a correspondingly low level of interference with activities of daily living. There were intermediate levels of symptom frequency and prevalence in Clusters 2–4, which were characterized by mixed patterns of voiding, storage and postvoiding symptoms. Cluster 5 consisted of predominantly older men (mean age 58.9 years), with a high prevalence and frequency of urological symptoms with a mean (sd ) number of symptoms of 9.9 (2.1), and with elevated levels of comorbid cardiovascular disease (P < 0.001). These men also had higher rates of kidney and bladder infections and previous urological surgery. Men with increased waist circumference and more sedentary lifestyles were over‐represented in the more symptomatic clusters.

CONCLUSION

Cluster analysis provides an empirically based method for categorizing men with LUTS. These findings provide a new framework for examining aetiological pathways and mechanisms, the potential impact of and consequences for comorbid conditions, and for assessing prognosis and outcomes associated with common urological disorders.     

Hysterectomies and Urologic Symptoms: Results from the Boston Area Community Health (BACH) Survey

OBJECTIVES: To describe the characteristics of women who have had a hysterectomy and to assess the association of a past hysterectomy on current urologic symptoms. METHODS: The Boston Area Community Health (BACH) survey is a random sample of Boston, Massachusetts residents aged 30-79 years using a stratified two-stage cluster design (3202 women; 1067 Black, 1111 Hispanic, 1024 White). Urologic symptoms, hysterectomy, co-morbidities, lifestyle factors, and medical indications for a hysterectomy were by self-report. Socioeconomic status was measured as a combination of education and income. RESULTS: Hysterectomies were reported by 587 women and 1782 women reported one or more urologic symptoms. Minorities and those of lower socioeconomic status are more likely to have had a hysterectomy, even after adjusting for age and potential medical indications for a hysterectomy. Hispanic women were least likely to report fibroids, polycystic ovarian syndrome, or genitourinary cancers, but they were more likely to have had a hysterectomy if they reported these conditions than Black or White women. Women with a hysterectomy were more likely to report lower urinary tract symptoms, painful bladder syndrome, urinary frequency, urgency, and overactive bladder after adjusting for age, race/ethnicity, socioeconomic status, body mass index, depression, diabetes, heart disease, hypertension, smoking history, alcohol use, and physical activity. CONCLUSIONS: Minorities and those of lower socioeconomic status are more likely to report having a hysterectomy and urologic symptoms (including painful bladder syndrome) may be an unintended consequence of a hysterectomy.     

Association of overactive bladder and C-reactive protein levels. Results from the Boston Area Community Health (BACH) Survey

Study Type – Aetiology (cohort) Level of Evidence 3a What's known on the subject? and What does the study add? Evidence of chronic inflammation in benign prostatic hyperplasia suggests a role of inflammation in the development of lower urinary tract symptoms. However, few studies have investigated the association of inflammation and overactive bladder in both men and women. Results of this population‐based study show a consistent association of increased C‐reactive protein levels with overactive bladder in both men and women. These results support the hypothesized role of inflammation in the development of overactive bladder.

OBJECTIVE

• ? To investigate the association between overactive bladder (OAB) and C‐reactive protein (CRP) in a population‐based sample of men and women.

SUBJECTS AND METHODS

• ? Epidemiological survey of urological symptoms among men and women aged 30–79 years. A multi‐stage stratified cluster design was used to randomly sample 5503 adults from the city of Boston. Analyses were conducted on 1898 men and 1854 women with available CRP levels.
• ? The International Continence Society defines OAB as ‘Urgency with or without urge incontinence, usually with frequency and nocturia.’ OAB was defined as: (1) urgency, (2) urgency with frequency, and (3) urgency with frequency and nocturia.
• ? Odds ratios (OR) and 95% confidence intervals (95% CI) of the CRP and OAB association were estimated using logistic regression.

RESULTS

• ? Prevalence of OAB increased with CRP levels in both men and women.
• ? In men, adjusted ORs (95% CI) per log₁₀(CRP) levels were 1.90 (1.26–2.86) with OAB defined as urgency, 1.65 (1.06–2.58) with OAB defined as urgency and frequency, and 1.92 (1.13–3.28) with OAB defined as urgency, frequency and nocturia.
• ? The association was more modest in women with ORs (95% CI) of 1.53 (1.07–2.18) for OAB as defined urgency, 1.51 (1.02–2.23) for OAB defined as urgency and frequency, and 1.34 (0.85–2.12) for OAB defined as urgency, frequency and nocturia.

CONCLUSIONS

• ? Results show a consistent association of increasing CRP levels and OAB among both men and women.
• ? These results support our hypothesis for the role of inflammation in the development of OAB and a possible role for anti‐inflammatory agents in its treatment.

     

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.     

Modifiable risk factors for benign prostatic hyperplasia and lower urinary tract symptoms: new approaches to old problems

PURPOSE: Benign prostatic hyperplasia is generally not regarded as a preventable disease. However, accumulating evidence suggests that modifiable factors may influence the risk of benign prostatic hyperplasia and lower urinary tract symptoms. MATERIALS AND METHODS: A structured, comprehensive literature review was done to identify modifiable risk factors for benign prostatic hyperplasia and lower urinary tract symptoms among observational studies of older men. RESULTS: Outcome measures used to define benign prostatic hyperplasia in clinical studies include histological analysis of prostate tissue, radiographically determined prostate enlargement, acute urinary retention, decreased urinary flow rate, pressure flow studies consistent with bladder outlet obstruction, history of benign prostatic hyperplasia surgery, physician diagnosed benign prostatic hyperplasia and American Urological Association symptom score or International Prostate Symptom Score. Factors that potentially increase the risk of benign prostatic hyperplasia and lower urinary tract symptoms include obesity and diabetes. Factors that potentially decrease the risk include increased physical activity and moderate alcohol consumption. Other candidate factors for which clear risk patterns have not yet emerged are dyslipidemia, hypertension, smoking, diet and environment. CONCLUSIONS: Obesity, diabetes, physical activity and alcohol intake may substantially influence the risk of benign prostatic hyperplasia and lower urinary tract symptoms in older men. Further analyses of these and other potential modifiable risk factors may identify novel interventions for the prevention, diagnosis and treatment of these highly prevalent conditions.     

Association between smoking, passive smoking, and erectile dysfunction: results from the Boston Area Community Health (BACH) Survey

INTRODUCTION: Although previous studies report an association between erectile dysfunction (ED) and smoking, few have examined the impact of passive smoke exposure on ED. This analysis examines the association of active and passive smoking and ED and investigates a dose-response effect of smoking. METHODS: The Boston Area Community Heath (BACH) survey is a study of urologic symptoms in a racially and ethnically diverse population. BACH used a multistage stratified random sample to recruit 2301 men, aged 30-79 yr, from the city of Boston. ED was assessed using the five-item International Index of Erectile Function. Smoking and passive smoking were assessed by self-report. Analyses adjusted for sociodemographic and lifestyle factors and important chronic illnesses. RESULTS: An association between smoking and ED was observed with a significant trend in increased risk of ED with cumulative pack-years of smoking (adjusted odds ratio [OR]=1.68; 95% confidence interval [CI], 1.03, 2.30 for > or =20 pack-years). Compared to never smokers not exposed to passive smoking, men who never smoked but were exposed to passive smoking had a moderate, statistically nonsignificant, increase in risk of ED (adjusted OR=1.33; 95%CI: 0.69, 2.55) comparable to the OR observed for a cumulative exposure of 10-19 pack-years of active smoking (adjusted OR=1.25; 95%CI, 0.68, 2.30). CONCLUSIONS: Results indicate a dose-response association between smoking and ED with a statistically significant effect observed with > or =20 pack-years of exposure. Passive smoking is associated with a small, statistically nonsignificant increase in risk of ED comparable to approximately 10-19 pack-years of active smoking.     

Measuring the urologic iceberg: design and implementation of the Boston Area Community Health (BACH) Survey

OBJECTIVES: To describe the Boston Area Community Health (BACH) survey, a National Institutes of Health-supported epidemiological study of symptoms suggestive of the following urologic conditions: urinary incontinence, benign prostatic hyperplasia, interstitial cystitis, chronic pelvic pain of bladder origin, prostatitis, hypogonadism, erectile dysfunction, and female sexual dysfunction. METHODS: BACH used a two-stage stratified cluster design to recruit a community-based random sample of 5506, divided between males (2301) and females (3205), three racial/ethnic groups (black, Hispanic, and white), and four age groups (30-39, 40-49, 50-59, 60-79 yr). Validated questionnaires were used to collect information on urologic symptoms, comorbidities, prescribed and over-the-counter medications, reproductive history, quality of life, health care utilization, physical activity, depressive symptoms, interpersonal stress, smoking, alcohol use, fluid intake, nutrition, menopausal status, sexual activity, abuse, anthropometrics (measured height, weight, hip and waist circumference, pulse rate, blood pressure), and sociodemographics including country of origin, marital status, employment status, and income. Blood samples were collected from 68% of all subjects. RESULTS: A large representative community-based sample was successfully recruited to provide both cross-sectional and eventually longitudinal data to address important urologic questions. CONCLUSIONS: BACH has features distinguishing it from most other epidemiological studies in urology. It uses a random community-based sample of people who are racially/ethnically diverse and includes a broad age range (30-79 yr). It includes both males and females The study focuses on symptoms rather than variably defined disease conditions, it is multidisciplinary, and it is designed to become longitudinal.     

Video urodynamics using transrectal ultrasonography for lower urinary tract symptoms in women

AIMS: To understand the properties of lower urinary tract disorders in women, we evaluated 60 female patients with lower urinary tract disorders or symptoms of recurrent cystitis by free uroflowmetry and video urodynamics using transrectal ultrasonography (VU-TRUS). METHODS: Results of urodynamic studies or symptoms of stress incontinence were used to divide 60 women into 7 normal controls and 53 with voiding dysfunctions. RESULTS: In normal controls, VU-TRUS showed that the mean posterior urethrovesical angle and anteroposterior diameter of the proximal urethra at maximum flow was 151.4 degrees and 4.9 mm, respectively. In patients with voiding dysfunction, VU-TRUS during voiding revealed various urethral abnormalities, including 16 detrusor sphincter dyssynergia, 4 detrusor bladder neck dyssynergia, and 13 insufficient opening of the entire urethra. VU-TRUS also showed pelvic floor abnormalities, including 24 urethral hypermobilities (group 1) and 11 cystoceles (group 2). Eighteen patients had neither urethral hypermobility nor cystocele (group 3). Major pressure-flow abnormalities in the 53 patients with voiding dysfunctions were weak detrusor (72%) and/or bladder outlet obstruction (25%). There were no significant differences in the distribution of the pressure-flow abnormalities among the three groups. However, the mean values of abdominal pressure at maximum flow of group 1 (20.9 cm H(2)O) and group 2 (17.9 cm H(2)O) were significantly higher than that of group 3 (6.3 cm H(2)O; each P < 0.05). The mean values of residual urine volume of group 2 (60.8 mL) and group 3 (77.6 mL) were significantly higher than that of group 1 (23.5 mL; each P < 0.05). CONCLUSIONS: The symptoms of women with lower urinary tract disorders were frequently accompanied by urethral and/or pelvic floor abnormalities during voiding that were clearly detected by VU-TRUS. VU-TRUS is useful for objective evaluation of female lower urinary tract symptoms.     

Nocturia in patients with lower urinary tract symptoms: association with diurnal voiding patterns

OBJECTIVE: To determine whether diurnal voiding patterns predict nocturia in patients with lower urinary tract symptoms (LUTS), as few studies have evaluated the association between diurnal and nocturnal voiding patterns. PATIENTS AND METHODS: We prospectively analysed the frequency-volume charts (FVCs) of consecutive patients with LUTS. At the initial visit patients had a detailed clinical evaluation and subsequently were requested to complete a 72-h FVC. In all, 104 (41 men and 63 women, mean age 63 years, range 50-83) were included in the primary analyses. Associations between daytime variables and nocturia were described using maximum likelihood estimates of the relative risk and by 95% confidence intervals (CIs) based on logistic regression models. RESULTS: When at least one night-time void was used to define nocturia the multivariate logistic model showed a negative association of mean daytime voided volume with nocturia (P = 0.001). The odds ratio for nocturia decreased with this variable to 0.98 (95% CI 0.96-0.99). When 'voiding at least twice per night' was used to define nocturia only the number of daytime voids was positively related to nocturia (odds ratio 1.22; 95% CI 1.01-1.48; P= 0.040). CONCLUSION: Nocturia may be associated with diurnal voiding patterns; these results also suggest that the causes of nocturia of one or of two or more voids may differ. This highlights the role of bladder function in more severe forms of nocturia.     

Intermittent tamsulosin therapy in men with lower urinary tract symptoms

PURPOSE: We investigated in what is to our knowledge the first prospective study the safety and efficacy of intermittent tamsulosin therapy in patients with lower urinary tract symptoms. MATERIALS AND METHODS: This study was performed between January 2001 and February 2003 in 140 patients. In phase 1 of this study patients received 1, 0.4 mg tamsulosin capsule daily for 3 months and were reevaluated after 3 months. At this assessment uroflowmetry, International Prostate Symptom Score and ultrasonographic estimation of residual urine were determined. In phase 2 responders to tamsulosin therapy were then randomized into 1 of 3 groups, namely group 1--continued 4 mg tamsulosin once daily every day, group 2--0.4 mg tamsulosin once daily every other day and group 3--discontinued tamsulosin. Efficacy assessments were done again at 4, 12 and 24 weeks. RESULTS: There were no statistically differences among the patients in groups 1 and 2 at 6 months for International Prostate Symptom Score, maximum or average urine flow, or residual urine. Differences between patients in groups 1 and 3 were statistically significant at 6 months. Differences between patients in groups 2 and 3 were also statistically significant at 6 months for these parameters. CONCLUSIONS: Tamsulosin at a dose of 0.4 mg once daily and 0.4 mg once daily every other day for lower urinary tract symptoms provide comparable improvements in urinary flow and symptoms. Each treatment was well tolerated.     

Tadalafil relieves lower urinary tract symptoms secondary to benign prostatic hyperplasia

PURPOSE: We assessed the efficacy and safety of tadalafil dosed once daily for lower urinary tract symptoms secondary to benign prostatic hyperplasia. MATERIALS AND METHODS: Following a 4-week, single-blind, placebo run-in 281 men were randomly assigned (1:1) to 5 mg tadalafil for 6 weeks, followed by dose escalation to 20 mg for 6 weeks or 12 weeks of placebo. RESULTS: Tadalafil significantly improved the mean change from baseline in International Prostate Symptom Score at 6 weeks (5 mg tadalafil -2.8 vs placebo -1.2) and at 12 weeks (5/20 mg tadalafil -3.8 vs placebo -1.7). Larger changes were observed with inclusion of the placebo run-in at 12 weeks (5/20 mg tadalafil -7.1 vs placebo -4.5). Significant improvements were also seen in the International Prostate Symptom Score irritative and obstructive domains, the International Prostate Symptom Score quality of life index, a question about urinary symptom improvement and the Benign Prostatic Hyperplasia Impact Index (significant at 12 weeks) vs placebo. International Prostate Symptom Score and International Index of Erectile Function erectile function domain scores significantly improved in the 56% of men with lower urinary tract symptoms/benign prostatic hyperplasia who were sexually active and had erectile dysfunction. Changes in uroflowmetry parameters were similar in the placebo and tadalafil groups. Commonly reported (2% or greater) treatment emergent adverse events were "erection increased," dyspepsia, back pain, headache, nasopharyngitis and upper respiratory tract infection (each 5.1% or less). No change in post-void residual volume was seen with tadalafil treatment. CONCLUSIONS: Tadalafil once daily was well tolerated and demonstrated clinically meaningful and statistically significant symptomatic improvement for lower urinary tract symptoms/benign prostatic hyperplasia. Tadalafil also improved erectile function in men with lower urinary tract symptoms and erectile dysfunction.     

Voiding diary for the evaluation of urinary incontinence and lower urinary tract symptoms: prospective assessment of patient compliance and burden

AIMS: Voiding diary duration may be related to patient compliance and burden. To test this hypothesis, we evaluated patient compliance and burden. METHODS: Between January and July 2002, we prospectively evaluated 162 patients (57 males and 105 females, mean age 53.0, range 20-81 years) with stress urinary incontinence or lower urinary tract symptoms. At the initial visit, all patients underwent a detailed clinical evaluation including an International Prostate Symptom Score (I-PSS) assessment and were randomly requested to complete 2-day, 3-day, or 7-day voiding diaries (the three study groups). At the second visit, a simple self-administered questionnaire was completed by all patients. The questionnaire included 11 items on subject demographics and voiding diary-keeping. RESULTS: No significant differences were found in either the accuracy of diary-keeping or the daily average number of omissions when the three groups were compared. However, as the diary duration increased, the mean burden scores increased (P = 0.005), and the mean preferred duration of the diary in the 7-day group was significantly higher than that of the 2-day or 3-day groups (P < 0.001). After categorizing patients into two groups according to the degree of patient burden, members of the group with a greater perceived burden were found to have a significantly higher I-PSS quality of life score (P = 0.045) and to have kept a diary for a longer time (P = 0.038). CONCLUSIONS: Our results suggest that keeping a diary for 7 days may increase patient burden and thus, we recommend that the 7-day diary should be reduced to cover fewer days.