the National Overactive BLadder Evaluation (NOBLE) Program was initiated to better understand the prevalence and burden of overactive bladder in a broad spectrum of the United States population.
to ...estimate the prevalence of overactive bladder with and without urge incontinence in the US, assess variation in prevalence by sex and other factors, and measure individual burden.
US national telephone survey using a clinically validated interview and a follow-up nested study comparing overactive bladder cases to sex- and age-matched controls.
noninstitutionalized US adult population.
a sample of 5,204 adults >/=18 years of age and representative of the US population by sex, age, and geographical region.
prevalence of overactive bladder with and without urge incontinence and risk factors for overactive bladder in the US. In the nested case-control study, SF-36, CES-D, and MOS sleep scores were used to assess impact.
the overall prevalence of overactive bladder was similar between men (16.0%) and women (16.9%), but sex-specific prevalence differed substantially by severity of symptoms. In women, prevalence of urge incontinence increased with age from 2.0% to 19% with a marked increase after 44 years of age, and in men, increased with age from 0.3% to 8.9% with a marked increase after 64 years of age. Across all age groups, overactive bladder without urge incontinence was more common in men than in women. Overactive bladder with and without urge incontinence was associated with clinically and significantly lower SF-36 quality-of-life scores, higher CES-D depression scores, and poorer quality of sleep than matched controls.
the NOBLE studies do not support the commonly held notion that women are considerably more likely than men to have urgency-related bladder control problems. The overall prevalence of overactive bladder does not differ by sex; however, the severity and nature of symptom expression does differ. Sex-specific anatomic differences may increase the probability that overactive bladder is expressed as urge incontinence among women compared with men. Nonetheless, overactive bladder, with and without incontinence, has a clinically significant impact on quality-of-life, quality-of-sleep, and mental health, in both men and women.
Objective To determine the prevalence of chronic and debilitating symptoms of the overactive bladder, defined here as the presence of chronic frequency, urgency and urge incontinence (either alone or ...in any combination), and presumed to be caused by involuntary detrusor contractions.
Subjects and methods Data were collected using a population‐based survey (conducted by telephone or direct interview) of men and women aged 40 years, selected from the general population in France, Germany, Italy, Spain, Sweden and the United Kingdom, using a random stratified approach. The main outcome measures were: prevalence of urinary frequency (> 8 micturitions/24 h), urgency and urge incontinence; the proportion of participants who had sought medical advice for symptoms of an overactive bladder; and current or previous therapy received for these symptoms.
Results In all, 16 776 interviews were conducted in the six European countries. The overall prevalence of overactive bladder symptoms in individuals aged 40 years was 16.6%. Frequency (85%) was the most commonly reported symptom, followed by urgency (54%) and urge incontinence (36%). The prevalence of overactive bladder symptoms increased with advancing age. Overall, 60% of respondents with symptoms had consulted a doctor but only 27% were currently receiving treatment.
Conclusion Symptoms of an overactive bladder, of which frequency and urgency are as bothersome as urge incontinence, are highly prevalent in the general population. However, only a few affected individuals currently receive treatment. Taken together, such findings indicate that there is considerable scope for improvement in terms of how physicians diagnose and treat this condition.
This pilot study was designed to evaluate the feasibility of a multicenter, randomized, clinical trial in interstitial cystitis (IC). Secondary objectives were to evaluate the safety and efficacy of ...oral pentosan polysulfate sodium (PPS), hydroxyzine, and the combination to consider their use in a larger randomized clinical trial.
A 2 × 2 factorial study design was used to evaluate PPS and hydroxyzine. Participants met the National Institutes of Health-National Institute for Diabetes and Digestive and Kidney Diseases criteria for IC and reported at least moderate pain and frequency for a minimum of 6 months before study entry. The primary end point was a patient reported global response assessment. Secondary end points included validated symptom indexes and patient reports of pain, urgency and frequency. The target sample size was 136 participants recruited during 10 months.
A total of 121 (89% of goal) participants were randomized over 18 months and 79% provided complete followup data. The response rate for hydroxyzine was 31% for those treated and 20% for those not treated (p = 0.26). A nonsignificant trend was seen in the PPS treatment groups (34%) as compared to no PPS (18%, p = 0.064). There were no treatment differences for any of the secondary end points. Adverse events were mostly minor and similar to those in previous reports.
The low global response rates for PPS and hydroxyzine suggest that neither provided benefit for the majority of patients with IC. This trial demonstrated the feasibility of conducting a multicenter randomized clinical trial in IC using uniform procedures and outcomes. However, slow recruitment underscored the difficulties of evaluating commonly available IC drugs.
1
The effectiveness of antimuscarinic agents in the treatment of the overactive bladder (OAB) syndrome is thought to arise through blockade of bladder muscarinic receptors located on detrusor smooth ...muscle cells, as well as on nondetrusor structures.
2
Muscarinic M3 receptors are primarily responsible for detrusor contraction. Limited evidence exists to suggest that M2 receptors may have a role in mediating indirect contractions and/or inhibition of detrusor relaxation. In addition, there is evidence that muscarinic receptors located in the urothelium/suburothelium and on afferent nerves may contribute to the pathophysiology of OAB. Blockade of these receptors may also contribute to the clinical efficacy of antimuscarinic agents.
3
Although the role of muscarinic receptors in the bladder, other than M3 receptors, remains unclear, their role in other body systems is becoming increasingly well established, with emerging evidence supporting a wide range of diverse functions. Blockade of these functions by muscarinic receptor antagonists can lead to similarly diverse adverse effects associated with antimuscarinic treatment, with the range of effects observed varying according to the different receptor subtypes affected.
4
This review explores the evolving understanding of muscarinic receptor functions throughout the body, with particular focus on the bladder, gastrointestinal tract, eye, heart, brain and salivary glands, and the implications for drugs used to treat OAB. The key factors that might determine the ideal antimuscarinic drug for treatment of OAB are also discussed. Further research is needed to show whether the M3 selective receptor antagonists have any advantage over less selective drugs, in leading to fewer adverse events.
British Journal of Pharmacology (2006) 148, 565–578. doi:10.1038/sj.bjp.0706780
The lower urinary tract constitutes a functional unit controlled by a complex interplay between the central and peripheral nervous systems and local regulatory factors. In the adult, micturition is ...controlled by a spinobulbospinal reflex, which is under suprapontine control. Several central nervous system transmitters can modulate voiding, as well as, potentially, drugs affecting voiding; for example, noradrenaline, GABA, or dopamine receptors and mechanisms may be therapeutically useful. Peripherally, lower urinary tract function is dependent on the concerted action of the smooth and striated muscles of the urinary bladder, urethra, and periurethral region. Various neurotransmitters, including acetylcholine, noradrenaline, adenosine triphosphate, nitric oxide, and neuropeptides, have been implicated in this neural regulation. Muscarinic receptors mediate normal bladder contraction as well as at least the main part of contraction in the overactive bladder. Disorders of micturition can roughly be classified as disturbances of storage or disturbances of emptying. Failure to store urine may lead to various forms of incontinence, the main forms of which are urge and stress incontinence. The etiology and pathophysiology of these disorders remain incompletely known, which is reflected in the fact that current drug treatment includes a relatively small number of more or less well-documented alternatives. Antimuscarinics are the main-stay of pharmacological treatment of the overactive bladder syndrome, which is characterized by urgency, frequency, and urge incontinence. Accepted drug treatments of stress incontinence are currently scarce, but new alternatives are emerging. New targets for control of micturition are being defined, but further research is needed to advance the pharmacological treatment of micturition disorders.
Background: Pathways involved in androgen metabolism have been implicated in the etiology of prostate cancer. The goal of this study was to evaluate the effect of CYP3A4, a gene associated with the ...oxidative deactivation of testosterone, on the clinical presentation of prostate cancers. Methods: A polymerase chain reaction-based approach was used to identify sequence variants of the human CYP3A4 gene. To ascertain whether allelic variants of the CYP3A4 gene were associated with tumor stage and grade and age of the patient at diagnosis, we determined CYP3A4 genotypes in 230 Caucasian men with incident prostate cancer. Results: We identified a novel genetic variant (CYP3A4-V) that has an altered 5′ regulatory element, containing an A to G mutation, upstream of the CYP3A4 gene. We then compared clinical characteristics of prostate cancers in men who did and did not carry this variant. The presence of the CYP3A4-V allele was associated with a higher tumor-lymph node-metastasis (TNM) stage and Gleason grade. The association between CYP3A4 genotype and tumor stage was most pronounced in men diagnosed at a relatively old age who reported no family history of prostate cancer. In this group, 46% of men with stage T3/T4 tumors carried CYP3A4-V, whereas only 5% of individuals with stage T1 tumors carried CYP3A4-V (adjusted odds ratio = 9.45; 95% confidence interval = 2.54–35.17; x2 1 = 12.28; two-sided P<.001). Conclusions: We determined that a single base change in the 5′ flanking region of the CYP3A4 gene was associated with higher clinical stage and grade in men with prostate tumors. Our results suggest that mutations in the CYP3A4 gene may influence prostate carcinogenesis. J Natl Cancer Inst 1998;90: 1225-9
Nocturia is a prevalent highly bothersome urinary symptom that may significantly detriment the health and well‐being of sufferers. It is characterized by waking at night to void, each void preceded ...and followed by sleep, hence leading to fragmentation of sleep and day‐time tiredness. This may result in reduced productivity in the workplace, which contributes to the significant burden to the wider society that nocturia incurs. Nocturia was traditionally viewed as one of the many urinary tract symptoms that occur due to lower urinary tract dysfunction. However, recently it has been recognized that due to its multi‐factorial aetio‐pathogenesis, nocturia should be viewed as distinct clinical condition in its own right. Careful assessment of the nocturic patient is essential so that treatment strategies are guided by the likely causes. Much research is currently being undertaken into the underlying causes and the optimal management approaches. This review will explore the contemporary status of research on nocturia with a focus on the current and newly available pharmacotherapies.
The last decade has seen a marked shift in how the internal structure of hadrons is understood. Modern experimental facilities, new theoretical techniques for the continuum bound-state problem and ...progress with lattice-regularised QCD have provided strong indications that soft quark+quark (diquark) correlations play a crucial role in hadron physics. For example, theory indicates that the appearance of such correlations is a necessary consequence of dynamical chiral symmetry breaking, viz. a corollary of emergent hadronic mass that is responsible for almost all visible mass in the universe; experiment has uncovered signals for such correlations in the flavour-separation of the proton’s electromagnetic form factors; and phenomenology suggests that diquark correlations might be critical to the formation of exotic tetra- and penta-quark hadrons. A broad spectrum of such information is evaluated herein, with a view to consolidating the facts and therefrom moving toward a coherent, unified picture of hadron structure and the role that diquark correlations might play.
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