Elarekibep (PRS-060/AZD1402), a new class of inhaled Anticalin medicine targeting IL-4Ra for type 2 endotype asthma.

BACKGROUND: Type 2 endotype asthma is driven by IL-4 and IL-13 signaling via IL-4Ra, which is highly expressed on airway epithelium, airway smooth muscle, and immunocytes in the respiratory mucosa, suggesting potential advantages of an inhalable antagonist. Lipocalin 1 (Lcn1), a 16 kDa protein abundant in human periciliary fluid, has a robust drug-like structure well suited to protein engineering, but it has never been used to make an inhaled Anticalin protein therapeutic. OBJECTIVES: We sought to reengineer Lcn1 into an inhalable IL-4Ra antagonist and assess its pharmacodynamic/kinetic profile. METHODS: Lcn1 was systematically modified by directed protein mutagenesis yielding a high-affinity, slowly dissociating, long-acting full antagonist of IL-4Ra designated PRS-060 with properties analogous to dupilumab, competitively antagonizing IL-4Ra-dependent cell proliferation, mucus induction, and eotaxin expression in vitro. Because PRS-060 displayed exquisite specificity for human IL-4Ra, with no cross-reactivity to rodents or higher primates, we created a new triple-humanized mouse model substituting human IL-4Ra, IL-4, and IL-13 at their correct syntenic murine loci to model clinical dosing. RESULTS: Inhaled PRS-060 strongly suppressed acute allergic inflammation indexes in triple-humanized mice with a duration of action longer than its bulk clearance, suggesting that it may act locally in the lung. CONCLUSION: Lcn1 can be reengineered into the Anticalin antagonist PRS-060 (elarekibep), exemplifying a new class of inhaled topical, long-acting therapeutic drugs with the potential to treat type 2 endotype asthma.

A phase 2 study to evaluate the safety, efficacy and pharmacokinetics of DP2 antagonist GB001 and to explore biomarkers of airway inflammation in mild-to-moderate asthma.

BACKGROUND: GB001 is an oral antagonist of the prostaglandin D2 receptor that may inhibit recruitment and activation of airway eosinophils, reducing airway inflammation. OBJECTIVE: To assess GB001 safety, efficacy and pharmacokinetics from a Phase 2 study and explore the association between type 2 biomarkers (fractional exhaled nitric oxide and blood eosinophils) and asthma control markers following GB001 administration. METHODS: A randomized, placebo-controlled, double-blind study evaluating 36 patients with mild-to-moderate atopic asthma. Patients receiving fluticasone propionate ≤500 mcg/day or equivalent were randomized (2:1) to GB001 (30 mg) or placebo once daily for 28 days. Safety, pharmacokinetics, forced expiratory volume in 1 second, asthma control questionnaire and rescue medication use were assessed. Clinical outcomes were analysed post hoc by baseline fractional exhaled nitric oxide (<35 and ≥35 ppb) and blood eosinophil (<250 and ≥250 cells/µL) subgroups. RESULTS: GB001 was well tolerated and rapidly absorbed with a 14.5-hour terminal half-life. Overall, GB001 demonstrated greater improvement relative to placebo in forced expiratory volume in 1 second at Day 28 (102 mL [95% CI: -110, 314]). Greater effects on forced expiratory volume in 1 second were observed in the high baseline fractional exhaled nitric oxide and blood eosinophil subgroups (207 mL [95% CI: -283, 698];133 mL [95% CI: -422, 687], respectively). These effects were observed as early as Day 2 (229 mL [95% CI: -170, 628]; 163 mL [95% CI: -223, 550] for the high baseline fractional exhaled nitric oxide and blood eosinophil subgroups, respectively) and were sustained through treatment completion. CONCLUSION AND CLINICAL RELEVANCE: GB001 was well tolerated, with the estimated half-life supporting once-daily (QD) dosing. GB001 may have a rapid and sustained effect on lung function, particularly in patients with type 2 phenotype. Further studies are needed to confirm these findings.

Rehabilitation of emergent awareness of errors post traumatic brain injury: A pilot intervention.

Impaired awareness of errors is common following traumatic brain injury (TBI) and can be a barrier to successful rehabilitation. The objective of this study was to develop and evaluate a computer-based intervention programme aimed at improving error awareness in individuals with TBI. A further aim was to explore its effects on metacognitive awareness and variability of performance. Participants were 11 individuals with TBI and impaired error awareness who performed a sustained attention task twice-weekly for four weeks. The intervention consisted of audio-visual feedback-on-errors during the sustained attention task. Six participants received audio-visual feedback-on-error, five did not receive feedback. Emergent and metacognitive awareness were measured pre- and post-intervention. Between-groups comparisons of emergent awareness from pre- to post-intervention showed that audio-visual feedback-on-error improved emergent awareness compared to no feedback-on-error. Some changes in metacognitive awareness of executive behaviours as a result of feedback were observed. Audio-visual feedback-on-error improved emergent awareness in individuals with TBI following a four-week/eight-session intervention. This improvement was not observed in the no-feedback group. This pilot intervention is not a stand-alone treatment but it has potential to be usefully incorporated into cognitive or clinical rehabilitation programmes to improve emergent awareness.

Dual behavior of N-acetylcysteine during ethanol-induced oxidative stress in embryonic chick brains.

OBJECTIVES: Ethanol (EtOH) causes oxidative stress in embryos. Because N-acetylcysteine (NAC) failures and successes in ameliorating EtOH-induced oxidative stress have been reported, the objective was to determine if exogenous NAC ameliorated EtOH-induced oxidative stress within embryonic chick brains. METHODS: Control eggs were injected with approximately 25 µl of water on day 0, 1, and 2 of development (E0-2). Experimental eggs were injected with dosages of either 3.0 mmol EtOH/kg egg; 747 µmol NAC/kg egg; 3.0 mmol EtOH and 747 µmol NAC/kg egg; 1000 µmol NAC/kg egg; or 3.0 mmol EtOH and 1000 µmol NAC/kg during the first 3 days of development (E0-2). At 11 days of development (E11; late embryogenesis), brains were harvested and subsequently assayed for oxidative stress markers including the loss of long-chain membrane polyunsaturated fatty acids (PUFAs); the accumulation of lipid hydroperoxides (LPO); decreased glutathione (GSH) and glutathione/glutathione disulfide (GSSG) levels; and decreased glutathione peroxidase (GPx) activities. RESULTS: EtOH (3 mmol/kg egg), medium NAC (747 µmol/kg egg), and EtOH and medium NAC promoted oxidative stress. These treatments caused decreased brain membrane long-chain PUFAs; increased LPO levels; decreased GSH levels and GSH/GSSG levels; and decreased Se-dependent GPx activities. High NAC dosages (1000 µmol/kg egg) attenuated EtOH-induced oxidative stress within EtOH and high NAC-treated chick brains. DISCUSSION: Exogenous EtOH and/or medium NAC propagated oxidative stress. Meanwhile, high NAC ameliorated EtOH-induced oxidative stress.

Strengthening nursing and midwifery capacity in rural New South Wales, Australia.

A small rural health service and two university schools of nursing joined forces to establish a rural clinical school to advance clinical education and research. The collaboration, while in its infancy, has given rise to outcomes that strength the capacity of nursing and midwifery services in the community.

Connecting Self-Awareness and Error-Awareness in Patients with Traumatic Brain Injury.

Impaired self-awareness after traumatic brain injury (TBI) is often seen in stark contrast to the observations of significant-others, who are acutely aware of the difficulties experienced by patients. Our objective was to investigate the relationship between metacognitive knowledge in daily life and emergent awareness of errors during laboratory tasks, since the breakdown of error detection mechanisms may impose limitations on the recovery of metacognitive knowledge after TBI. We also examined the extent to which these measures of awareness can predict dysexecutive behaviors. A sample of TBI patients (n=62) and their significant-others, provided reports of daily functioning post injury. In addition, patients underwent a neuropsychological assessment and were instructed to signal their errors during go/no-go tests. Interrelationships between metacognitive and emergent levels of awareness were examined, after controlling for the influence of secondary cognitive variables. Significant-other ratings correlated with errors made by the patients on neuropsychological tests but not with their premorbid function. Patients who under-reported daily life difficulties or over-reported their competency, compared to significant-other reports, were less likely to show awareness of laboratory errors. Emergent awareness was also identified as the sole predictor of performance on the modified six-element test, an ecologically valid test of multitasking. The online breakdown of error awareness after brain injury is related to difficulties with metacognitive awareness as reported in daily life, and is also predictive of dysexecutive behaviors. These findings are discussed in the context of multidimensional and neural models of awareness and error monitoring.

Development and reliability testing of the quality clinical placement evaluation tool.

AIMS AND OBJECTIVES: To develop and test the content and face validity, and reliability of the quality clinical placement evaluation tool. BACKGROUND: The importance of clinical experience during undergraduate nursing degrees is undisputed. To date, tools available to measure quality of clinical placements have focused on single perspectives, that of the undergraduate or that of the supervising nurse. The quality clinical placement evaluation tool was proposed to provide an assessment of clinical placement experiences informed by supervising ward nurses and undergraduate stakeholders. DESIGN: The study employed a cross-sectional design. METHODS: The internal validity of an existing instrument was evaluated by an expert panel and modified for use in the acute care sector. Surveys were completed by undergraduate students (n = 48) and supervising ward nurses (n = 47). Factor analysis was used to identify themes drawn from the literature and explore redundancy of items. Reliability was assessed using Cronbach's alpha for internal consistency and test-retest (five to seven days apart). RESULTS: Reliability testing showed good internal consistency for the tool; test-retest reliability testing results were moderate to good for students and fair to moderate for nurses. Factor analysis identified three core themes related to supervising ward nurse responses that could also be applied to undergraduate nurses. The domains identified were the following: welcome and belonging; support to meet learning needs; and confidence and competence: reflections on learning. CONCLUSIONS: The quality clinical placement evaluation has shown statistically acceptable levels of reliability and validity for measuring the quality of clinical placement from perspectives of undergraduates and supervising ward nurses. RELEVANCE TO CLINICAL PRACTICE: The tool provides tertiary institutions, acute care facilities, wards and individuals with the means to capture views of the quality of clinical placement which can also be used to undertake comparisons over time and between sites.

Efficacy and safety of flexible dose fesoterodine in men and women with overactive bladder symptoms including nocturnal urinary urgency.

PURPOSE: Awakening from sleep to urinate is the hallmark of nocturia, a condition that impacts several facets of health related quality of life and for which current therapy is suboptimal. Given the paucity of prospective data on antimuscarinics for the management of nocturia, we investigated the efficacy and safety of flexible dose fesoterodine for the treatment of nocturnal urgency in subjects with nocturia and overactive bladder. MATERIALS AND METHODS: Subjects with 2 to 8 nocturnal urgency episodes per 24 hours began a 2-week, single-blind, placebo run-in followed by 1:1 randomization to 12 weeks of double-blind treatment with fesoterodine (4 mg daily for 4 weeks with an optional increase to 8 mg) or placebo using predefined criteria for nocturnal urgency episodes, nocturnal urine volume voided and total 24-hour urine volume voided. The primary end point was change from baseline to week 12 in the mean number of micturition related nocturnal urgency episodes per 24 hours. RESULTS: Overall 963 subjects were randomized from 2,990 screened, and 82% of subjects treated with fesoterodine and 84% of those treated with placebo completed the study. Significant improvements in the primary end point (-1.28 vs -1.07), in nocturnal micturitions per 24 hours (-1.02 vs -0.85) and in nocturnal frequency urgency sum (-4.01 vs -3.42) were observed with fesoterodine vs placebo (all p ≤0.01). Health related quality of life measures (overactive bladder questionnaire Symptom Bother -20.1 vs -16.5, sleep 22.3 vs 19.9 and other domains; all p <0.05) were improved with fesoterodine. CONCLUSIONS: To our knowledge this is the first prospective study to assess antimuscarinic efficacy for reducing nocturnal urgency. Flexible dose fesoterodine significantly reduced nocturnal urgency episodes vs placebo in subjects with overactive bladder.

Randomized multicenter feasibility trial of myofascial physical therapy for the treatment of urological chronic pelvic pain syndromes.

PURPOSE: We determined the feasibility of conducting a randomized clinical trial designed to compare 2 methods of manual therapy (myofascial physical therapy and global therapeutic massage) in patients with urological chronic pelvic pain syndromes. MATERIALS AND METHODS: We recruited 48 subjects with chronic prostatitis/chronic pelvic pain syndrome or interstitial cystitis/painful bladder syndrome at 6 clinical centers. Eligible patients were randomized to myofascial physical therapy or global therapeutic massage and were scheduled to receive up to 10 weekly treatments of 1 hour each. Criteria to assess feasibility included adherence of therapists to prescribed therapeutic protocol as determined by records of treatment, adverse events during study treatment and rate of response to therapy as assessed by the patient global response assessment. Primary outcome analysis compared response rates between treatment arms using Mantel-Haenszel methods. RESULTS: There were 23 (49%) men and 24 (51%) women randomized during a 6-month period. Of the patients 24 (51%) were randomized to global therapeutic massage, 23 (49%) to myofascial physical therapy and 44 (94%) completed the study. Therapist adherence to the treatment protocols was excellent. The global response assessment response rate of 57% in the myofascial physical therapy group was significantly higher than the rate of 21% in the global therapeutic massage treatment group (p = 0.03). CONCLUSIONS: We judged the feasibility of conducting a full-scale trial of physical therapy methods and the preliminary findings of a beneficial effect of myofascial physical therapy warrants further study.

The impact of dispositional optimism on symptoms and treatment choices in patients with pelvic floor disorders.

INTRODUCTION AND HYPOTHESIS: The objective of this study is to evaluate dispositional optimism, pelvic floor disorder symptoms, and treatment decisions. METHODS: Scores of the Life Orientation Test-Revised were used to categorize women seeking clinical treatment for pelvic floor disorders as pessimists (scores in lowest third) or optimists (scores in highest third). Participants also listed their treatment goals and quantified pelvic floor symptom severity by completing the Pelvic Floor Distress Inventory (PFDI-20). We compared symptoms, goals, and treatment choices between optimists and pessimists. RESULTS: Three hundred sixteen patients were included, 31% pessimists and 38% optimists. Pessimists reported more goals and different types of treatment goals. Pessimists were also more likely to elect surgical treatment over more conservative treatment methods, although this trend did not reach statistical significance. Among patients with prolapse (≥stage 2), PFDI-20 prolapse subscale scores were inversely correlated with level of optimism, with pessimists reporting a higher level of bother than optimists. CONCLUSIONS: In our study, pessimists reported more treatment goals, were more bothered by prolapse symptoms, and tended to be more likely to choose surgical treatments for their pelvic floor disorders than optimistic women.

Reliability and responsiveness of the Urgency Severity and Life Impact Questionnaire (USIQ).

INTRODUCTION AND HYPOTHESIS: The aims of this study are (1) to assess the reliability (test-retest) of the Urgency Severity and Life Impact Questionnaire (USIQ) and (2) to test the effect of extended-release tolterodine on symptoms of urinary urgency using this validated instrument. METHODS: To measure reliability, women with overactive bladder (OAB) completed the USIQ on two separate occasions, prior to treatment for OAB. To assess the responsiveness, the USIQ participants completed the above-mentioned questionnaires prior to and following 4 weeks of treatment for OAB with extended-release tolterodine. RESULTS: USIQ-S and USIQ-QoL scores at the two visits did not differ significantly. Repeated measures of USIQ-S and USIQ-QoL demonstrated a moderate to excellent intraclass correlation coefficient (0.64-0.74; P < 0.0001 and 0.48-0.91, P < 0.0001, respectively). A significant decrease in mean USIQ-S and USIQ-QOL (71 ± 14 vs. 44 ± 19, P < 0.0001 and 51 ± 22 vs. 39 ± 10, P < 0.01, respectively) scores following treatment with tolterodine. CONCLUSIONS: This valid, reliable measure can be used in clinical practice and research trials to measure urgency severity.

Quality clinical placements for undergraduate nursing students: a cross-sectional survey of undergraduates and supervising nurses.

AIM: This article is a report of a mixed method study of the quality of clinical placements for second year undergraduate nursing students in an acute care hospital. BACKGROUND: In response to the current and predicted workforce shortages, greater numbers of nursing undergraduate places are being offered at tertiary institutions. This means that requests for clinical places in hospitals to support undergraduate students has risen. Little is known about the impact of increased numbers on the quality of clinical placement as a learning experience and this is of concern as demand grows and the means of assessing capacity is still unknown. METHODS: A 5-point Likert Scale questionnaire, including free text fields, was administered to undergraduates (n = 178), clinical facilitators (n = 22) and supervising ward nurses (n = 163) at two time points in 2009. The survey targeted the quality of the clinical placement in four domains: welcoming and belongingness; teaching and learning; feedback; confidence and competence. Findings. The findings demonstrated consistently high scoring of the clinical placement experience by both undergraduates and registered nurses. There were higher ratings of levels of support from clinical facilitators compared to supervising ward nurses evident in data associated with the items on the questionnaire relating to teaching and learning. CONCLUSION: The results are indicative of the professional commitment of nursing staff to support the next generation of nurses. The findings also give a mechanism to communicate outcomes of undergraduate support to nurses in practice, and highlight steps which can be taken to ensure high quality clinical placement continues.

Design, Synthesis, and Biological Characterization of Inhaled p38α/ß MAPK Inhibitors for the Treatment of Lung Inflammatory Diseases.

The identification of novel inhaled p38α/ß mitogen-activated protein kinases (MAPK) (MAPK14/11) inhibitors suitable for the treatment of pulmonary inflammatory conditions has been described. A rational drug design approach started from the identification of a novel tetrahydronaphthalene series, characterized by nanomolar inhibition of p38α with selectivity over p38γ and p38δ isoforms. SAR optimization of 1c is outlined, where improvements in potency against p38α and ligand-enzyme dissociation kinetics led to several compounds showing pronounced anti-inflammatory effects in vitro (inhibition of TNFα release). Targeting of the defined physicochemical properties allowed the identification of compounds 3h, 4e, and 4f, which showed, upon intratracheal instillation, low plasma levels, prolonged lung retention, and anti-inflammatory effects in a rat acute model of a bacterial endotoxin-induced pulmonary inflammation. Compound 4e, in particular, displayed remarkable efficacy and duration of action and was selected for progression in disease models of asthma and chronic obstructive pulmonary disease (COPD).

Nonsteroidal antiinflammatory drug use and lower urinary tract symptoms: results from the Boston area community health survey.

There is evidence for a role of inflammation in the etiology of lower urinary tract symptoms (LUTS), raising the possibility that use of nonsteroidal antiinflammatory drugs (NSAIDs) may inhibit the development or progression of LUTS. The authors examined the association between use of prescription and over-the-counter NSAIDs and LUTS among 1,974 men and 2,661 women in the Boston Area Community Health Survey (2002-2005). Multivariable-adjusted logistic regression was used to estimate odds ratios and 95% confidence intervals for LUTS, voiding symptoms, storage symptoms, and nocturia. There was no clear association between use of prescription or over-the-counter NSAIDs (compared with no NSAID use) and overall LUTS, voiding symptoms, or nocturia in men or women. However, over-the-counter NSAID use was positively associated with storage symptoms in women (odds ratio = 1.37, 95% confidence interval: 1.03, 1.83), and there was a positive association between over-the-counter NSAID use and overall LUTS among women with a history of arthritis (odds ratio = 2.09, 95% confidence interval: 1.20, 3.64). These results do not provide strong support for an association between NSAIDs and LUTS. However, the associations between over-the-counter NSAID use and certain urologic symptoms, particularly among women with arthritis, and the potential mechanisms involved should be evaluated in future studies.

Size does matter: donor renal volume predicts recipient function following live donor renal transplantation.

PURPOSE: With the now routine use of computerized tomography angiography with 3-dimensional reconstruction in the donor evaluation, renal volume can be easily determined using volume calculating software. We evaluated whether donor renal volume could predict recipient renal function. MATERIALS AND METHODS: Clinical data of all donor and recipient pairs undergoing live donor kidney transplantation at our institution between January 2006 and October 2009 were reviewed. The volume of the kidney selected for transplant was determined using volume calculating software, and correlated to transplant recipient nadir and 1-year serum creatinine. Multivariate regression analysis was performed to adjust for demographic and clinical variables. RESULTS: During the study period 114 patients underwent live donor renal transplantation. Recipient nadir and 1-year serum creatinine levels were significantly correlated with the volume of donated kidney even after adjusting for age, body mass index, body surface area and donor creatinine clearance. Kidney volume also retained significance after excluding recipients from analysis who experienced acute rejection episodes. CONCLUSIONS: Larger kidney volumes calculated using 3-dimensional computerized tomography with volume calculating software are correlated with lower recipient nadir and 1-year serum creatinine levels.

Association of nocturia and mortality: results from the Third National Health and Nutrition Examination Survey.

PURPOSE: Nocturia, a common problem in men and women, has been associated with chronic illnesses such as heart disease and hypertension. Using data from the Third National Health and Nutrition Examination Survey we investigated the association of nocturia with subsequent mortality risk. MATERIALS AND METHODS: NHANES III is a national probability survey of the United States between 1988 and 1994. Mortality data were obtained by linkage of NHANES III to the National Death Index. Cox proportional hazards regression models were used to assess the association between nocturia and all cause mortality, controlling for potential confounders in a sample of 15,988 men and women 20 years old or older. RESULTS: The prevalence of nocturia, defined as 2 or more voiding episodes nightly, was 15.5% in men and 20.9% in women. Multivariate analyses showed a statistically significant trend of increased mortality risk with increased number of voiding episodes in men and women. The magnitude of the nocturia and mortality association was greater in those younger than 65 years with attenuated associations in the 65 years old or older age group. CONCLUSIONS: Nocturia is a strong predictor of mortality, more so in younger men and women than in the elderly, with a dose-response pattern in increased mortality risk with increasing number of voiding episodes nightly. Potential underlying mechanisms of the observed association of nocturia and increased mortality risk include sleep disruption and subsequent development of related comorbid conditions.

AUA guideline for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome.

PURPOSE: To provide a clinical framework for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. MATERIALS AND METHODS: A systematic review of the literature using the MEDLINE® database (search dates 1/1/83-7/22/09) was conducted to identify peer reviewed publications relevant to the diagnosis and treatment of interstitial cystitis/bladder pain syndrome. Insufficient evidence-based data were retrieved regarding diagnosis and, therefore, this portion of the Guideline is based on Clinical Principles and Expert Opinion statements. The review yielded an evidence base of 86 treatment articles after application of inclusion/exclusion criteria. These publications were used to create the majority of the treatment portion of the Guideline. When sufficient evidence existed, the body of evidence for a particular treatment was assigned a strength rating of A (high), B (moderate) or C (low). Additional treatment information is provided as Clinical Principles and Expert Opinion when insufficient evidence existed. See text and algorithm for definitions, and detailed diagnostic management, and treatment frameworks. RESULTS: The evidence-based guideline statements are provided for diagnosis and overall management of interstitial cystitis/bladder pain syndrome as well as for various treatments. The panel identified first through sixth line treatments as well as developed guideline statements on treatments that should not be offered. CONCLUSIONS: Interstitial cystitis/bladder pain syndrome is best identified and managed through use of a logical algorithm such as is presented in this Guideline. In the algorithm the panel identifies an overall management strategy for the interstitial cystitis/bladder pain syndrome patient. Diagnosis and treatment methodologies can be expected to change as the evidence base grows in the future.

Early termination of a trial of mycophenolate mofetil for treatment of interstitial cystitis/painful bladder syndrome: lessons learned.

PURPOSE: We evaluated the efficacy and tolerability of mycophenolate mofetil in patients with treatment refractory interstitial cystitis/painful bladder syndrome. MATERIALS AND METHODS: A total of 210 patients with interstitial cystitis/painful bladder syndrome were to be randomized into a multicenter, placebo controlled trial using a 2:1 randomization. Participants in whom at least 3 interstitial cystitis/painful bladder syndrome specific treatments had failed and who had at least moderately severe symptoms were enrolled in a 12-week treatment study. The primary study end point was the global response assessment. Secondary end points were general and disease specific symptom questionnaires, and voiding diaries. RESULTS: Only 58 subjects were randomized before a black box warning regarding mycophenolate mofetil safety was issued by the manufacturer in October 2007. The trial was halted, and interim analysis was performed and presented to an independent data and safety monitoring board. Six of the 39 subjects (15%) randomized at study cessation were considered responders for mycophenolate mofetil compared to 3 of 19 controls (16%, p=0.67). Secondary outcome measures reflected more improvement in controls. CONCLUSIONS: In a randomized, placebo controlled trial that was prematurely halted mycophenolate mofetil showed efficacy similar to that of placebo to treat symptoms of refractory interstitial cystitis/painful bladder syndrome. The results of this limited study cannot be used to confirm or refute the hypothesis that immunosuppressive therapy may be beneficial to at least a subgroup of patients with interstitial cystitis/painful bladder syndrome. Despite study termination lessons can be gleaned to inform future investigations.

Spousal support decreases the negative impact of pain on mental quality of life in women with interstitial cystitis/painful bladder syndrome.

OBJECTIVE: • To examine whether spousal responses to patient pain would alter the association between pain and patient health-related quality of life (HRQL), depression and disability. METHODS: • Ninety-six women with IC/PBlS (mean age = 50.6 (13.8); mean time since diagnosis = 6.2 years) completed questionnaires on demographics, depressive symptoms (Center for Epidemiological Studies-Depression Scale), disability (Pain Disability Index), HRQL (Medical Outcomes Study Short Form 12) and a measure of perceived spousal responses to their pain (Multidimensional Pain Inventory). • A repeated measures multivariate analysis of variance examined association changes between pain and adjustment variables at high, moderate and low levels of negative, solicitous and distracting spousal responses. RESULTS: • The association between pain and all outcome variables did not vary as a function of levels of solicitous and negative spousal responses. • However, the association between pain and mental HRQL was stronger at lower levels (ß=-1.25) of distracting responses than it was at moderate (ß=-0.66) and higher (ß=-0.06) levels. CONCLUSION: • Distracting spousal responses act to 'buffer' the deleterious effects of pain on mental HRQL for women suffering from IC/PBlS. Spousal support training may be a useful HRQL intervention.

The role of urgency, frequency, and nocturia in defining overactive bladder adaptive behavior.

AIM: To determine the relation between urgency alone, or in combination with frequency and nocturia, and adaptive behavior in overactive bladder (OAB) syndrome. METHODS: We used survey data from the General Longitudinal Overactive Bladder Evaluation (GLOBE) of primary care patients over 40. Participants (n=2,752: 1,557 females; 1,195 males) completed the same survey at two time points, 6 months apart. Questions assessed OAB symptoms and adaptive behavior. We estimated correlation coefficients (R(2)) between urgency, frequency, and nocturia symptom scores (alone and in combination) and adaptive behavior measures at baseline and change in symptom scores and behavioral measures from baseline to 6 months. RESULTS: At baseline, urgency was the dominant predictor of all behavioral measures for females (R(2)=0.19-0.48) and males (R(2)=0.15-0.39). Lower R(2) values were observed for the change in measures from baseline to 6 months, but again change in urgency was the strongest predictor of change in adaptive behavior (R(2)=0.04-0.13 in females, and 0.02-0.08 in males). The correlation between symptoms and measures of adaptive behavior was almost completely explained by the urgency score. Frequency and nocturia did not substantially improve the overall correlation. CONCLUSION: The relation between measures of OAB symptoms and adaptive behavior at baseline and over time are largely explained by urgency, not by frequency and nocturia.