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.

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).

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.

Human lung tissue provides highly relevant data about efficacy of new anti-asthmatic drugs.

Subgroups of patients with severe asthma are insensitive to inhaled corticosteroids and require novel therapies on top of standard medical care. IL-13 is considered one of the key cytokines in the asthma pathogenesis, however, the effect of IL-13 was mostly studied in rodents. This study aimed to assess IL-13 effect in human lung tissue for the development of targeted therapy approaches such as inhibition of soluble IL-13 or its receptor IL-4Rα subunit. Precision-cut lung slices (PCLS) were prepared from lungs of rodents, non-human primates (NHP) and humans. Direct effect of IL-13 on human lung tissue was observed on inflammation, induction of mucin5AC, and airway constriction induced by methacholine and visualized by videomicroscopy. Anti-inflammatory treatment was evaluated by co-incubation of IL-13 with increasing concentrations of IL-13/IL-13 receptor inhibitors. IL-13 induced a two-fold increase in mucin5AC secretion in human bronchial tissue. Additionally, IL-13 induced release of proinflammatory cytokines eotaxin-3 and TARC in human PCLS. Anti-inflammatory treatment with four different inhibitors acting either on the IL-13 ligand itself (anti-IL-13 antibody, similar to Lebrikizumab) or the IL-4Rα chain of the IL-13/IL-4 receptor complex (anti-IL-4Rα #1, similar to AMG 317, and #2, similar to REGN668) and #3 PRS-060 (a novel anticalin directed against this receptor) could significantly attenuate IL-13 induced inflammation. Contrary to this, IL-13 did not induce airway hyperresponsiveness (AHR) in human and NHP PCLS, although it was effective in rodent PCLS. Overall, this study demonstrates that IL-13 stimulation induces production of mucus and biomarkers of allergic inflammation in human lung tissue ex-vivo but no airway hyperresponsiveness. The results of this study show a more distinct efficacy than known from animals models and a clear discrepancy in AHR induction. Moreover, it allows a translational approach in inhibitor profiling in human lung tissue.

Retroperitoneal Laparoscopic Radical Nephrectomy Allows Continuation of Peritoneal Dialysis in Patients with End-Stage Renal Disease.

Patient outcomes for retroperitoneal laparoscopic radical nephrectomy (RLRN) in adults on peritoneal dialysis (PD) have not been described in the literature. This is the first series on the successful application of RLRN for renal cell carcinoma (RCC) among adults with end-stage renal disease (ESRD) on PD. In our series of 5 patients, all were able to promptly resume PD, no wound complications were noted at postoperative visits, and no evidence of recurrence was identified on surveillance imaging at follow-up. We propose that RLRN should be considered in PD patients as it allows immediate reinstitution of PD and prevents the morbidity and complications associated with interim hemodialysis.

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.

Freezing the Bioactive Conformation to Boost Potency: The Identification of BAY†85-8501, a Selective and Potent Inhibitor of Human Neutrophil Elastase for Pulmonary Diseases.

Human neutrophil elastase (HNE) is a key protease for matrix degradation. High HNE activity is observed in inflammatory diseases. Accordingly, HNE is a potential target for the treatment of pulmonary diseases such as chronic obstructive pulmonary disease (COPD), acute lung injury (ALI), acute respiratory distress syndrome (ARDS), bronchiectasis (BE), and pulmonary hypertension (PH). HNE inhibitors should reestablish the protease-anti-protease balance. By means of medicinal chemistry a novel dihydropyrimidinone lead-structure class was identified. Further chemical optimization yielded orally active compounds with favorable pharmacokinetics such as the chemical probe BAY-678. While maintaining outstanding target selectivity, picomolar potency was achieved by locking the bioactive conformation of these inhibitors with a strategically positioned methyl sulfone substituent. An induced-fit binding mode allowed tight interactions with the S2 and S1 pockets of HNE. BAY 85-8501 ((4S)-4-[4-cyano-2-(methylsulfonyl)phenyl]-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-1,2,3,4-tetrahydropyrimidine-5-carbonitrile) was shown to be efficacious in a rodent animal model related to ALI. BAY 85-8501 is currently being tested in clinical studies for the treatment of pulmonary diseases.

Delirium: the lived experience of older people who are delirious post-orthopaedic surgery.

Delirium is a common, potentially preventable and reversible cause of postoperative functional disability, morbidity, and mortality. It can lead to increased health-care use and also poses a substantial challenge for nurses caring for patients who experience delirium after surgery. Predominantly, the published work concentrates on diagnosis, reduction of the modifiable risk factors, and treatments. Compared with this body of published work, the experience of delirium from a patient's perspective has been largely ignored except for a limited number of qualitative research reports. The importance of researching the lived experience of delirium is that a better understanding may lead to more empathic, therapeutic nursing care and help other sufferers to know they are not alone. The aims of the study were to explore and clarify the lived experience of delirium. Eleven patients were recruited to the study following discharge post-surgery from an orthopaedic ward of a major tertiary hospital. The study used a qualitative descriptive approach and incorporated grounded theory data analysis processes. The findings of this study provide an insight into the incomprehensible emotional pain suffered by patients while they were delirious and the disparate feelings of remorse, guilt, and shame they experienced after the episode of delirium. Following this study, recommendations for nursing practice include formal follow-up support for patients with post-delirium episodes and more research into the long-term impact of the experience of delirium.

Key influences identified by first year undergraduate nursing students as impacting on the quality of clinical placement: A qualitative study.

BACKGROUND: Despite the fact that high quality clinical placement is an integral component of pre-registration nursing education for the development of the future nursing workforce, the literature identifies an ongoing struggle to 'get it right'. OBJECTIVE: To examine qualitative data gathered through the Quality Clinical Placements Evaluation project to identify what pre-registration nursing students deemed helpful and not helpful influences on their first year Professional Experience Placement. DESIGN: A total of 553 first year undergraduate nursing students from 2010 to 2012 were enrolled in the programme and all were invited to complete a validated survey to measure the quality of their first clinical placement. A total of 361 completed surveys were returned. This paper examines the data provided through open-ended questions within the survey related to most helpful and least helpful aspects of their clinical experience. METHODS: An inductive analysis approach using NVIVO allowed inherent areas to emerge from the raw data forming three key themes that influenced the experience of students. RESULTS: Feeling welcomed, individual versus team attitudes, and student expectations of supervising ward nurses were the themes identified that were perceived by the student as important to the success of learning and the quality of the experience overall. CONCLUSION: The findings echo previous research into the student experience of clinical placement; however the focus regarding the need for students to have a quality relationship with the supervising nurse is an area that warrants further exploration. Furthermore, we argue that students should be purposely engaged in the tertiary sector and provided guidance and strategies related to forming and maintaining relationships with those that supervise their clinical placement, in order to ensure consistent positive experiences. The outcomes from this study suggest that a missing component is teaching undergraduates how to manage relationships in clinical settings.

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.

Post-discharge experiences of children and their families following children's surgery.

Increasing rates of day surgery and decreasing length of hospital stay mean children's recovery from surgery extends beyond hospital and into the home. The objective of this study is to improve the understanding of experiences of children and their families during recovery at home post surgery. This is an exploratory, interpretive study using diaries and semi-structured interviews with children and parents. Results from this research show that children recovering at home after surgery have increased dependency and are likely to become the centre of family life; re-establishing independence is a marker of recovery. When present, pain dominates the experience. The families that go home ill-prepared experience high levels of worry. In conclusion, recovery from surgery is influenced by multiple factors; overall, families and children are resilient. There is a role for health professionals to tailor and improve information provision to parents and children about post-operative recovery, including assessment and management of pain. Information should be made available that describes the experience of other families who have undergone a similar surgery, and families should be made aware of what information they need and how to access it before and after discharge.

Perioperative bowel habits of women undergoing gynecologic surgery: a pilot study.

OBJECTIVES: To describe perioperative bowel habits of women undergoing gynecologic surgery. METHODS: This prospective cohort study included women undergoing gynecologic surgery. Before surgery, participants completed the Bristol Stool Form Scale (BSFS), a validated instrument describing stool characteristics consistent with transit categories: slow (BSFS 1-2), normal (BSFS 3-5), and fast (BSFS 6-7). For 2 weeks after surgery, the participants recorded daily medications and bowel movements (BM), and completed BSFS. The χ(2) test, the Fisher exact test, analysis of variance, t tests, and ordinal regression were used. RESULTS: Preoperatively, most (70%) of 340 women had normal stool transit, with 15% having slow transit and 7% having fast transit. Complete postoperative data were available for 170 (50%). Mean ± SD time to first postoperative BM was 2.8 ± 1.4 days with transit classification: 48% normal, 32% slow, and 20% fast. CONCLUSIONS: Most women had normal stool transit both preoperatively and postoperatively. Time to first BM was longer after open surgery by approximately 3 days.

Solifenacin objectively decreases urinary sensation in women with overactive bladder syndrome.

PURPOSE: To evaluate the test-retest reliability of a device that measures urinary sensation during cystometry, and to use that device to determine whether treatment of overactive bladder syndrome (OAB) with solifenacin is associated with a change in urinary sensation. METHODS: Overall 15 women were recruited for this study, ten women with OAB and urodynamically demonstrated detrusor overactivity and five controls without OAB underwent filling cystometry twice with contemporaneous, continuous recording of urinary sensation. Women with OAB received solifenacin 10 mg daily during the weeks between testing. We compared the areas under the initial and repeat sensation-volume curves. RESULTS: While taking solifenacin, the maximum cystometric capacity increased from 329 ± 168 ml to 464 ± 123 ml (P < 0.002), and the area under the bladder volume-sensation curve decreased (P < 0.0001). Untreated controls did not exhibit these changes. CONCLUSION: We present psychometric data demonstrating improved bladder sensation during the treatment of OAB with solifenacin. If clinical correlations are confirmed by future study, such urinary sensation measures may prove useful as assessment, treatment predictor, or outcome measures in OAB research and/or clinical care.

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.