Depression and Coping Behaviors Are Key Factors in Understanding Pain in Interstitial Cystitis/Bladder Pain Syndrome.

BACKGROUND: Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a urologic chronic pelvic pain syndrome with suboptimal treatment outcomes. Catastrophizing is an empirically supported risk factor for greater IC/BPS pain. AIMS: In this study, a moderated multiple mediation model is tested in which several additional psychosocial risk factors (depression, illness and wellness-focused behavioral coping strategies) are proposed as mediators or moderators in the existing relationship between catastrophizing and IC/BPS pain. DESIGN: The present questionnaire study employed a cross-sectional design. SETTINGS AND PARTICIPANTS: Female patients with an IC/BPS diagnosis (n = 341) were recruited at tertiary care sites. METHODS: Participants completed questionnaires assessing pain, catastrophizing, behavioral coping strategies, and depressive symptoms. Aggregate factor scores were calculated following exploratory factor analyses. RESULTS: It was found that patients with a greater tendency to catastrophize were more likely to engage in illness-focused coping strategies, which contributed to the reporting of greater sensory and affective pain. Furthermore, this mediating effect of illness-focused coping on affective pain was more likely to occur in those patients reporting greater depressive symptoms. CONCLUSIONS: Illness-focused behavioral coping is an important mechanism between maladaptive pain cognition and aspects of patient pain, with patients reporting greater depressive symptoms at increased risk for elevated pain. Patient management techniques, including screening for catastrophizing, coping, and depression, are recommended to enrich IC/BPS management.

Understanding pain and coping in women with interstitial cystitis/bladder pain syndrome.

OBJECTIVES: To examine a self-regulation and coping model for interstitial cystitis/bladder pain syndrome (IC/BPS) that may help us understand the pain experience of patients with chronic IC/BPS. PATIENTS AND METHODS: The model tested illness perceptions, illness-focused coping, emotional regulation, mental health and disability in a stepwise method using factor analysis and structural equation modelling. Step 1, explored the underlying constructs. Step 2, confirmed the measurement models to determine the structure/composition of the main constructs. Step 3, evaluated the model fit and specified pathways in the proposed IC/BPS self-regulation model. In all, 217 female patients with urologist diagnosed IC/BPS were recruited and diagnosed across tertiary care centres in North America. The data were collected through self-report questionnaires. RESULTS: An IC/BPS self-regulation model was supported. Physical disability was worsened by patient's negative perception of their illness, attempts to cope using illness-focused coping and poorer emotional regulation. Mental health was supported by perceptions that individuals could do something about their illness, using wellness-focused behavioural strategies and adaptive emotion regulation. CONCLUSIONS: The results clarify the complex and unique process of self-regulation in women with IC/BPS, implicating cognitive and coping targets, and highlighting emotional regulation. This knowledge should help clinicians understand and manage these patients' distress and disability.

Assessment of the Lower Urinary Tract Microbiota during Symptom Flare in Women with Urologic Chronic Pelvic Pain Syndrome: A MAPP Network Study.

PURPOSE: We compared culture independent assessment of microbiota of the lower urinary tract in standard culture negative female patients with urological chronic pelvic pain syndrome who reported symptom flare vs those who did not report a flare. MATERIALS AND METHODS: Initial stream (VB1) and midstream (VB2) urine specimens (233 patients with urological chronic pelvic pain syndrome) were analyzed with Ibis T-5000 Universal Biosensor system technology for comprehensive identification of microorganism species. Differences between flare and nonflare groups for presence or number of different species within a higher level group (richness) were examined by permutational multivariate analysis of variance and logistic regression. RESULTS: Overall 81 species (35 genera) were detected in VB1 and 73 (33) in VB2. Mean (SD) VB1 and VB2 species count per person was 2.6 (1.5) and 2.4 (1.5) for 86 flare cases and 2.8 (1.3) and 2.5 (1.5) for 127 nonflare cases, respectively. Overall the species composition did not significantly differ between flare and nonflare cases at any level (p=0.14 species, p=0.95 genus in VB1 and VB2, respectively) in multivariate analysis for richness. Univariate analysis, unadjusted as well as adjusted, confirmed a significantly greater prevalence of fungi (Candida and Saccharomyces) in the flare group (15.7%) compared to the nonflare group in VB2 (3.9%) (p=0.01). When adjusted for antibiotic use and menstrual phase, women who reported a flare remained more likely to have fungi present in VB2 specimens (OR 8.3, CI 1.7-39.4). CONCLUSIONS: Among women with urological chronic pelvic pain syndrome the prevalence of fungi (Candida and Saccharomyces sp.) was significantly greater in those who reported a flare compared to those who did not.

Cost analysis of fixed-dose combination of dutasteride and tamsulosin compared with concomitant dutasteride and tamsulosin monotherapy in patients with benign prostatic hyperplasia in Canada.

INTRODUCTION: We estimate the lifetime cost of treatment for moderate/severe symptoms associated with benign prostatic hyperplasia (BPH) in a cohort of Canadian men aged 50 to 59, and we evaluate the costs of 2 daily bioequivalent treatment options: fixed-dose combination (FDC) of dutasteride (0.5 mg) and tamsulosin (0.4 mg), or concomitant administration of dutasteride (0.5 mg) and tamsulosin (0.4 mg) monotherapies. METHODS: The expected lifetime costs were estimated by modelling the incidence of acute urinary retention (AUR), BPH-related surgery and clinical progression over a patient's lifetime (up to 25 years). A model was developed to simulate clinical events over time, based on a discrete Markov process with 6 mutually exclusive health states and annual cycle length. RESULTS: The estimated lifetime budget cost for the cohort of 374 110 men aged 50 to 59 in Canada is between $6.35 billion and $7.60 billion, equivalent to between $16 979 and $20 315 per patient with moderate/severe symptoms associated with BPH. Costs are lower for FDC treatment, with the net difference in lifetime budget impact between the 2 treatment regimens at $1.25 billion. In this analysis, the true costs of BPH in Canada are underestimated for 2 main reasons: (1) to make the analysis tractable, it is restricted to a cohort aged 50 to 59, whereas BPH can affect all men; and (2) a closed cohort approach does not include the costs of new (incident) cases. CONCLUSION: Canadian clinical guidelines recommend the use of the combination of tamsulosin and dutasteride for men with moderate/severe symptoms associated with BPH and enlarged prostate volume. This analysis, using a representational patient group, suggests that the FDC is a more cost-effective treatment option for BPH.

Cost-effectiveness of dutasteride-tamsulosin combination therapy for the treatment of symptomatic benign prostatic hyperplasia: A Canadian model based on the CombAT trial.

INTRODUCTION: Benign prostatic hyperplasia (BPH) is common in men 50 years old and older. The main treatment options are alpha-blockers (such as tamsulosin), which reduce symptoms, and 5-alpha reductase inhibitors (such as dutasteride), which reduce symptoms and slow disease progression. Clinical studies have demonstrated that dutasteride-tamsulosin combination therapy is more effective than either monotherapy to treat symptomatic BPH. We studied the cost-effectiveness in Canada of the dutasteride (0.5 mg/day) and tamsulosin (0.4 mg/day) combination compared with tamsulosin or dutasteride monotherapy. METHODS: A Markov model was developed which follows a cohort of male BPH patients ≥50 with moderate to severe lower urinary tract symptoms (LUTS). The model estimates costs to the Canadian health care system and outcomes (in terms of quality adjusted life years [QALYs]) at 10 years and over a patient's lifetime. The dutasteride-tamsulosin combination was compared to each of tamsulosin monotherapy and dutasteride monotherapy. RESULTS: Compared with tamsulosin, the combination was more costly and produced better patient outcomes. Over a lifetime, the incremental cost-effectiveness ratio was CAN$25 437 per QALY gained. At a willingness to pay CAN$50 000 per QALY, the probability of combination therapy being cost-effective was 99.6%. Compared with dutasteride, the combination therapy was the dominant option from year 2, offering improved patient outcomes at lower cost. The probability that combination therapy is more cost-effective than dutasteride was 99.8%. CONCLUSION: Combination therapy offers important clinical benefits for patients with symptomatic BPH, and there is a high probability that it is cost-effective in the Canadian health care system relative to either monotherapy.

National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) symptom evaluation in multinational cohorts of patients with chronic prostatitis/chronic pelvic pain syndrome.

BACKGROUND: The assessment of patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in everyday practice and clinical studies relies on National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) scores for symptom appraisal, inclusion criteria for clinical trials, follow-up, and response evaluation. OBJECTIVE: We investigated multiple databases of CP/CPPS patients to determine the prevalence and impact of pain locations and types to improve our strategy of individualized phenotypically guided treatment. DESIGN, SETTING, AND PARTICIPANTS: Four major databases with CPSI scores for nonselected CP/CPPS clinic patients from Canada, Germany, Italy, and the United States. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Individual question scores and subtotal and total scores of CPSI were described and correlated with each other. Ordinal regression analysis was performed to define pain severity categories. RESULTS AND LIMITATIONS: A total of 1563 CP/CPPS patients were included. Perineal pain/discomfort was the most prevalent pain symptom (63%) followed by testicular pain (58%), pain in the pubic area (42%) and penis (32%); reports of pain during ejaculation and voiding were 45% and 43%, respectively. European patients had a significantly higher number of pain localizations and symptoms compared with North American patients (p<0.001). Severity of pain correlated well with frequency of pain (r = 0.645). No specific pain localization/type was associated with more severe pain. Correlation of pain domain with quality of life (QoL) (r = 0.678) was higher than the urinary domain (r = 0.320). Individually, pain severity (r = 0.627) and pain frequency (r = 0.594) correlated better with QoL than pain localization (r = 0.354). Pain severity categories results for NIH-CPSI item 4 (0-10 numerical rating scale for average pain) were mild, 0-3; moderate, 4-6; severe, 7-10; CPSI pain domain (0-21): mild, 0-7; moderate, 8-13; and severe, 14-21. CONCLUSIONS: Pain has more impact on QoL than urinary symptoms. Pain severity and frequency are more important than pain localization/type. Cut-off levels for disease severity categories have been identified that will prove valuable in symptom assessment and the development of therapeutic strategies.

Preliminary assessment of safety and efficacy in proof-of-concept, randomized clinical trial of tanezumab for chronic prostatitis/chronic pelvic pain syndrome.

OBJECTIVE: To assess the efficacy and safety of tanezumab, a humanized monoclonal antibody directed against the pain-mediating neurotrophin, nerve growth factor, to treat pain and other symptoms of chronic prostatitis/chronic pelvic pain syndrome in a Phase IIa, proof-of-concept clinical trial powered to provide 2-sided 90% confidence interval around the primary endpoint. METHODS: Patients received a single intravenous dose of tanezumab (20 mg) or placebo. The primary efficacy endpoint was the change from baseline to week 6 in average daily numerical rating scale pain score. The secondary endpoints included the change from baseline to week 6 in the National Institutes of Health Chronic Prostatitis Symptom Index and urinary symptoms. Safety was also assessed. RESULTS: Overall, 62 patients were randomized (30 to tanezumab and 32 to placebo). At week 6, tanezumab marginally improved the average daily pain (least-squares mean difference from placebo -0.47, 90% confidence interval -1.150-0.209) and urgency episode frequency (least-squares mean difference from placebo -1.37, 90% confidence interval -3.146-0.401). No difference was seen in the National Institutes of Health chronic prostatitis symptom index total score or micturition frequency at week 6. The most common adverse events were paresthesia and arthralgia. The odds of having a ≥ 30% reduction in pain were 1.75-fold greater (90% confidence interval 0.65-4.69) for patients receiving tanezumab versus placebo. CONCLUSION: Tanezumab might improve symptoms for some patients with chronic prostatitis/chronic pelvic pain syndrome. Although proof of concept was not demonstrated in the present study, additional studies with larger populations and stricter inclusion criteria according to patient phenotype might identify populations in which antinerve growth factor treatment will provide clinical benefit.

The economics of medical therapy for lower urinary tract symptoms associated with benign prostatic hyperplasia.

Medical therapy is currently the most popular treatment choice for lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). Because medical therapy of BPH-related LUTS is considered a life-long strategy, short- and long-term cost considerations should play a major role in therapeutic decision-making. The effectiveness in terms of long and short amelioration of symptoms, flow rate, and quality of life are well documented for 5alpha-blockers and 5alpha-reductase inhibitors as well as for the gold standard treatment for BPH, transurethral resection of the prostate and minimally invasive therapies. Short- and long-term safety concerns also are well documented for these various treatment options. On the contrary, short- and long-term costs have been less well studied and comparisons depend on the model or analyses undertaken in the few studies available. However, the economic studies based on prospective clinical trial data that have become available throughout the past several decades allow us to rationalize our use of alpha- blockers, 5alpha-reductase inhibitors, and combination therapy, taking into consideration age, severity of symptoms, prostate volume, prostate-specific antigen, and the differential response of the various medications (and combination) in selected patients. Based on current studies, 5alpha-blockers generally provide cost-effective therapy for most patients, whereas 5alpha-reductase therapy and combination therapy provide cost-effective treatment for patients with larger prostate glands or higher baseline prostate-specific antigen levels.

BPH: costs and treatment outcomes.

The current treatments for benign prostatic hyperplasia (BPH) include pharmacotherapy with alpha1-selective adrenergic receptor (a1-AR) antagonists, 5-alpha-reductase inhibitors (5-aRIs), and a range of invasive and minimally invasive interventions, each of which is effective in the amelioration of lower urinary tract symptoms (LUTS) and the prevention of symptom progression and BPH-related complications. Pharmacotherapy is considered the mainstay of treatment for LUTS caused by BPH. The available a1-AR antagonists have comparable efficacy for the relief of LUTS and to enhance patients' quality of life. The use of nonsubtype-selective drugs in this class may precipitate vasodilatory adverse events such as dizziness, somnolence, and orthostatic hypotension. Based on current studies, a1-AR antagonists are more cost effective (particularly the subtype-selective a1-AR antagonist, tamsulosin) than the 5-aRIs (eg, finasteride) and comparable in cost to transurethral resection of the prostate and minimally invasive therapies. There are few cost-effectiveness studies comparing the various pharmacologic interventions for BPH. Only 1 cost-analysis model has addressed the impact of adverse events on the cost effectiveness of pharmacotherapy for BPH. The publication of additional analyses would contribute to the appropriate selection of therapy in patients with BPH.

An economic evaluation of doxazosin, finasteride and combination therapy in the treatment of benign prostatic hyperplasia.

OBJECTIVE: The Proscar Long-Term Efficacy and Safety Study (PLESS) and the Medical Therapy of Prostatic Symptoms (MTOPS) study provide new evidence regarding the benefits of finasteride in the treatment of benign prostatic hyperplasia (BPH). The objective of this study was to utilize data from the PLESS and MTOPS studies to assess the cost-utility of finasteride and finasteride in combination with doxazosin, compared to doxazosin alone in men with moderate to severe BPH symptoms. METHODS: A semi-Markov decision analytic model was constructed to estimate the clinical consequences, costs and cost-utility of doxazosin, finasteride, and combination therapy. Analyses were conducted for a 15-year time frame from the perspective of the Ontario Ministry of Health and Long Term Care (MOHLTC). Results are reported stratified by baseline serum prostate-specific antigen (PSA) level according to all baseline serum PSA levels, patients with baseline serum PSA > 1.3 ng/ml, and patients with baseline serum PSA > 3.2 ng/ml. RESULTS: Compared to doxazosin alone, combination therapy was more expensive but more effective. Cost-utility ratios ranged from 27,823 dollars/QALY for patients with PSA > 3.2 ng/ml to 34,085 dollars/QALY for all patients. Finasteride, although dominated by doxazosin, may be cost-effective compared to watchful waiting in patients who fail doxazosin and do not choose to proceed to surgery. Compared to watchful waiting, cost-utility ratios for finasteride ranged from 35016 dollars/QALY for patients with PSA > 3.2 ng/ml to 44,336 dollars/QALY for all patients. Results were robust across a wide range of sensitivity analyses. CONCLUSIONS: Combination therapy is cost-effective compared to doxazosin with cost-utility ratios under 40,000 dollars/QALY across a wide range of scenarios. The cost-effectiveness of combination therapy increases as serum PSA level increases.