Inhibition of the BTK-IDO-mTOR axis promotes differentiation of monocyte-lineage dendritic cells and enhances anti-tumor T cell immunity.

Monocytic-lineage inflammatory Ly6c+CD103+ dendritic cells (DCs) promote antitumor immunity, but these DCs are infrequent in tumors, even upon chemotherapy. Here, we examined how targeting pathways that inhibit the differentiation of inflammatory myeloid cells affect antitumor immunity. Pharmacologic inhibition of Bruton's tyrosine kinase (BTK) and the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) or deletion of Btk or Ido1 allowed robust differentiation of inflammatory Ly6c+CD103+ DCs during chemotherapy, promoting antitumor T cell responses and inhibiting tumor growth. Immature Ly6c+c-kit+ precursor cells had epigenetic profiles similar to conventional DC precursors; deletion of Btk or Ido1 promoted differentiation of these cells. Mechanistically, a BTK-IDO axis inhibited a tryptophan-sensitive differentiation pathway driven by GATOR2 and mTORC1, and disruption of the GATOR2 in monocyte-lineage precursors prevented differentiation into inflammatory DCs in vivo. IDO-expressing DCs and monocytic cells were present across a range of human tumors. Thus, a BTK-IDO axis represses differentiation of inflammatory DCs during chemotherapy, with implications for targeted therapies.

Activation of p53 in Immature Myeloid Precursor Cells Controls Differentiation into Ly6c+CD103+ Monocytic Antigen-Presenting Cells in Tumors.

CD103+ dendritic cells are critical for cross-presentation of tumor antigens. Here we have shown that during immunotherapy, large numbers of cells expressing CD103 arose in murine tumors via direct differentiation of Ly6c+ monocytic precursors. These Ly6c+CD103+ cells could derive from bone-marrow monocytic progenitors (cMoPs) or from peripheral cells present within the myeloid-derived suppressor cell (MDSC) population. Differentiation was controlled by inflammation-induced activation of the transcription factor p53, which drove upregulation of Batf3 and acquisition of the Ly6c+CD103+ phenotype. Mice with a targeted deletion of p53 in myeloid cells selectively lost the Ly6c+CD103+ population and became unable to respond to multiple forms of immunotherapy and immunogenic chemotherapy. Conversely, increasing p53 expression using a p53-agonist drug caused a sustained increase in Ly6c+CD103+ cells in tumors during immunotherapy, which markedly enhanced the efficacy and duration of response. Thus, p53-driven differentiation of Ly6c+CD103+ monocytic cells represents a potent and previously unrecognized target for immunotherapy.

Nonclinical Profile of PF-06952229 (MDV6058), a Novel TGFßRI/Activin Like Kinase 5 (ALK-5) Inhibitor Supports Clinical Evaluation in Cancer.

The development of TGFßR inhibitors (TGFßRi) as new medicines have been affected by cardiac valvulopathy and arteriopathy toxicity findings in nonclinical toxicology studies. PF-06952229 (MDV6058) selected using rational drug design is a potent and selective TGFßRI inhibitor (TGFßRIi) with a relatively clean off-target selectivity profile and good pharmacokinetic properties across species. PF-06952229 inhibited clinically translatable phospho-SMAD2 biomarker ({greater than or equal to}60%) in human and cynomolgus monkey peripheral blood mononuclear cells, as well as in mouse and rat splenocytes. Using an optimized, intermittent dosing schedule (7 day-on, 7-off/cycle; five cycles), PF-06952229 demonstrated efficacy in a 63-day syngeneic MC38 colon carcinoma mouse model. In the pivotal repeat dose toxicity studies (rat and cynomolgus monkey), PF-06952229 on an intermittent dosing schedule (5 day-on, 5-off/cycle; five cycles, 28 doses) showed no cardiac-related adverse findings. However, new toxicity findings related to PF-06952229 included reversible hepatocellular (hepatocyte necrosis with corresponding clinically monitorable transaminase increases) and lung (hemorrhage with mixed cell inflammation) findings at {greater than or equal to} targeted projected clinical efficacious exposures. Furthermore, partially reversible cartilage hypertrophy (trachea and femur in rat; femur in monkey), and partially to fully reversible, clinically monitorable decreases in serum phosphorus and urinary phosphate, at {greater than or equal to} projected clinically efficacious exposures were observed. Given the integral role of TGFß in endochondral bone formation, cartilage findings in toxicity studies have been observed with other TGFßRi class of compounds. The favorable cumulative profile of PF-06952229 in biochemical, pharmacodynamic, pharmacokinetic and nonclinical studies, allowed for its evaluation in cancer patients using the intermittent dosing schedule (7-on/7-off) and careful protocol-defined monitoring. Significance Statement Only a few TGFßRi have progressed for clinical evaluation due to adverse cardiac findings in pivotal nonclinical toxicity studies. Potential translation of such findings in patients are of major concern. Using a carefully optimized intermittent dosing schedule PF-06952229 has demonstrated impressive pharmacological efficacy in the syngeneic MC38 colon carcinoma mouse model. Additionally, a nonclinical toxicology package without cardiovascular liabilities and generally monitorable toxicity profile has been completed. The compound presents an acceptable ICHS9 compliant profile for the intended-to-treat cancer patients.

Referent Values for Commonly Used Clinical Mobility Tests in Black and White Adults Aged 50-95 Years.

OBJECTIVE: To estimate referent values for performance on clinical mobility tests conducted amongst racially diverse adults aged 50-95 years in the Southeast US. DESIGN: This is an observational study of community-dwelling older adults from diverse racial groups who participated in observational and rehabilitative studies conducted from 2011-2019. SETTING: Rehabilitation clinics around the greater metropolitan Atlanta, Georgia, region. PARTICIPANTS: A total of 314 adults (N=314; 222 women). Individuals were predominantly Black (n=121) or White (n=164), with some participants from other racial groups (n=29). INTERVENTIONS: Clinical and demographic data were collected at individual visits for each participant. MAIN OUTCOME MEASURES: Four Square Step Test (FSST), timed Up and Go (TUG) test, dual TUG test, 6-minute walk test (6MWT), 30-second chair stand, and gait speed were all used as assessments in each cohort. RESULTS: Performance slowly declines with increasing age, with a sharp drop in the ninth decade for preferred forward, backward, and fast gait speed; backward gait cadence; 6MWT, TUG test, dual-task TUG-Cognitive, and the 360° turn test. Declines were also seen in the eighth and ninth decades in the FSST. Among White participants, there were significant overall differences across age groups except in the assessment variable, preferred gait cadence. For Black individuals, there were significant overall differences across age groups for backward gait speed, fast gait speed, TUG-Cognitive, dual task, 6MWT, FSST, and 30-second chair stand. CONCLUSIONS: These data enrich current referent values for brief, commonly used clinical tests in a diverse, older Southeast US cohort. These data include representatives of the oldest old cohort. This study will support race- and age-specific fall prevention and mobility-enhancing therapeutic application among older patients in clinical practice.

Perioperative Mobile Telehealth Program for Post-Prostatectomy Incontinence: A Randomized Clinical Trial.

PURPOSE: Perioperative pelvic floor muscle training can hasten recovery of bladder control and reduce severity of urinary incontinence following radical prostatectomy. Nevertheless, most men undergoing prostatectomy do not receive this training. The purpose of this trial was to test the effectiveness of interactive mobile telehealth (mHealth) to deliver an evidence-based perioperative behavioral training program for post-prostatectomy incontinence. MATERIALS AND METHODS: This was a 3-site, 2-arm, randomized trial (2014-2019). Men with prostate cancer scheduled to undergo radical prostatectomy were randomized to a perioperative behavioral program (education, pelvic floor muscle training, progressive exercises, bladder control techniques) or a general prostate cancer education control condition, both delivered by mHealth for 1-4 weeks preoperatively and 8 weeks postoperatively. The primary outcome was time to continence following surgery measured by the ICIQ (International Consultation on Incontinence Questionnaire) Short-Form. Secondary outcomes measured at 6, 9 and 12 months included Urinary Incontinence Subscale of Expanded Prostate Cancer Index Composite; pad use; International Prostate Symptom Score QoL Question and Global Perception of Improvement. RESULTS: A total of 245 men (ages 42-78 years; mean=61.7) were randomized. Survival analysis using the Kaplan-Meier estimate showed no statistically significant between-group differences in time to continence. Analyses at 6 months indicated no statistically significant between-group differences in ICIQ scores (mean=7.1 vs 7.0, p=0.7) or other secondary outcomes. CONCLUSIONS: mHealth delivery of a perioperative program to reduce post-prostatectomy incontinence was not more effective than an mHealth education program. More research is needed to assess whether perioperative mHealth programs can be a helpful addition to standard prostate cancer care.

Minimal differentiation of classical monocytes as they survey steady-state tissues and transport antigen to lymph nodes.

It is thought that monocytes rapidly differentiate to macrophages or dendritic cells (DCs) upon leaving blood. Here we have shown that Ly-6C⁺ monocytes constitutively trafficked into skin, lung, and lymph nodes (LNs). Entry was unaffected in gnotobiotic mice. Monocytes in resting lung and LN had similar gene expression profiles to blood monocytes but elevated transcripts of a limited number of genes including cyclo-oxygenase-2 (COX-2) and major histocompatibility complex class II (MHCII), induced by monocyte interaction with endothelium. Parabiosis, bromodoxyuridine (BrdU) pulse-chase analysis, and intranasal instillation of tracers indicated that instead of contributing to resident macrophages in the lung, recruited endogenous monocytes acquired antigen for carriage to draining LNs, a function redundant with DCs though differentiation to DCs did not occur. Thus, monocytes can enter steady-state nonlymphoid organs and recirculate to LNs without differentiation to macrophages or DCs, revising a long-held view that monocytes become tissue-resident macrophages by default.

Mirabegron and antimuscarinic use in frail overactive bladder patients in the United States Medicare population.

INTRODUCTION: Overactive bladder (OAB) and frailty are independently associated with patient burden. However, economic burden and treatment-taking behavior have not been well characterized among frail patients with OAB, which, given the varying safety and tolerability profiles of available treatments, is crucial. OBJECTIVES: To assess costs, health care resource utilization, treatment-taking behavior (persistence and adherence) to OAB medication in older, frail OAB patients. METHODS: This was a retrospective cohort study using international business machines MarketScan Medicare Supplemental claims data. Eligible frail patients (per Claims-based Frailty Index score) initiating mirabegron were 1:2 propensity score matched (based on age, sex, and other characteristics) with those initiating antimuscarinics and were followed up to 1 year. All-cause, per-person, per-month costs, health care encounters, persistence (median days to discontinuation assessed using Kaplan-Meier methods) and adherence (≥80% of proportion of days covered at Day 365) were compared. RESULTS: From 2527 patients with incident mirabegron (21%) or antimuscarinic (79%) dispensations, 516 incident mirabegron users (median age: 82 years, 64% female) were matched to 1032 incident antimuscarinic users (median age: 81 years, 62% female). Median cost was higher in mirabegron group ($1581 vs. $1197 per month); this was primarily driven by medication cost. There was no difference in medical encounters. Adherence (39.1% vs. 33.8%) and persistence (103 vs. 90 days) were higher in mirabegron users. CONCLUSIONS: Among frail older adults with OAB, mirabegron use was associated with higher costs and potential improvements in treatment-taking behaviors, particularly with respect to treatment adherence, versus those initiating antimuscarinics.

Exploratory evaluation of baseline cognition as a predictor of perceived benefit in a study of behavioral therapy for urinary incontinence in Parkinson disease.

AIMS: While behavior-based pelvic floor muscle exercise therapy is an effective treatment for overactive bladder in Parkinson's disease (PD) patients, cognitive function may be a predictor of rehabilitation outcomes. METHODS: In a planned exploratory analysis, participants who had a Montreal Cognitive Assessment (MoCA) with a score ≥18 who were randomized in a clinical trial to behavioral treatment were classified by perceived improvement (Benefit vs. No Benefit) as reported on a validated Satisfaction and Benefit Questionnaire. General cognition (MoCA), motor procedural learning (Serial reaction time task), verbal memory (Buschke delayed recall), spatial memory (Nonverbal/Spatial selective reminding test), and working memory (Wisconsin card sorting task) were compared between the two groups using Wilcoxon rank-sum test. RESULTS: Of the 26 participants randomized to behavioral treatment (70% male, mean age 71 ± 6.1 years), 22 participants (85%) reported Benefit and four reported No Benefit. General cognition, motor procedural learning, verbal memory, spatial memory, and working memory did not differ between these groups. While the difference between the time to complete the final practiced series and the random series of the Serial Reaction Time Task (SRTT) was statistically similar between the groups, the Benefit group performed the random sequence more quickly (567.0 ± 136.5 ms) compared to the No Benefit group (959.4 ± 443.0 ms; p = 0.03) and trended toward faster performance in the final practiced series. CONCLUSIONS: Perceived benefit from behavioral treatment for overactive bladder was not associated with measures of baseline cognition other than faster completion of the SRTT. This is noteworthy because many behavior-based therapy studies exclude participants with mild cognitive impairment. Additional studies may evaluate if domain-specific cognitive function, particularly the assessment of implicit memory, could lead to individualized behavioral therapy recommendations.

Incontinence in frail elderly persons: Report of the 6th International Consultation on Incontinence.

BACKGROUND: Evidence-based guidelines for the management of frail older persons with urinary incontinence are rare. Those produced by the International Consultation on Incontinence represent an authoritative set of recommendations spanning all aspects of management. AIMS: To summarize the available evidence relating to the management of urinary incontinence in frail older people published since the 5th International Consultation on Incontinence. MATERIALS AND METHODS: A series of systematic reviews and evidence updates were performed by members of the working group to update the 2012 recommendations. RESULTS: Along with the revision of the treatment algorithm and accompanying text, there have been significant advances in several areas of the management of lower urinary tract symptoms in frail older people. DISCUSSION: The committee continues to note the relative paucity of data concerning frail older persons and draw attention to knowledge gaps and research opportunities. Clinicians treating older people with lower urinary tract symptoms should use the available evidence from studies of older people combined with careful extrapolation of those data from younger subjects. Due consideration to an individual's frailty and wishes is crucial.

A Framework for Mobilizing Health Care to Respond to the Community Within the COVID-19 Pandemic.

Cultural mistrust of government with regard to health issues has pressed the need to engage trusted community leaders with influence and reach in disproportionately affected communities to ensure that essential public health activities related to COVID-19 occur among populations experiencing disproportionate impact from the pandemic. In April of 2020, a Georgia-based integrated academic health care system created a Community Outreach and Health Disparities Collaborative to unite trusted community leaders from faith-based, civic, and health-sector organizations to work with the health system and Emory University to develop tailored approaches and mobilize support within the context of the communities' cultural and individual needs to reduce the burden of COVID-19. We describe the framework used to join health care and academic collaborators with community partners to mobilize efforts to address the disproportionate impact of COVID-19 on racial, ethnic, and socioeconomic minority groups. The framework outlines a series of steps taken that led to a community-driven collaboration designed to engage local influential community leaders as partners in improving access to care for disproportionately affected communities, collaborations that could be replicated by other large health care systems. This framework can also be applied to other chronic diseases or future public health emergencies to improve communication, education, and health care access for communities experiencing disproportionate impact.

Palliative care aspects of wound healing in complex patients: a case report.

DECLARATION OF INTEREST: The authors have no conflicts of interest to declare.

Development and evolution of a two-day intensive resident experience in geriatric medicine.

As the older adult population increases, the need to enhance medical education and training in Geriatric Medicine (GM) is essential. To enhance resident training, faculty at two southeastern universities developed a Resident Award Summit, a two-day active learning experience, designed to expose family and internal medicine residents to GM principles and the various career options available in GM.Over 10 years, 353 residents from 108 residency programs participated. Resident feedback indicated that attending the event had a positive impact on future practice (M = 4.65, SD = .58) and showed that the amount of GM training received was limited, with 83.5% and 70.2% ranking adequacy of medical student and resident training as limited, respectively.To impact practice, long-term change must occur. Experiences such as the Resident Award Summit allow GM faculty to educate and prepare residents though positive teaching experiences, providing residents with the skills needed to care for older adults in their communities.

The Impact of Nocturia on Falls and Fractures: A Systematic Review and Meta-Analysis.

PURPOSE: Although nocturia is associated with various comorbidities, its impact on falls and fractures remains unclear. We performed a systematic review and meta-analysis to evaluate the association between nocturia and falls and fractures as a prognostic and as a causal risk factor. MATERIALS AND METHODS: We searched PubMed®, Scopus®, CINAHL (Cumulative Index to Nursing and Allied Health Literature) and abstracts of major urological meetings up to December 31, 2018. We conducted random effects meta-analyses of adjusted relative risks of falls and fractures. We applied the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to rate the quality of evidence for nocturia as a prognostic and causal factor of falls and fractures. RESULTS: Among 5,230 potential reports 9 observational longitudinal studies provided data on the association between nocturia and falls or fractures (1 for both, 4 for falls, 4 for fractures). Pooled estimates demonstrated a risk ratio of 1.20 (95% CI 1.05-1.37, I2=51.7%, annual risk difference 7.5% among the elderly) for association between nocturia and falls and 1.32 (95% CI 0.99-1.76, I2=57.5%, annual risk difference 1.2%) for association between nocturia and fractures. Subgroup analyses showed no significant effect modification by age, gender, followup time, nocturia case definition or risk of bias. We rated the quality of evidence for nocturia as a prognostic factor as moderate for falls and low for fractures, and as very low as a cause of falls/fractures. CONCLUSIONS: Nocturia is probably associated with an approximately 1.2-fold increased risk of falls and possibly an approximately 1.3-fold increased risk of fractures.

Association of peripheral artery disease with life-space mobility restriction and mortality in community-dwelling older adults.

OBJECTIVE: Symptomatic peripheral artery disease (PAD) impairs walking, but data on the impact of PAD on community mobility is limited. Life-space mobility measures the distance, frequency, and assistance needed as older adults move through geographic areas extending from their bedroom (life-space mobility score: 0) to beyond their town (life-space mobility score: 120). We evaluated the association of PAD with longitudinal life-space mobility trajectory. METHODS: Participants were part of the University of Alabama at Birmingham Study of Aging, a longitudinal study of community-dwelling older adults who were observed from 2001 to 2009. We limited our analysis to those who survived at least 6 months (N = 981). PAD was based on self-report with verification by physician report and hospital records. Our primary outcome was life-space mobility score assessed every 6 months. A multilevel change model (mixed model) was used to determine the association between PAD and life-space mobility trajectory during a median 7.9 years of follow-up. RESULTS: Participants had a mean age of 75.7 (standard deviation, 6.7) years; 50.5% were female, and 50.4% were African American. PAD prevalence was 10.1%, and 57.1% of participants with PAD died. In participants with both PAD and life-space restriction, defined as life-space mobility score <60, we observed the highest mortality (73.1%). In a multivariable adjusted mixed effects model, participants with PAD had a more rapid decline in life-space mobility by -1.1 (95% confidence interval [CI], -1.9 to -0.24) points per year compared with those without PAD. At 5-year follow-up, model-adjusted mean life-space mobility was 48.1 (95% CI, 43.5-52.7) and 52.4 (95% CI, 50.9-53.8) among those with and without PAD, respectively, corresponding to a restriction in independent life-space mobility at the level of one's neighborhood. CONCLUSIONS: Life-space mobility is a novel patient-centered measure of community mobility, and PAD is associated with significant life-space mobility decline among community-dwelling older adults. Further study is needed to mechanistically confirm these findings and to determine whether better recognition and treatment of PAD alter the trajectory of life-space mobility.

Assessment of the Risk Analysis Index for Prediction of Mortality, Major Complications, and Length of Stay in Patients who Underwent Vascular Surgery.

BACKGROUND: Frailty is a risk factor for adverse postoperative outcomes. We aimed to test the performance of a prospectively validated frailty measure, the Risk Analysis Index (RAI) in patients who underwent vascular surgery and delineate the additive impact of procedure complexity on surgical outcomes. METHODS: We queried the 2007-2013 American College of Surgeons National Surgical Quality Improvement Program database to identify 6 major elective vascular procedure categories (carotid revascularization, abdominal aortic aneurysm [AAA] repair, suprainguinal revascularization, infrainguinal revascularization, thoracic aortic aneurysm [TAA] repair, and thoracoabdominal aortic aneurysm [TAAA] repair). We trained and tested logistic regression models for 30-day mortality, major complications, and prolonged length of stay (LOS). The first model, "RAI," used the RAI alone; "RAI-Procedure (RAI-P)" included procedure category (e.g., AAA repair) and procedure approach (e.g., endovascular); "RAI-Procedure Complexity (RAI-PC)" added outpatient versus inpatient surgery, general anesthesia use, work relative value units (RVUs), and operative time. RESULTS: The RAI model was a good predictor of mortality for vascular procedures overall (C-statistic: 0.72). The C-statistic increased with the RAI-P (0.78), which further improved minimally, with the RAI-PC (0.79). When stratified by procedure category, the RAI predicted mortality well for infrainguinal (0.79) and suprainguinal (0.74) procedures, moderately well for AAA repairs (0.69) and carotid revascularizations (0.70), and poorly for TAAs (0.62) and TAAAs (0.54). For carotid, infrainguinal, and suprainguinal procedures, procedure complexity (RAI-PC) had little impact on model discrimination for mortality, did improve discrimination for AAAs (0.84), TAAs (0.73), and TAAAs (0.80). Although the RAI model was not a good predictor for major complications or LOS, discrimination improved for both with the RAI-PC model. CONCLUSIONS: Frailty as measured by the RAI was a good predictor of mortality overall after vascular surgery procedures. Although the RAI was not a strong predictor of major complications or prolonged LOS, the models improved with the addition of procedure characteristics like procedure category and approach.

Feasibility of Tele-Prompt: A tablet-based prompted voiding intervention to support informal caregivers of older adults with urinary incontinence.

Urinary incontinence (UI) is a highly prevalent condition, burdening older adults and their informal caregivers. This study explored the development and feasibility of a 6-week evidence-based, educational/skill building program delivered via tablet-personal computer aimed at developing informal caregiver UI knowledge; and enhancing informal caregiver skill set in prompted voiding and toileting strategies. Caregivers also received individualized weekly coaching sessions from a nurse expert. Feasibility and preliminary efficacy were tested in three caregiver/care-recipient dyads. Recruitment of eligible participants through community-based resources was a challenge to feasibility. Most caregivers found the technology acceptable, but adherence to prompted voiding was inconsistent. All caregivers rated the intervention highly, reported improvements in their care-recipient's urine leakage, found access to a UI expert beneficial, and would recommend it to a friend. The results suggest that the tablet-facilitated intervention was feasible and acceptable to informal caregivers and showed promise for improving both caregiver and care recipient outcomes.

The Role of the Comprehensive Geriatric Assessment in the Evaluation of the Older Cancer Patient.

Geriatric assessments have now been recommended as part of the standard evaluation of an older adult considering cancer therapy. While the need for a more in-depth performance status evaluation of an older person with cancer was identified over 20 years ago, completion of a comprehensive geriatric assessment (CGA) is time-consuming and not frequently performed as part of the standard assessment of older cancer patients. Evidence suggests that incorporating such an evaluation could be useful for potentially determining the patient's chemotherapy tolerability or treatment completion, toxicity, and survival, as age alone has been shown to poorly predict treatment failure, and performance status assessments commonly used in oncology practice may lack predictability. This review describes the increasing role of the CGA and geriatric assessment screening tools as well as their pertinent domains across various settings in the evaluation of the older adult with cancer who is considering cancer treatment.

Behavioral therapy for urinary symptoms in Parkinson's disease: A randomized clinical trial.

AIM: Determine the efficacy of behavioral therapy for urinary symptoms in Parkinson's disease. METHODS: Randomized trial of behavioral therapy compared with control condition among adults (aged 54-85 years, 74% male, 10% Black/ 83% White) with Parkinson's and greater than or equal to 4 incontinence episodes weekly. Behavioral therapy included pelvic floor muscle exercises, bladder training, fluid and constipation management. Both groups completed bladder diary self-monitoring. Outcomes included diary-derived incontinence and ICIQ-overactive bladder (OAB) score (range, 0-16) with bother and quality of life questionnaires (higher scores = worse outcomes). RESULTS: Fifty-three participants randomized and 47 reported 8-week outcomes including 26 behavioral therapy and 21 control. Behavioral vs control participants were similar with respect to age (71.0 ± 6.1 vs 69.7 ± 8.2 years), sex (70% vs 78% male), motor score, cognition, mean weekly incontinence episodes (13.9 ± 9.6 vs 15.1 ± 11.1) and OAB symptoms (8.9 ± 2.4 vs 8.3 ± 2.2). Weekly incontinence reduction was similar between behavioral (-6.2 ± 8.7) and control participants (-6.5 ± 13.8) (P = 0.89). After multiple imputation analysis, behavioral therapy participants reported statistically similar reduction in OAB symptoms compared to control (-3.1 ± 2.8 vs -1.9 ± 2.2, P = 0.19); however quality of life (-22.6 ± 19.1 vs -7.0 ± 18.4, P = 0.048) and bother (-12.6 ± 17.2 vs - 6.7 ± 8.8, P = 0.037) improved significantly more with behavioral therapy. CONCLUSION: Self-monitoring resulted in fewer urinary symptoms; however, only multicomponent behavioral therapy was associated with reduced bother and improved quality of life. Providers should consider behavioral therapy as initial treatment for urinary symptoms in Parkinson's disease.

Outcomes, accreditation, interprofessional education, and the Tower of Babel.

Effective education necessitates a shared mental model of what and how learners should be taught. Students in various healthcare professions education programs learn together most effectively when programs have a shared mental model for education. Because healthcare professions education programs must satisfy their respective accreditation standards, the terminology of those standards reflects that body's shared mental model for education. Thus, interprofessional education (IPE) would be facilitated by common educational lexicon across accrediting bodies. In this study, the terminology used in the accreditation standards from several healthcare professions educational programs was measured. An analysis was conducted to illustrate whether terms used by accreditors were internally consistent and whether there was consistency across professions. Counts of learning outcomes terms used revealed little internal consistency within each set of standards. Additionally, the terms in the various standards documents used to describe educational outcomes were not consistent across accreditors. Individual healthcare professions educational programs find IPE difficult to implement and maintain for pre-professional students. This study suggests that these programs' learning outcomes, which are regulated by accreditation standards, probably conflict with implementation of IPE initiatives. Strategies to normalize learning outcomes language and develop shared mental models for IPE are needed.

Cluster analysis of multiple chronic conditions associated with urinary incontinence among women in the USA.

OBJECTIVE: To identify patterns of prevalent chronic medical conditions among women with urinary incontinence (UI). MATERIALS AND METHODS: We combined cross-sectional data from the 2005-2006 to 2011-2012 US National Health and Nutrition Examination Surveys, and identified 3 800 women with UI and data on 12 chronic conditions. Types of UI included stress UI (SUI), urgency UI (UUI), and mixed stress and urgency UI (MUI). We categorized UI as mild, moderate or severe using validated measures. We performed a two-step cluster analysis to identify patterns between clusters for UI type and severity. We explored associations between clusters by UI subtype and severity, controlling for age, education, race/ethnicity, parity, hysterectomy status and adiposity in weighted regression analyses. RESULTS: Eleven percent of women with UI had no chronic conditions. Among women with UI who had at least one additional condition, four distinct clusters were identified: (i) cardiovascular disease (CVD) risk-younger; (ii) asthma-predominant; (iii) CVD risk-older; and (iv) multiple chronic conditions (MCC). In comparison to women with UI and no chronic diseases, women in the CVD risk-younger (age 46.7 ± 15.8 years) cluster reported the highest rate of SUI and mild UI severity. In the asthma-predominant cluster (age 51.5 ± 10.2 years), women had more SUI and MUI and more moderate UI severity. Women in the CVD risk-older cluster (age 57.9 ± 13.4 years) had the highest rate of UUI, along with more severe UI. Women in the MCC cluster (age 61.0 ± 14.8 years) had the highest rates of MUI and the highest rate of moderate/severe UI. CONCLUSIONS: Women with UI rarely have no additional chronic conditions. Four patterns of chronic conditions emerged with differences by UI type and severity. Identification of women with mild UI and modifiable conditions may inform future prevention efforts.